Anti­epidermal growth factor receptor monoclonal antibody therapy in locally advanced head and neck cancer: A systematic review of phase III clinical trials.

The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m2 weekly, instead of the standard doses of 100 mg/m2 every 3 weeks or 40 mg/m2 every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.

Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl.

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 µg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 µg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.

Role of Intelligence Quotient (IQ) on anxiety and behavior in children with hearing and speech impairment.

AIM: To assess and compare the role of IQ on anxiety and behavior of children with and without hearing and speech impairment. MATERIAL AND METHODS: A total of 120 children of age group 7-14 years were included in the study, of which control group comprised of 60 normal healthy children and 60 hearing and speech impaired children formed the study group. The study was done in two consecutive sessions. First appointment for Culture Fair Intelligence Test and second appointment for RMS pictorial anxiety score (RMS-PS) and Frankl behavior rating which were assessed during oral prophylaxis. RESULTS: IQ of children with hearing and speech impairment was lower as compared to normal healthy children. There was a positive correlation between IQ and anxiety in children with hearing and speech impairment while no correlation was found with behavior. CONCLUSION: Children with hearing and speech impairment are less anxious and more cooperative compared to normal healthy child in the dental setting and are, therefore, easier to manage.

Salivary antioxidants and oral health in children with autism.

UNLABELLED: Individuals with autism vary widely in abilities, intelligence, and behaviours. Autistic children have preferences for soft and sweetened food making them susceptible to caries. A wide spectrum of medical and behavioural symptoms is exhibited by children with autism, which makes routine dental care very difficult in them. Mental retardation is evident in approximately 70% of individuals with autism and most psychiatric disorders including autism are associated with increased oxidative stress. OBJECTIVES: To evaluate the oral health status of children with autism and to determine the salivary pH and total salivary antioxidant concentration (TAC). MATERIALS AND METHODS: 101 subjects with autism between age group of 6 and 12 year were part of the study and 50 normal healthy siblings of same age group were taken as control group. Oral health status was analysed using oral hygiene index-simplified and dentition status index. The salivary total anti-oxidant level was estimated using phosphomolybdic acid using spectrophotometric method and the salivary pH using the pH indicating paper. The results were statistically analyzed using Mann-Whitney U test. RESULTS: A statistically very highly significant difference was seen in the mean oral hygiene index scores (autistic group--1.2 and control group--1, P<0.001) and the mean salivary total antioxidant concentration (autistic group--5.7 µg/ml and control group--38 µg/ml, P<0.001). No statistical significant difference was observed in the dental caries status and the salivary pH of autistic group and the control group. CONCLUSIONS: Similar dental caries status was observed in children with autism and their healthy normal siblings. Oral hygiene was poor in children with autism whereas the Salivary TAC was significantly reduced in autistic children.