| 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. |
- 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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| 6. |
- 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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