| 1. |
- Studahl, Marie, 1957, et al.
(författare)
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Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.
- 2013
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 73:2, s. 131-58
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Forskningsöversikt (refereegranskat)abstract
- Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.
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| 2. |
- Egstrup, Kenneth, et al.
(författare)
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QT Response after a Test Dose and during Maintenance Therapy with AZD1305 in Patients with Atrial Fibrillation: A Double-Blind, Randomized, Placebo-Controlled Trial.
- 2011
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Ingår i: American journal of cardiovascular drugs : drugs, devices, and other interventions. - : Springer Science and Business Media LLC. - 1179-187X. ; 11:3, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance treatment with AZD1305. Methods: This was a randomized, double-blind, parallel-group, placebo-controlled trial carried out at multiple hospital cardiac facilities in Denmark, Norway, Poland, Slovakia, and Sweden. Patients with documented atrial fibrillation (AF) but currently in stable sinus rhythm for ≥2 hours and ≤90 days were eligible for inclusion. Patients were randomized in a 1:1:1 ratio to receive AZD1305 extended-release or matching placebo tablets as follows: group A - test dose 250mg, evening dose 125mg on day 1, maintenance dose 125mg twice daily; group B - test dose 500mg, placebo evening dose, maintenance dose 125mg twice daily; placebo group - placebo test and maintenance dose. Maintenance dosing was for 9 days. QTcF >550ms at any time during the in-patient phase or >500ms after discharge (day 4) were predefined study drug discontinuation criteria. The main outcome measure was the relationship between QTcF following the test dose and during maintenance treatment. Results: Sixty-five patients were randomized (n=21, 22, and 22 in group A, group B, and the placebo group, respectively). AZD1305 dose-dependently increased QTcF. There was a positive, linear correlation between the change in QTcF during the first 6 hours after the test dose and during the maintenance phase. Three patients, all from group B, discontinued treatment on day 1 due to QTcF >550ms. All other patients completed the study without events related to QT prolongation. There was a trend for reduced AF recurrence with AZD1305 compared with placebo. Conclusion: In this exploratory study a test dose predicted the QT response during maintenance treatment with AZD1305 and may thus be employed in further studies. [ClinicalTrials.gov Identifier: NCT00643448].
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| 3. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Early diagnosis of autism and impact on prognosis: a narrative review.
- 2013
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 5, s. 33-43
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008–2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband “early intervention” programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autism-friendly environment be “created” around affected individuals.
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| 4. |
- Hjalmarsson, Clara, 1969, et al.
(författare)
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Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke
- 2014
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Ingår i: Journal of Central Nervous System Disease. - 1179-5735. ; 19:6, s. 51-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS: A total of 20 patients (mean age 76 years) were included within 5-10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS: Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann-Whitney test). CONCLUSIONS: Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.
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| 5. |
- Skillgate, Eva, et al.
(författare)
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Healthy lifestyle behavior and risk of long duration troublesome neck pain or low back pain among men and women : results from the Stockholm Public Health Cohort
- 2017
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 9, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of healthy lifestyle behavior (HLB) in terms of physical activity, alcohol intake, smoking, and diet put together has not yet been explored for the risk of low back pain (LBP) and neck pain (NP). Our aim was to study if an HLB is protective against the onset of long duration troublesome LBP and NP in men and women.Methods: Two cohorts from the Stockholm Public Health Cohort, free from LBP (n=12,483) and NP (n=10,539), respectively, in 2006, were surveyed with questionnaires. Baseline information about physical activity, alcohol intake, diet, and smoking were dichotomized into being healthy/not healthy and combined in a categorical variable according to the number of healthy behaviors present. Binomial regression analyses were used to evaluate the role of HLB for the outcomes 4 years later.Results: When men with three or four healthy lifestyles were compared to men with none or one, the risk ratio (RR) of LBP was 0.63 (95% confidence interval [CI]: 0.39-1.02). The corresponding RR for LBP in women was 0.86 (95% CI: 0.56-1.32). When men with three or four healthy lifestyles were compared to men with none or one, the RR for NP was 1.13 (95% CI: 0.74-1.71). The corresponding RR for NP in women was 0.52 (95% CI: 0.35-0.77).Conclusion: An HLB seems to be protective for long duration troublesome LBP in men, and for long duration troublesome NP in women.
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| 6. |
- Stewart, Robert A. C., et al.
(författare)
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Looking forward to our 40th year of publication
- 2012
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Ingår i: Social behavior and personality. - : Scientific Journal Publishers Ltd. - 0301-2212 .- 1179-6391. ; 40:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
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| 9. |
- Christidis, Nikolaos, et al.
(författare)
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Pharmacological Treatments of Temporomandibular Disorders : A Systematic Review Including a Network Meta-Analysis
- 2023
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Ingår i: Drugs. - : Springer. - 0012-6667 .- 1179-1950.
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Temporomandibular disorders (TMD) comprise a cluster of conditions with a wide range of etiological factors that causes pain and discomfort in the masticatory muscles (TMD-M) and temporomandibular joints (TMD-J). More than 50% of the patients with TMD report regular usage of drugs. However, there is still no consensus, nor is there any evidence-based support for clinicians when choosing between different drugs. Therefore, this systematic review, including a network meta-analysis (NMA), aimed to evaluate the scientific evidence and discuss the pharmacological treatment options available to treat painful TMD.METHOD: An electronic search was undertaken to identify randomized controlled trials (RCTs) investigating pharmacological treatments for TMD-M and/or TMD-J, published until 6 April 2023. Since only 11 articles could be used for an NMA regarding TMD-M, a narrative synthesis was also performed for all 40 included RCTs. The quality of evidence was rated according to Cochrane's tool for assessing risk of bias, while the certainty of evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE).RESULTS: When it comes to TMD-M, evidence arises for wet needling therapies with BTX-A, granisetron, and PRP as well as muscle relaxants. For TMD-J, evidence points toward pharmacological treatment approaches including non-steroidal antiinflammatory drugs (NSAIDs) and glucocorticosteriods (for inflammatory conditions) as well as hyaluronic acid and dextrose.CONCLUSIONS: The evidence clearly indicates that the pharmacological treatment approaches differ between TMD-M and TMD-J. Therefore, it is of great importance to first try to uncover each patient's individual and multifactorial etiology and then employ a multifaceted treatment strategy, including pharmacological treatment approaches.
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| 10. |
- Currow, David C., et al.
(författare)
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Opioids for Chronic Refractory Breathlessness: Right Patient, Right Route?
- 2014
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 74:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Chronic breathlessness at rest or on minimal exertion despite optimal treatment of the underlying chronic cause(s) is termed chronic refractory breathlessness. This is prevalent across the community and is an independent indicator of poor prognosis. This narrative review focuses on the palliation of chronic refractory breathlessness in people predominantly with non-cancer diagnoses. Breathlessness is a complex sensation with at least three dimensions-intensity, distress/unpleasantness and its impact on function. It is the conscious representation of a mismatch between central ventilatory drive (the demand to breathe) and the responding respiratory output (the ability to breathe). Measurement relies on subjective reports by patients using a choice of uni- and multi-variable tools; the minimal clinically important difference is the smallest change conceived as clinically meaningful by the patients. Exogenous and endogenous opioids work centrally to reduce the sensation of breathlessness, with morphine as a mu opioid receptor agonist the most widely studied. Regular, low doses of sustained-release morphine have been shown to safely reduce breathlessness in this setting without evidence of respiratory depression nor obtundation. Patients should be initiated at a dosage of 10 mg/24 h and titrated by 10 mg if there is no benefit once in steady state. The highest dosage in the only dose-ranging study published to date was only 30 mg/24 h. Predictors of response to opioids for chronic refractory breathlessness include younger people with more severe breathlessness at baseline. Future research should address whether upward titration delivers further clinical benefit and whether all underlying aetiologies respond as predictably to opioids.
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| 11. |
- De la Torre Canales, Giancarlo, et al.
(författare)
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Botulinum toxin-a for the treatment of myogenous temporomandibular disorders : an umbrella review of systematic reviews
- 2024
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Ingår i: Drugs. - : Adis. - 0012-6667 .- 1179-1950.
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Forskningsöversikt (refereegranskat)abstract
- Objective: Temporomandibular disorders (TMDs) encompass several conditions that cause pain and impair function of the masticatory muscles (M-TMDs) and temporomandibular joints. There is a large interest among clinicians and researchers in the use of botulinum toxin-A (BoNT-A) as a treatment for M-TMD. However, due to the lack of consistent evidence regarding the efficacy as well as adverse events of BoNT-A, clinical decision making is challenging. Therefore, this umbrella review aimed to systematically assess systematic reviews (SRs) evaluating BoNT-A treatment effects on pain intensity, mandibular movements, and adverse events in patients with M-TMDs.Method: An electronic search was undertaken in the databases MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL), Web of Science, Epistemonikos, ClinicalTrials.gov, and ICTRP to identify SRs investigating BoNT-A effects on M-TMDs, published from the inception of each database until 6 December 2023. The quality of evidence was rated according to the critical appraisal checklist developed by the umbrella review methodology working group. Only high-quality SRs were included.Results: In total, 18 SRs were included. BoNT-A was shown to be more effective than placebo to reduce pain intensity, but not compared to standard treatments. Additionally, BoNT-A was not superior to placebo or standard treatments regarding improvement of mandibular movements. BoNT-A was considered to have a higher risk for adverse events on muscle and bony tissue compared with other treatments.Conclusion: The synthesis in this umbrella review provides the highest level of evidence present. Taken together, there are indications of effectiveness of BoNT-A for treatment of M-TMDs, supported by moderate evidence. However, considering the risk of causing serious adverse events, treatment with BoNT-A is recommended to be the last treatment alternative.
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| 12. |
- Eapen, Mathew Suji, et al.
(författare)
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Chronic Obstructive Pulmonary Disease and Lung Cancer : Underlying Pathophysiology and New Therapeutic Modalities
- 2018
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 78:16, s. 1717-1740
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.
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| 13. |
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| 14. |
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| 17. |
- Hey, John A., et al.
(författare)
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Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease
- 2024
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Ingår i: DRUGS. - 0012-6667 .- 1179-1950. ; 84, s. 811-823
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Tidskriftsartikel (refereegranskat)abstract
- Introduction ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (A beta) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments.Methods The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) >= 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau181, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma A beta 42 and A beta 40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau181 at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test.Results The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau181 reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks.Conclusions The effect of ALZ-801 on reducing plasma p-tau181 over 2 years demonstrates target engagement and supports its anti-A beta oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD.Trial Registration https://clinicaltrials.gov/study/NCT04693520.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Kim, HoUng, et al.
(författare)
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The Future of Biosimilars : Maximizing Benefits Across Immune-Mediated Inflammatory Diseases
- 2020
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Ingår i: Drugs. - : Adis International. - 0012-6667 .- 1179-1950. ; 80:2, s. 99-113
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Tidskriftsartikel (refereegranskat)abstract
- Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars-biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators-can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.
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| 22. |
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| 23. |
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| 24. |
- Källén, Bengt, et al.
(författare)
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Ongoing Pharmacological Management of Chronic Pain in Pregnancy
- 2016
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 76:9, s. 915-924
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Tidskriftsartikel (refereegranskat)abstract
- The article discusses possible effects of the use of analgesics during pregnancy. It summarizes the pertinent literature and reports some previously unpublished data from the Swedish Medical Birth Register. Most likely the use of analgesics does not cause spontaneous abortion. Only small malformation risk increases are seen after the use of opioids and perhaps non-steroid anti-inflammatory drug (NSAID) use. If possible, the latter should be avoided during the first trimester. If exposure has occurred there is no reason to consider an interruption of the pregnancy. Continued use of analgesics may increase the risk of preeclampsia and of preterm birth, especially valid for opioids. Use of acetylsalicylic acid (ASA) in late pregnancy should be avoided because of the risk of bleeding and (valid also for NSAIDs) premature closure of the ductus arteriosus. A small risk for neonatal abstinence syndrome may exist after the use of opioids for chronic pain, notably during the third trimester and long-lasting effects on child development can possibly occur. For a woman with chronic pain, adequate use of pain killers during pregnancy is needed. It is prudent to avoid ASA and NSAIDs towards the end of the pregnancy, while acetaminophen is an acceptable option all through pregnancy. If continued use of opioids is necessary, the associated risks are low. Triptans can be used for migraine during pregnancy. If possible sumatriptan is preferable to other triptans as data for the latter are largely lacking. Ergots are preferably avoided as not enough data are available.
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| 25. |
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| 26. |
- Landgren, Valdemar, 1988, et al.
(författare)
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Pharmacological Treatment for Pedophilic Disorder and Compulsive Sexual Behavior Disorder: A Review
- 2022
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 82:6, s. 663-681
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines for the pharmacological treatment of paraphilic disorders have historically been based on data from forensic settings and on risk levels for sexual crime. However, emerging treatment options are being evaluated for individuals experiencing distress because of their sexual urges and preferences, targeting both paraphilic disorders such as pedophilic disorder (PeD) and the new diagnosis of compulsive sexual behavior disorder (CSBD) included in the International Classification of Diseases, 11th Revision (ICD-11). As in other mental disorders, this may enable individualized pharmacological treatment plans, taking into account components of sexuality (e.g. high libido, compulsivity, anxiety-driven/sex as coping), medical and psychiatric comorbidity, adverse effects and patient preferences. In order to expand on previous reviews, we conducted a literature search focusing on randomized controlled trials of pharmacological treatment for persons likely to have PeD or CSBD. Our search was not restricted to studies involving forensic or criminal samples. Twelve studies conducted between 1974 and 2021 were identified regardless of setting (outpatient or inpatient), with only one study conducted during the last decade. Of a total of 213 participants included in these studies, 122 (57%) were likely to have PeD, 34 (16%) were likely to have a CSBD, and the remainder had unspecified paraphilias (40, 21%) or sexual offense (17, 8%) as the treatment indication. The diagnostic procedure for PeD and/or CSBD, as well as comorbid psychiatric symptoms, has been described in seven studies. The studies provide some empirical evidence that testosterone-lowering drugs reduce sexual activity for patients with PeD or CSBD, but the body of evidence is meager. There is a need for studies using larger samples, specific criteria for inclusion, longer follow-up periods, and standardized outcome measures with adherence to international reporting guidelines.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Ludvigsson, Johnny
(författare)
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Therapies to Preserve beta-Cell Function in Type 1 Diabetes
- 2016
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Ingår i: Drugs. - : ADIS INT LTD. - 0012-6667 .- 1179-1950. ; 76:2, s. 169-185
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Forskningsöversikt (refereegranskat)abstract
- In spite of modern techniques, the burden for patients with type 1 diabetes mellitus will not disappear, and type 1 diabetes will remain a life-threatening disease causing severe complications and increased mortality. We have to learn of ways to stop the destructive process, preserve residual insulin secretion or even improve the disease via beta-cell regeneration. This will give a milder disease, a more stable metabolism, simpler treatment and perhaps even cure. Therapies based on single drugs have not shown sufficient efficacy; however, there are several treatments with encouraging efficacy and no apparent, or rather mild, adverse events. As the disease process is heterogeneous, treatments have to be chosen to fit relevant subgroups of patients, and step by step efficacy can possibly be improved by the use of combination therapies. Thus immunosuppressive therapies like anti-CD3 and anti-CD20 monoclonal antibodies might be combined with fusion proteins such as etanercept [tumor necrosis factor (TNF)-alpha inhibitor] and/or abatacept (CTLA4-Ig) early after onset to stop the destructive process, supported by beta-cell protective agents. The effect may be prolonged by using autoantigen therapy [glutamate decarboxylase (GAD) proinsulin], and by adding agents facilitating beta-cell regeneration [e.g. glucagon-like peptide-1 (GLP-1)] there should be a good chance to make the disease milder, perhaps leading to cure in some patients.
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| 31. |
- Melkersson, Kristina, et al.
(författare)
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Adverse metabolic effects associated with atypical antipsychotics : literature review and clinical implications
- 2004
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 64:7, s. 701-23
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Tidskriftsartikel (refereegranskat)abstract
- Adverse metabolic effects, such as diabetes mellitus, lipid abnormalities and weight gain, have increasingly been recognised with the use of the newer, so-called atypical antipsychotic drugs. This article reviews the current literature in the field and attempts to answer the question of whether the atypical antipsychotics differ in their effects on glucose-insulin homeostasis and lipid metabolism. It also addresses how then to manage the use of the atypical antipsychotics that do interfere with these metabolic systems. Differences in effects of atypical antipsychotics on leptin levels are also summarised and put into context; bodyweight gain associated with atypical antipsychotics is reviewed elsewhere.In summary, there are no large controlled trials published quantifying the prevalence of adverse effects on glucose-insulin homeostasis and lipid metabolism in patients receiving atypical antipsychotics. Nevertheless, the published articles and case reports reviewed in this article give a fairly good view of those adverse effects occurring with clozapine, olanzapine and risperidone, whereas little data are available regarding quetiapine, ziprasidone and zotepine, and no data exist for amisulpride and aripiprazole. Estimated rankings of the atypical agents, based on the available literature, show that the relative risk of glucose intolerance/diabetes mellitus, hyperlipidaemia and hyperleptinaemia is highest for clozapine and olanzapine, moderately high for quetiapine, rather low for risperidone and lowest for ziprasidone. Since adverse metabolic effects of atypical antipsychotics may have a negative influence on both the antipsychotic treatment outcome as well as the physical health of the patient, these effects have to be recognised and adequately managed. In this review, recommendations for prevention and treatment of the adverse metabolic effects are outlined.
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| 32. |
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| 34. |
- Nicolau, Jose C., et al.
(författare)
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Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor : A Pre-Specified Analysis of the RE-DUAL PCI Trial
- 2020
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Ingår i: Drugs. - : Springer Nature. - 0012-6667 .- 1179-1950. ; 80:10, s. 995-1005
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy? Methods The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1-3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor. Results Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interactionpvalues > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interactionpvalues 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy). Conclusions Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor.
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| 35. |
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| 36. |
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| 37. |
- Pereira, Maria J, 1981-, et al.
(författare)
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Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity
- 2019
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Ingår i: Drugs. - : ADIS INT LTD. - 0012-6667 .- 1179-1950. ; 79:3, s. 219-230
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Tidskriftsartikel (refereegranskat)abstract
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.
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| 38. |
- Ambrosioni, E
(författare)
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Delapril/manidipine: viewpoints
- 2006
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667. ; 66:7, s. 970-971
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Andersson, Karl-Erik, et al.
(författare)
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CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention.
- 2003
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Ingår i: Drugs. - 0012-6667. ; 63:23, s. 2595-2611
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Forskningsöversikt (refereegranskat)abstract
- The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson’s disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may be found in the CNS. Several CNS transmitters/transmitter systems are known to be involved in micturition control, but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and duloxetine) have been used for the treatment of voiding disorders. GABA, glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine receptors and mechanisms are known to influence micturition, and drugs influencing these systems could potentially be developed for the treatment of OAB. Preclinical studies in different animal models have shown that modulation of normal micturition and detrusor overactivity by drugs acting within the spinal cord or supraspinally is possible. Promising results have been obtained in such models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering the limited predictability of existing animal models for efficacy in humans, positive proof of concept studies in humans are mandatory. Such studies are scarce and further investigations are needed.
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| 40. |
- Andersson, Roland, et al.
(författare)
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Treatment of acute pancreatitis: focus on medical care.
- 2009
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Ingår i: Drugs. - 0012-6667. ; 69:5, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis has an incidence of about 300 per 1 million individuals per year, of which 10-15% of patients develop the severe form of the disease. Novel management options, which have the potential to improve outcome, include initial proper fluid resuscitation, which maintains microcirculation and thereby potentially decreases ischaemia and reperfusion injury. The traditional treatment concept in acute pancreatitis, fasting and parenteral nutrition, has been challenged and early initiation of enteral feeding in severe pancreatitis and oral intake in mild acute pancreatitis is both feasible and provides some benefits. There are at present no data supporting immunonutritional supplements and probiotics should be avoided in patients with acute pancreatitis. There is also no evidence of any benefits provided by prophylactic antibacterials in patients with predicted severe acute pancreatitis. A variety of specific medical interventions have been investigated (e.g. intense blood glucose monitoring by insulin) but none has become clinically useful. Lessons can probably be learned from critical care in general, but studies are needed to verify these interventions in acute pancreatitis.
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| 41. |
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| 42. |
- Battino, D, et al.
(författare)
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Management of epilepsy during pregnancy
- 2007
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667. ; 67:18, s. 2727-2746
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Tidskriftsartikel (refereegranskat)
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Edlund, C, et al.
(författare)
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Effect of quinolones on intestinal ecology
- 1999
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667. ; 5858 Suppl 2, s. 65-70
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Tidskriftsartikel (refereegranskat)
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| 47. |
- Ekbom, K, et al.
(författare)
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Cluster headache - Aetiology, diagnosis and management
- 2002
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667. ; 62:1, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- Cluster headache is characterised by repeated attacks of strictly unilateral pain in the orbital region associated with local autonomic symptoms or signs. The attacks are brief but of a very severe, almost excruciating intensity. For unknown reasons males are affected more often than females. Recent studies suggest that an autosomal dominant gene has a role in some families with cluster headache. Hormonal studies indicate a dysfunction in the central nervous system. Neuro-imaging has revealed primary defects in the hypothalamic grey matter. Local homolateral dilatation in the intracranial segment of the internal carotid and ophthalmic arteries during attacks is the result of a generic neurovascular activation, probably mediated by trigeminal parasympathetic reflexes. Sumatriptan 6mg subcutaneously is the drug of choice in the treatment of acute attacks. Inhalation of 100% oxygen can also be recommended. In the prophylactic treatment, verapamil is the first option. Other drugs that can be considered are corticosteroids, which may induce a remission of frequent, severe attacks, and lithium. Oral ergotamine tartrate may be sufficient for patients with night attacks and/or short, rather mild to moderately severe cluster headache periods. Third line drugs are serotonin inhibitors (methysergide and pizotifen) and valproic acid. Patients should he encouraged to keep headache diaries and be carefully instructed about the nature and treatment of the headaches. Alcohol can bring on extra attacks and should not be consumed during active periods of cluster headache.
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| 48. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery
- 2006
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Ingår i: Drugs. - 0012-6667. ; 66:11, s. 1411-29
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Tidskriftsartikel (refereegranskat)abstract
- Current anticoagulant provision is dominated by parenteral heparin and oral warfarin, which act by inhibiting several steps of the coagulation pathway indirectly. Recent research efforts have focused on the identification of small molecule inhibitors of the coagulation enzymes as novel therapies for thrombotic disorders. There has been particular success in developing nonpeptidic, orally available, small molecules to directly inhibit the key proteases, factor IIa and factor Xa.Of the new oral anticoagulants in development, the two agents in the most advanced stage are dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factor IIa and factor Xa, respectively. Other agents in the early stages of development include several Xa inhibitors (LY-517717, YM150, DU-176b and apixaban [BMS-562247]), a factor IXa inhibitor (TTP889), and an orally active glycosaminoglycan enhancer (odiparcil [SB-424323]), which indirectly enhances thrombin inhibition via heparin cofactor II. Results have been reported from important, phase II dose-finding studies, and a number of registration-track phase III studies have been initiated, reflecting the drive towards potentially more effective, but primarily safer and more convenient therapies for the prevention and treatment of venous and arterial thrombosis. Indeed, two unmet needs for anticoagulation that can be easily identified are safety and ease of use. Safety relates primarily to the incidence of major bleeding and this remains the key concern of orthopaedic surgeons, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections.The clinical development of these new anticoagulants is following the well tested strategy of dose-ranging and registration studies in major orthopaedic surgery, prior to development in arterial indications. There are a number of subtle issues, including the timing of the first perioperative dose, duration of prophylactic treatment and definition/assessment of study endpoints that can influence study outcome and require careful consideration when evaluating study results with new agents and in the comparison with established agents, and which are considered in this review.It is anticipated that over the next 3 years, at least one of these agents will be successfully licensed for the prevention of venous thromboembolism after major orthopaedic surgery, which will act as a springboard for the gradual replacement of current anticoagulants.
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| 49. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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Prevention of venous thromboembolism following orthopaedic surgery: clinical potential of direct thrombin inhibitors
- 2004
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Ingår i: Drugs. - 0012-6667. ; 64:6, s. 577-95
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing total hip or total knee replacement are at high risk of venous thromboembolism (VTE), and are therefore considered to be populations well suited for the evaluation and dose optimisation of new anticoagulants. Deep vein thrombosis may lead to life-threatening pulmonary embolism, disabling morbidity in the form of the post-thrombotic syndrome, and risk of recurrent thrombotic events. There is increasing evidence that anticoagulant treatment for the prevention of VTE should be extended from 1 to at least 4 weeks after surgery. Anticoagulation with vitamin K antagonists (such as warfarin), low molecular weight heparin or unfractionated heparin effectively lowers the risk of VTE, but these anticoagulants have limitations such as the need for coagulation monitoring and subsequent dose adjustment (vitamin K antagonists), difficulty of continuing prophylaxis out of hospital because of the requirement for parenteral administration, and risk of heparin-induced thrombocytopenia. The development of new anticoagulants has been pursued with the aim of finding more effective, safer and/or more convenient therapies.Thrombin is a central regulator in the coagulation and inflammation process and several direct thrombin inhibitors (DTIs) with distinct pharmacological profiles, as well as pharmacological differences from the conventional anticoagulants, are currently in clinical use for certain indications or are under development. Clinical experience with parenterally administered DTIs has accumulated since the mid 1990s, although only desirudin (a recombinant hirudin) is currently approved for use in patients undergoing orthopaedic surgery. Two oral DTIs, ximelagatran and dabigatran etexilate, are in clinical development. Dabigatran etexilate has recently been evaluated in phase II clinical trials in patients undergoing total hip replacement. Several large phase III trials have now demonstrated the efficacy and safety of ximelagatran in the prevention of VTE following total hip or knee replacement. Ximelagatran can be used with an oral fixed dose without the need for coagulation monitoring or dose adjustment. Hence, it offers significant potential to facilitate the management of anticoagulation in or out of hospital.
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| 50. |
- Eriksson, Henry, 1946
(författare)
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Treatment of venous thromboembolism and long-term prevention of recurrence: present treatment options and ximelagatran
- 2004
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Ingår i: Drugs. - 0012-6667. ; 64 Suppl 1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Despite the effectiveness of anticoagulant therapy for the treatment of acute venous thromboembolism and the prevention of recurrent venous thromboembolism, existing antithrombotic therapies are suboptimal. Unfractionated heparin, low-molecular-weight heparin (LMWH) and warfarin have practical limitations and carry the risk of treatment-related adverse events that restrict their clinical benefits and reduce cost-effectiveness. Efforts to achieve optimal venous thromboembolism prophylaxis by modifying the intensity of oral warfarin treatment have produced equivocal results, and there is a need for new, efficacious antithrombotic drugs providing predictable, well-tolerated oral dosing without the need for coagulation monitoring. Such agents would ideally have no significant food or drug interactions, and be suitable for both short- and long-term treatment. Ximelagatran, the first oral direct thrombin inhibitor, has the potential to fulfill many of the unmet needs in the management of venous thromboembolism.
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