Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model.

The synergistic effects of Korean Red ginseng (KRG, Panax ginseng C.A. Mey.) on conventional systemic therapeutics of atopic dermatitis (AD) have not been studied yet. To analyze the synergistic effects of KRG extract and the conventional systemic therapeutics of AD in TNCB-induced AD mouse model, we determined the change in modified scoring of index, the transepidermal water loss, the skin pathology, serum IgE, and the expression of various cytokines after combination treatment to the five-week-old NC/Nga female mice. The severity of AD was significantly decreased in the KRG + hydroxyzine (AH) group than AH group, and in the KRG + evening primrose oil (EPO) group than EPO group. A significant decrease in dermal inflammation was observed in the KRG + AH group than that in the AH group, and in the KRG + EPO group than that in the EPO group (p = 0.008), respectively. A decrease in CD1a expression was observed in the KRG + AH group when compared to the AH group (p = 0.008), and KRG + EPO group when compared to the EPO group. Compared to the CS group, the KRG + CS group showed a significant decrease in IL-17 expression. A combination of KRG and conventional systemic therapeutics can safely and effectively manage the AD.

Intestinal failure in adults: Recommendations from the ESPEN expert groups.

BACKGROUND & AIMS: Intestinal failure (IF) is defined as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth". Functionally, it may be classified as type I acute intestinal failure (AIF), type II prolonged AIF and type III chronic intestinal failure (CIF) The ESPEN Workshop on IF was held in Bologna, Italy, on 15-16 October 2017 and the aims of this document were to highlight the current state of the art and future directions for research in IF. METHODS: This paper represents the opinion of experts in the field, based on current evidence. It is not a formal review, but encompasses the current evidence, with emphasis on epidemiology, classification, diagnosis and management. RESULTS: IF is the rarest form of organ failure and can result from a variety of conditions that affect gastrointestinal anatomy and function adversely. Assessment, diagnosis, and short and long-term management involves a multidisciplinary team with diverse expertise in the field that aims to reduce complications, increase life expectancy and improve quality of life in patients. CONCLUSIONS: Both AIF and CIF are relatively rare conditions and most of the published work presents evidence from small, single-centre studies. Much remains to be investigated to improve the diagnosis and management of IF and future studies should rely on multidisciplinary, multicentre and multinational collaborations that gather data from large cohorts of patients. Emphasis should also be placed on partnership with patients, carers and government agencies in order to improve the quality of research that focuses on patient-centred outcomes that will help to improve both outcomes and quality of life in patients with this devastating condition.

An evaluation of the pharmacotherapy for interstitial cystitis.

INTRODUCTION: Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies. AREAS COVERED: The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest. EXPERT OPINION: IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.

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

BACKGROUND: 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 used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings. SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). 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-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence). AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding 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 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 the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

Comparison of Avena sativa, vinegar, and hydroxyzine for uremic pruritus of hemodialysis patients: a crossover randomized clinical trial.

INTRODUCTION: Uremic pruritus is a common complication in patients with chronic kidney disease. While its cause is not known for certain, different treatments are currently applied. This study aimed to compare the effects of Avena sativa, diluted vinegar, and hydroxyzine on the reduction of uremic pruritus. MATERIALS AND METHODS: In this crossover randomized clinical trial, 23 hemodialysis patients with uremic pruritus were randomly divided into 3 groups. The first group was treated with Avena sativa lotion, twice a day, for as long as 2 weeks; the second group received diluted vinegar; and the third group took hydroxyzine tablets for the same time span. After 3-day-long washout periods, the therapeutic methods were crossed over. The data were collected by a pruritus scale and a visual analogue scale, which were completed before and after the interventions. RESULTS: Avena sativa lotion significantly decreased the mean scores of pruritus intensity, consequences, and the verbal descriptor, although it did not have a significant effect on the frequency of pruritus and the pruritic surface. Vinegar and hydroxyzine significantly decreased all of the scores.  Conclusions. Avena sativa, vinegar, and hydroxyzine were effective in decreasing pruritus. Diluted vinegar and Avena sativa can be used as a complement to hydroxyzine, which is itself a common pharmaceutical therapy.

Development and validation of a method for the analysis of hydroxyzine hydrochloride in extracellular solution used in in vitro preclinical safety studies.

In the process of drug development, preclinical safety studies are to be performed that require the analysis of the compound at very low concentrations with high demands on the performance of the analytical methods. In the current study, a UPLC-MS/MS method was developed and validated to quantify hydroxyzine hydrochloride in an extracellular solution used in a hERG assay in concentrations ranging from 0.01 to 10µM (4.5ng/ml-4.5µg/ml). Chromatographic separation was achieved isocratically on an Acquity BEH C18 analytical column. The assay was validated at concentrations of 0.11-1.1ng/ml in end solution for hydroxyzine hydrochloride. Linearity was demonstrated over the range of concentrations of 0.06-0.17ng/ml and over the range of concentrations of 0.6-1.7ng/ml in end solution with the coefficient of correlation r>0.99. Accuracy of the achieved concentration, intra-run, and inter-run precision of the method were well within the acceptance criteria (being mean recovery of 80-120% and relative standard deviation ≤10.0%). The limit of quantification in extracellular solution was 0.09ng/ml. Hydroxyzine hydrochloride in extracellular solution proved to be stable when stored in the fridge at 4-8°C for at least 37 days, at room temperature for at least 16 days and at +35°C for at least 16 days. The analytical method was successfully applied in hERG assay.

Melatonin reduces the need for sedation in ICU patients: a randomized controlled trial.

BACKGROUND: Critically ill patients suffer from physiological sleep deprivation and have reduced blood melatonin levels. This study was designed to determine whether nocturnal melatonin supplementation would reduce the need for sedation in patients with critical illness. METHODS: A single-center, double-blind randomized placebo-controlled trial was carried out from July 2007 to December 2009, in a mixed medical-surgical Intensive Care Unit of a University hospital, without any form of external funding. Of 1158 patients admitted to ICU and treated with conscious enteral sedation, 82 critically-ill with mechanical ventilation >48 hours and Simplified Acute Physiology Score II>32 points were randomized 1:1 to receive, at eight p.m. and midnight, melatonin (3+3mg) or placebo, from the third ICU day until ICU discharge. Primary outcome was total amount of enteral hydroxyzine administered. RESULTS: Melatonin treated patients received lower amount of enteral hydroxyzine. Other neurological indicators (amount of some neuroactive drugs, pain, agitation, anxiety, sleep observed by nurses, need for restraints, need for extra sedation, nurse evaluation of sedation adequacy) seemed improved, with reduced cost for neuroactive drugs. Post-traumatic stress disorder prevalence did not differ between groups, nor did ICU or hospital mortality. Study limitations include the differences between groups before intervention, the small sample size, and the single-center observation. CONCLUSION: Long-term enteral melatonin supplementation may result in a decreased need for sedation, with improved neurological indicators and cost reduction. Further multicenter evaluations are required to confirm these results with different sedation protocols.

Analysis of benzodiazepine withdrawal program managed by primary care nurses in Spain.

BACKGROUND: Benzodiazepine (BZD), the long-term treatment of which is harmful for cognitive function, is widely prescribed by General Practitioners in Spain. Based on studies performed in other countries we designed a nurse-led BZD withdrawal program adapted to Spanish Primary Care working conditions. RESULTS: A pseudo-experimental (before-after) study took place in two Primary Care Centres in Barcelona. From a sample of 1150 patients, 79 were identified. They were over 44 years old and had been daily users of BZD for a period exceeding six months. Out of the target group 51 patients agreed to participate. BZD dosage was reduced every 2-4 weeks by 25% of the initial dose with the optional support of Hydroxyzine or Valerian. The rating measurements were: reduction of BZD prescription, demographic variables, the Short-Form Health Survey (SF-12) to measure quality of life, the Medical Outcomes Study (MOS) Sleep Scale, and the Goldberg Depression and Anxiety Scale.By the end of the six-month intervention, 80.4% of the patients had discontinued BZD and 64% maintained abstinence at one year. An improvement in all parameters of the Goldberg scale (p <0.05) and in the mental component of SF-12 at 3.3 points (p = 0.024), as well as in most components of the MOS scale, was observed in the group that had discontinued BZD. No significant differences in these scales before and after the intervention were observed in the group that had not discontinued. CONCLUSIONS: At one year approximately 2/3 of the patients had ceased taking BZD. They showed an overall improvement in depression and anxiety scales, and in the mental component of the quality of life scale. There was no apparent reduction in the sleep quality indicators in most of the analysed components. Nurses in a Primary Care setting can successfully implement a BZD withdrawal program.

Paediatric painful bladder syndrome/interstitial cystitis: diagnosis and treatment.

To describe the pathophysiology, diagnosis and controversies surrounding the diagnosis and pharmacological treatments of painful bladder syndrome/interstitial cystitis (PBS/IC) in children, we reviewed adult and paediatric literature pertaining to PBS/IC. Paediatric PBS/IC presents similarly to adult PBS/IC. The diagnosis is made by exclusion. Paediatric PBS/IC patients complain most commonly of urinary frequency, and abdominal pain occurs in up to 88% of affected children. Enuresis may also be a presenting complaint. Urinalysis and urine cultures are unremarkable. Management of paediatric PBS/IC is similar to that of adult PBS/IC, and non-surgical management includes dietary, lifestyle and pharmacological therapy. Pharmacological options include pentosan polysulfate, amitriptyline, hydroxyzine, cimetidine or intravesical therapies (dimethyl sulfoxide or 'therapeutic solution').

Treatment modalities, health care resource utilization, and costs in patients diagnosed with interstitial cystitis.

OBJECTIVE: The aim of this study was to examine treatment modalities, health care resource utilization, and costs in patients diagnosed with interstitial cystitis (IC). STUDY DESIGN: Patients with a diagnosis of IC were identified from a national managed care administration claims database and classified into treatment cohorts. All-cause health care resource utilization and costs were calculated by treatment cohort. RESULTS: Patients treated with narcotics plus nonnarcotic analgesics were associated with higher mean health care costs. Patient cohorts treated with some of the more common oral therapies for interstitial cystitis, including pentosan polysulfate sodium, amitriptyline, and hydroxyzine, were associated with lower costs. Physician visits were fewest among patients treated with pentosan polysulfate sodium plus amitriptyline and hydroxyzine. Physician visits were higher for cohorts that included dimethyl sulfoxide plus cystoscopy or bladder irrigation, or narcotics plus nonnarcotic analgesics. CONCLUSION: Interstitial cystitis is associated with substantial costs and health care resource utilization.

[The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 2: Treatment]. / Die Komplexität chronischer Beckenschmerzen am Beispiel der Interstitiellen Zystitis. Teil 2: Therapie.

The so-called interstitial cystitis is a chronic pain syndrome rather than a purely end organ disease of the urinary bladder. New suggestions for definitions and nomenclature take this into consideration. Since aetiology and pathogenesis are still unknown a treatment of the cause is still not possible. There are neither evidence-based treatment algorithms nor a so-called standard therapy. Numerous therapeutic approaches have been tried up to now. These attempts can be divided into oral, intravesical, surgical and physical procedures. There are also meaningful supplementary therapy procedures beyond the boundaries of classical school medicine. The WHO staging scheme provides the basis for every pain therapy. For the oral therapeutic procedures in current use the following medications with differing levels of evidence have been recommended: amitriptylin, hydroxyzin, pentosan polysulfate. Many other orally administered drugs have also been used although in many cases evidence of efficacy is lacking, these included anticonvulsants, L-arginine and various immunomodulators and immunosuppressants. Among the intravesical therapeutic procedures botulinum toxin A, dimethyl sulfoxide, heparin and glycosaminoglycan substitutes have been used. For the physical procedures, besides bladder distension, hyperbaric oxygen therapy shows efficacy. When the conventional therapeutic methods fail, surgical (partial) removal of the urinary bladder or urinary diversion procedures represent the therapeutic ultimo ratio. There are hardly any controlled studies on alternative curative procedures although rather good results have been obtained in chronic pelvic pain syndrome with acupuncture as an additional therapeutic modality.

Rational approaches to the treatment of patients with interstitial cystitis.

Symptoms of interstitial cystitis can usually be successfully managed with heparinoid therapy to theoretically alter bladder urothelial abnormalities, and with oral medications to inhibit neural upregulation or to control mast cell dysfunction. Other forms of care ranging from intravesical therapy to endoscopic, percutaneous, or open surgery are options that may be used singly or in combination to optimize symptom reduction.

Patient response in a screened population for interstitial cystitis.

The purpose of this study was to screen a general patient population for interstitial cystitis (IC) and to determine the outcome of combination therapy (pentosan polysulfate sodium [PPS] and hydroxyzine) in newly diagnosed patients. Screening for IC symptoms was performed on 3883 patients (>or=18 yr of age). After further evaluation, a diagnosis of IC was made in 160 patients. These patients were subsequently treated with PPS 200 mg twice a day (off-label usage) and hydroxyzine hydrochloride 25 mg nightly for 1 to 12 mo. Clinically meaningful (>or=50%) improvement in IC symptoms, as measured by the Patient's Overall Rating of Improvement of Symptoms index, was reported by 59 of 122 patients (48.4%) who completed 1 mo of therapy. This effect was sustained for 12 mo in 26 of 28 patients (92.9%) completing the study. The combination of PPS and hydroxyzine hydrochloride was well tolerated and effective in relieving symptoms associated with IC.

Pityriasis rosea-like eruptions due to mustard oil application.

A young man employed in a construction company, presented with cutaneous lesions clinically simulating pityriasis rosea. Satisfactory and complete response to corticosteroids and antihistamines was followed by recurrence. Multiple recurrences within a short span of time arose a suspicion of alternative diagnosis. Site visit helped us to rule out occupational contact dermatitis. Further history taking revealed that he was recently using mustard oil for body massage. Subsequent patch testing confirmed contact hypersensitivity to mustard oil. Avoidance of the contact with mustard oil arrested appearance of further skin lesions. We stress the importance of taking a good history in clinical practice in disclosing a possible contactant.

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.