The Assessment and Management of Childhood Masturbation: An Analysis of 90 Cases.

AIM: The child's self-stimulating pleasure behavior is defined as childhood masturbation (CM). Diagnosis of CM is mainly based on behavior and analysis of video recordings. This study aims to investigate etiological factors, movement patterns, and treatment options.Medical records and video recordings of CM in our clinic between 2015 and 2020 were retrospectively reviewed. RESULTS: Ninety patients aged 8 months to 9 years were included in our study. The male-to-female ratio was 23/67. The mean age at onset of masturbation (mean ± standard deviation) was 21.42 ± 18.44 (6-107) months. Note that 27.7% (32) of the patients were taking antiepileptic drugs before admission.Eight of the 90 patients had abnormal electroencephalograms. The time of onset of CM was related to cessation of breast milk in 24.4%, separation from the mother in 43.3%, new siblings in 16.6%, initiation of toilet training in 7.7%, and parental divorce in 6.6%. Behavioral therapy was sufficient in 71.1%. Hydroxyzine hydrochloride in 19 (21.1%) and risperidone in 9 (10%) were given in the remaining cases. Overall, 23/28 of the cases receiving medication improved during follow-up. CONCLUSION: Physicians may have difficulty identifying repetitive movements in CM. Misdiagnosis or delayed diagnosis may lead to unnecessary use of antiepileptic drugs, delayed initiation of treatment, and prolonged treatment duration. Video recordings are important in the differential diagnosis of CM. CM may have psychosocial causes and can often be effectively treated with behavioral therapy. Pharmacological treatment (hydroxyzine hydrochloride and risperidone) may be considered in cases that do not respond to behavioral treatment.

Design of resonance Rayleigh scattering and spectrofluorimetric methods for the determination of the antihistaminic drug, hydroxyzine, based on its interaction with 2,4,5,7-tetraiodofluorescein: Evaluation of analytical eco-scale and greenness/whiteness algorithms.

In this work, two validated approaches were used for estimating hydroxyzine HCl for the first time using resonance Rayleigh scattering (RRS) and spectrofluorimetric techniques. The suggested approaches relied on forming an association complex between hydroxyzine HCl and 2,4,5,7-tetraiodofluorescein (erythrosin B) reagent in an acidic media. The quenching in the fluorescence intensity of 2,4,5,7-tetraiodofluorescein by hydroxyzine at 551.5 nm (excitation = 527.5 nm) was used for determining the studied drug by the spectrofluorimetric technique. The RRS approach is based on amplifying the RRS spectrum at 348 nm upon the interaction of hydroxyzine HCl with 2,4,5,7-tetraiodofluorescein. The spectrofluorimetric methodology and the RRS methodology produced linear results within ranges of 0.15-1.5 µg ml-1 and 0.1-1.2 µg ml-1, respectively. LOD values for these methods were determined to be 0.047 µg ml-1 and 0.033 µg ml-1, respectively. The content of hydroxyzine HCl in its pharmaceutical tablet was estimated using the developed procedures with acceptable recoveries. Additionally, the application of four greenness and whiteness algorithms shows that they are superior to the previously reported method in terms of sustainability, economics, analytical performance, and practicality.

Efficacy and safety of hydroxyzine for sleep in adults: Systematic review.

OBJECTIVE: The purpose of this systematic review is to assess the efficacy and safety of hydroxyzine for insomnia in adults. METHODS: A comprehensive literature search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through October 2022 using the search terms: hydroxyzine and sleep, insomnia, sleep disorder or sleep initiation and maintenance disorders. Studies identified for review included prospective, interventional designs or cohort trials that reported impact of hydroxyzine on sleep in adults. Animal studies, case reports, non-English articles, letters to the editor, case studies, and conference abstracts were excluded. Data were extracted using a standardized systematic process. RESULTS: Five articles were identified for inclusion, including 1 open-label and 4 randomized controlled trials, evaluating a total of 207 patients receiving hydroxyzine 25 mg, 50 mg, or 100 mg at bedtime. Mixed efficacy was demonstrated in the sleep measures of sleep onset, sleep maintenance, and sleep quality. The most common adverse drug effect was dry mouth, although 4 of the 5 studies did not report safety outcomes. CONCLUSIONS: The studies in this review suggest hydroxyzine could be considered as a short-term treatment option for adults with insomnia for whom previous therapy was ineffective, not tolerated, or contraindicated. Additional long-term studies with an active comparator are needed to further establish its role in insomnia treatment.

Vanadium-Containing Anionic Chelate for Spectrophotometric Determination of Hydroxyzine Hydrochloride in Pharmaceuticals.

Four azo dyes known to form anionic complexes with V(V) were investigated as potential liquid-liquid extraction-spectrophotometric reagents for the antihistamine medication hydroxyzine hydrochloride (HZH). A stable ion-association complex suitable for analytical purposes was obtained with 6-hexyl-4-(2-thiazolylazo)resorcinol (HTAR). The molar absorption coefficient, limit of detection, linear working range, and relative standard deviation in the analysis of real pharmaceutical samples (tablets and syrup) were 3.50 × 104 L mol-1 cm-1, 0.13 µg mL-1, 0.43-12.2 µg mL-1, and ≤2.7%, respectively. After elucidating the molar ratio in the extracted ion-association complex (HZH:V = 1:1), the ground-state equilibrium geometries of the two constituent ions-HZH+ and [VO2(HTAR)]--were optimized at the B3LYP level of theory using 6-311++G** basis functions. The cation and anion were then paired in four different ways to find the most likely structure of the extracted species. In the lowest-energy structure, the VO2 group interacts predominantly with the heterochain of the cation. A hydrogen bond is present (V-O···H-O; 1.714 Å) involving the terminal oxygen of this chain.

Do medication prescription patterns follow guidelines in a cohort of women with interstitial cystitis/bladder pain syndrome?

OBJECTIVE: To describe prescription prevalence of oral bladder pain medications among women with interstitial cystitis/bladder pain syndrome (IC/BPS) and to compare with current treatment guidelines. METHODS: We sampled female patients with an ICD-9/10 diagnosis of IC/BPS (595.1/N30.10) by querying active users of the Veterans Health Administration. Medical records were reviewed to determine whether patients met IC/BPS diagnostic criteria. A cohort of women with other pelvic pain disorders was identified. Prescription prevalence of typical non-narcotic oral bladder pain medications was compared between the two groups and healthy controls. Prescription prevalence was also compared before and after the diagnosis of IC/BPS was made using Poisson regression. RESULTS: There were 641 women who met criteria for IC/BPS and 197 women with "Other pelvic pain" disorders. Women with IC/BPS were prescribed a pain medication more often than those with "Other pelvic pain" (77% vs. 59%, p < 0.0001). Of the women with IC/BPS, 44% tried three or more pain medications. Of women with a diagnosis of IC/BPS, only 67% were prescribed an American Urological Association-recommended medication. Prescription prevalence increased after diagnosis for both pentosan polysulfate (10%-29%, p < 0.0001) and hydroxyzine (17%-40%, p < 0.0001), but not for amitriptyline or cimetidine. Amitriptyline was prescribed to 223 women with IC/BPS, only 125 of which (56%) had a documented history of depression. CONCLUSIONS: Many women with IC/BPS required multiple bladder prescriptions, highlighting the difficulty in finding an effective treatment for IC/BPS. Pentosan polysulfate and hydroxyzine were preferred IC/BPS medications. Our next step will be to analyze treatment patterns in those patients who did not receive medications.

A retrospective comparison of haloperidol and hydroxyzine combination therapy with haloperidol alone in the treatment of overactive delirium.

BACKGROUND: For the treatment of delirium, antipsychotics such as haloperidol are used as standard treatments. However, haloperidol has a little sedative effect and may not be sufficiently effective in controlling overactive delirium. Hydroxyzine, an antihistamine, may be used in combination with haloperidol to supplement its sedative effect. The aim of this study was to investigate the effect of haloperidol alone or in combination with hydroxyzine on the improvement of overactive delirium retrospectively. METHOD: Delirium was assessed from medical records using the Intensive Care Delirium Screening Checklist (ICDSC). The number of patients and days with an ICDSC score of < 4, indicating an absence of delirium after haloperidol alone or haloperidol and hydroxyzine was surveyed for 6 days. RESULTS: A total of 157 patients were diagnosed with delirium from April 2019 to July 2021, of which 18 patients received haloperidol alone, and 21 patients received the combination of haloperidol and hydroxyzine for overactive delirium. The number of patients with a mean ICDSC score of < 4 on days 1-6 was two patients (11%) in the haloperidol groups and two patients (10%) in the combination of haloperidol and hydroxyzine group (P = 0.999). The days within < 4 of the ICDSC score on days 1-6 were 0.8 (1.3) and 0.8 (1.5), respectively (P = 0.848). CONCLUSION: Haloperidol alone and haloperidol plus hydroxyzine are both effective in the treatment of overactive delirium. However, the concomitant use of hydroxyzine with haloperidol may not improve the efficacy of treatment of overactive delirium compared to haloperidol alone.

Case report of a phencyclidine false positive due to lamotrigine use with confirmatory testing.

BACKGROUND: Urine toxicology screens are useful in diagnosing patients who present with acute psychosis with a history of substance abuse. Being aware of potential false positive reactants is paramount in diagnostic accuracy. Currently, lamotrigine is not listed among common cross-reactants with phencyclidine (PCP). CASE REPORT: A 49 year old male (98 kg) was brought to the ED by a family member for worsening confusion and agitation. He had a history of Bipolar I, PTSD, schizoaffective disorder, hypertension, and cannabis/opioid abuse. His home medications included paliperidone, duloxetine, lamotrigine, tizanidine, hydroxyzine, and lisinopril. Upon examination, he denied intentional overdose or illicit substances, but largely mumbled incoherently. Blood pressure was 140/90 mmHg, pulse 113. A urine toxicology screen was positive for PCP and cannabinoids. Other labs were unremarkable, co-ingestants negative. By day three, his mental status vacillated but he largely gave unintelligible responses. Given the short half-life of PCP, false positives were investigated. A confirmatory blood test (collected upon admission) for PCP was found to be negative, and a serum lamotrigine level was confirmed to be positive (1.5µg/ml). Once more lucid, the patient admitted to taking large quantities of mirtazapine and tizanidine, making serotonin syndrome the more likely diagnosis. DISCUSSION: There is little in the medical literature describing cross-reactivity of lamotrigine and PCP on urine drug screens. This can be especially difficult to deduce in a known drug abuser who presents psychotic and non-contributory in their work up.

Development and validation of liquid chromatography-tandem mass spectrometry method for the estimation of a potential genotoxic impurity 2-(2-chloroethoxy)ethanol in hydroxyzine.

2-(2-Chloroethoxy)ethanol (CEE) belongs to the so-called cohort of concerns which were classified as highly potent mutagenic carcinogens by the World Health Organization. It is widely used in the synthesis of the essential anti-histamine drug hydroxyzine. In addition, it is used as a primary solvent in dyes, nitrocellulose, paints, inks and resins. Owing to its potential genotoxicity, an efficient liquid chromatography-tandem mass spectrometry method was developed for the quantitative estimation of CEE traces in an active pharmaceutical ingredients and in tablet dosage forms of hydroxyzine-free base. The chromatographic separation was achieved on a C18 column using a gradient elution mode with a binary solvent system (ammonium formate and methanol). Mass detection was performed for CEE using a positive mode with selected ion monitoring technique at m/z value of [M + NH4 ]+ . The developed method was validated as per the International Conference on Harmonizaiton guidelines. The quantitation limit, linearity and recoveries were found to be 0.56 ppm, 0.56-7.49 ppm (r2 > 0.9985) and 93.6-99.3%, respectively. The proposed method was highly compatible and was used effectively to estimate CEE traces in different stages of drug synthesis and in tablet dosage forms of hydroxyzine for routine and stability testing.

Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses.

Hydroxyzine and cetirizine are first- and second-generation oral antihistamine drugs, respectively, used to treat allergic reactions in horses. Cetirizine is also a metabolite of hydroxyzine, which may lead to complexities in regulating their use in equine sporting events. The aim of the research was to be able to provide detection times (DT) from pharmacokinetic studies in thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Six and two horses were given 9 repeated administrations of hydroxyzine HCl (500 mg BID) or cetirizine HCl (190 mg BID), respectively. Plasma and urine hydroxyzine and cetirizine concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A holistic non-linear mixed effects PK model was developed that described both plasma and urine concentrations of hydroxyzine and cetirizine, either from administration of each individually or cetirizine as a metabolite of hydroxyzine. Using the parameters obtained from this PK model in conjunction with methodology developed by Toutain afforded possible screening limits (SL) that can regulate for a DT of 4 days in either plasma or urine. Hydroxyzine and cetirizine concentration prediction intervals for the 80th , 95th and 99th percentiles of a virtual horse population were performed in order to assess the statistical protection of the DT. However, it is down to the individual racing authorities to apply their own risk management.

Comparisons of Varying Dosages of Chloral Hydrate-Hydroxyzine with and without Meperidine for Managing Challenging Pediatric Dental Behavior: A Retrospective study of 35 years of Sedation Experiences.

PURPOSE: This retrospective study compares the efficacy and safety of variable dosing of Chloral Hydrate - Hydroxyzine with and without Meperidine (Mep)for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a 35-year period. STUDY DESIGN: Reviews of the sedation logs of 2,610 children, 3-7 years were compared in search of what dosing proves safe and effective for differing levels of challenging behavior. Variable dosing of CH with and without Mep were judged using a pragmatic approach which defined sedation success as optimal, adequate, inadequate, or over-dosage using oneway analysis of variance. Descriptive analyses of behavior and physiologic assessment was included with regard to the extent to which physical restraint occurred to control interfering behavior. Arousal levels requiring stimulation, oxygen desaturation, and adverse reactions were included as indications of safety. RESULTS: Where Mep was used, success rates were consistently higher; need for higher-end dosing of CH was not found beneficial when Mep was included. Significantly less need for physical restraint accompanied the addition of Mep. CONCLUSIONS: There appears to be strong basis for the safety and efficacy of the use of CH-H-Mep in combination at lower dosing than historically used. Addition of Mep was observed to enhance sedations, permit lower CH dosing, lessen or eliminate the need for physical restraint and adverse reactions.

Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands: An interrupted time series regression analysis.

BACKGROUND: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. METHOD: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. RESULTS: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (-12.05, 95%CI -18.47 to -5.63) and Scotland (-19.01, 95%CI -26.99 to -11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (-1.72, 95%CI -2.69 to -0.75) and Scotland (-2.38, 95%CI -3.32 to -1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. CONCLUSION: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.

Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence). AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.

Hydroxyzine-induced priapism.

Priapism is a severe urologic condition requiring emergency management. Ischemic priapism is the most common subtype which is characterized by a long-lasting, painful, and rigid erection which can be caused by medications with alpha-adrenergic properties such as hydroxyzine. Typically, medication-induced priapism is reported at therapeutic doses and few case reports exist implicating medication overdose as the cause. We report a case of a patient taking hypercompliant doses of hydroxyzine hydrochloride for worsening insomnia (200-600 mg), including the night before admission. Blood-gas analysis of blood from the right corpora was completed and revealed a pH of 6.736, pCO2 of 147, HCO3 of 18.6 and a base excess of 17.7. The patient required aspiration and 560 µg of intracavernosal phenylephrine to achieve sustained detumescence. Emergency physicians should be aware of this risk as priapism is a medical emergency and this is the first report with hydroxyzine after an intentional overdose to our knowledge.

Hydroxyzine for lowering patient's anxiety during prehospital morphine analgesia: A prospective randomized double blind study.

STUDY OBJECTIVE: Hydroxyzine is an antihistamine drug used for symptomatic relief of anxiety and tension. We hypothesized that managing the anxiety of patients with severe pain by adding hydroxyzine to a conventional intravenous morphine titration would relieve their pain more effectively. METHODS: This was a randomized, double-blind, controlled group study of prehospital patients with acute pain scored greater than or equal to 6 on a 0-10 verbal numeric rating scale (NRS). Patients'anxiety was measured with the self-reported Face Anxiety Scale (FAS) ranking from 0 to 4. The percentage of patients with pain relief (NRS score ≤ 3) 15 min after the first injection was the primary outcome. RESULTS: One hundred forty patients were enrolled. Fifty-one percent (95% CI 39% to 63%) of hydroxyzine patients versus 52% (95% CI 40% to 64%) of placebo patients reported a pain numeric rating scale score of 3 or lower at 15 min. Ninety-one percent (95% CI 83% to 98%) of patients receiving hydroxyzine reported no more severe anxiety versus 78% (95% CI 68% to 88%) of patients with placebo (p > 0.05). Adverse events were minor, with no difference between groups (6% in hydroxyzine patients and 14% in placebo patients). CONCLUSION: Addition of hydroxyzine to morphine in the prehospital setting did not reduce pain or anxiety in patients with acute severe pain and therefore is not indicated based on our results.

Pitfalls of toxicological investigations in hair, bones, and nails in extensively decomposed bodies: illustration with two cases.

It is difficult to carry out toxicological investigations in biological samples collected from extensively decomposed bodies and to interpret obtained results as several pitfalls should be considered: redistribution phenomena, degradation of xenobiotics during the postmortem period, contamination by putrefaction fluids, and external contamination. This work aims to present two cases in order to illustrate and discuss these difficulties in this tricky situation. Case#1: the body of a 30-year-old woman was found in a wooded area (1 month after she has been reported missing by her family): hair and a femur section were sampled. Case#2: the decomposed corpse of a 52-year-old man was found in a ditch: hair and nails were sampled. After decontamination steps, toxicological investigations were performed using liquid chromatography with high-resolution mass spectrometry and tandem mass spectrometry detection methods. In case#1, the same drugs or metabolites (benzodiazepines, propranolol, tramadol, acetaminophen, paroxetine, and oxetorone) were detected in hair and in bone specimens. This result combination strongly suggests intakes close to the time of death for three of them (oxazepam, lormetazepam, and propranolol). In case#2, results of toxicological investigations in hair and nails [(hair/nail concentration in ng/mg) nordiazepam (1.12/1.06), oxazepam (0.113/0.042), zolpidem (0.211/< 0.01), hydroxyzine (0.362/< 0.01), and cetirizine (0.872/1.110)] were both consistent with several drug intakes but were not contributory to cause of death determination. In case of positive toxicological results in biological samples collected from extensively decomposed bodies (such as hair, bones, or nails), it is challenging to determine the time, and even more, the level of the dose of exposure(s).

Comparison of gabapentin and hydroxyzine in the treatment of pruritus in patients on dialysis.

BACKGROUND: Pruritus is one of the most common problems in patients with chronic renal failure. Of all patients with end-stage renal disease (ESRD), 60-80% report pruritus during their life. AIM: To compare the effect of gabapentin (GBP) and hydroxyzine (HYDZ) in treating pruritus in patients on dialysis. METHODS: In a double-blind, randomized, crossover clinical trial, 32 patients on dialysis who reported pruritus were assigned randomly to receive either GBP or HYDZ for 6 weeks; the first group received GBP 100 mg/day orally and the second group received HYDZ 25 mg/day orally for 6 weeks. After this 6-week period (Period 1) there was a washout period of 2 weeks then patients were crossed over to the other drug (the first group receiving HYDZ and second group receiving GBP) and followed up for a further 6 weeks (Period 2). A visual analogue scale was used to measure pruritus intensity in the groups before and after the first and second period. RESULTS: In Period 1, pruritus severity decreased from 7.1 ± 1.46 at baseline to 2.17 ± 1.82 at 6 weeks in the GBP group (P = 0.001) and from 6.83 ± 2.11 to 2.86 ± 1.67 in the HYDZ group (P = 0.001). In Period 2, pruritus severity decreased from 5.1 ± 1.61 at baseline to 1.56 ± 0.82 at 6 weeks in the GBP group (P < 0.01) and from 5.23 ± 2.11 to 2.1 ± 1.87 in the HYDZ group (P = 0.001). CONCLUSION: Results showed that both HYDZ and GBP significantly improved and controlled pruritus in patients on dialysis, with no significant difference observed between the two drugs.

Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients.

BACKGROUND: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications. OBJECTIVES: To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation. METHODS: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale. RESULTS: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase. 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.

Trends in Insomnia Diagnosis and Treatment Among Medicare Beneficiaries, 2006-2013.

OBJECTIVE: Insomnia is an important clinical problem affecting the elderly. We examined trends in insomnia diagnosis and treatment among Medicare beneficiaries over an eight-year period. METHODS: This was a time-series analysis of Medicare administrative data for years 2006-2013. Insomnia was defined as the presence of at least one claim containing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 307.41, 307.42, 307.49, 327.00, 327.01, 327.09, 780.52, or V69.4 in any given year. Insomnia medications were identified by searching the Part D prescription drug files in each year for barbiturates, benzodiazepines, chloral hydrate, hydroxyzine, nonbenzodiazepine sedative hypnotics, and sedating antidepressants. RESULTS: Prevalence of physician-assigned insomnia diagnoses increased from 3.9% in 2006 to 6.2% in 2013. Prevalence of any insomnia medication use ranged from 21.0% in 2006 to 29.6% in 2013 but remained steady. A sharp increase in use of benzodiazepines from 2012-2013 (1.1% to 17.6%) drove up total insomnia medication use for 2013. Prevalence of both insomnia diagnosis and medication use ranged from 3.5% in 2006 to 5.5% in 2013, while prevalence of either insomnia diagnosis or medication use ranged from 22.7% in 2006 to 31.0% in 2013. CONCLUSION: 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.

Determination of cocaine adulterants in human urine by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

This study aimed to determine simultaneously five major street cocaine adulterants (caffeine, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction (DLLME) and high-performance liquid chromatography. The chromatographic separation was obtained in gradient elution mode using methanol:water plus trifluoroacetic acid 0.15% (v/v) (pH = 1.9) at 1 mL min-1 as mobile phase, at 25 °C, detection at 235 nm, and analysis time of 20 min. The effect of major DLLME operating parameters on extraction efficiency was explored using the multifactorial experimental design approach. The optimum extraction condition was set as 4 mL human urine sample alkalized with 0.5 M sodium phosphate buffer (pH 12), NaCl (15%, m/v), 300 µL acetonitrile (dispersive solvent), and 800 µL chloroform (extraction solvent). Linear response (r2 ≥ 0.99) was obtained in the range of 180-1500 ng mL-1 with suitable selectivity, quantification limit (180 ng mL-1), mean recoveries (33.43-76.63%), and showing relative standard deviation and error (within and between-day assays) ≤15%. The analytes were stable after a freeze-thaw cycle and a short-term room temperature stability test. This method was successfully applied in real samples of cocaine users, suggesting that our study may contribute to the appropriate treatment of cocaine dependence or with the cases of cocaine acute intoxication.

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial.

BACKGROUND: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. METHODS: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. RESULTS: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). CONCLUSIONS: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.