Breathalyser-Based eHealth Data Suggest That Self-Reporting of Abstinence Is a Poor Outcome Measure for Alcohol Use Disorder Clinical Trials.

AIMS: To evaluate the efficacy and monitoring capabilities of a breathalyser-based eHealth system for patients with alcohol use disorder (AUD) and to investigate the quality and validity of timeline follow-back (TLFB) as outcome measure in clinical trials and treatment. METHODS: Patients (n = 115) were recruited to clinical trials from a 12-step aftercare programme (12S-ABS) and from hospital care with abstinence (HC-ABS) or controlled drinking (HC-CDR) as goal and randomly divided into an eHealth and a control group. The effect of the eHealth system was analysed with TLFB-derived primary outcomes-change in number of abstinent days (AbsDay) and heavy drinking days (HDDs) compared to baseline-and phosphatidyl ethanol (PEth) measurements. Validity and quality of TLFB were evaluated by comparison with breath alcohol content (BrAC) and eHealth digital biomarkers (DBs): Addiction Monitoring Index (AMI) and Maximum Time Between Tests (MTBT). TLFB reports were compared to eHealth data regarding reported abstinence. RESULTS: The primary outcome (TLFB) showed no significant difference between eHealth and control groups, but PEth did show a significant difference especially at months 2 and 3. Self-reported daily abstinence suffered from severe quality issues: of the 28-day TLFB reports showing full abstinence eHealth data falsified 34% (BrAC measurements), 39% (MTBT), 54% (AMI) and 68% (BrAC/MTBT/AMI). 12S-ABS and HC-ABS patients showed severe under-reporting. CONCLUSIONS: No effect of the eHealth system was measured with TLFB, but a small positive effect was measured with PEth. The eHealth system revealed severe quality problems with TLFB, especially regarding abstinence-should measurement-based eHealth data replace TLFB as outcome measure for AUD?

Myrcene Attenuates Renal Inflammation and Oxidative Stress in the Adrenalectomized Rat Model.

Physiological Glucocorticoids are important regulators of the immune system. Pharmacological GCs are in widespread use to treat inflammatory diseases. Adrenalectomy (ADX) has been shown to exacerbate renal injury through inflammation and oxidative stress that results in renal impairment due to depletion of GCs. In this study, the effect of myrcene to attenuate renal inflammation and oxidative stress was evaluated in the adrenalectomized rat model. Rats were adrenalectomized bilaterally or the adrenals were not removed after surgery (sham). Myrcene (50 mg/kg body weight, orally) was administered post ADX. Myrcene treatment resulted in significant downregulation of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) compared to untreated ADX rats. In addition, myrcene resulted in significant downregulation of immunomodulatory factors (IFNγ and NF-κB) and anti-inflammatory markers (IL-4 and IL-10) in treated ADX compared to untreated ADX. Myrcene significantly increased the antioxidant molecules (CAT, GSH, and SOD) and decreased MDA levels in treated ADX compared to untreated. Moreover, myrcene treatment reduced the expression of COX-2, iNOS, KIM-1, and kidney functional molecules (UREA, LDH, total protein, and creatinine) in ADX treated compared to ADX untreated. These results suggest that myrcene could be further developed as a therapeutic drug for treatment of kidney inflammation and injury.

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

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.

Aquaporin gene therapy corrects Sjögren's syndrome phenotype in mice.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjögren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjögren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjögren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjögren's syndrome.

An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice.

The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1-7 (SP1-7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1-7 and the tetrapeptide endomorphin-2 that is also binding to the SP1-7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50) of 4 was superior as compared to gabapentin and morphine that are used in clinic.

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

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 ClinicalTrials.gov (NCT03195894).

The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro.

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.

Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain.

Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the µ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/µ- and κ-/µ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/µ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.

Depressed mood, anxiety, and the use of labor analgesia.

Relatively little is known about mental health and labor pain. The aim of this study was to assess if self-rated antenatal depressed mood and anxiety are associated with pain-related behaviors and self-reported labor pain. We also wanted to replicate our previous finding of altered labor pain behavior in carriers of a specific guanosine triphosphate cyclohydrolase 1 gene (GCH1) haplotype. Ninety-nine women in gestational weeks 37 to 40 filled out questionnaires on depression and anxiety symptoms and later rated their labor pain by use of visual analog scales. Each subject was also genotyped for GCH1. Following adjustment for relevant confounders, women who arrived early to the delivery unit (cervical dilation <5 cm) had a significantly higher antenatal Montgomery-Åsberg Depression Rating Scale (MADRS-S) score, p < 0.05, than late arrivers (cervical dilation >5 cm). Women with increased Spielberger State-Trait Anxiety Inventory (STAI-T) scores reported higher self-rated pain prior to labor analgesia, p < 0.05, than women with low STAI-T scores. No association between the GCH1 pain-protective haplotype and cervical dilation was found, but a previously demonstrated association with increased use of second-line analgesia was confirmed. Depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia.

Brief Intervention Within Primary Care for At-Risk Gambling: A Pilot Study.

Studies on interventions for at-risk gambling are scarce. This pilot study is the first step in a larger project aimed to develop methods to prevent more serious gambling problems. Drawing on experiences from the alcohol field, the brief intervention (BI) model was tested in a primary care setting. Primary care personnel was trained for 2 days. Patients were screened, and those with signs of problematic gambling were offered a return visit to discuss their gambling habits. Of the 537 screened, 34 (6.3 %) screened positive for problem gambling. Of those, 24 were at-risk gamblers whereof 19 agreed to participate. Six of those 19 took part in a 1-month follow-up. Important information for the planning of upcoming studies was collected from the pilot work. Given that the rate of at-risk gamblers was elevated in this setting we consider primary care a suitable arena for intervention. Staff training and support appeared essential, and questionnaires should be selected that are clear and well-presented so staff feel secure and comfortable with them. The BI model was found to be most suitable for patients already known to the caregiver. The number of participants who were willing to take part in the follow-up was low. To ensure power in future studies, a much larger number of screened patients is evidently necessary.

Serotonin receptor gene (5HT-2A) polymorphism is associated with provoked vestibulodynia and comorbid symptoms of pain.

INTRODUCTION: Provoked vestibulodynia (PVD) is a common type of dyspareunia among young women. The patho-physiology remains largely unclear. Women with PVD have general pain hypersensitivity and often report additional pain symptoms. Signs point towards PVD being a chronic pain disorder similar to other syndromes of longstanding pain, including a common comorbidity of anxiety and depression. Polymorphism in the serotonin receptor gene, 5HT-2A, has been associated with other chronic pain disorders such as fibromyalgia but has not been investigated in PVD patients. AIM: We aimed to investigate a possible contribution of polymorphism in the 5HT-2A gene to the etiology of PVD as well as a potential influence on pain sensitivity. METHODS: In this case-control study 98 women with PVD and 103 healthy controls between 18 and 44 years and in the same menstrual cycle phase completed questionnaires and underwent quantitative sensory testing. Venous blood samples were collected for DNA isolation. MAIN OUTCOME MEASURES: Concomitant pain was reported, a bodily pain score was created and pressure pain thresholds (PPTs) on the arm, leg, and in the vestibule were measured. Intensity of coital pain was rated on a visual analog scale, range 0-100. The T102C (rs6313) and A-1438G (rs6311) single nucleotide polymorphisms (SNPs) in the 5HT-2A gene were analyzed. RESULTS: The probability of PVD was elevated in participants carrying the 1438G- and 102C-alleles of the 5HT-2A gene (OR 2.9). The G-/C- genotypes were also associated with more concomitant bodily pain in addition to the dyspareunia, but not with experimental PPTs or coital pain ratings. PVD patients reported more concomitant bodily pain and had lower PPTs compared with controls. CONCLUSION: The results indicate a contribution of alterations in the serotonergic system to the patho-genesis of PVD and gives further evidence of PVD being a general pain disorder similar to other chronic pain disorders.

Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23.

Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria. We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia. PDYN is the precursor protein for the opioid neuropeptides, α-neoendorphin, and dynorphins A and B (Dyn A and B). Dynorphins regulate pain processing and modulate the rewarding effects of addictive substances. Three mutations were located in Dyn A, a peptide with both opioid activities and nonopioid neurodegenerative actions. Two of these mutations resulted in excessive generation of Dyn A in a cellular model system. In addition, two of the mutant Dyn A peptides induced toxicity above that of wild-type Dyn A in cultured striatal neurons. The fourth mutation was located in the nonopioid PDYN domain and was associated with altered expression of components of the opioid and glutamate system, as evident from analysis of SCA23 autopsy tissue. Thus, alterations in Dyn A activities and/or impairment of secretory pathways by mutant PDYN may lead to glutamate neurotoxicity, which underlies Purkinje cell degeneration and ataxia. PDYN mutations are identified in a small subset of ataxia families, indicating that SCA23 is an infrequent SCA type (∼0.5%) in the Netherlands and suggesting further genetic SCA heterogeneity.

Recombinant human growth hormone affects the density and functionality of GABAB receptors in the male rat brain.

The beneficial effects of growth hormone (GH) on memory and learning have previously been confirmed in both humans and in animal models. An important role of GABAB receptors for multiple forms of learning and memory has also been reported. In this study, we examined the effect of GH on the density and functionality of the metabotropic GABAB receptors in the rat brain. Male Sprague-Dawley rats (n = 24) divided into 3 groups were injected twice daily with recombinant human GH (0.07 or 0.7 IU/kg) for 7 days. The effects of the hormone were determined by quantitative autoradiography and by GABAB stimulated [(35)S]-GTPγS binding using the selective GABAB receptor agonist baclofen. The results demonstrate moderate but significant alterations in both receptor density and functionality in a number of brain regions. For example, a dose-dependent upregulation of GABAB receptors was found in the cingulate cortex, primary motor cortex and caudate putamen, whereas attenuation in the receptor density was encountered in, for example, the medial geniculate nucleus. Although the GH-induced effects on the GABAB receptor in brain areas associated with cognition were fairly pronounced, they were significant and we propose that the physiological responses observed after GH administration at least partly can be mediated through a mechanism involving GABAB receptors.

Effects of dehydration and blockade of angiotensin II AT1 receptor on stress hormones and anti-oxidants in the one-humped camel.

BACKGROUND: The objective of this study was to provide for the first time data on plasma catecholamines, cortisol, glutathione and malondialdehyde after long term dehydration (20 days) in the presence and absence of angiotensin II (Ang II) AT1 receptor blocker (losartan) versus levels in time-matched, non-dehydrated control camels and to record the responses of glutathione and malondialdehyde activity in liver and kidney homogenates in control, dehydrated-losartan treated and dehydrated camels. Eighteen male camels were studied, six hydrated (control group), six dehydrated and treated with losartan (treated group) and six dehydrated not treated (dehydrated). RESULTS: Plasma levels of norepinephrine and dopamine were significantly increased (P < 0.01) in both treated and dehydrated groups compared to time matched control, whereas Plasma epinephrine level showed significant decrease (P < 0.05) in both treated and dehydrated groups compared to control. Plasma cortisol also showed significant increase (P < 0.01) in both treated and dehydrated groups compared to control. Glutathione levels in plasma, liver and kidney homogenates for both treated and dehydrated groups reveled significant increase (P < 0.05) Likewise, malondialdehyde levels in plasma, liver and kidney homogenates were substantially and significantly increased in both treated and dehydrated groups. CONCLUSION: In conclusion, the results of this study demonstrated that dehydration substantially increased the circulating levels of norepinephrine, dopamine and cortisol but decreased plasma epinephrine. Similarly, losartan showed similar effects to that of dehydration. In addition, this investigation showed dehydration alone or in combination with losartan induced significant increments in glutathione and malondialdehyde activities in plasma, liver and kidney homogenates, presumably in order to counteract the potentially damaging effects of free radicals. Blockade of angiotensin II AT1 receptors did not alter significantly the response of dehydration in any of these indices.

The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction.

The endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations in this system may be specific for different stages of addiction cycle and neurocircuitries involved and therefore may differentially contribute to the initiation and maintenance of addiction. Here we evaluated whether the EOS is altered in brain areas involved in cognitive control of addiction including the dorsolateral prefrontal cortex (dl-PFC), orbitofrontal cortex (OFC) and hippocampus in human alcohol-dependent subjects. Levels of EOS mRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and levels of dynorphins by radioimmunoassay (RIA) in post-mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mRNA and dynorphins in dl-PFC, κ-opioid receptor mRNA in OFC and dynorphins in hippocampus were up-regulated in alcoholics. No significant changes in expression of proenkephalin, and µ- and δ-opioid receptors were evident; pro-opiomelanocortin mRNA levels were below the detection limit. Activation of the κ-opioid receptor by up-regulated dynorphins in alcoholics may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.

Neuropeptide Y and measures of stress in a longitudinal study of women with the fibromyalgia syndrome.

OBJECTIVES: Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other. METHODS: Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed. RESULTS: Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study. CONCLUSIONS: After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y.

Evaluation of 6 years of eHealth data in the alcohol use disorder field indicates improved efficacy of care.

Background: Predictive eHealth tools will change the field of medicine, however long-term data is scarce. Here, we report findings on data collected over 6 years with an AI-based eHealth system for supporting the treatment of alcohol use disorder. Methods: Since the deployment of Previct Alcohol, structured data has been archived in a data warehouse, currently comprising 505,641 patient days. The frequencies of relapse and caregiver-patient messaging over time was studied. The effects of both introducing an AI-driven relapse prediction tool and the COVID-19 pandemic were analyzed. Results: The relapse frequency per patient day among Previct Alcohol users was 0.28 in 2016, 0.22 in 2020 and 0.25 in 2022 with no drastic change during COVID-19. When a relapse was predicted, the actual occurrence of relapse in the days immediately after was found to be above average. Additionally, there was a noticeable increase in caregiver interactions following these predictions. When caregivers were not informed of these predictions, the risk of relapse was found to be higher compared to when the prediction tool was actively being used. The prediction tool decreased the relapse risk by 9% for relapses that were of short duration and by 18% for relapses that lasted more than 3 days. Conclusions: The eHealth system Previct Alcohol allows for high resolution measurements, enabling precise identifications of relapse patterns and follow up on individual and population-based alcohol use disorder treatment. eHealth relapse prediction aids the caregiver to act timely, which reduces, delays, and shortens relapses.

GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia.

BACKGROUND: Provoked vestibulodynia (PVD) is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. RESULTS: We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98) and healthy controls (n = 102). However, among patients with current treatment (n = 36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain thresholds on the arm (p = 0.04). PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. CONCLUSIONS: The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this intervention.

Processing incomplete questionnaire data into continuous digital biomarkers for addiction monitoring.

PURPOSE: eHealth systems allow efficient daily smartphone-based collection of self-reported data on mood, wellbeing, routines, and motivation; however, missing data is frequent. Within addictive disorders, missing data may reflect lack of motivation to stay sober. We hypothesize that qualitative questionnaire data contains valuable information, which after proper handling of missing data becomes more useful for practitioners. METHODS: Anonymized data from daily questionnaires containing 11 questions was collected with an eHealth system for 751 patients with alcohol use disorder (AUD). Two digital continuous biomarkers were composed from 9 wellbeing questions (WeBe-i) and from two questions representing motivation/self-confidence to remain sober (MotSC-i). To investigate possible loss of information in the process of composing the digital biomarkers, performance of neural networks to predict exacerbation events (relapse) in alcohol use disorder was compared. RESULTS: Long short-term memory (LSTM) neural networks predicted a coming exacerbation event 1-3 days (AUC 0.68-0.70) and 5-7 days (AUC 0.65-0.68) in advance on unseen patients. The predictive capability of digital biomarkers and raw questionnaire data was equal, indicating no loss of information. The transformation into digital biomarkers enable a continuous graphical display of each patient's clinical course and a combined interpretation of qualitative and quantitative aspects of recovery on a time scale. CONCLUSION: By transforming questionnaire data with large proportion of missing data into continuous digital biomarkers, the information captured by questionnaires can be more easily used in clinical practice. Information, assessed by the capability to predict exacerbation events of AUD, is preserved when processing raw questionnaire data into digital biomarkers.