Publications by authors named "E Olof Karlberg"

19 Publications

Maximum Time Between Tests: A Digital Biomarker to Detect Therapy Compliance and Assess Schedule Quality in Measurement-Based eHealth Systems for Alcohol Use Disorder.

Alcohol Alcohol 2019 Jan;54(1):70-72

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Aim: To evaluate, in a breathalyzer-based eHealth system, whether the time-based digital biomarker 'maximum time between tests' (MTBT) brings valuable information on alcohol consumption patterns as confirmed by correlation with blood phosphatidyl ethanol (PEth), serum carbohydrate deficient transferrin (CDT) and timeline follow-back data.

Method: Data on 54 patients in follow-up for treatment of alcohol use disorder were analysed.

Results: The model of weekly averages of 24-log transformed MTBT adequately described timeline follow-back data (P  <  0.0001, R =  0.27-0.38, n  =  650). Significant correlations were noted between MTBT and PEth (P  <  0.0001, R  =  0.41, n  =  148) and between MTBT and CDT (P  <  0.0079, R  =  0.22, n  =  120).

Conclusions: The time-based digital biomarker 'maximum time between tests' described here has the potential to become a generally useful metric for all scheduled measurement-based eHealth systems to monitor test behaviour and compliance, factors important for 'dosing' of eHealth systems and for early prediction and interventions of lapse/relapse.
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January 2019

Real-time Monitoring using a breathalyzer-based eHealth system can identify lapse/relapse patterns in alcohol use disorder Patients.

Alcohol Alcohol 2018 Jul;53(4):368-375

Department of Pharmaceutical Biosciences, Uppsala University, Box 591, Uppsala, Sweden.

Aim: We introduce a new remote real-time breathalyzer-based method for monitoring and early identification of lapse/relapse patterns for alcohol use disorder (AUD) patients using a composite measure of sobriety, the Addiction Monitoring Index (AMI).

Methods: We constructed AMI from (a) obtained test results and (b) the pattern of ignored tests using data from the first 30 patients starting in the treatment arms of two on-going clinical trials. The patients performed 2-4 scheduled breath alcohol content (BrAC)-tests per day presented as blood alcohol content (BAC) data. In total, 10,973 tests were scheduled, 7743 were performed and 3230 were ignored during 3982 patient days.

Results: AMI-time profiles could be used to monitor the daily trends of alcohol consumption and detect early signs of lapse and relapses. The pattern of ignored tests correlates with the onset of drinking. AMI correlated with phosphatidyl ethanol (n = 61, F-ratio = 34.6, P < 0.0001, R = -0.61). The recognition of secret drinking could further be improved using a low alcohol detection threshold (BrAC = 0.025 mg/l, BACSwe = 0.05‰ or US = 0.0053g/dl), in addition to the legal Swedish traffic limit (BrAC = 0.1 mg/l, BACSwe = 0.2‰ or US = 0.021 g/dl). Nine out of 10 patients who dropped out from the study showed early risk signs as reflected in the level and pattern in AMI before the actual dropout.

Conclusions: AMI-time profiles from an eHealth system are useful for monitoring the recovery process and for early identification of lapse/relapse patterns. High-resolution monitoring of sobriety enables new measurement-based treatment methods for proactive personalized long-term relapse prevention and treatment of AUD patients.

Clinical Trial Registration: The data used for construction of AMI was from two clinical trials approved by the Regional Ethics Committee of Uppsala, Sweden and performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participating subjects. The study was registered at (NCT03195894).
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July 2018

A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis.

Mult Scler 2011 Jun 12;17(6):708-19. Epub 2011 Jan 12.

Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010.

Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded.

Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n=901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials.

Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.
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June 2011

A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes.

Proc Natl Acad Sci U S A 2008 Dec 22;105(52):20870-5. Epub 2008 Dec 22.

Center for Biological Sequence Analysis, Kemitorvet building 208, Technical University of Denmark, DK-2800 Lyngby, Denmark.

Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were systematically mapped to tissues they affect from disease-relevant literature in PubMed to create a disease-tissue covariation matrix of high-confidence associations of >1,000 diseases to 73 tissues. By retrieving >2,000 known disease genes, and generating 1,500 disease-associated protein complexes, we analyzed the differential expression of a gene or complex involved in a particular disease in the tissues affected by the disease, compared with nonaffected tissues. When this analysis is scaled to all diseases in our dataset, there is a significant tendency for disease genes and complexes to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also identified complexes in Parkinson disease, cardiomyopathies, and muscular dystrophy syndromes that are similarly tissue specific. Our method represents a conceptual scaffold for organism-spanning analyses and reveals an extensive list of tissue-specific draft molecular pathways, both known and unexpected, that might be disrupted in disease.
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December 2008