INDIVIDUAL ARTICLE: Efficacy of a Prebiotic Skincare Regimen on Improving Mild Atopic Dermatitis and Severe Xerosis in Diverse Ethnically Patients.

Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin disease associated with a significant patient burden on quality-of-life. Given skin barrier including skin microbiome changes are linked to AD pathogenesis, prebiotic emollients are shown to improve disease symptoms and maintain skin barrier integrity, normalizing skin microbiota. In this study, we evaluated the efficacy and safety of a prebiotic skincare routine in improving AD and xerosis, and ultimately quality-of-life in ethnically diverse patients. A total of 140 subjects from different racial/ethnic backgrounds, aged 3-80 years old with skin phototypes I-VI, and presenting with mild-AD or severe xerosis completed study. Expert grading, instrumentation, self-assessment questionnaires, plus clinical imaging demonstrated that a prebiotic cleanser and moisturizer routine significantly reduced skin conditions severity, strengthened skin barrier properties in both lesional and normal skin, and improved patients' quality-of-life while providing itch relief as soon as 4 weeks. The results of this research indicate that a prebiotic cleanser and moisturizer regimen offers benefits for diverse patient’s daily skincare routine by effectively managing AD and xerosis severity and symptoms, normalizing skin microbiota, plus preserving skin barrier integrity to prevent long-term sequelae. J Drugs Dermatol. 2024;23:3(Suppl 2):s12-22.

Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

Precipitated opioid withdrawal in a patient started on olanzapine/samidorphan.

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored. Methods: The GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a 'core active ingredient-key target-disease pathway' network was established. Finally, molecular docking was performed. Results: In total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of 'cytokine cytokine receptor interaction', etc. targeting the CTSC. Moreover, PDE5A might be involved in 'ECM receptor interaction', etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury. Conclusion: CTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

Green micellar liquid chromatographic method for simultaneous determination of antihistaminic drugs tripelennamine hydrochloride and diphenhydramine in pharmaceutical gel.

A new green micellar liquid chromatographic method has been developed and validated for the simultaneous determination of diphenhydramine (DPH) and tripelennamine hydrochloride (TRP) using a micellar mobile phase consisting of 1 mM Tween 20 in phosphate buffer pH 4:isopropanol (85:15, %v/v). The method was linear in the range of 4-150 and 5-120 µg/mL for TRP and DPH, respectively. The method was successfully applied for the simultaneous determination of DPH and TRP in a laboratory-prepared gel containing all possible excipients with mean percent recoveries ± standard deviation of 100.346 ± 1.265 and 100.754 ± 1.117 for TRP and DPH, respectively. The method was validated according to the International Conference on Harmonization guidelines. The method is confirmed to have excellent greenness.

Medicating the coast in a metropolitan city: Enantiomeric profiles and joint probabilistic risk assessment of antidepressants and antihistamines.

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.

Diphenhydramine-involved Fatal and Nonfatal Drug Overdoses in Tennessee, 2019-2022.

BACKGROUND: Diphenhydramine (DPH), known as the brand name Benadryl, is an over-the-counter medication associated with accidental ingestion leading to nonfatal overdoses. Additionally, DPH has been used in tandem with illicit substances leading to fatal drug overdoses. OBJECTIVE: In response to DPH being seized with illicit drugs as an adulterant, as well as its growing intentional misuse, we sought to explore its recent involvement in fatal and nonfatal drug overdoses in the state of Tennessee. METHODS: We conducted a statewide cross-sectional study to determine the characteristics of DPH-involved fatal and nonfatal overdoses in Tennessee during 2019-2022 using data from the State Unintentional Drug Overdose Reporting System, the Electronic Surveillance System for the Early Notification of Community-based Epidemics, and the National Forensic Laboratory Information System Public Data Query System. Frequencies were generated to compare demographic characteristics, circumstances, and toxicology between fatal and nonfatal DPH-involved overdoses. RESULTS: We identified 143 suspected nonfatal DPH and 409 fatal DPH-involved overdoses in Tennessee from 2019 to 2022. Nonfatal overdoses remained consistent while fatal overdoses peaked in 2021. Most nonfatal overdoses were under 18 (63.4%), while most fatal overdoses were between 18 and 64 years of age (95.7%). For fatal overdoses, fentanyl was the most prevalent substance on toxicology followed by prescription opioids. CONCLUSION: Nonfatal overdoses remained consistent while fatal overdoses peaked in 2021 in Tennessee. Use of DPH among other illicit substances lends to evidence suggesting its use as an adulterant. Monitoring of DPH-involved fatal and nonfatal overdoses is critical to inform harm reduction initiatives.

Early itch relief with upadacitinib predicts later skin clearance in Atopic dermatitis.

BACKGROUND: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. OBJECTIVES: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. METHODS: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. RESULTS: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. CONCLUSIONS: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.

Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics.

The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy. This underscores the urgent need to investigate alternative therapeutic approaches. Sigma receptors have been unexpectedly linked to the SARS-CoV-2 life cycle due to the direct antiviral effect of their ligands. Coronavirus-induced cell stress facilitates the formation of an ER-derived complex conducive to its replication. Sigma receptor ligands are believed to prevent the formation of this complex. Repurposing FDA-approved drugs for COVID-19 offers a timely and cost-efficient strategy to find treatments with established safety profiles. Notably, diphenhydramine, a sigma receptor ligand, is thought to counteract the virus by inhibiting the creation of ER-derived replication vesicles. Furthermore, lactoferrin, a well-characterized immunomodulatory protein, has shown antiviral efficacy against SARS-CoV-2 both in laboratory settings and in living organisms. In the present study, we aimed to explore the impact of sigma receptor ligands on SARS-CoV-2-induced mortality in ACE2-transgenic mice. We assessed the effects of an investigational antiviral drug combination comprising a sigma receptor ligand and an immunomodulatory protein. Mice treated with sigma-2 receptor ligands or diphenhydramine and lactoferrin exhibited improved survival rates and rapid rebound in mass following the SARS-CoV-2 challenge compared to mock-treated animals. Clinical translation of these findings may support the discovery of new treatment and research strategies for SARS-CoV-2.

Operational outcomes of propofol sedation versus fentanyl, midazolam and diphenhydramine sedation for endoscopies and colonoscopies at an academic medical center.

BACKGROUND: On July 1st, 2021, the University of Colorado Hospital (UCH) implemented new sedation protocols in the luminal gastrointestinal (GI) suite. GI proceduralist supervised, Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS) sedation was transitioned to Monitored Anesthesia Care with propofol under physician anesthesiologist supervision (MAC). OBJECTIVE: To determine if there are statistically significant reductions in Sedation-Start to Scope-In time (SSSI) when using Monitored Anesthesia Care with propofol (MAC) versus Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS). Secondary objectives were to determine if statistically significant improvements to other operational times, quality measures, and satisfaction metrics were present. METHOD: This study was a retrospective analysis of a natural experiment resultant of a change from NAS to MAC sedation protocols. Outcomes for NAS protocols from 1/1/21-6/30/21 were compared to outcomes of MAC protocols from the dates 8/1/21-10/31/21. Results were analyzed using Quasi-Poisson regression analysis and stratified based on upper GI, lower GI, and combined procedures. Patient demographic data including age, biological sex, comorbidities, and BMI, were adjusted for in the analysis. ASA matching was not performed as nursing sedation does not use ASA classifications. Pre-anesthesia co-morbidities were assessed via evaluation of a strict set of comorbidities abstracted from the electronic medical record. Perioperative operational outcomes include Sedation Start to Scope-In (SSSI), In-Room to Scope-In Time (IRSI), Scope Out to Out of Room (SOOR), Total Case Length (TCL), and Post Anesthesia Care Unit Length of Stay (PACU LOS). Quality outcomes include PACU Administered Medications (PAM), and Clinician Satisfaction Scores (CSS). RESULTS: A total of 5,582 gastrointestinal (GI) endoscopic cases (upper, lower, and combined endoscopies) were observed. Statistically significant decreases in SSSI of 2.5, 2.1, and 2.2 minutes for upper, lower, and dual GI procedures were observed when using MAC protocols. A statistically significant increase in satisfaction scores of 47.0 and 19.6 points were observed for nurses and proceduralists, respectively, when using MAC. CONCLUSION: MAC protocols for endoscopic GI procedures at UCH led to statistically significant decreases in the time required to complete procedures thus increasing operational efficiency.

Individual Article: Evaluation of Efficacy and Tolerability of Two Over-the-Counter Eczema Itch Relief Products.

BACKGROUND: Study to compare efficacy, tolerability, and patient perception between an over-the-counter itch relief gel (IRG) and itch relief moisturizing cream (IRMC) after a single application.  Methods: Single-center, randomized, blinded, split-body study comparing IRG vs IRMC in adults with eczema-prone skin and mild-to-moderate itch. Assessments included itch relief duration upon application, itch severity (0=none to 9=severe at baseline [BL], 8, 12, and 24 hours), tolerability (0=none to 3=severe), and self-assessment questionnaire about product attributes and preference.  Results: Thirty-three females and males with a mean age of 49.7 completed the study. Average time to itch relief was 28.5 seconds for IRG vs 41.8 for IRMC (P<0.05), with first onset at 5 seconds. In the IRG group, itch severity was reduced from 4.4 at BL to 1.4 at 8 hours; in comparison, itch was reduced from 4.4 at BL to 2.6 at 8 hours in the IRMC group (P<0.05). Both products significantly relieved itch vs baseline at all time points. IRG had better tolerability, with burning/stinging going from 1.5 at BL to 0.8 at 24 hours vs 1.5 at BL to 1.2 at 24 hours for IRMC (P<0.05). There was a trend in favor of IRG vs IRMC on the patient satisfaction self-assessment questionnaire. CONCLUSIONS: IRG provided rapid itch relief and significantly outperformed IRMC. Both products significantly improved itch severity for up to 24 hours after application, with IRG outperforming IRMC at 8 hours. Additionally, IRG moderated stinging/burning sensations better than IRMC. Further, IRG was preferred by participants over IRMC.J Drugs Dermatol. 2023;22:10(Suppl 2):s10-15.  .

Diphenhydramine overdose detected early by integration of toxidrome and electrocardiography and treated with venoarterial extracorporeal membrane oxygenation: a case report.

Drug overdose can lead to a range of symptoms, including potentially life-threatening cardiac arrhythmias. However, identifying the specific causative drug upon admission can be challenging in many cases. The toxidrome approach is a method that utilizes toxidromes, which are collections of findings obtained from physical examination and ancillary tests, that may be caused by a specific toxin. In this particular case, a man presented with an unknown drug overdose that caused symptoms indicative of anticholinergic effects and abnormal electrocardiogram (ECG) findings. The ECG revealed an R wave in lead aVR, S waves in leads I and aVL, and wide QRS tachycardia with a Brugada pattern. Shortly after arrival, the patient developed cardiac arrest due to a lethal arrhythmia. Prompt initiation of venoarterial extracorporeal cardiopulmonary membrane oxygenation (VA-ECMO) was performed. Fortunately, the patient achieved full neurological recovery, and the overdosed drug was identified as diphenhydramine. When diagnosing and treating drug overdose caused by an unidentified substance, diphenhydramine toxicity should be considered when an anticholinergic toxidrome is present and a Brugada pattern is observed on the ECG. VA-ECMO demonstrates potential as a viable treatment option when initial interventions prove ineffective.

Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Application of Gd2ZnMnO6/ZnO nanocomposite for electrochemical measurement of acetaminophen, diphenhydramine, and phenylephrine.

An electrochemical sensor with high sensitivity was designed and used to measure several drugs, including acetaminophen (AC), diphenhydramine (DPH), and phenylephrine (PHE). This sensor was created using a carbon paste electrode (CPE) that has been modified with a Gd2ZnMnO6/ZnO nanocomposite. In order to analyze the developed sensor, scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR) techniques were used. The electrochemical behavior of the modified electrode was investigated by cyclic voltammetry, chronoamperometry, and apparent resistance spectroscopy methods. Also, the compound's diffusion coefficient (D) was calculated. By using the differential pulse voltammetry, AC, DPH, and PA were determined with detection limits of 2.5 × 10-8, 3.3 × 10-8, and 1.4 × 10-8 M in the linear concentration ranges of 0.09-900 µM. Finally, the designed sensor was utilized to measure the drug in real samples, and acceptable results were obtained.

Abrocitinib for the treatment of atopic dermatitis.

Abrocitinib is an oral small molecule which selectively inhibits JAK1, modulating multiple cytokine pathways involved in atopic dermatitis. Both abrocitinib 200 mg and 100 mg reached efficacy results comparable to dupilumab and superior to placebo. Abrocitinib 200 mg was superior to dupilumab in some trials, consistently providing a faster response and itch relief from week 2 to 26. Continuous abrocitinib 200 mg is the most effective at controlling this disease, but with an induction-maintenance approach with abrocitinib 200 mg followed by 100 mg, over 55% of patients did not flare for 40 weeks. Abrocitinib common adverse effects are nonserious. A self-limited dose-related decrease in platelet counts was consistently observed, without clinical repercussion. Abrocitinib demonstrated high efficacy and a favorable safety profile.

Atopic dermatitis is the most common form of eczema, a condition that causes the skin to become itchy, dry and cracked. Abrocitinib is a medication taken orally (by mouth) that specifically targets JAK1, a protein involved in inter- (within cells) and intracellular (between cells) pathways that cause atopic dermatitis. Both the 200 mg and 100 mg doses of abrocitinib were effective compared with a placebo, a substance that looks like the treatment drug but doesn't have any of its chemical effects. Abrocitinib 200 mg was even better than dupilumab, another recently available injectable treatment option, especially by reducing itch from week 2. Using continuous abrocitinib 200 mg showed the best results for controlling the disease. However, an approach of starting with abrocitinib 200 mg and then reducing it to 100 mg also worked well, with over 55% of patients not experiencing a worsening of their condition for 40 weeks. The most common side effects of abrocitinib are not serious. There was a temporary decrease in platelet counts, tiny blood cells that help your body form clots to stop bleeding, but this did not cause any clinical issues. It has also proven effectiveness and safety in adolescents from 12 years of age. Overall, abrocitinib was highly effective and had a positive safety profile.

Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

Development of Bitter-Taste Masked Instant Jelly Formulations of Diphenhydramine Hydrochloride with Easy-to-Consume Granules.

This study developed easy-to-consume bitter taste-masking granules for the preparation of instant jelly formulations. Composite granules containing diphenhydramine hydrochloride (DPH) and polymers were prepared via spray drying. The taste-masking effect on DPH was evaluated with acceptable linearity between DPH concentration and intensity of bitterness using an electronic tongue sensor. The results indicated that ι-carrageenan could provide the greatest suppression effect on the DPH bitterness among the polymers selected for preparing spray-dried particles (SDPs). The thixotropic index (TI) of ι-carrageenan was higher than that of the other polymers. In addition, two sulfate groups per two galactose molecules in one unit of ι-carrageenan improved interaction with DPH. Compared to κ-carrageenan, the electrostatic interaction with DPH may be stronger. Easy-to-consume SDPs with ι-carrageenan were used to prepare instant jelly formulations. The instant jelly formulation containing DPH with ι-carrageenan (3.0%) met the criteria for texture properties (hardness, adhesiveness, and cohesiveness) for patients with difficulty swallowing, as specified by the Consumer Affairs Agency. Furthermore, instant jelly enhanced the bitter taste suppression of DPH. Overall, using spray-dried granules with ι-carrageenan, this technique for preparing instant jelly formulations is simple and inhibits the bitter taste of drugs, contributing to the development of oral dosage forms suitable for patients of all ages.

Deep learning neural network derivation and testing to distinguish acute poisonings.

INTRODUCTION: Acute poisoning is a significant global health burden, and the causative agent is often unclear. The primary aim of this pilot study was to develop a deep learning algorithm that predicts the most probable agent a poisoned patient was exposed to from a pre-specified list of drugs. RESEARCH DESIGN & METHODS: Data were queried from the National Poison Data System (NPDS) from 2014 through 2018 for eight single-agent poisonings (acetaminophen, diphenhydramine, aspirin, calcium channel blockers, sulfonylureas, benzodiazepines, bupropion, and lithium). Two Deep Neural Networks (PyTorch and Keras) designed for multi-class classification tasks were applied. RESULTS: There were 201,031 single-agent poisonings included in the analysis. For distinguishing among selected poisonings, PyTorch model had specificity of 97%, accuracy of 83%, precision of 83%, recall of 83%, and a F1-score of 82%. Keras had specificity of 98%, accuracy of 83%, precision of 84%, recall of 83%, and a F1-score of 83%. The best performance was achieved in the diagnosis of single-agent poisoning in diagnosing poisoning by lithium, sulfonylureas, diphenhydramine, calcium channel blockers, then acetaminophen, in PyTorch (F1-score = 99%, 94%, 85%, 83%, and 82%, respectively) and Keras (F1-score = 99%, 94%, 86%, 82%, and 82%, respectively). CONCLUSION: Deep neural networks can potentially help in distinguishing the causative agent of acute poisoning. This study used a small list of drugs, with polysubstance ingestions excluded.Reproducible source code and results can be obtained at https://github.com/ashiskb/npds-workspace.git.

[Comparative study of the clinical efficacy and safety of the fixed dose combination Levroso Long with Melaxen and Diphenhydramine in patients with insomnia]. / Rezul'taty sravnitel'nogo klinicheskogo issledovaniya effektivnosti i bezopasnosti kombinirovannogo lekarstvennogo preparata Levroso Long s preparatami Melaksen i Dimedrol u patsientov s bessonnitsei.

OBJECTIVE: Evaluation of the efficacy and safety of Levroso Long (fixed dose combination (hereinafter referred to as «FDC¼) diphenhydramine and melatonin, 25 mg + 3 mg and FDC diphenhydramine and melatonin 50 mg + 3 mg, respectively, capsules with modified release, NovaMedica Innotech LLC) in comparison with diphenhydramine medicines 50 mg (Diphenhydramine tablets, DALHIMFARM OJSC, Russia) and 3 mg melatonin (Melaxen tablets, Unipharm Inc., USA) in patients with insomnia. MATERIALS AND METHODS: Material and methods. A multicenter open randomized comparative clinical trial was conducted in parallel groups. The study included 312 patients with an insomnia diagnosis verified in accordance with the DSM-IV criteria (ICD code F51.0-10) and an insomnia severity index (ICI) >8 points. The patients were randomized into 4 groups and took the following medications for 10 days: patients of group 1 - Levroso Long (25 mg diphenhydramine and 3 mg melatonin), group 2 - Levroso Long combination drug (50 mg diphenhydramine and 3 mg melatonin), Group 3 -Diphenhydramine 50 mg, 4th - Melaxen 3 mg. A comparative assessment was performed on the 7th and 10th days of therapy according to the primary endpoint - ICI, and secondary endpoints - the results of the assessment based on the Leeds Sleep Assessment Questionnaire, the Pittsburgh Sleep Quality Questionnaire, the Scale of the overall clinical impression of improvement and the analysis of the profile of adverse events (NA). RESULTS: The FDC of diphenhydramine 25 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg, and FDC diphenhydramine 50 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg or melatonin 3 mg on both primary and secondary endpoints. In a safety assessment, the highest incidence of adverse events (48.7%) in the diphenhydramine 50 mg group was significantly lower in groups 1 (29.5%), 2 (12.8%) and 4 (1.3%). All reported adverse events in the FDC groups were mild or moderate in severity. CONCLUSION: The study showed that Levroso Long in two dosages surpassed monotherapy with 50 mg of Diphenhydramine (50 mg) or Melaxen (3 mg) in patients with insomnia in terms of efficacy parameters. The benefit/risk ratio of the studied drug is favorable compared to monotherapy.