Otolaryngology : Vitamin D levels in children diagnosed with acute otitis media,Selenium supplement for treatment of geriatric rhinitis,extraturbinal microdebrider-assisted inferior turbinoplasty in children,local anesthetics in the tonsillar fossa after tonsillectomy,

Selenium supplement for treatment of geriatric rhinitis Esin Yalcinkaya, Hasmet Yazici, Hakan Kayir, Fatih K Soy, Hesham Negm The Egyptian Journal of Otolaryngology 2019 35(2):135-139 With the aging of population, the incidence of geriatric problems is increasing. However, the diagnosis and treatment of geriatric problems are usually ignored. This study investigated the efficacy of supplemental selenium in patients with geriatric rhinitis (GR). The study was conducted at an academic secondary referral center in a prospective design. Patients were divided into two groups, and they were compared with healthy volunteers. The treatment group, including patients with GR, was given nasal saline wash four times daily and 100 µg of seleno-6 dietary supplements twice daily. The patient control group and the healthy volunteers were given only the nasal saline wash four times daily. Glutathione peroxidase, superoxide dismutase, and catalase levels were measured in all participants before and after treatment. In addition, the sino-nasal outcome test-20 and visual analog scale were applied before and after treatment. In the selenium supplement group, the visual analog scale, sino-nasal outcome test-20 scores, and enzyme levels were significantly improved compared with the untreated group. No adverse effects occurred in the selenium supplement group during the study. Supplemental selenium might be effective in the treatment of GR in terms of aging physiology and the oxidative system. However, large-scale randomized studies are needed to determine the optimal treatment.

Safety and efficacy of extraturbinal microdebrider-assisted inferior turbinoplasty in children Osama Galal Abdelnaby Awad The Egyptian Journal of Otolaryngology 2019 35(2):140-146 Background Nasal obstruction is commonly seen in children and can be caused by a variety of factors. Turbinate hypertrophy has become a more frequent entity in pediatric patients presenting with nasal obstruction. Aim This study aims to assess the effectiveness and safety of extraturbinal microdebrider-assisted inferior turbinoplasty (MAIT) in relieving inferior turbinate hypertrophy in children. Patients and methods This prospective study was conducted from May 2016 to May 2017 in a tertiary referral hospital. Fifty pediatric patients with chronic hypertrophic rhinitis were enrolled in the study. We tried the extraturbinal MAIT technique to reduce inferior turbinate size. The degree of nasal obstruction was assessed using subjective, clinical symptom grading tools, visual analogue scale, and saccharin clearance test at 1 and 6 months postoperatively. Any postoperative complications were also noted. Results Mean age of patients were 12.7±9.5 years (range: 6–18 years). Significant postoperative improvement (P<0.001) was noted in the degree of nasal obstruction in 1 month and was maintained after a follow-up period of 6 months. Majority of patients had minimal crusting with good tissue healing with no adhesions or atrophic changes and with significant improvement of saccharin clearance time at 6 months postoperatively. Conclusion Extraturbinal MAIT is an effective and safe procedure in children compared with other reported procedures.

Endoscopic endonasal prelacrimal recess approach for antrochoanal polyp Wael F Ismaeil, Mohamed H Abdelazim The Egyptian Journal of Otolaryngology 2019 35(2):147-154 Background The purpose of this study was to assess the effectiveness of endoscopic transnasal prelacrimal recess approach (ETPRA) in preventing the recurrence of antrochoanal polyps. Patients and methods A total of 32 patients with antrochoanal polyp were divided into two equal groups: group 1 included 16 patients who underwent endoscopic middle meatal antrostomy (EMMA), and group 2 included 16 patients who underwent a combined surgical technique using EMMA together with ETPRA. They were followed up from 24 to 36 months. Success rates for visualization of the origin of the polyps, surgical complications, and recurrence were evaluated. Results The most common symptoms were nasal obstruction (100%), snoring (75%), rhinorrhea (59.38%), headache (96.88%), and hyposmia (53.13%). The study found that postoperative complications varied between both groups. Recurrence was found in 18.75% in EMMA group and 0% in ETPRA group. They were statistically significant (P<0.05). However, nasolacrimal duct injury was found in two patients in ETPRA group, and postoperative lacrimation presented in only one (6.25%) patient of the same group. They were statistically insignificant (P>0.05). Conclusion Recurrence rate of antrochoanal polyp has been reduced with the usage of ETPRA in comparison with EMMA alone.

The relation between chronic rhinosinusitis and sleep-disordered breathing Yasser F El-Beltagy, Alaa F Ghita, Ossama M Mady, Ahmed M Ibrahim The Egyptian Journal of Otolaryngology 2019 35(2):155-161 Background Chronic sinusitis is one of the most prevalent chronic illnesses affecting persons of all age groups. It is an inflammatory process that involves the paranasal sinuses and persists for 12 weeks or longer. Purpose The aim of this study was to investigate the effect of chronic rhinosinusitis (CRS) on sleep-disordered breathing. Patients and methods This study was conducted prospectively during the period spanning from June 2017 to June 2018 on 100 patients with CRS who attended to the ENT Departments of El-Maadi Armed Forces Medical Complex, Kobry El-Kobba Armed Forces Medical Complex, and El-Demerdash Hospitals. An additional 10 control patients were included in the study. All these patients gave informed consent to participate in this study. Results As regards apnea–hypopnea index, a comparative study between preoperative and postoperative measurements revealed a nonsignificant difference (P>0.05). As regards snore index and snore episodic measurements, the comparative study between preoperative and postoperative measurements revealed a highly significant decrease (P<0.01). As regards sleep efficiency and minimal and basal oxygen saturation measurements, the comparative study between preoperative and postoperative measurements revealed a highly significant increase (P<0.05). Conclusion Surgery decreased snoring and Epworth Sleepiness Scale scores, increased sleep efficiency and minimal and basal oxygen saturation measurements without changes in the apnea–hypopnea index, and improved sleep quality.

Vitamin D levels in children diagnosed with acute otitis media Mohamed A. M Salem, Mohamed Abdullah M., Zakria A Mohamed, Mohamed O. A Gad, Walla G Gadalla The Egyptian Journal of Otolaryngology 2019 35(2):162-167 Objective To investigate the relationship between acute otitis media (AOM) and vitamin D level in children. Patients and methods This prospective study was conducted at Assiut University Hospital between December 2016 and March 2017. The study group comprised ambulatory children who were diagnosed with AOM and healthy controls. The blood sample (5 cm) was taken immediately after the diagnosis of AOM in the laboratory for measuring serum 25-hydroxyvitamin D. Abnormal value=deficiency+insufficiency. Results Of the 40 children included in this study, 30 were the cases and 10 were controls. The mean age of the cases was 4.92±3.08 and 5.92±4.04 years for the controls besides 18 (60%) of the AOM group were boys and 12 (40%) were girls, compared with five (50%) boys and five (50%) were girls in the control group. Otalgia and congested tympanic membrane were present in all children of the diseased group. Also 70% had upper respiratory tract infection preceding the attack of AOM and 33.3% had previous attack of AOM. Twenty-two (73.3%) out of 30 children of the AOM group have an abnormal value of vitamin D and it was statistically significant than the control group. Conclusion Both vitamin D deficiency and insufficiency were significant in children suffering from AOM than normal children.

Impact of mastoidectomy on tympanoplasty for recurrent suppurative otitis media Sayed Mohammed Said Kadah, Sayed Mohammed Mokhemar, Hoda. Ali Ibrahim, Hanem Elsayed Ibrahim The Egyptian Journal of Otolaryngology 2019 35(2):168-172 Background There are still many questions about the pathogenesis of chronic suppurative otitis media (CSOM) and consequently about the optimal management medical or surgical interventions. Many otolaryngologists continue to routinely perform mastoidectomy with tympanoplasty, arguing that surgical aeration of the mastoid will improve outcomes by providing a reservoir of air that can buffer pressure changes in the middle ear according to Boyle’s law. Patients and methods During the period from December 2013 to October 2017, the mean age was ranging from 20 to 50 years; 25 (62.5%) patients were females, whereas 15 (37.5%) patients were male who were attending the Otorhinolaryngology Department, Al Zahraa University Hospital, with recurrent suppurative otitis media refractory to medical treatment. The 20 patients selected for this study were randomly assigned to undergo tympanoplasty with cortical mastoidectomy (n=20) and tympanoplasty alone (n=20). Results The factors that may influence surgery success rates are age, perforation location and size, Eustachian tube conditions, status of the middle-ear mucosa, the type of graft used, and surgeon experience. The primary argument in favor of mastoidectomy has been an improvement in the middle ear and mastoid environment through clearance of the diseased mucosa and through the ventilatory mechanisms of an open mastoid system, as a buffer to the changes in pressure within the middle ear. Conclusion There was no additional benefit to performing mastoidectomy with tympanoplasty for uncomplicated perforations. Mastoidectomies were generally performed with a worst disease, as suggested by the presence of extensive inflammation, or a sclerotic middle ear or mastoid.

Effect on postoperative pain after topical application of local anesthetics in the tonsillar fossa after tonsillectomy Ahmed El Daly, Moustafa Abd El Naby, Pola Emad The Egyptian Journal of Otolaryngology 2019 35(2):173-181 Background Tonsillectomy is one of the most commonly performed surgeries in ENT practice. Despite improvements in anesthetic and surgical techniques, post-tonsillectomy morbidities continue to be a significant clinical concern. Pain is the cause of most of the postoperative morbidity after tonsillectomy. An effective pain therapy to block or modify the physiological responses to stress has become an essential component of modern pediatric anesthesia and surgical practice. Aim The present study compares the results between the effect of lidocaine 2% infiltration, lidocaine 10 % spray, and bupivacaine 0.5% spray in the tonsillar bed after tonsillectomy on postoperative pain. Materials and methods The study included a total of 120 patients aged 5–18 years who were candidates for tonsillectomy at the Otorhinolaryngology Department of Alexandria Main University Hospital. The patients were randomly divided into three groups of 40 patients each. Group A received lidocaine 2% (Xylocaine) peritonsillar infiltration 2 ml in one tonsillar bed and posterior pillar; group B received lidocaine 10% (Xylocaine) spray 2 puff in one tonsillar bed; group C received bupivacaine 0.5% (Marcaine) solution 2 ml in one tonsillar bed spray by syringe and the other tonsillar bed in each group receives pack with similar amounts of normal saline for 5 min as a control group after tonsillectomy before recovery from anesthesia. Results There was no statistical difference between the three studied groups as regards age and sex. There is significant statistical difference according to the frequency of throat pain and ear pain by comparing cases and controls of each group within the first 24 h after surgery. It appears that increased frequency of postoperative throat pain and ear pain is present with the control side (saline). Conclusion Topical application of the tonsillar bed with a local anesthetic after tonsillectomy results in significant reduction of postoperative throat pain and referred otalgia and should be used during surgery for tonsillectomy.

Impact of voice disorders and microlaryngeal surgery on psychological profiles of Arabic-speaking professional and nonprofessional voice users Ayatallah Sheikhany, Ahmed Atef, Osama Refaat, Ahmad Al Ali The Egyptian Journal of Otolaryngology 2019 35(2):182-188 Introduction Voice disorders that impair normal social communication may cause subsequent emotional distress and are significantly associated with greater risk of anxiety and depression. The occurrence of vocal symptoms and voice disorders in professions where voice is an essential tool may cause stress and anxiety to the professionals suffering from them. Voice disorders in professionals have a major psychoemotional and social impact because they can threaten, shorten, or even end teachers’ and singers’ careers. Aim of the work Psychological impact of various voice disorders of professional and nonprofessional voice users has not yet been adequately studied according to the authors’ knowledge in the Egyptian population. It is therefore of great importance to shed light on the psychological impact of voice disorders on patients in an attempt to improve the quality of life of those patients. Patients and methods During the period of 6 months from June 2014 to December 2014, 40 patients were included prospectively in this work. Results and conclusion Professional voice users are more susceptible to psychological diseases than nonprofessional voice users. The degree of improvement postoperatively in professional voice users was statistically significant in all assessments of this study when compared with the nonprofessional voice users except in self-confidence and worth (Rosenberg self-esteem test). The best degree of improvement postoperatively was detected in the professional voice physically according to Jacobson scoring guidelines. There was a moderate relation between dysphonia and anxiety and depression according to the Voice Handicap Index and Kessler psychological distress scale results in this study.

Formulation of a program for treatment of childhood dysphonia Riham M Elmaghraby, Yehia A.A Ras, Maha M Elkaraksy The Egyptian Journal of Otolaryngology 2019 35(2):189-194 Background Dysphonia is a disorder characterized by change in voice quality, pitch, loudness, or vocal effort that impairs communication or reduces voice-related quality of life. Childhood dysphonia has several adverse educational and psychosocial implications. Dysphonic children are not aware or not bothered by their voice disorder. Although dysphonia might, in some cases, improve by itself in adulthood, it can be of important value to treat the dysphonic voice already during childhood. Aim The aim of this study was to adapt and formulate a program of voice intervention for childhood dysphonia and apply it on Egyptian children to explore its effectiveness as a therapeutic tool. Patients and methods This study was conducted on 20 children of both sexes attending the Phoniatrics Unit in Alexandria Main University Hospital complaining of dysphonia. The remediation program aims to improve dysphonia in children using a combination of indirect and direct treatment techniques. It is a modification of The Boone Voice Program for Children combined with new technologies such as the voice games by Kay Elementrics. It is designed to provide the clinician with step-by-step procedures and materials to remediate voice disorders in school-aged children. The program was translated to Arabic and a number of modifications were done in order to adapt it to the Egyptian children. Results The study showed effectiveness of the remediation program for childhood dysphonia regarding some of the auditory perceptual assessment and acoustic analysis values. Some of the laryngeal examination findings also showed improvement post-therapy. The study showed significant relation between the children’s age, sex, diagnosis, and some pretherapy and post-therapy findings. Conclusion Data from the current study suggests that voice therapy may prove to be a valid alternative to just planned follow-up.

A preliminary study on the composition of the early expressive lexicon in Egyptian infants and toddlers Aisha F Abdel Hady, Heba M Farag, Ayatallah R Sheikhany The Egyptian Journal of Otolaryngology 2019 35(2):195-206 Objective The aim of this study was to gain insight into early vocabulary size in Egyptian children aged between 12 and 30 months and to study the children’s lexicon composition at that young age while studying some demographic factors that might affect early vocabulary development. Participants and methods Parents of 150 children joining day care nurseries in Cairo were asked to fill in the Arabic vocabulary checklist designed in this study. The children were divided according to their age into three groups and then further subdivided according to their vocabulary size into low-vocabulary and high-vocabulary groups. Results Range and median and vocabulary percentages were estimated. Vocabulary size in older children is larger than younger children. More word types developed in the high-vocabulary group in younger age than in low-vocabulary group. All types of vocabulary continued to grow in older children in both low-vocabulary and high-vocabulary groups. There are differences between high-vocabulary and low-vocabulary groups in some demographic factors. Conclusion In this study, the vocabulary size for Arabic infants and toddlers is less than some languages. There are delays and differences between low-vocabulary and high-vocabulary groups regarding the linguistic composition and some demographic factors.

Dentistry and Medical Research

Waterpipe smoking: A traditional health hazard passed through generations A Thirumal Raj, Shankargouda Patil, Kamran Habib Awan Dentistry and Medical Research 2019 7(1):1-2

Patient-reported outcome measures in orthodontics Elbe Peter, RM Baiju, Jolly Mary Varughese, NO Varghese Dentistry and Medical Research 2019 7(1):3-11 Psychological perspective of orthodontic patients due to malocclusion and treatment is less explored in orthodontics until recently. Use of psychometric tools is the method to measure this intangible dimension of malocclusion and treatment. However, many generic and condition-specific tools are available now for this purpose. Patient-reported outcome measures (PROMs) will supplement normative outcome measures in the future and will remain an important aspect in patient-centered orthodontic care. In general, with the use of these tools, there has been a conflicting report regarding the effect of malocclusion on a person's Oral Health-Related Quality of Life (OHRQoL). However, orthodontic treatment has shown consistently to improve OHRQoL though there is a transient worsening in the initial phases of treatment. The effect of self-esteem and psychosocial well-being as mediators influencing OHRQoL and contextual factors such as socioeconomic status and family support mechanism on QoL need further evidence from long-term studies.

Genotoxicity evaluation of locally produced nano-hydroxyapatite-silica: An in vitro study using the bacterial reverse mutation test Nik Rozainah Nik Abdul Ghani, Aifa Nadhirah Muhammad Sazri, Chan Yunn Yee, Norhayati Luddin, Kannan Thirumulu Ponnuraj Dentistry and Medical Research 2019 7(1):12-15 Background: Nanohydroxyapatite-silica (nanoHA-Silica) has been produced by one-pot sol-gel technique. The material when incorporated into commercial Glass Ionomer Cement (GIC) was found to exhibit higher Vickers hardness, compressive strength, and flexural strength compared to conventional GIC. However, before starting to be used and exposed to the human cell, every material product should undergo for genotoxic evaluation. Thus, the objective of this in vitro study was to evaluate the genotoxicity of locally produced nanoHA-Silica under bacterial reverse mutation assay (Ames test). Materials and Methods: Four Salmonella typhimurium strains TA98, TA102, TA1535, and TA1537 were incubated with nanoHA-Silica in the presence and absence of exogenous metabolic activation system (S9) at five different concentrations (0.3125, 0.625, 1.25, 2.5, and 5 mg/plate) along with appropriate positive and negative controls. The assessment of the results was based on the number of revertant colonies in each plate, and the results were regarded as mutagenic when the number of revertant colonies was more than two-fold of the negative control. Results: There was no significant increase in the number of revertant colonies corresponding to the increase in the concentrations of the test substance for all the five bacterial strains treated with or without S9. Conclusion: NanoHA-Silica-GIC was non-genotoxic and had no mutagenic potential under present test conditions.

Evaluation of the core thickness and resin cement on the fracture strength of zirconia-based multilayer computer-aided design/computer-aided manufacturing ceramic crowns Idris Kavut, Safak Külünk Dentistry and Medical Research 2019 7(1):16-22 Aim: The purpose of this study was to evaluate the effect of thickness of zirconia core and different resin cements on the fracture strength of veneered zirconia crowns designed by multilayer technique. Materials and Methods: Forty metal dies were constructed to replica maxillary molar. Forty zirconia cores (Sirona inCoris ZI) were designed and constructed (inLab 4.4) with different thicknesses. The thickness of zirconia core was selected as 0.5 and 0.7 mm. Forty Feldspathic ceramic (VITABLOCS Mark II) veneers were fabricated (inLab 4.4) onto the zirconia cores. The zirconia cores were divided into two subgroups, and veneers were cemented with one of the following resin cement: self-cure, self-adhesive resin cement with light-cured option (Multilink N), and a dual-cure resin cement (Panavia F 2.0). Then, crowns were cemented to the metal dies. All the specimens were subjected to thermal cycling 5000 times (5°C–55°C ± 2°C, immersion time: 30 s). A universal testing machine was used for fracture strength test at a crosshead speed of 1 mm/min. The data were analyzed with one-way analysis of variance (α = 0.05). Stereomicroscopy was used to evaluate the failure modes and surface structure. Results: Zirconia core thickness and resin cement material affected the fracture strength (P < 0.05). Increase in core thickness increased the fracture strength of multilayer veneer crown (P < 0.05). Higher fracture strength values were obtained with light-cured, self-adhesive cement in both core thicknesses. Conclusion: Although 0.5-mm thickness zirconia cores showed lower flexural strength, it was higher than the maximum loads which may occur clinically (Fmax= 600 N on one tooth). Furthermore, light-cured, self-adhesive resin cement is advisable to increase the fracture strength with different core thickness.

Comparative evaluation of silver nanoparticles and 5.25% sodium hypochlorite for rapid chairside decontamination of artificially infected gutta-percha with Escherichia coli: An In vitro Study Priyesh Mishra, Sanjeev Tyagi, Divya Tripathi Dentistry and Medical Research 2019 7(1):23-27 Introduction: The aim of this in vitro study was to evaluate the efficacy of 50 ug/ml silver nanoparticle (AgNPs), 70 ug/ml AgNPs and 5.25% sodium hypochlorite (NaOCl) as a final irrigant for rapid chair-side decontamination of artificially infected gutta-percha (GP) with Escherichia coli. Materials and Methods: A series 120 GP cones size 40 were taken from new batch. The GP cones were divided into six experimental group: Group I - Evaluation of the contamination of GP cones in manufacturer's Box-(20 GP cones), Group II - Evaluation of GP artificially contaminated with E. coli(100 GP cones), Group III - Evaluation of the effectiveness of 50 ug/ml of AgNPs for decontamination of the cones contaminated with E. coli(n = 20 GP infected cones from Group II), Group IV - Evaluation of the effectiveness of 70 ug/ml of AgNPs for decontamination of the cones contaminated with E. coli(n = 20 GP infected cones from Group II), Group V - Evaluation of the effectiveness of 5.25% NaOCl for decontamination of the cones contaminated with E. coli(n = 20 GP cones infected from Group II). Aliquots from the experimental GP cones were plated on brain heart infusion agar (HiMedia Lab, Mumbai, India), and the colony-forming units were evaluated under colonimeter. Results: 70 ug/ml of AgNPs, 5.25% NaOCl exhibited similar antimicrobial effect (P = 1). Highly significant difference were found when 50 ug/ml compared with 70 ug/ml and 5.25% NaOCl (P < 0.0001). Conclusion: 70 ug/ml of AgNPs (0.007%) proved to be highly effective against E. coli and showed similar antimicrobial efficacy as 5.25% NaOCl at 750 times lesser concentration.

Awareness of Oral Health Changes during Menstruation: A Questionnaire-Based Survey among Adolescent Girls Sheiba R Gomes, Sandhya Tamgadge, Siddharth S Acharya, Prem R Thapar, Rutika R Patil, Sneha C Khanapure Dentistry and Medical Research 2019 7(1):28-32 Background: Periodontal health in women is affected by sex hormones. Puberty, menstruation, use of oral contraceptives, pregnancy, and menopause influence the periodontal health in women. Aim: This study was conducted to assess the awareness of oral health changes during menstruation in adolescent girls. Materials and Methods: A self-administered cross-sectional survey was conducted at a node in Navi Mumbai to assess the awareness of adolescent school-going girls on the subject of menstruation and the oral changes associated with the same. Results: Majority of the participants were aware of menstruation and associated problems, but only 4% of participants were aware that oral health changes can occur during menstruation. Conclusion: There is a definite lacuna in the awareness of adolescents about menstruation and the oral health changes associated with the same, and creating awareness on this association is necessary to prevent periodontal disease in adulthood.

Targeted Oncology

Crizotinib in Chinese Patients with ROS1 -Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice Abstract Background Approximately 1–2% of patients with non‒small-cell lung cancer (NSCLC) harbor ROS1 rearrangements. Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC. Objective Our objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice. Methods We included 35 patients with ROS1-positive NSCLC in this retrospective analysis. All received crizotinib 250 mg twice daily between March 2016 and April 2018 at the Fudan University Shanghai Cancer Center. All had histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangements, which were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or next-generation sequencing. The main outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results The median age of the patients was 51.0 years; 23 (65.7%) were female and 28 (80.0%) were never smokers. All were diagnosed as having adenocarcinoma; eight patients (22.9%) had brain metastases at baseline. The ORR and DCR were 71.4% and 94.3%, respectively. The estimated median PFS was 11.0 months (95% confidence interval [CI] 7.8–14.2). The estimated median OS was 41.0 months (95% CI 22.5–59.5). Elevated transaminases (54.3%), vision disorder (25.7%), elevated blood creatinine (22.9%), diarrhea (20.0%), and vomiting (20.0%) were the most commonly reported adverse effects. Conclusion Crizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice.

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib Abstract Background ALK-rearranged non-small cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC. However, heterogeneity of clinical responses exists among different ALK fusion partners. Several small studies have investigated the correlation between fusion partners and efficacy, but not yielded consistent results. Objective We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants. Patients and methods We retrospectively reviewed genomic profiling and clinical data of 110 ALK-rearranged NSCLC patients from five centers. The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed. Results A total of 134 ALK rearrangements with 39 partners were identified in 110 patients (5.6%) among a cohort of 1971 NSCLC patients. The most frequently occurring ALK fusion partner was EML4, which was identified in 71.6% (96/134) of all of the rearrangements in 87.3% (96/110) patients, and with variant 3 (41/96, 42.7%) as the main variant type. No statistically significant differences in terms of progression-free survival (PFS) and overall survival (OS) were found between EML4-ALK and non-EML4-ALK NSCLC patients in our cohort (PFS, p = 0.207; OS, p = 0.678). Outcomes did not differ significantly between patients above and below 40 years of age (PFS, p = 0.427; OS, p = 0.686), nor between patients treated with crizotinib in different lines of therapy (PFS, p = 0.171; OS, p = 0.922). For EML4-ALK-positive NSCLC (n = 96), patients harboring variant 3 or variant 5 displayed significantly lower PFS and OS than those with other variants (PFS, 8.6 vs. 11.3 months, p = 0.046; OS, 31.0 vs. 37.6 months, p = 0.026). In addition, patients with a single EML4-ALK rearrangement event displayed favorable PFS (10.0 vs. 7.2 months, p = 0.040) and OS (36.0 vs. 20.0 months, p = 0.029) compared to those harboring multiple ALK rearrangements. Conclusions This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.

Prognostic Markers for Refined Stratification of IMDC Intermediate-Risk Metastatic Clear Cell Renal Cell Carcinoma Treated with First-Line Tyrosine Kinase Inhibitor Therapy Abstract Background Patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate-risk group have heterogeneous prognoses and thus may benefit from improved risk stratification. Objective The aim of this study was to analyze inflammatory parameters such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for IMDC intermediate-risk patients. Methods Patients with metastatic clear cell renal cell carcinoma (n = 71) with IMDC intermediate risk who received tyrosine kinase inhibitors as first-line therapy were included in this retrospective study. Multivariate Cox regression analyses were performed to identify prognostic factors for overall survival (OS). Results As first-line systemic therapy, 46 (65%), 19 (27%), and 6 (8%) patients received sunitinib, sorafenib, and pazopanib, respectively. An IMDC prognostic score of 1 and 2 were observed in 34 (48%) and 37 (52%) patients, respectively. Mean CRP level was 1.06 mg/dL, and mean NLR was 3.0. Multivariate Cox regression revealed several factors significantly associated with poor OS, including NLR ≥ 3 (vs NLR < 3; hazard ratio [HR] 2.57; p = 0.0228), CRP level ≥ 1 mg/dL (vs CRP < 1 mg/dL; HR 2.89; p = 0.0279), and two or more metastatic organs (vs one organ; HR 3.77; p = 0.0008). Using these risk factors, patients were stratified into the following three risk categories: F0 (no prognostic factors; n = 20), in which the median OS (mOS) was not achieved; F1 (1 prognostic factor; n = 31), in which the mOS was 31 months; and F2–3 (2 or 3 prognostic factors; n = 20) in which the mOS was 13 months (log-rank p < 0.0001). Conclusion CRP, NLR, and the number of metastatic organs were independent prognostic factors in IMDC intermediate-risk patients.

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System Abstract Background Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized. Objective The aim of this study was to characterize the spectrum, frequency, and clinical features of ICI-related adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Patients and methods AEs from FAERS (up to June 2018) recording ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab) as suspect were extracted. Comprehensive disproportionality analyses were performed through the reporting odds ratio (ROR) with 95% confidence interval (95% CI), using other oncological drugs as comparison. An overview of systematic reviews (OoSRs) was also undertaken to identify irAEs with consistent positive associations. Results ICIs were recorded in 47,266 reports, submitted mainly by consumers receiving monotherapy with anti-PD1/PDL1 drugs. Three areas of toxicity emerged from both disproportionality analysis and the OoSRs (32 studies): endocrine (N = 2863; ROR = 6.91; 95% CI 6.60–7.23), hepatobiliary (2632; 1.33; 1.28–1.39), and respiratory disorders (7240; 1.04; 1.01–1.06). Different reporting patterns emerged for anti-CTLA4 drugs (e.g., hypophysitis, adrenal insufficiency, hypopituitarism, and prescribed overdose) and anti-PD1/PDL1 agents (e.g., pneumonitis, cholangitis, vanishing bile duct syndrome, tumor pseudoprogression, and inappropriate schedule of drug administration). No increased reporting emerged when comparing combination with monotherapy regimens, but multiple hepatobiliary/endocrine/respiratory irAEs were recorded. Conclusions This parallel approach through contemporary post-marketing analysis and OoSRs confirmed that ICIs are associated with a multitude of irAEs, with different reporting patterns between anti-CTLA4 and anti-PD1/PDL1 medications. Close clinical monitoring is warranted to early diagnose and timely manage irAEs, especially respiratory, endocrine, and hepatic toxicities, which warrant further characterization; patient- and drug-related risk factors should be assessed through analytical pharmaco-epidemiological studies and prospective multicenter registries.

Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors Abstract Background Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. Objective We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics. Methods Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman's correlation coefficient. Results Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399–3.966, p = 0.001; and HR 1.994; 95% CI 1.360–2.923, p < 0.001, respectively). In our cohort, α1-globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α1-globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001). Conclusions High serum α1-globulin correlates with high tumor load. Serum α1-globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.

EGFR Mutations in Cell-free Plasma DNA from Patients with Advanced Lung Adenocarcinoma: Improved Detection by Droplet Digital PCR Abstract Background Analysis of cell-free DNA from blood could provide an alternative method for identifying genomic changes in the tumors of patients with advanced lung adenocarcinoma. Objective We compared the performance of droplet digital PCR (ddPCR) and Cobas® EGFR Mutation Test v2 (Cobas) for detecting EGFR mutations in cell-free plasma DNA. Patients and Methods Plasma samples from patients with advanced EGFR-mutated lung adenocarcinoma were analyzed for EGFR T790M, exon 19 deletions, and L858R mutations by both ddPCR and Cobas. Results T790M testing was performed in 354 plasma samples collected from 129 patients. The concordance rate between ddPCR and Cobas for T790M, sensitivity, and specificity were 86, 100, and 85%, respectively. Exon 19 deletions were analyzed in 196 plasma samples obtained from 71 of the 129 patients using both platforms. The concordance rate between ddPCR and Cobas for exon 19 deletions, sensitivity, and specificity were 90, 92, and 89%, respectively. L858R mutations were studied in 124 plasma samples obtained from 44 of the 129 patients using both assays. The concordance rate between ddPCR and Cobas for L858R, sensitivity, and specificity were 90, 91, and 89%, respectively. In patients who progressed under treatment with an EGFR TKI (n = 50), the T790M positivity rate was 66% using ddPCR, but only 24% using Cobas. Conclusions We observed a high concordance between ddPCR and Cobas in detecting EGFR mutations in plasma samples of patients with advanced EGFR-mutated lung adenocarcinoma, but ddPCR was more sensitive than Cobas.

Clinical Management of Non-Small Cell Lung Cancer with Concomitant EGFR Mutations and ALK Rearrangements: Efficacy of EGFR Tyrosine Kinase Inhibitors and Crizotinib Abstract Background Patients harboring concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) arrangements constitute a small subgroup of non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR tyrosine kinase inhibitors (TKIs) and the ALK-specific TKI crizotinib in these patients has not been well-established. Objective This study investigated the efficacy of targeted therapies in these patients compared with patients with EGFR or ALK alterations alone. Methods Patients were screened for EGFR mutation and ALK rearrangement at the Shanghai Chest Hospital (2011–2017). Progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) were retrospectively analyzed. Results A total of 5816 patients were screened, and 26 patients were identified as having concomitant EGFR mutations and ALK rearrangements; 22 patients were eligible for survival analysis. Additionally, 95 EGFR-mutant patients and 60 ALK-rearranged patients were randomly selected for analysis. The ORR to EGFR TKIs was 63.2% (12/19) for EGFR/ALK co-altered patients and 62.1% (59/95) for EGFR-mutant patients (p = 0.93) with a median PFS of 10.3 and 11.4 months, respectively (hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.59–1.57; p = 0.87). The ORR to crizotinib was 66.7% (8/12) for double-positive patients and 65.0% (39/60) for ALK-rearranged patients (p = 1.00), with a median PFS of 11.1 and 12.5 months, respectively (HR 1.39; 95% CI 0.69–2.80; p = 0.28). OS was 27.1, 36.2, and 36.8 months for EGFR-mutant, ALK-rearranged, and EGFR/ALK co-altered patients, respectively, and the EGFR/ALK co-existing subgroup tended to have a longer survival period than EGFR-mutant cohorts, though no statistical difference was found (p = 0.12). The median PFS of crizotinib as a sequential therapy after failure of EGFR TKIs was 15.0 months, which exhibited no statistically significant difference compared with the median PFS of ALK-altered patients who received crizotinib (p = 0.80). Conclusions Both first-generation EGFR TKIs and the ALK TKI crizotinib were effective in these patients. Sequential treatment with EGFR TKIs and crizotinib should be considered as a management option.

Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study Abstract Background Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. Objective As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL. Patients and Methods In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1–14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m2/week for 6 weeks in 7-week cycles (with vitamin B12/folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%). Results The study's primary objective was met: ORR (95% CI) was 52% (40–64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3–14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1–8.1) months and 18.0 (10.4–NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]). Conclusions These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects. Trial Registration ClinicalTrials.gov identifier: NCT03349333.

Inhibiting Bruton's Tyrosine Kinase in CLL and Other B-Cell Malignancies Abstract Inhibitors of Bruton's tyrosine kinase (BTK), a major kinase in the B-cell receptor (BCR) signaling pathway, mediating B-cell proliferation and apoptosis, have substantially altered the management, clinical course, and outcome of patients with B-cell malignancies. This is especially true for patients with previously limited treatment options due to disease characteristics or coexisting diseases. Ibrutinib was the first orally available, nonselective and irreversible inhibitor of BTK approved for the treatment of patients with various B-cell malignancies. Newer and more selective BTK inhibitors are currently in clinical development, including acalabrutinib, which is currently US FDA approved for previously treated mantle cell lymphoma. Significant efforts are underway to investigate the optimal combinations, timing, and sequencing of BTK inhibitors with other regimens and targeted agents, and to capitalize on the immunomodulatory modes of action of BTK inhibitors to correct tumor-induced immune defects and to achieve long-lasting tumor control. This review describes the major milestones in the clinical development of BTK inhibitors in chronic lymphocytic leukemia and other B-cell malignancies, highlights the most recent long-term follow-up results, and evaluates the role of BTK inhibitors and their combination with other agents in B-cell malignancies and other indications.

Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models Abstract Background Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits. Objectives This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma. Methods We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2′-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models. Results In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models. Conclusions Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.

Advanced Pharmaceutical Technology & Research

Neuroblastoma cancer in children Upendra Nagaich Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):45-45

Biomaterial selection for bone augmentation in implant dentistry: A systematic review Erfan Shamsoddin, Behzad Houshmand, Mehdi Golabgiran Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):46-50 In the present study, a systematic review was conducted to evaluate the biomaterials and their effectiveness for bone augmentation in implant dentistry. The databases of Cochrane Library, Google Scholar, PubMed (National Center for Biotechnology Information), and Scopus were searched for published studies between 2006 and March 30, 2018. We only included clinical studies in this research. Due to a lack of quantitative evidence and the vast heterogeneity of the biomaterials, implant surgery sites, implant types, follow-up periods, and various implant placement techniques (1-stage or 2-stage), we could not manage to do a meta-analysis on the 13 included studies. Several techniques can result in vertical bone augmentation. Complications can be seen in vertical bone augmentation and especially in the autogenous bone grafting; however, some biomaterials showed promising results to be practical substitutes for autogenous bone. Bio-Oss and beta-tricalcium phosphate are our second-level candidates for vertical bone augmentation due to their promising clinical results with the least infection and immunologic response risk. The gold standard, however, remains the autogenous bone graft. Further clinical studies in the future with exact report of bone measures are needed to develop new comparisons and quantitative analyses.

Evaluation of cytotoxic activity from Temurui (Murraya koenigii [Linn.] Spreng) leaf extracts against HeLa cell line using MTT assay Ulil Amna, Halimatussakdiah , Puji Wahyuningsih, Nurdin Saidi, Rosnani Nasution Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):51-55 Temurui (Murraya koenigii [Linn.] Spreng) is a local plant of Aceh. The leaves of M. koenigii are used in most of the local foods as spices. Nowadays, cancer is claimed as the second deadly disease in the world where the number of sufferers increases every year. Cervical cancer (HeLa) is one of the most dominant cancers that happen in developing country, including Indonesia. Some chemotherapeutic agents using synthetic drugs have been used to treat cancer, but they are relatively expensive and cause poisoning that limits their use. Based on literatures, M.koenigii serves the potential secondary metabolites that could be developed as anticancer agent. This study aims to evaluate the cytotoxic activity from three extracts of M. koenigii leaves against HeLa cell line, including hexane, ethyl acetate, and methanol. Methodology used included extraction process, phytochemical screening, and cytotoxicity evaluation. The result showed that all the three extracts demonstrated a potent cytotoxic activity for HeLa cancer cells. Hexane and ethyl acetate showed a very strong cytotoxic effect with CD50 values <1 μg/mL, whereas methanol extract showed cytotoxic effect with CD50 value of 2.25 μg/mL. These results prove the potential of M. koenigii as an anticancer agent.

Study and modeling of the distribution process of some phenolic compounds between the solid and liquid phases Nikolay Boyko, Dmitriy Pisarev, Elena Zhilyakova, Alina Pravlotskaya, Oleg Novikov, Nikolay Makarevich, Viktoria Kuznietsova, Natalia Sushchuk Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):56-62 The article presents the results related to the study of distribution of biologically active substances from the plant raw material between solid and liquid phases. The aim of this study is to develop theoretical bases of the extraction process in the equilibrium state by the example of study and modeling of the distribution process of biologically active substances from Eucalyptus viminalis leaves. In these studies, we used ground plant raw material of E. viminalis leaves with particle fraction of 0.1–0.5 mm; and ethanol with concentration 80% ±1% v/v was used as an extractant. Qualitative and quantitative analyses were carried out by reversed phase high-performance liquid chromatography with rutin, chlorogenic acid, and euglobal standards equivalent to spissum extract of chlorophyllipt of the State Pharmacopoeia of Ukraine. A hypothesis has been suggested that Henry's adsorption law and the law of conservation of matter play a fundamental role in this process. The experimental data are described well by the suggested equation with high value of determination coefficient R2 =0.99. At the same time, F-test and the significance of coefficients in equations satisfy the statistic condition, which means that the current hypothesis about the adsorption mechanism of distribution of biologically active substances in the extraction system is not refuted. The results of these studies demonstrate good agreement of experimental data and theoretical model based on Henry's adsorption law and mass balance. The numerical values of constants in the model suggested have been calculated.

Antibacterial activity of cinnamon essential oils and their synergistic potential with antibiotics Yassine El Atki, Imane Aouam, Fatima El Kamari, Amal Taroq, Kaotar Nayme, Mohammed Timinouni, Badiaa Lyoussi, Abdelfattah Abdellaoui Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):63-67 The objective of this study was to evaluate the antibacterial activity of Cinnamomum cassia (cinnamon) essential oil (EO) alone and in combination with some classical antibiotics against three multidrug-resistant bacteria, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, to search a possible synergy. The antibacterial activity of all tested compounds was determined by agar disc diffusion and minimum inhibitory concentration assays. The checkerboard method was used to quantify the efficacy of cinnamon EO in combination with these antibiotics. Fractional inhibitory concentrations were calculated and interpreted as synergy, addition, indifferent, or antagonism. A synergistic interaction was shown against S. aureus with the combination cinnamon EO and ampicillin or chloramphenicol and against E. coli when cinnamon EO was combined with chloramphenicol. However, the combination of cinnamon oil and streptomycin displayed additive effects against all bacteria stains. The combinations of cinnamon EO and antibiotics can be used as an alternative therapeutic application, which can decrease the minimum effective dose of the drugs, thus reducing their possible adverse effects and the costs of treatment.

The comparative evaluation of knowledge, attitude, and practice of different health-care professionals about the pharmacovigilance system of India Asmatanzeem Bepari, Shaik Kalimulla Niazi, Ishrat Rahman, Asmabi Makandar Dervesh Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):68-74 In India, the under-reporting of adverse drug reactions (ADRs) by health professionals is recognized as one of the leading reasons of poor ADR signal detection. The knowledge of ADRs and positive attitude of health-care professionals toward ADRs reporting is vital for decreasing the irrational use of an inappropriate pharmacy. The present study was directed to assess the knowledge, attitude, and practice (KAP) of pharmacovigilance (PV) among the physicians, nurses, and pharmacists of a teaching tertiary care hospital of India. A structured questionnaire was designed using previous studies and standardized. Questions were categorized into three groups: Group 1 tested the knowledge (K1–K8), Group 2 tested attitude (A1–A6), and Group 3 tested the level of practice of PV (P1–P5) of the participant. Such 250 questionnaires were distributed to different health-care professionals of VIMS, Ballari. The participants were graded in three categories as poor, unsatisfactory, and satisfactory depending on the mean score. The data were interpreted by calculating the frequencies, one-way ANOVA and Scheffe's test. Furthermore, factors that discourage them from taking part in the PV program were recorded. A total of 182 questionnaires were statistically analyzed. It was found that KAP of PV among doctors, nurses, and pharmacists was unsatisfactory. Our study showed that knowledge, attitude, and level of practice of PV among doctors, nurses, and pharmacists stand inadequate. Educational interventions periodically can improve these parameters of PV.

Formulation, characterization, and in vitro testing of azelaic acid ethosome-based cream against Propionibacterium acnes for the treatment of acne Elsa Fitria Apriani, Yeva Rosana, Iskandarsyah Iskandarsyah Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):75-80 Azelaic acid is an antiacne drug by inhibiting thioredoxin reductase enzyme of Propionibacterium acnes (P. acnes) that affects the inhibition of bacterial DNA synthesis which occurs in the cytoplasm. Azelaic acid must penetrate through the stratum corneum to the sebaceous tissue and into cytoplasm by passing through thick peptidoglycan of P. acnes. Thus, it is necessary to increase the penetration of azelaic acid that formulated based ethosome. This study using thin-layer hydration method forms an ethosomal suspension with variations of concentration ethanol (30%, 35%, and 40%). Antibacterial activity was conducted using broth dilution method to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of azelaic acid ethosome cream based was compared with the marketed cream (Zelface®cream). Azelaic acid ethosome with 35% ethanol has given best result with entrapment efficiency of 94.48% ± 0.14%. Antibacterial activity to P. acnes showed that azelaic acid ethosome-based cream was given better activity than marketed cream (Zelface®cream). The value of MIC and MBC of azelaic acid ethosome-based cream was 250 μg/ml while the marketed cream (Zelface®cream) was shown MIC of 250 μg/ml and MBC of 500 μg/ml. This study proved that the azelaic acid ethosome-based cream has better antibacterial activity.

Patency and outcomes of tunneled hemodialysis catheter via femoral versus jugular vein access Hosein Najd Sepas, Alireza Negahi, Seyed Hamzeh Mousavie, Fereshteh Vosough, Behnood Farazmand Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):81-84 The design of a suitable catheter to achieve a permanent, economical, and efficient vascular pathway for hemodialysis has been always accompanied by difficult and potential complications. Various strategies have been adopted to minimize the use of tunneled catheters that are used for dialysis. Regarding this, the present study aimed to assess the success, patency, as well as early and late complications of cuffed femoral and jugular hemodialysis catheters. This case–control study was performed on 145 hemodialysis patients who were candidates for the insertion of tunneled hemodialysis catheters at Rasoul-e-Akram Hospital in Tehran, Iran, during 2015–2016. The data were collected retrospectively by reviewing the patients' medical records. The participants were divided into two groups of femoral and jugular accesses, based on the type of catheter they had. To determine the procedure-related outcomes, they were assessed 1 week, 1 month, and 6 months after catheterization. According to the results, the mean times of catheter efficacy (patency) were 4.43 ± 3.11 and 5.65 ± 4.57 months in the femoral and jugular access groups, respectively, showing no significant difference between the two groups (P = 0.095). Furthermore, the femoral and jugular access groups had the infection prevalence of 23.2% and 16.2%, thrombosis prevalence of 28.6% and 20.9%, and mortality rates of 3.5% and 1.4%, respectively. According to the multivariable linear regression model, the history of catheterization could predict reduced catheter patency. In addition, catheter-related infection could be predicted among females based on the multivariate logistic regression analysis. As the findings indicated, femoral and jugular hemodialysis catheter insertions showed no significant difference in terms of the mean patency, complications (e.g., infection and thrombosis), and mortality rate.

Effect of Thai traditional antinausea remedy on hypnotic and sedative activity in animal experimental models: Interaction with drugs acting at GABAA receptor Watchara Damjuti, Juthaporn Kwansang, Jurairat Boonruab Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):85-89 Thai traditional antinausea remedy is drug registered in the National List of Essential Medicines for the treatment of blood circulation disorders, dizziness, fatigue, and insomnia. Antinausea remedies have long been used, but their effects and action mechanisms remain poorly understood. Here, hypnotic, sedative, and anxiolytic activities of antinausea remedies were evaluated. This preclinical trial assessed the hypnotic, sedative, and anxiolytic activities of antinausea remedies. Thai traditional antinausea remedy was extracted by decoction in deionized water until exhaustion and concentrated to dryness. Anxiolytic activities were evaluated using elevated plus-maze and open-field tests for vehicle control group compared to treatment groups (50, 100, and 200 mg/kg). Hypnotic and mechanistic studies were performed using thiopental sodium-induced sleeping time with benzodiazepine receptor antagonist test. In the thiopental sodium-induced sleeping time test, vehicle control groups were compared to treatment groups (10, 50, and 100 mg/kg). In addition, GABAergic agonistic effect vehicle control groups were pretreated with 3.5-mg/kg flumazenil before sterile water and compared to the treatment group which also received flumazenil before 100 mg/kg extract. Data were statistically analyzed using analysis of variance followed by multiple comparison testing. The aqueous extract was found to be a hypnotic and sedative agent with a dose response either as latent period or prolonged sleeping time (P < 0.05) and a successive GABAergic agonistic effect. Locomotor determination revealed the tendency to relieve anxiety. Thai traditional antinausea remedy can induce sleep and be safely used to reduce anxiety.

Comparison of the disinfectant effects of Nanosil D2 and Korsolex extra solutions on thermoset acrylic resin contaminated with Streptococcus mutans and Bacillus subtilis Tahereh Ghaffari, Fahimeh Hamedi Rad, Tahereh Pirzadeh, Gahanbaksh Asgari Journal of Advanced Pharmaceutical Technology & Research 2019 10(2):90-94 This study was conducted to compare the disinfectant effects of Nanosil D2 and Korsolex extra on thermoset acrylic resin contaminated with Streptococcus mutans and Bacillus subtilis. In this experimental study, 90 acrylic samples were made and sterilized. Two samples were cultured as a sterilization control in brain–heart infusion (BHI) and the rest of samples were divided into two groups. Samples of one group were placed in a bacterial suspension of S. mutans and the samples of another group were placed in a suspension containing B. subtilis. Each group was divided into two subgroups for immersion in Nanosil or Korsolex extra solutions. Seven samples were selected from each group at each of 30 min, 1 h, and 2 h and transferred to the BHI test tube, and their turbidity was evaluated after 24 h. SPSS 17 software was used to analyze the data, and the significance level of test was considered P < 0.05. At 1 h, Bacillus level of Nanosil D2 was significantly lower than that of Korsolex extra, and at all ½, 1, and 2 h, the level of Streptococcus in Nanosil D2 solution was significantly lower than that of Korsolex extra (P < 0.05). Bacillus and Streptococcus levels showed significant reduction in both solutions over time. The disinfecting power of Nanosil D2 is more than that of Korsolex extra.

Preventive and Community Dentistry

Botulinum toxin application in facial esthetics and recent treatment indications (2013-2018) Vivekanand Kattimani, Rahul Vinay Chandra Tiwari, Khalid Gufran, Bharti Wasan, PH Shilpa, Anas Abdul Khader Journal of International Society of Preventive and Community Dentistry 2019 9(2):99-105 Background: Ever-changing perception of beauty from childhood to old age is changing with the revolution in cosmeceuticals science. Esthetics is an individual's perception since time immemorial. Standards of beauty have changed through centuries with increased awareness about esthetics. The face remains main source of information for identification and discrimination. It constitutes a structural ground for many nonverbal messages including the emotional state of a person, so the proverb “Face is an index of mind” holds good. The wrinkles and laxity are considered to be one of the factors for aging. Hence, escalating demand for cosmetic treatment to reduce facial wrinkles and laxity has stimulated us to search for published literature for nonsurgical techniques for enhancement of facial beauty. The review analyzed the published data to provide narrative basic review in a concise way to the beginners, clinicians, and students. Materials and Methods: We have adopted search criteria using keywords: Botox, Botulinum toxin, incobotulinumtoxinA, esthetics, face, uses of Botox, with various Boolean operators and or in title, and abstract using PubMed search engine. The database search limited to PubMed only from January 2013 to June 2018. Results: Various search results have been appended as annexures at the end of the article for further reference for the readers. Finally, 17 references were selected to write narrative review to meet our objectives. Conclusion: The advancing front in the use of toxins is an emerging science for the beautification of a face. Botox exploded in to market because of efficacy, tolerability, and minimally invasive nature. The present review gives brief about the history of Botulinum toxin, types, mechanism of action, clinical indications, preparations, storage, and technique for various uses with a brief note on patient selection, contraindications, and complications.

The impact of sibling behavior on oral health: A narrative review Sunaina Puri, Ramprasad Vasthare, Ravindra Munoli Journal of International Society of Preventive and Community Dentistry 2019 9(2):106-111 Objective: The repetition of any behavior until it becomes a learned behavior begins in childhood. Oral health practices being no exception to this, are also acquired at this tender age, and have the potential of greatly affecting one in their lives. Oral health behaviors are learned through a multifactorial interplay, of which the family is a crucial and relatively unexplored area and will be highlighted in this review. This review discusses gender differences among siblings in relation to oral health, familial influence on acquisition and maintenance of oral hygiene habits, media influence on oral health attitudes and more. Methods: A thorough literature search between 1972 and 2017 was done using Scopus, PubMed, and Google Scholar databases, results reviewed, prioritized, and findings compiled. The keywords of the search strategy was as below: Siblings, sibling behavior, sibling oral health, siblings in dentistry, maternal oral health, family influence on oral health. 35 studies were evaluated for the review. The keywords were limited to activities of siblings and their behavior patterns in relation to dentistry and oral health. Results: Results showed that sibling dynamics have been involved in influencing the learning of oral health behaviors in children. Other factors include peer pressure and maternal influences. Conclusion: Sibling relationships play a vital role in shaping behavior characteristics including tooth brushing, oral hygiene, dental perceptions, and snacking behaviors which are pertinent to dentistry.

Critical appraisal of bidirectional relationship between periodontitis and hyperlipidemia Seba Abraham, Arya Premnath, PR Arunima, Reejamol Mohammed Kassim Journal of International Society of Preventive and Community Dentistry 2019 9(2):112-118 Periodontal disease and hyperlipidemia are both multifactorial disease with a high prevalence Worldwide. Cross-sectional and longitudinal prospective clinical studies show some evidence for a bidirectional relationship. Periodontitis and hyperlipidemia share some common risk factors and there exist a mechanistic link between both. Studies have found a positive response to periodontal therapy among hyperlipidemic patients, and statin use by hyperlipidemic patients has shown to influence the periodontal health. However, in spite of the rising prevalence of both diseases, many people remain unaware of their association with each other. Hence, this article summarizes the cyclic relationship between periodontal disease and hyperlipidemia.

The efficacy of different sealant modalities for prevention of pits and fissures caries: A randomized clinical trial Wahdan Mohammed Abdelghany Elkwatehy, Omair Mohammed Bukhari Journal of International Society of Preventive and Community Dentistry 2019 9(2):119-128 Objectives: This clinical trial evaluates the efficacy of different pit and fissure sealant modalities as a caries prevention tool. Materials and Methods: Forty-four children aged 6–8 years with completely erupted first permanent molars participated in sealant placement randomized clinical trial. Split-mouth technique used and each child received four treatment modalities (ICON, Seal It, GCP glass seal, ICON/Seal It combination). Caries progression and sealant retention monitored over a period of 24 months. Results: Seal It and combination modalities had the highest efficacy in the prevention of pits and fissures caries, whereas the ICON had the lowest efficacy. Regarding retention, there were no significant differences among the four modalities during the 1, 3, and 6 months follow-up intervals. However, at 12, 18, and 24 months, the retention of Seal It and combination modalities were better than ICON and better than GCP, but the differences were not statistically significant. In addition, the retention of combination modality was better than Seal It, but the difference was not significant. At the end of the trial, the caries incidence was the highest in ICON group (20 lesions) followed by GCP group (13 lesions), Seal It group (3 lesions) and the lowest observed in combination group (2 lesions). Conclusions: Both Seal It and combination modalities are highly effective in the prevention of pits and fissures caries, GCP has acceptable effect while the use of ICON alone was not effective. The Seal It and ICON combination improves their clinical efficacy in caries prevention.

A cephalometric evaluation of sexual dimorphism of the angle sella-nasion-frankfort horizontal plane in different sagittal classes of malocclusion in south Indian population Sivareddy Rohit Reddy, Singaraju Gowri Sankar, Prasad Mandava, Vivek Reddy Ganugapanta, Surendra Gangavarapu, Swaroop Doddavarapu Journal of International Society of Preventive and Community Dentistry 2019 9(2):129-136 Aims and Objectives: The present study aims to evaluate the gender dimorphism of the angle SN-FH between the sella-nasion (SN) plane and the Frankfort horizontal (FH) plane among the three types of skeletal malocclusion in South Indian population. The objectives included measurement of angle SN-FH, FH to the nasion (NFH), FH to the sella (SFH), and the difference of NFH and SFH (Δ). The null hypothesis was that there exists no variation of the angle SN-FH, NFH, SFH, and Δ between males and females and in the different skeletal relationship of jaws. Materials and Methods: Cephalometric data were retrieved from the archived records of 180 patients, comprising 90 males and 90 females, within three subgroups. Class I (60), Class II (20), and Class III (10) in each of the gender class were examined. Student's “t” test was used to analyze means of the gender differences and analysis of variance between subgroups, and significance was set at P < 0.05. Results: The average values obtained from this study for the overall population are 8.06 ± 3.34; for males, it is 7.42 ± 3.62, and for females, it is 8.7 ± 3.48. The gender difference is statistically significant only in Class I malocclusion (0.002). There is no statistical difference between different skeletal classes of malocclusion. Conclusion: The null hypothesis is partially rejected for as significant difference is established only for some of the parameters under the study.

Oral behavior and dental status of orthodox christian priests and monks Oksana Avdeenko, Irina Novikova, Anna Turkina, Irina Makeeva Journal of International Society of Preventive and Community Dentistry 2019 9(2):137-143 Aims and Objectives: Common conditions of daily routine and diet may affect the dental status of individuals in organized groups and professional communities. The aim of this study was to reveal the specific aspects of dental status in orthodox priests and monks of the Yaroslavl region, Russia. Materials and Methods: Dental assessment of 311 participants (111 monks; 111 priests; and 90 local residents, not clergymen – as a control group) was performed, including Decayed, Missed, Filled Teeth, oral hygiene index (simplified), gingival, and Modified Papillary Bleeding Indices (MPBIs). The participants completed a questionnaire on food habits and awareness concerning dental health preservation. Statistical Analysis Used: Statistical analysis of the data was performed in SPSS software with the use of Shapiro–Wilk, Dunn's, Fisher tests, z-test as well as Spearman correlation, and ANOVA. Results: The median values of MPBI in monks were higher than in the groups of priests and local residents (P = 0.005). The differences in number of missing teeth were significantly higher in priests compared with local residents (P = 0.011), and the number of filled teeth was significantly higher in priests (P = 0.006) and local residents (P = 0.007) compared with monks. Wedge-shaped defects and erosions were more prevalent in the groups of priests (0.0018 and 0.001, respectively) and monks (0.004 and 0.001, respectively). ANOVA resulted in statistically significant influence of teeth brushing frequency and frequency of food intake on hygienic and periodontal indices values. Conclusions: The increased prevalence of some dental diseases among priests and monks could be attributed to the specific diet, lifestyle, and limited access to dental care.

Comparison of the effect for fracture resistance of different coronally extended post length with two different post materials Niharika Singh Chauhan, Nidhi Saraswat, Ankita Parashar, Kuldeep Singh Sandu, Kapil Jhajharia, Nirav Rabadiya Journal of International Society of Preventive and Community Dentistry 2019 9(2):144-151 Aims and Objectives: To compare the effect for fracture resistance of different coronally extended post length with two different post materials. Materials and Methods: One hundred and sixty endodontically treated maxillary central incisors embedded in acrylic resin with decoronated root portion were taken for the study. The postspaces were prepared according to standard protocol. The samples were divided into two groups according to the post material: glass-fiber post and Quartz fiber post. These groups were further subdivided on the basis of coronal extension of 4 and 6 mm for glass fiber and Quartz fiber posts, respectively. The posts were then luted with dual-polymerizing resin cement followed by core buildup. Samples were subjected to increasing compressive oblique load until fracture occurred in a universal testing machine. Data were analyzed with one-way ANOVA and independent Student's t-test. Analysis was done using SPSS version 15 (SPSS Inc., Chicago, IL, USA) Windows software program. Results: Glass fiber post with coronal extension of 4 mm (182.8 N) showed better results than with 6-mm length (124.1 N). Similarly, in quartz fiber posts group, 4-mm postlength (314 N) was better when compared with 6 mm (160 N). The 4-mm coronal extension of quartz fiber post displayed superior fracture resistance. Conclusions: Glass fiber posts showed better fracture resistance than Quartz fiber posts. 4-mm coronal length showed more fracture resistance than 6 mm.

Comparative evaluation of the effect of chemical disinfectants and ultraviolet disinfection on dimensional stability of the polyvinyl siloxane impressions Sharayu Vinod Nimonkar, Vikram M Belkhode, SR Godbole, Pranali Vinod Nimonkar, Trupti Dahane, Seema Sathe Journal of International Society of Preventive and Community Dentistry 2019 9(2):152-158 Context: Infection control is an important concept in the present day practice of dentistry. Disinfection of dental impressions is part of the daily routine in a dental clinics. After disinfection, it is important that impressions remain dimensionally stable. Aim: The purpose of this study was to compare the effect of chemical disinfectants and ultraviolet (UV) disinfection on the dimensional stability of the polyvinyl siloxane impressions. Objectives: The objective of the study is (1) To evaluate the effect of chemical disinfectant (2% glutaraldehyde and 1% sodium hypochlorite) and UV disinfectant on the dimensional stability of polyvinyl siloxane impression material. (2) Comparative evaluation of the dimensional discrepancy between the cast poured from the polyvinyl impressions material, that is subjected to chemical disinfectant and UV disinfectant to that of cast poured from impressions that were nondisinfected. Materials and Methods: A customized tray was fabricated to make impressions. Impressions were divided into four groups, 10 samples were disinfected with 2% glutaraldehyde for 20 min, 10 samples were disinfected with 1% sodium hypochlorite for 20 min, 10 samples were disinfected with UV light for 20 min, and 10 samples were not subjected to disinfection which served as control group. All the samples were poured after 30 min in die stone. Measurements were recorded using traveling microscope of 0.001 accuracy. Statistical analysis used in this study was the one-way ANOVA test. Results: The result showed significant dimensional changes in samples disinfected with 2% glutaraldehyde and 1% sodium hypochlorite, whereas samples disinfected with UV disinfectant unit showed no significant dimensional changes when compared with control group samples. Within the chemical groups, impressions disinfected with 1% sodium hypochlorite showed more discrepancy in the dimensions when compared to the 2% glutaraldehyde disinfected group. Conclusions: UV light disinfectant can be safely used to disinfect impressions as compared to chemical disinfectants in clinical prosthodontic procedures.

The prognostic role of maximum standardized uptake value of 18 F-flourodeoxy glucose positron emission tomography-computed tomography in head and neck cancer patients undergoing chemoradiotherapy Kondaveeti Satish Srinivas, M Arunan, E Venkatachalapathy, Christopher John, M Manickavasagam, CV Divyambika Journal of International Society of Preventive and Community Dentistry 2019 9(2):159-165 Aims and Objectives: This retrospective study aims at correlating the pre- and post-therapy maximal standardized uptake values (SUVmax) of the whole-body 18-flourodeoxy glucose positron emission tomography (FDG-PET) scan with tumor response in patients with head and neck squamous cell cancer undergoing chemoradiotherapy. Materials and Methods: Data for this retrospective study were taken from the clinical records of 20 evaluable head and neck cancer patients who had availed treatment and evaluation at our institute during the previous year (March 2017–April 2018). All these above-mentioned patients had undergone chemoradiation at our center for locally advanced squamous cell carcinoma of the head and neck and had undergone pre- and post-therapy whole-body FDG PET scan. The posttherapy PET-computed tomography (CT) was advised after 8 weeks' postcompletion of therapy. During the PET CT scan, images were acquired 1 h after injection of FDG. Pre- and post-therapy SUVmax were recorded and correlated with immediate treatment response. Results: The mean pretherapy SUVMax of the primary tumor was 10.27 ranging from 4.5 to 26.17. The mean pretherapy SUVMax of the node was 5.34 ranging from 0 to 17.9. The mean time of recording the posttherapy SUVMax was 3 months (range 2–5 months). The mean posttherapy SUVMax of the primary tumor was 1.05 ranging from complete metabolic response to 6.4. The mean posttherapy SUVMax of the node was 0.7 ranging from complete metabolic response to 5.43. The statistical analysis based on Wilcoxon–Signed Rank test revealed a statistically significant difference in the pre- and post-therapy SUVmax values for both primary tumor (P < 0.001) and regional node (P = 0.001). Majority of patients (n = 15) showed clinical remission; however, five patients had progressive disease at the time of evaluation. Conclusion: Although the retrospective study revealed that complete responders had a statistically significant reduction in the posttherapy SUVmax in comparison to the pretherapy SUVmax it failed to identify a cutoff value for pretherapy SUVmax which could predict the probable outcome of therapy. In view of the same further prospective studies need to be conducted with larger patient numbers including various other tumor metabolic markers for greater clarity.

Effect of weight reduction on the serum adiponectin and tumor necrosis factor-α levels and the clinical parameters of obese patients with and without periodontal disease Lalith Vivekananda, Mohamed Faizuddin Journal of International Society of Preventive and Community Dentistry 2019 9(2):166-171 Objective: The objective of the current study was to assess the impact of weight reduction on the attenuation of obesity-related periodontal inflammation. Methods: This study was conducted enrolling 60 obese subjects. They were divided into three groups of 20 each. Group 1-healthy group, Group 2-gingivitis group, and Group 3-periodontitis group. The body mass index and waist/hip ratio, periodontal parameters such as plaque index, bleeding index, full mouth periodontal probing depth (PPD) using the University of North Carolina 15 (UNC 15) probe and full mouth clinical attachment loss (CAL) with cementoenamel junction as the reference using UNC 15 probe was evaluated at baseline and after the attainment of ≥10% weight loss by the subjects. Adiponectin and tumor necrosis factor-alpha (TNF-α) levels were measured in the serum at baseline and after attainment of ≥10% reduction in weight in a period of 3–18 months. Results: Adherence to weight reduction program until the achievement of ≥10% reduction in body weight resulted in statistically significant (P < 0.0001) elevated serum adiponectin and reduced serum TNF-α levels in all three groups. Furthermore, elevations of adiponectin following weight reduction showed significant negative correlations with PPD in all the three groups and in patients with periodontitis, (Group 3) serum adiponectin levels showed significant negative correlations (P = 0.0001) with CAL in Group 3. Conclusions: Controlling obesity presents a good opportunity to alleviate the burden of periodontal disease. Simple weight reduction programs with diet and exercise-related lifestyle modifications may be an efficacious and barrier-free option.