Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study.

OBJECTIVES: To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators. METHODS: This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale. FINDINGS: FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported. CONCLUSIONS: This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg. CLINICALTRIALS.GOV IDENTIFIER: NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403.

Report of a Rare Case of Spindle Cell Ameloblastic Carcinoma and the Diagnostic Utility of Immunohistochemistry.

Ameloblastic carcinoma is a rare aggressive malignant epithelial odontogenic tumor. The spindle cell variant of ameloblastic carcinoma (SCAC) is exceedingly rare with 15 cases of SCAC having been reported. Therefore, because of the paucity of cases in literature related to SCAC, the biological behavior of the entity has not been well evaluated. Herein the authors report a case of incidentally diagnosed SCAC in a 20-year-old woman identified on imaging as part of the evaluation of a work-related facial injury. Histologically, the tumor had background of cystic ameloblastoma with areas of dense hypercellular spindle cells with short-to-long intersecting fascicles and occasional herringbone pattern intermixed with solid epithelial nests. Both the epithelial and spindle cells were positive for cytokeratin including cytokeratin 19, D2-40, and transducin-like enhancer of split proteins-1 immunohistochemical stains. The patient was followed for 18 months with no evidence of recurrence or metastasis. To the knowledge this is a first case of reporting D2-40 positivity in spindle ameloblastic carcinoma and this immunostain could be used as helpful marker to diagnose this entity.

An investigation of the effect of an essential oil mouthrinse on induced bacteraemia: a pilot study.

AIM: This pilot study was designed to assess the effect of an essential oil antiseptic mouthrinse (EOM) in reducing bloodstream bacteria after chewing an apple. MATERIAL AND METHODS: From a panel of 200, we screened 62 individuals with mild-to-moderate gingivitis. Twenty-two individuals who showed a bacteraemia after chewing an apple were enrolled. Subjects were recalled, instructed to chew an apple, had blood drawn (first baseline), and were randomly assigned EOM or a control (C) treatment for 2 weeks. Subjects were recalled, given an apple, and had blood taken for bacterial counts. Following a 1-week fluoride dentifrice wash-out, subjects were recalled, given the apple challenge, had blood drawn (second baseline), assigned the alternate treatment, and recalled for testing. Differences between baseline and 2-week post-treatment (EOM versus C) in blood-borne bacteria were assessed by analysis of covariance. RESULTS: Mean aerobic blood-borne bacteria decreased by 68.5% (17.7 viable counts from baseline; p<0.001), while anaerobic counts decreased by 70.7% (14.5 mean viable counts from baseline; p<0.001) for the EOM treatment. No reduction was seen for the C treatment. CONCLUSIONS: This double-blind, placebo-controlled, randomized, 2-week cross-over study showed that rinsing with essential oils reduced the level of bloodstream bacteria in subjects with mild-to-moderate gingivitis.

Validation of the anti-bacteremic efficacy of an essential oil rinse in a Brazilian population: a cross-over study.

This cross-over study was conducted to assess the germ-killing efficacy of an essential oil mouthrinse (EOM) by determining the blood levels of microorganisms associated with induced bacteremia and investigating the prevalence of this event in Brazilians with mild-to-moderate gingivitis. Thirty four (31.19%) subjects positive for bacteremia induced by chewing a ration of apple were enrolled out of 109 screened subjects (50 males and 59 females). A difference of at least 10 colony forming units between the pre- and post-insult blood samples was defined as a positive result. For the following two weeks patients underwent a toothbrush plus fluoride dentifrice normalization period, and were then scheduled for the Phase I protocol as follows. At baseline I, subjects were instructed to chew a new apple ration, had new blood samples taken before and after this oral stimulus, and were randomly assigned to an experimental essential oil (n = 17) or placebo (P) mouthrinse (n = 17) treatment for 2 weeks. These procedures were repeated at the end of Phase I and then followed by a two-week wash-out period (tooth brushing with fluoride dentifrice). Bacteremia was again induced at baseline and at the end of Phase II, when subjects were crossed-over to the other EOM or placebo groups. Bacterial count differences between baseline and 2-week post-treatment (EOM versus P) in the blood samples collected were assessed by analysis of covariance. Mean aerobic counts decreased by 45.8%, whereas mean anaerobic counts decreased by 63.3% after EOM treatment. After the P treatment, aerobic bacteria increased by 28.4% and anaerobic bacteria decreased by 18.5%. This study validated this novel methodology and showed that the germ-killing action of EOM significantly reduced bacteremia.

Validation of the anti-bacteremic efficacy of an essential oil rinse in a Brazilian population: a cross-over study

This cross-over study was conducted to assess the germ-killing efficacy of an essential oil mouthrinse (EOM) by determining the blood levels of microorganisms associated with induced bacteremia and investigating the prevalence of this event in Brazilians with mild-to-moderate gingivitis. Thirty four (31.19%) subjects positive for bacteremia induced by chewing a ration of apple were enrolled out of 109 screened subjects (50 males and 59 females). A difference of at least 10 colony forming units between the pre- and post-insult blood samples was defined as a positive result. For the following two weeks patients underwent a toothbrush plus fluoride dentifrice normalization period, and were then scheduled for the Phase I protocol as follows. At baseline I, subjects were instructed to chew a new apple ration, had new blood samples taken before and after this oral stimulus, and were randomly assigned to an experimental essential oil (n = 17) or placebo (P) mouthrinse (n = 17) treatment for 2 weeks. These procedures were repeated at the end of Phase I and then followed by a two-week wash-out period (tooth brushing with fluoride dentifrice). Bacteremia was again induced at baseline and at the end of Phase II, when subjects were crossed-over to the other EOM or placebo groups. Bacterial count differences between baseline and 2-week post-treatment (EOM versus P) in the blood samples collected were assessed by analysis of covariance. Mean aerobic counts decreased by 45.8%, whereas mean anaerobic counts decreased by 63.3% after EOM treatment. After the P treatment, aerobic bacteria increased by 28.4% and anaerobic bacteria decreased by 18.5%. This study validated this novel methodology and showed that the germ-killing action of EOM significantly reduced bacteremia.