Faster Relief Research Articles

Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial

BackgroundUterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgical treatment to reduce leiomyoma size. The aim of this study was to evaluate the efficacy and safety of three dose levels of oral relugolix, a small molecule GnRH receptor antagonist, in Japanese women with uterine leiomyomas and heavy menstrual bleeding.Methods This phase 2, multicenter, double-blind, parallel-group study was conducted at 36 sites in Japan in women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of ≥ 120 in one menstrual cycle. Patients were randomized 1:1:1:1 to relugolix 10, 20, or 40 mg, or placebo, orally once daily for 12 weeks. The primary endpoint was the proportion of patients with a total PBAC score of < 10 from week 6 to 12. A sample size of 50 patients per group was estimated to provide ≥ 95% power, based on the comparison of relugolix 40 mg with placebo using a chi-square test with a significance level of 5% (two-sided).ResultsFrom November 2011 to September 2012, 216 patients were randomized and 214 patients (99.1%) were analyzed. The proportion (difference vs. placebo) of patients that achieved the primary endpoint in the placebo and 10-, 20-, and 40-mg relugolix groups were 0%, 20.8% (95% confidence interval [CI]: 9.3–32.3, P < .001), 42.6% (95% CI: 29.4–55.8, P < .001), and 83.3% (95% CI: 73.4–93.3, P < .001), respectively. Though treatment-emergent adverse events were similar between the 20- and 40-mg groups, the incidence rates were more frequent compared with the placebo group. Most of these adverse events were mild or moderate in intensity.ConclusionsRelugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose–response manner, and was generally well tolerated.Clinical trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01452659, NCT01452659 (registered 17/10/2011); JAPIC Clinical Trial Information, https://www.clinicaltrials.jp, JapicCTI-111590 (registered 31/08/2011).

Сравнительный анализ частоты развития синдрома сухого глаза после кераторефракционных операций ReLEx SMILE и FemtoLASIK

The main factor in pathogenesis of postoperative dry eye syndrome (DES) is damage to subbasal nerve plexus and stromal nerve endings. Taking into account the different principles of photorefractive effect on cornea of FemtoLASIK and ReLEx SMILE technologies, we decided on our own clinical experience to evaluate incidence of this undesirable complication. Purpose. Comparative study of frequency and timing of relief of postoperative DES after FemtoLASIK and ReLEx SMILE in patients with myopia. Material and methods. The study involved 32 patients (64 eyes) with varying degrees of myopia. The patients were divided into 2 groups: 1st group - 17 patients (34 eyes) after FemtoLASIK surgery, 2nd group - 15 people (30 eyes) after ReLEx SMILE procedure. Control group consist of 15 patients with comparable myopia who had not undergone refractive surgery was also observed. Patients underwent an assessment of the OSDI index, Norn and Schirmer tests, as well as degree of staining of anterior ocular surface 1, 6 and 12 months after refractive surgery. Results. There was statistically significant difference in total tear production, in tear breakup time (TBUT) and in the OSDI index between study groups 1 month after surgery in favor of ReLEx SMILE procedure. After 6 months, TBUT after FemtoLASIK significantly differed from control values. 12 months after surgery, studied parameters did not differ significantly from control. Conclusion. According to our datas, ReLEx SMILE procedure has lower negative effect on ocular surface compared to FemtoLASIK technique, which is manifested by less pronounced subjective symptoms of DES, as well as their faster relief. Key words: dry eye syndrome, ReLEx SMILE, FemtoLASIK.

Importance of Jaloukavacharana in Dadru Kushta (Tinea Corporis) - A Case Study

In today’s busy lifestyle people are suffering from stress and strain, which effects on skin as a pathological condition. Even though spending lakhs together for beauty purpose, due to unhygienic and improper behaviour and not following Sadrutta they are getting skin diseases, due to atmospheric temperature and negligence towards health workers, labors, and women are more prone to get skin diseases like Dadru (Tinea corporis), scabies, eczema, dermatitis etc. Dadru is among them. It is treated with the unique procedure using Jaloukavacharana and some Shamanaoushadis as explained under the classics.&#x0D; As Dadru was explained under the Kshudra kustha in Charaka Samhita. In Shushruta, explained Aseta and Seta Dardu, usually the Seta Dadru is Sukha Sadhya. Mandalakara, Kandu delayed diagnosis and elevations are the classical Lakshanas explained in Dadru. Jaloukavacharana is advised in Vata pitta kapha dushta shonita kushta rogas and it is also known as Tinea corporis.&#x0D; In the present era Jalouka is trending treatment for skin disease, speciality of this Jalouka is less pain, fast relief, less cost, OPD level treatment. Jaloukas which contains Hirudine it increases the blood flow and it reduces itching. If we follow the Sadrutta it will help to prevent from skin diseases and specific Pathya apathya is also very important. You can clearly observe in this article that we followed treatment and Pathy apathy are followed by our classics.

Patient Expectations and Experiences of Antidepressant Therapy for Major Depressive Disorder: A Qualitative Study.

PurposeThis qualitative study explored patient perceptions of the most burdensome symptoms of major depressive disorder (MDD), the impact of symptoms on patients’ daily lives, and patient expectations and experiences regarding the timing of onset of antidepressant pharmacotherapy.Patients and MethodsData were collected through facilitated, patient focus-group sessions in the USA between May and June 2019. Participants were adults with confirmed MDD who reported a major depressive episode within the past 2 years, for which they had received pharmacologic treatment for ≥6 weeks. The semi-structured discussion focused on the key topics of bothersome symptoms of MDD, the impact of symptoms on quality of life, and the effects of antidepressant treatment. Interviews were audio-recorded; findings were summarized using a content-analysis approach.ResultsFive focus-group sessions were undertaken, involving a total of 29 patients (each attended one session; mean age, 43.4 years; 72.4% female). Mean time since confirmed diagnosis of MDD was 13.1 years. The most commonly prescribed antidepressants received were bupropion (41.4% of participants), escitalopram (34.5%), and sertraline (34.5%). The most frequently reported bothersome MDD symptoms were fatigue (mentioned by 58.6% of participants), lack of motivation/loss of interest (51.7%), anxiety/panic (44.8%), sadness (41.4%), and lack of concentration/brain fog (41.4%). Socialization, family life, and work were the areas in which quality of life was most impacted. Participants expressed dissatisfaction with their antidepressant treatment. Fast symptom resolution was mentioned as a priority (defined as <1 week by 38.5% of participants and ≤1 month by 65.4%). Most participants had not experienced fast relief from their symptoms with current or previous antidepressant medications.ConclusionResults of this qualitative study suggest that fatigue, anhedonia, cognitive symptoms, and anxiety are some of the most bothersome symptoms for patients with MDD and highlight the importance of obtaining rapid relief from these symptoms in order to improve outcomes and patient satisfaction with antidepressant medication.

PREPARATION AND EVALUATION OF MEFENAMIC ACID AND DICYCLOMINE HYDROCHLORIDE AS ORAL DISINTEGRATING TABLET BY DIRECT COMPRESSION METHOD

A new dosage form, Oral disintegrating tablets (ODT’s) as a replacement to conventional oral dosage forms. ODT’s are dosage forms they disintegrate in mouth offering various advantages such as better mouth feel, dose accuracy, improved stability and convenient dosing as compared to oral liquids. So, there is need to designed oral disintegrating tablet to release the medicaments with an enhanced rate. Mefenamic acid is an anti- inflammatory drug while Dicyclomine HCl is anti-cholinergic drug. The combination of Mefenamic acid &amp; Dicyclomine HCl controls pain very effectively, also relaxes bodily spasm which commonly arises during menstruation or intestinal colic spasm. This combination gives the quick onset of action and fast relief than conventional dosage form. For preparation of oral disintegrating tablet nine formulations were designed using Croscarmellose sodium and Crospovidone as superdisintegrants in varying concentration. All the formulations were prepared by direct compression method. Thus, all the formulations of Mefenamic acid and Dicyclomine HCl oral disintegrating tablets were investigated, in which F9 formulation was optimized. The % drug release of, Oral disintegrating tablet batch F9 has shown 96.98% of Mefenamic acid and 94.02 % of Dicyclomine HCl in 18 min, disintegration time in 40 sec and wetting time in 25sec.

A Systematic Review of Current Clinical Practice Guidelines on Intra-articular Hyaluronic Acid, Corticosteroid, and Platelet-Rich Plasma Injection for Knee Osteoarthritis: An International Perspective.

Background:There are many clinical practice guidelines (CPGs) for the prevention, diagnosis, and treatment of knee osteoarthritis (OA). They differ by region, considering local health care systems, along with cultural and economic factors. Currently, there are conflicting CPG recommendations across the various publications, which makes it difficult for clinicians to fully understand the optimal treatment decisions for knee OA management.Purpose:To summarize the current published CPG recommendations for the role of injections in the nonoperative management of knee OA, specifically with the use of intra-articular hyaluronic acid (IA-HA), intra-articular corticosteroids (IA-CS), and platelet-rich plasma (PRP).Study Design:Systematic review.Methods:A comprehensive search identified all nonoperative knee OA CPGs within the ECRI (formerly Emergency Care Research Institute) Guidelines Trust database, the Guidelines International Network database, Google Scholar, and the Trip (formerly Turning Research Into Practice) database. Guideline recommendations were categorized into strong, conditional, or uncertain recommendations for or against the use of IA-HA, IA-CS, or PRP. Guideline recommendations were summarized and depicted graphically to identify trends in recommendations over time.Results:The search strategy identified 27 CPGs that provided recommendations. There were 20 recommendations in favor of IA-HA use, 21 recommendations in favor of IA-CS use, and 9 recommendations that were uncertain or unable to make a formal recommendation for or against PRP use based on current evidence. Most recommendations considered IA-HA and IA-CS use for symptom relief when other nonoperative options are ineffective. IA-CS were noted to provide fast and short-acting symptom relief for acute episodes of disease exacerbation, while IA-HA may demonstrate a relatively delayed but prolonged effect in comparison. The CPGs concluded that PRP recommendations currently lack evidence to definitively recommend for or against use.Conclusion:Available CPGs provide recommendations on injectables for knee OA treatment. General guidance from a global perspective concluded that IA-CS and IA-HA are favored for different needed responses and can be utilized within the knee OA treatment paradigm, while PRP currently has insufficient evidence to make a conclusive recommendation for or against its use.

Response Surface Methodology (RSM) Approach for Optimizing the Actuator Nozzle Design of Pressurized Metered-Dose Inhaler (pMDI)

Recently, a remarkable scientific interest in the inhalation therapy for respiratory disease was spiked attributed to the growing prevalence of asthma, chronic obstructive pulmonary disease (COPD), and coronavirus disease 2019 (COVID-19) pandemic. A pressurized metered-dose inhaler (pMDI) is the best option by providing fast and efficient symptomatic relief within the lung. However, the rapid development of new inhalation devices could be critical in this competitive environment, and optimizing the inhalation devices could be costly and time-consuming. Therefore, the computational fluid dynamic (CFD) approach was used to shorten the development time. In this study, response surface methodology (RSM) in ANSYS version 19.2 was introduced to discover the optimal design for the actuator nozzle to increase the performance of pMDI. Three (3) parameters (orifice diameter, length, and actuator angle) were optimized, and the best design was selected according to the analysis of particle tracking. The analysis of spray plume was also conducted and compared to analyze the spray plume characteristic produced by three designs. The result showed that RSM generated three (3) models for the new design of the actuator nozzle (Design A, Design B, and Design C). Among three (3) designs, actuator nozzle design C showed the highest injection particle number (232457) and the only one that produced maximum particles velocity magnitude in the acceptable ranges (35.67m/s). All three designs showed a similar pattern as maximum particle velocity magnitude decreased along the axial length until they match the air velocity (0.03-0.04 m/s). Furthermore, the spray plume length, angle, and width were observed to increase linearly with the decreasing maximum particle velocity magnitude. Thus, this study suggested that design C might have the potential as a new actuator nozzle to develop future pMDI to relieve the respiratory condition.

Nanostructured Lipid Carrier (NLC) and Solid Lipid Nanoparticles (SLN) Based Hydrogel for Delivery of Etodolac: A Comparative Investigation on Dermal Pharmacokinetic on Rat Skin

Objectives: The present work focus on to create Solid lipid nanoparticles (SLN) and nanostructured lipid Carrier (NLC) as transporters for effective delivery of Etodolac (ETD). Methods: Etodolac stacked SLN and NLC were set up by melting emulsification and hardening at low temperature method and they were portrayed for molecule size, zeta potential, encapsulation efficacy and in vitro discharge rate. Ex vivo dermatokinetic by tape stripping technique was explored in rat skin utilizing altered Franz diffusion cells. The praticle size and the surface electrical charge (ZP) have been assessed following after manufacturing of dispersion. Results: The particles stayed in their colloidal range after production by melt emulsification method. For all nano dispersion the encapsulation efficacy was higher than 75%. Differential Scanning calorimetry (DSC) were performed to portray the physicochemical properties of the SLN and NLC. Approximately Same amount of Etodolac release was facilitated through skin of rats from SLN-SA and NLC-SA. Conclusion: Research work could be concluded as successful development of Etodolac loaded SLN and NLC to increase the encapsulation efficiency of colloidal lipid carriers with benefit of higher performance in terms of long term stability and impart a sustaining Etodolac topical effect as well as faster relief from pain associated with arthritis.

Comparison of two marketed effervescent fast relief formulations for antacid activity-an in vitro study

Background: Hyper-acidity is excessive formation of acid (pH=1.5-3.5) in the stomach by parietal cells which causes a burning sensation in the chest. The preservation of gastric acid insult is crucial because of the implications of hyperacidity in gastroesophageal reflux disease (GERD), peptic ulcers and duodenal ulcers. Acidity is controlled by use of some over-the-counter (OTC) antacid formulations containing magnesium or aluminum hydroxides.Methods: In the present study, the preliminary antacid test (PAT), the pH acid neutralizing capacity (ANC), acid neutralizing potential (ANP) along with buffering capacity of two well-known quick release formulations (F1 [Digene Ultra Fizz] and F2 [a standard, commercially available product]) were determined. Results: According to US pharmacopeia USP, both the antacid formulations passed the PAT test. PAT results revealed that the pH of the acid-antacid solution was higher in F1 (8.20±0.02) as compared to F2, (6.53±0.01). The ANC results revealed that F1 (46.89±0.6 mEq/dosage) had higher neutralizing capacity as compared to F2(30.12±1.3 mEq/dosage). Higher ANP was observed for F1 (245 mins), and it was 2.7 times that of F2 (90 min). The onset of action for both the antacids was &lt;2 seconds. Additionally, buffering capacity was evidently observed during ANP analysis in the case of F1. Independent T test performed for all the tests revealed that the data obtained was highly significant (p&lt;0.01).Conclusions: F1 showed high antacid and buffering properties when tested in vitro. The present study highlights the need for future research on specific OTC non-prescribed antacid formulations with respect to their price, efficacy and side effects.

Formulation of Medicated Chewing Gum Containing Sceletium tortuosum and Process Optimization Utilizing the SeDeM Diagram Expert System.

Sceletium tortuosum is one of the most promising medicinal plant species for treating anxiety and depression. Traditionally, aerial parts are chewed (masticatory herbal medicine) providing fast relief and rendering the masticatory route for delivery, ideal. This study intended formulating novel medicated chewing gum containing S. tortuosum to alleviate depression and anxiety. S. tortuosum extract was formulated into directly compressed medicated chewing gum (MCG) containing different Health-in-Gum® (HIG) bases through process optimization with the SeDeM Diagram Expert System. Physical properties of MCGs were characterized, and specialized drug release studies performed. According to the manufacturer, only HIG-03 was specifically developed for direct compression; however, the SeDeM System was successfully applied to all HIG-bases investigated. HIG-01 and HIG-04 are also considered useful in direct compression as no considerable differences in these MCG formulations' physical properties were recognized. Inclusion of a lubricant, however, is deemed essential, and MCG comprising HIG-01, most suited for direct compression. Dissolution experiments found only two alkaloids used as markers, mesembrine and mesembrenone, were released in quantifiable concentrations regardless formulation constituents. Novel directly compressed MCG-containing S. tortuosum extract was successfully formulated by which the biologically active phytochemicals of S. tortuosum can be scientifically delivered through the traditionally applied mastication method.

The Scenario of Patented Ayurvedic Drugs in Perspective of Ayurveda Doctors in Kerala

In the Ayurveda scenario, the doctors are prescribing patent drugs along with traditional medicines. The doctor’s experience in the prescription of patent drugs is the major factor which influences the success of patent drugs. The doctors can easily identify the quality and availability related to patent drugs and also identifies the success of the product in the market. In the doctor’s side, patient’s fast relief make them prescribe the particular medicine to the large volume. The quality of medicine and the manufactures frequent researches and studies to improve the quality of products. So, the manufacturers of patent drugs also inform about their patent drugs to doctors. Of course, the doctors prescribe such drugs only if the drug is relevant to community. This study investigates the factors that have influenced Ayurveda doctors to prescribe patent drugs. It is based on 225 samples units of Ayurveda doctors in the state of Kerala. The results obtained show that Knowledge, Consumer affordability, Social benefits have greater influences on prescription of patent drugs.

Pruritus in psoriasis and atopic dermatitis: current treatments and new perspectives

Psoriasis and atopic dermatitis (AD) are two common chronic inflammatory skin diseases. Although showing different etiology and clinical manifestations, patients with either disease suffer from low health-related quality of life due to pruritus (dermal itch). Recent studies have revealed that more than 85% of psoriasis patients suffer from pruritus, and it is also the dominating symptom of AD. However, as this is a non-life treating symptom, it was partly neglected for years. In this review, we focus on current findings as well as the impact and potential treatments of pruritus in these two skin diseases. We first distinguish the type of itch based on involved mediators and modulators. This clear delineation between the types of pruritus based on involved receptors and pathways allows for precise treatment. In addition, insights into recent clinical trials aimed to alleviate pruritus by targeting these receptors are presented. We also report about novel advances in combinatorial treatments, dedicated to the type of pruritus linked to a causal disease. Altogether, we suggest that only a focused treatment tailored to the primary disease and the underlying molecular signals will provide fast and sustained relief of pruritus associated with psoriasis or AD.

Remote W.A.R.A. Compared With Face-to-Face W.A.R.A.: A Pilot Study.

BackgroundSince the outbreak of the COVID-19 pandemic and its social restriction measures, online therapy is a life-saving possibility for patients with acute stress. Wiring Affect with ReAttach (W.A.R.A.) is a brief psychological intervention aiming to decrease negative affect, that can be offered online.MethodsWe assessed the effect of remote W.A.R.A. on negative affect in 37 patients. Consequently, we compared the effect of remote W.A.R.A. versus face-to-face W.A.R.A on negative affect in a cross-sectional design.ResultsW.A.R.A. remote therapy provoked a significant reduction of negative affect with a large effect size (d = 3.08, p < 0.001). However, the reduction on negative affect was smaller than with W.A.R.A. face-to-face. We found a substantial difference between W.A.R.A. remote therapy and W.A.R.A. face-to-face in decrease of negative affect (d = 1.36, p < 0.001).LimitationsThe major limitation of the pilot-study is the sample size of 37 patients. Besides, we designed a numeric rating scale for evaluating negative affect. We investigated the impact on negative affect by assessing “unpleasant feelings.” This conceptualization of negative affect might still be a point of discussion.ConclusionThe study’s findings indicated that W.A.R.A. remote therapy significantly reduced negative affect, but to a lesser extent than W.A.R.A. face-to-face. Nevertheless, W.A.R.A. remote therapy might offer a fast relief, especially when personal contact is difficult.

Clinical and surgical outcomes of enneking stage III aneurysmal bone cysts of the spine

Objective: To study the clinicoradiological characteristics and surgical outcomes in patients with aggressive aneurysmal bone cyst (ABC) of spine. Materials and Methods: In this retrospective study, data was collected from patients with aggressive ABC of spine managed between January 2007 and December 2016. Clinical findings, radiological, and histological characteristics were studied. Follow-up was done either in the outpatient clinic or through a telephonic interview. Results: Seven patients (mean age, 15.6 years, range, 6–23 years) diagnosed with Enneking stage III aneurysmal bone cyst of the spine were included in the study. Local pain with restriction of movement was the most common presenting complaint (100%). Four patients presented with myelopathy. Thoracic spine was the most common site of involvement (43%). Of the patients, 71% had involvement of all three columns. All patients underwent surgical management; gross total resection in four patients (57%) and subtotal in three patients (43%). Of the seven patients, six required instrumented fusion. None of the patients developed any perioperative complication except for one patient who developed transient hip flexion worsening. Two patients received conformal radiation therapy (RT) postoperatively. The follow-up ranged from 40 months to 108 months (mean follow-up was 4.5 years). There were no recurrences. At last follow-up, all patients were alive and had significant improvement. Conclusions: ABC of the spine is found predominantly in the pediatric population. Intralesional en bloc resection with instrumented stabilization provides effective and fast relief from pain, early mobility, good surgical, and long-term outcomes. Conformal RT following a planned subtotal excision prevents the progression of the disease.

Using sodium dithionite as a reducing agent in the synthesis of propacetamol hydrochroride from phenol

Propacetamol, a prodrug form of paracetamol, is used in injections for fast and effective pain relief. Propacetamol is water soluble and is used in postoperative care as well as intravenous administration in case the patients cannot take oral or rectal paracetamol. Studies on propacetamol synthesis at laboratory scale as well as industrial scale with safe, simple and economic procedures are crucial. In this study, we synthesized propacetamol from phenol as the starting material. In the first step, phenol was converted to p-nitrosophenol through a nitrosation process. This nitrosation reaction yielded the optimal result as the reaction selectively occured, the product was not plasticized. Next, p-nitrosophenol was reduced to p-aminophenol in the presence of sodium dithionite as the reducing agent. The reaction produced p-aminophenol at a yield of 89,6% with high selectivity and less impurity. After that, paracetamol was obtained through acetylation of p-aminophenol. Ochloroacetylation of paracetamol was performed by using the amount of diethylamine reduced by 2,5 times compared to previous studies to form 4-acetamidophenyl-2-chloroacetate in 85,5% yield. This intermediate was then alkylated to form propacetamol base, followed by treatment with HCl solution in acetone at low temperature to obtain propacetamol hydrochloride in 32,5% yield. The study has shown that propacetamol hydrochloride was successfully achieved with high efficiency and safety from phenol as the starting compound.

Suprascapular Nerve Block Is an Effective Pain Control Method in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

Background:Effective pain control in patients who have undergone arthroscopic rotator cuff surgery improves functional recovery and early mobilization. Interscalene blocks (ISBs), a widely used approach, are safe and provide fast pain relief; however, they are associated with complications. Another pain management strategy is the use of a suprascapular nerve block (SSNB).Hypothesis:We hypothesized that indwelling SSNB catheters are a more effective pain control method than single-shot ISBs. We also hypothesized that indwelling SSNB catheters will reduce the level of rebound pain and the demand for opioid analgesics.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:Included in this study were 93 patients who underwent arthroscopic rotator cuff surgery between May 2012 and January 2019. These patients were assigned to either the indwelling SSNB catheter group, the single-shot ISB group, or the control (sham/placebo) group (31 patients per group). Level of pain was measured with a visual analog scale (VAS; 0 to 10 [worst pain]) on the day of the operation. The preoperative VAS score was recorded at 6 AM on the day of operation, and the postoperative scores were recorded at 1, 8, and 16 hours after surgery and then every 8 hours until postoperative day 3.Results:The VAS pain scores were lower in the SSNB and ISB groups than in the control group up to postoperative hour (POH) 8, with the most significant difference at POH 8. At POH 1 and POH 8, the mean VAS scores for each group were 2.29 and 1.74 (SSNB), 2.59 and 2.50 (ISB), and 3.42 and 4.48 (control), respectively. VAS scores in the SSNB and ISB groups were consistently <3, compared with a mean VAS score of 3.1 ± 1.58 in the control group (P < .001). Compared with the ISB group, the SSNB group had significantly fewer side effects such as rebound pain duration as well as lower VAS scores (P < .001).Conclusion:VAS scores were the lowest in the indwelling SSNB catheter group, with the most pronounced between-group difference in VAS scores at POH 8. Severity and recurring frequency of pain were lower in the indwelling SSNB catheter group than in the single-shot ISB group.

Management of recurrent aphthous ulcers exploiting polymer-based Muco-adhesive sponges: in-vitro and in-vivo evaluation

Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.

Thermal-fluid-structure analysis of fast pressure relief valve under severe nuclear accident

Fast pressure relief valve (FPRV) equipped at the pressurizer of nuclear power system is used to release steam with high pressure and high temperature rapidly from the primary circuit loop and to prevent high temperature core melting in case of severe accident condition. When releasing the steam, the time-varying temperature, mass flow and interior pressure of the inlet will affect the reliability of FPRV. In this study, the thermal analysis and the static structural analysis of FPRV under severe transient thermal shock are conducted by a 3D thermal-fluid-structure coupling numerical simulation considering the transient coupled flow, heat transfer and mechanical load. In the analysis, one-way coupling simulation is conducted. Firstly, the fluid flow and heat transfer in the valve and valve body are simulated with time. Then the instantaneous temperature fields of FPRV structure obtained from the CFD analysis at different critical moments, at which the valve is bearing high temperature, high mass flow or high interior pressure, are imported into static structural analysis as thermal load for stress analysis. Through comparative analysis of stress under mechanical load, thermal load and their combined effect, it is found that the thermal stress is the primary component of the coupled stress of FPRV and the thermal loads rather than the pressure loads are responsible for accidents related to stress overload in nuclear power plants. Therefore, the coupled stress including thermal stress should be less than the allowable stress intensity for the safety evaluation of the FPRV in a nuclear power plant.

Early postoperative pain relief after total shoulder arthroplasty

BackgroundPatients undergoing elective shoulder arthroplasty have highly variable pain experiences. We sought to characterize preoperative patient characteristics associated with fast and slow pain relief after elective total shoulder arthroplasty and evaluated whether differences in early pain recovery predicted longer term pain relief. MethodsWe identified 324 patients undergoing elective primary shoulder arthroplasty, reverse and anatomic, between 2015 and 2018 from our prospective registry. Postoperative pain relief was defined as the difference in preoperative and 2-week postoperative pain intensity. Three groups were then created: fast responders (top decile), slow responders (bottom decile), and normal responders. Multinomial regression was used to identify preoperative patient factors associated with either slow or fast pain responses. ResultsFactors associated with a fast pain response included older age and being married. A slow pain response was associated with being unmarried. Pain intensity was lower in the fast responders at 6 weeks (0.60 ± 0.80 vs. 3.4 ± 2.50, P < .05) and 3 months (0.60 ± 0.90 vs. 2.60 ± 2.30, P < .05), but there was no difference at 1 year (0.30 ± 0.60 vs. 1.00 ± 1.10, P = .068) and 2 years (0.50 ± 1.30 vs. 1.40 ± 2.10, P = .183) postoperatively. ConclusionThe postoperative pain experience after shoulder arthroplasty seems to be influenced by patient age and marital status. Patients with marginal improvement in pain relief should be counseled that their recovery may be more prolonged, but by the 1-year mark they are likely to achieve comparably low pain levels to other patients. Level of evidenceLevel III; Retrospective Design; Prognosis Study

Formulation and Evaluation of Novel Formulation for Diabetes Induced Hypertension using Modified Innate Superdisintegrant

Objectives: Diabetes is a chronic disease and is a group of metabolic disorders characterized by high levels of sugar in blood (hyperglycemia). Hypertension is a major modifiable risk factor for cardiovascular morbidity and mortality in patients with diabetes. The objective of this research is to formulate Fast dissolving tablets of Pioglitazone and Cilnidipine for the effective treatment of diabetes induced hypertension.&#x0D; Methods: Six formulations were prepared by direct compression technique by using Opuntia ficus-indica as an innate superdisintegrant.&#x0D; Result and Discussion: All the formulations were subjected for precomprression, post compression parameters and shows all the data within the specific limits. F5 formulation with the mixture of polymers viz. Opuntia ficus indica, SSG, croscarmellose sodium, magnesium stearate, DiCOM showed comparatively fast disintegration and best release of drug than that of all other formulation. The tablets of F5 formulation disintegrated within 18.53 seconds can provide fast relief in the body. The in-vitro dissolution results revealed that the drug release of F5 formulation tablets was more than 90% for Pioglitazone and near to 70% for Cilnidipine within 30 minutes. Stability studies were performed on F5 formulation tablets showed no significant changes in color, disintegration time and in-vitro dissolution which showed that appearance of tablets was having no effect.&#x0D; Conclusion: Fast dissolving tablets of Pioglitazone and Cilnidipine can be successfully prepared using direct compression technique and it will enhance the drug dissolution, which will further increase absorption and bioavailability of both drugs.&#x0D; Keywords: Pioglitazone, Cilnidipine, diabetes induced hypertension, fast dissolving tablets, direct compression.