Chronotherapy in dentistry: A scoping review.

The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.

NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial.

OBJECTIVES: Postoperative pain management impacts patients' quality of life and morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used for this following a 3-doses-per-day regime. However, pain and inflammation follow a circadian rhythm, and animal models assessing the scheduling of NSAID administration (e.g., chronotherapy) have shown that while their use during the active phase of the day enhances postoperative recovery, their administration during the resting phase could have detrimental effects. This observation has led us to hypothesize that night administration of NSAID might be unnecessary in post-surgical scenarios. Therefore, a randomized clinical trial was conducted to test this hypothesis in surgical third molar extractions. MATERIALS AND METHODS: Seventy (18-35 years) healthy participants requiring surgical removal of impacted lower third molars were recruited and randomized into a double-blind placebo-controlled study. For three days postoperatively, the treatment group (n = 33) received ibuprofen (400 mg) at 8 AM, 1 PM, and a placebo at 8 PM, while the control group (n = 37) received ibuprofen (400 mg) at 8 AM, 1 PM, and 8 PM. Pain severity was assessed by visual analog scale (VAS) and healing indicators including facial swelling, mouth opening, and C-reactive protein blood levels were also measured. RESULTS: Pain VAS measures showed a circadian variation peaking at night. Also, no significant differences were observed between the two groups of the study in terms of postoperative pain scores (estimate: 0.50, 95% CI = [- 0.38, 1.39]) or any other healing indicator. CONCLUSIONS: Postoperative pain follows a circadian rhythm. Moreover, night administration of ibuprofen might not provide any significant benefits in terms of pain management and control of inflammation, and two doses during the day only could be sufficient for pain management after surgical interventions. KNOWLEDGE TRANSFER STATEMENT: Even though this study cannot rule out the possibility that a reduced regime is different than a standard regime, nocturnal doses of ibuprofen seem to have no clinical significance in the short term, and the results of this study provide evidence in favor of reducing ibuprofen administration from three doses to two doses only after third molar surgery.

Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli.

Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.

Isolation of Fully Vancomycin-Resistant Streptococcus thoraltensis from the Nasal Cavity of a Healthy Young Adult.

BACKGROUND: Streptococcus thoraltensis was first isolated from pigs and rabbits. Later, isolation from human oral and nasal cavities and from throat and oropharynx was documented. S. thoraltensis was isolated from patients with periodontitis, tonsillopharyngitis, and chorioamnionitis suggesting a possible pathological role in human infections. All S. thoraltensis isolates of animal and human origins were sensitive to vancomycin. METHODS: Standard microbiological identification methods, biochemical analysis, and antibiotic susceptibility testing using disk diffusion and E methods were used. Automatic species identification and antibiotic susceptibility testing were carried out using the Vitek 2 compact system. Molecular analysis of vancomycin resistance gene was carried out using a PCR with specific primers for vanA. RESULTS: We report a healthy young female adult, aged 19 years, with history of exposure to pet rabbit who had nasal colonization with S. thoraltensis. Identification of S. thoraltensis was based on traditional microbiological methods (culture, Gram stain, and biochemical tests), and the Vitek 2 compact system with 97% confidence rate. Antibiotic susceptibility testing of the isolate indicated resistance to most antibiotics, including penicillins, cephalosporins, methicillin, and glycopeptides. The minimal inhibitory concentration for vancomycin and teicoplanin was exceptionally high (>256 µg/mL). Molecular analysis indicated the absence of vanA gene in S. thoraltensis. CONCLUSION: We report for the first time the isolation of a fully vancomycin-resistant S. thoraltensis independent of vanA from a healthy human anterior nasal cavity. The pathological role of this newly identified organism with an exceptionally rare resistance pattern in human infections is yet to be identified.