- Trends in Insomnia Diagnosis and Treatment Among Medicare Beneficiaries, 2006-2013. [Journal Article]
- AJAm J Geriatr Psychiatry 2018 Nov 02
- CONCLUSIONS: In this large national analysis of Medicare beneficiaries, prevalence of physician-assigned insomnia diagnoses was low but increased over time. Prevalence of insomnia medication use was up to four-times higher than insomnia diagnoses and remained steady over time. Notably, prevalence of benzodiazepine use increased dramatically from 2012-2013 after these medications were included in the Medicare Part D formulary.
- Sleep disturbances in patients with liver cirrhosis: prevalence, impact, and management challenges. [Review]
- NSNat Sci Sleep 2018; 10:369-375
- Sleep-wake disturbances are common in liver cirrhosis and associated with impaired quality of life. The most common abnormalities are insomnia (difficulties falling asleep and maintaining sleep, or u...
Sleep-wake disturbances are common in liver cirrhosis and associated with impaired quality of life. The most common abnormalities are insomnia (difficulties falling asleep and maintaining sleep, or unrefreshing sleep), excessive daytime sleepiness, and sleep-wake inversion (disturbances of circadian rhythmicity). The underlying pathophysiological mechanisms for sleep disturbances in cirrhosis are complex and may include disturbed metabolism of melatonin and glucose, alterations in thermoregulation, and altered ghrelin secretion profiles. Sleep-wake abnormalities are related to the presence of hepatic encephalopathy (HE) and improvement in sleep parameters can be observed when HE is properly managed. A few non-specific treatments for sleep-wake abnormalities have been tried with encouraging results for hydroxyzine and modafinil. However, due to the potential for medication toxicity in these disabled patients, further studies are needed to address the potential role of non-drug therapies in this population (eg, cognitive behavioral therapy, mindfulness, yoga) that have demonstrated usefulness in insomnia disorders.
- Drug eruption by antihistamine mistaken for chronic urticaria in a child. [Journal Article]
- KJKorean J Pediatr 2018 Oct 30
- Although rare, antihistamines can casue adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after ad...
Although rare, antihistamines can casue adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax® (hydroxyzine) or leptizine® (levocetirizine), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.
- A Retrospective Study of Dosing Weight and Outcomes for One Pediatric Dental Sedation Regimen. [Journal Article]
- PDPediatr Dent 2018 Sep 15; 40(5):346-351
- Purpose: The purpose of this study was to assess the use of a dosing scalar for association with the success of procedural sedation in pediatric dentistry. Methods: This cross-sectional, retrospect...
Purpose: The purpose of this study was to assess the use of a dosing scalar for association with the success of procedural sedation in pediatric dentistry. Methods: This cross-sectional, retrospective study assessed healthy two- to 12-year-olds who received an elixir of midazolam (0.3 mg/kg), meperidine (1.5 mg/kg), and hydroxyzine (1.0 mg/kg). The scaled body weight (SBW) for each patient was determined using the 50th percentile weight-for-age from the 2000 Centers for Disease Control and Prevention (CDC) growth chart. Children under the 50th percentile were dosed at their actual weight. Children weighing over the 50th percentile received a dose that was reduced to the 50th percentile weight-for-age. Statistical analysis evaluated sedation success, measured by the Houpt scale. Lean body weight (LBW) and ideal body weight (IBW) were calculated to compare SBW with other available dosing scalars. Results: The sample consisted of 427 children. The success was 73.8 percent. There was no significant difference in sedation success by dose delivered. The calculated LBW and IBW were significantly greater than the SBW (P<.001, P<.001). Conclusions: Sedation success was not affected by use of a scalar that reduced dosing weight to the 2000 CDC growth chart's 50th percentile weight-for-age.
- Using Machine Learning to Predict Synergistic Antimalarial Compound Combinations With Novel Structures. [Journal Article]
- FPFront Pharmacol 2018; 9:1096
- The parasite Plasmodium falciparum is the most lethal species of Plasmodium to cause serious malaria infection in humans, and with resistance developing rapidly novel treatment modalities are current...
The parasite Plasmodium falciparum is the most lethal species of Plasmodium to cause serious malaria infection in humans, and with resistance developing rapidly novel treatment modalities are currently being sought, one of which being combinations of existing compounds. The discovery of combinations of antimalarial drugs that act synergistically with one another is hence of great importance; however an exhaustive experimental screen of large drug space in a pairwise manner is not an option. In this study we apply our machine learning approach, Combination Synergy Estimation (CoSynE), which can predict novel synergistic drug interactions using only prior experimental combination screening data and knowledge of compound molecular structures, to a dataset of 1,540 antimalarial drug combinations in which 22.2% were synergistic. Cross validation of our model showed that synergistic CoSynE predictions are enriched 2.74 × compared to random selection when both compounds in a predicted combination are known from other combinations among the training data, 2.36 × when only one compound is known from the training data, and 1.5 × for entirely novel combinations. We prospectively validated our model by making predictions for 185 combinations of 23 entirely novel compounds. CoSynE predicted 20 combinations to be synergistic, which was experimentally validated for nine of them (45%), corresponding to an enrichment of 1.70 × compared to random selection from this prospective data set. Such enrichment corresponds to a 41% reduction in experimental effort. Interestingly, we found that pairwise screening of the compounds CoSynE individually predicted to be synergistic would result in an enrichment of 1.36 × compared to random selection, indicating that synergy among compound combinations is not a random event. The nine novel and correctly predicted synergistic compound combinations mainly (where sufficient bioactivity information is available) consist of efflux or transporter inhibitors (such as hydroxyzine), combined with compounds exhibiting antimalarial activity alone (such as sorafenib, apicidin, or dihydroergotamine). However, not all compound synergies could be rationalized easily in this way. Overall, this study highlights the potential for predictive modeling to expedite the discovery of novel drug combinations in fight against antimalarial resistance, while the underlying approach is also generally applicable.
- An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs. [Journal Article]
- PlosPLoS One 2018; 13(10):e0204648
- Different computational approaches are employed to efficiently identify novel repositioning possibilities utilizing different sources of information and algorithms. It is critical to propose high-val...
Different computational approaches are employed to efficiently identify novel repositioning possibilities utilizing different sources of information and algorithms. It is critical to propose high-valued candidate-repositioning possibilities before conducting lengthy in vivo validation studies that consume significant resources. Here we report a novel multi-methodological approach to identify opportunities for drug repositioning. We performed analyses of real-world data (RWD) acquired from the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) and the claims database maintained by the Japan Medical Data Center (JMDC). These analyses were followed by cross-validation through bioinformatics analyses of gene expression data. Inverse associations revealed using disproportionality analysis (DPA) and sequence symmetry analysis (SSA) were used to detect potential drug-repositioning signals. To evaluate the validity of the approach, we conducted a feasibility study to identify marketed drugs with the potential for treating inflammatory bowel disease (IBD). Primary analyses of the FAERS and JMDC claims databases identified psycholeptics such as haloperidol, diazepam, and hydroxyzine as candidates that may improve the treatment of IBD. To further investigate the mechanistic relevance between hit compounds and disease pathology, we conducted bioinformatics analyses of the associations of the gene expression profiles of these compounds with disease. We identified common biological features among genes differentially expressed with or without compound treatment as well as disease-perturbation data available from open sources, which strengthened the mechanistic rationale of our initial findings. We further identified pathways such as cytokine signaling that are influenced by these drugs. These pathways are relevant to pathologies and can serve as alternative targets of therapy. Integrative analysis of RWD such as those available from adverse-event databases, claims databases, and transcriptome analyses represent an effective approach that adds value to efficiently identifying potential novel therapeutic opportunities.
- Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients. [Journal Article]
- BJBr J Dermatol 2018 Oct 03
- CONCLUSIONS: Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.
- Socheongryong-tang for improving nasal symptoms associated with allergic rhinitis: A study protocol for a randomized, open-label, cetirizine controlled, clinical trial. [Randomized Controlled Trial]
- MMedicine (Baltimore) 2018; 97(34):e11812
- CONCLUSIONS: The findings of this study are expected to provide the basis for a full-scale randomized controlled trial to confirm the safety and effectiveness of SCRT for the treatment of nasal symptoms in patients with AR patients not controlled by conventional therapy.
- Pheniramine maleate: an apparently safe drug causing bullous fixed drug eruption. [Journal Article]
- DODermatol Online J 2018 08 23; 24(6)
- Fixed drug eruption is a delayed type hypersensitivity reaction to a drug seen most frequently with antibiotics such as tetracyclines, sulfonamides, and NSAIDs such as naproxen and ibuprofen. Althoug...
Fixed drug eruption is a delayed type hypersensitivity reaction to a drug seen most frequently with antibiotics such as tetracyclines, sulfonamides, and NSAIDs such as naproxen and ibuprofen. Although H1-antihistamines rarely elicit cutaneous adverse effects, there have been a few reports in the literature implicating them in causing fixed drug eruption, particularly the piperazine derivatives (hydroxyzine, cetirizine, levocetirizine), and loratadine. However, cutaneous drug reactions with the alkylamine derivatives like pheniramine maleate are extremely uncommon and fixed drug eruptions have not been reported with any of the alkylamine antihistamines to date. We herein report a case of multifocal bullous fixed drug eruption following ingestion of pheniramine maleate.
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- Effects of Premedication on Heart Rate Variability at Induction of Anaesthesia: Comparison between Midazolam and Hydroxyzine. [Journal Article]
- TJTurk J Anaesthesiol Reanim 2018; 46(3):229-232
- CONCLUSIONS: Midazolam but not hydroxyzine premedication inhibited sympathetic activation at induction of anaesthesia.