Background
Pain during dental treatment, which is a common fear of patients, can be controlled successfully by local anaesthetic. Several different local anaesthetic formulations and techniques are ...available to dentists.
Objectives
Our primary objectives were to compare the success of anaesthesia, the speed of onset and duration of anaesthesia, and systemic and local adverse effects amongst different local anaesthetic formulations for dental anaesthesia. We define success of anaesthesia as absence of pain during a dental procedure, or a negative response to electric pulp testing or other simulated scenario tests. We define dental anaesthesia as anaesthesia given at the time of any dental intervention.
Our secondary objective was to report on patients' experience of the procedures carried out.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2018, Issue 1), MEDLINE (OVID SP), Embase, CINAHL PLUS, WEB OF SCIENCE, and other resources up to 31 January 2018. Other resources included trial registries, handsearched journals, conference proceedings, bibliographies/reference lists, and unpublished research.
Selection criteria
We included randomized controlled trials (RCTs) testing different formulations of local anaesthetic used for clinical procedures or simulated scenarios. Studies could apply a parallel or cross‐over design.
Data collection and analysis
We used standard Cochrane methodological approaches for data collection and analysis.
Main results
We included 123 studies (19,223 participants) in the review. We pooled data from 68 studies (6615 participants) for meta‐analysis, yielding 23 comparisons of local anaesthetic and 57 outcomes with 14 different formulations. Only 10 outcomes from eight comparisons involved clinical testing.
We assessed the included studies as having low risk of bias in most domains. Seventy‐three studies had at least one domain with unclear risk of bias. Fifteen studies had at least one domain with high risk of bias due to inadequate sequence generation, allocation concealment, masking of local anaesthetic cartridges for administrators or outcome assessors, or participant dropout or exclusion.
We reported results for the eight most important comparisons.
Success of anaesthesia
When the success of anaesthesia in posterior teeth with irreversible pulpitis requiring root canal treatment is tested, 4% articaine, 1:100,000 epinephrine, may be superior to 2% lidocaine, 1:100,000 epinephrine (31% with 2% lidocaine vs 49% with 4% articaine; risk ratio (RR) 1.60, 95% confidence interval (CI) 1.10 to 2.32; 4 parallel studies; 203 participants; low‐quality evidence).
When the success of anaesthesia for teeth/dental tissues requiring surgical procedures and surgical procedures/periodontal treatment, respectively, was tested, 3% prilocaine, 0.03 IU felypressin (66% with 3% prilocaine vs 76% with 2% lidocaine; RR 0.86, 95% CI 0.79 to 0.95; 2 parallel studies; 907 participants; moderate‐quality evidence), and 4% prilocaine plain (71% with 4% prilocaine vs 83% with 2% lidocaine; RR 0.86, 95% CI 0.75 to 0.99; 2 parallel studies; 228 participants; low‐quality evidence) were inferior to 2% lidocaine, 1:100,000 epinephrine.
Comparative effects of 4% articaine, 1:100,000 epinephrine and 4% articaine, 1:200,000 epinephrine on success of anaesthesia for teeth/dental tissues requiring surgical procedures are uncertain (RR 0.85, 95% CI 0.71 to 1.02; 3 parallel studies; 930 participants; very low‐quality evidence).
Comparative effects of 0.5% bupivacaine, 1:200,000 epinephrine and both 4% articaine, 1:200,000 epinephrine (odds ratio (OR) 0.87, 95% CI 0.27 to 2.83; 2 cross‐over studies; 37 participants; low‐quality evidence) and 2% lidocaine, 1:100,000 epinephrine (OR 0.58, 95% CI 0.07 to 5.12; 2 cross‐over studies; 31 participants; low‐quality evidence) on success of anaesthesia for teeth requiring extraction are uncertain.
Comparative effects of 2% mepivacaine, 1:100,000 epinephrine and both 4% articaine, 1:100,000 epinephrine (OR 3.82, 95% CI 0.61 to 23.82; 1 parallel and 1 cross‐over study; 110 participants; low‐quality evidence) and 2% lidocaine, 1:100,000 epinephrine (RR 1.16, 95% CI 0.25 to 5.45; 2 parallel studies; 68 participants; low‐quality evidence) on success of anaesthesia for teeth requiring extraction and teeth with irreversible pulpitis requiring endodontic access and instrumentation, respectively, are uncertain.
For remaining outcomes, assessing success of dental local anaesthesia via meta‐analyses was not possible.
Onset and duration of anaesthesia
For comparisons assessing onset and duration, no clinical studies met our outcome definitions.
Adverse effects (continuous pain measured on 170‐mm Heft‐Parker visual analogue scale (VAS))
Differences in post‐injection pain between 4% articaine, 1:100,000 epinephrine and 2% lidocaine, 1:100,000 epinephrine are small, as measured on a VAS (mean difference (MD) 4.74 mm, 95% CI ‐1.98 to 11.46 mm; 3 cross‐over studies; 314 interventions; moderate‐quality evidence). Lidocaine probably resulted in slightly less post‐injection pain than articaine (MD 6.41 mm, 95% CI 1.01 to 11.80 mm; 3 cross‐over studies; 309 interventions; moderate‐quality evidence) on the same VAS.
For remaining comparisons assessing local and systemic adverse effects, meta‐analyses were not possible. Other adverse effects were rare and minor.
Patients' experience
Patients' experience of procedures was not assessed owing to lack of data.
Authors' conclusions
For success (absence of pain), low‐quality evidence suggests that 4% articaine, 1:100,000 epinephrine was superior to 2% lidocaine, 1:100,000 epinephrine for root treating of posterior teeth with irreversible pulpitis, and 2% lidocaine, 1:100,000 epinephrine was superior to 4% prilocaine plain when surgical procedures/periodontal treatment was provided. Moderate‐quality evidence shows that 2% lidocaine, 1:100,000 epinephrine was superior to 3% prilocaine, 0.03 IU felypressin when surgical procedures were performed.
Adverse events were rare. Moderate‐quality evidence shows no difference in pain on injection when 4% articaine, 1:100,000 epinephrine and 2% lidocaine, 1:100,000 epinephrine were compared, although lidocaine resulted in slightly less pain following injection.
Many outcomes tested our primary objectives in simulated scenarios, although clinical alternatives may not be possible.
Further studies are needed to increase the strength of the evidence. These studies should be clearly reported, have low risk of bias with adequate sample size, and provide data in a format that will allow meta‐analysis. Once assessed, results of the 34 ‘Studies awaiting classification (full text unavailable)’ may alter the conclusions of the review.
Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel ...running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.
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•Exercise reduces tumor incidence and growth in several mouse models•Exercise increases NK cell infiltration, thereby controlling tumor growth•Epinephrine mobilizes NK cells and β-blockade blunts the tumor suppression•Exercise-induced muscle-derived IL-6 is involved in NK cell redistribution
The beneficial effects of exercise are countless. Pedersen et al. now link exercise, cancer, and immunity and reveal that exercise decreases tumor incidence and growth by over 60% across several mouse tumor models through a direct regulation of NK cell mobilization and trafficking in an epinephrine- and IL-6-dependent manner.
Introduction/Objective Insect stings are the second most common cause of allergic reactions and anaphylaxis. Allergic reactions after insect stings (bee, wasp, hornet) can vary from local skin ...changes to fatal anaphylactic reactions. The objective of the article is to present prehospital treatment of an anaphylactic reaction after an insect sting in the Infirmary of the Municipal Institution for Emergency Medical Aid. Case study Half an hour before coming to the Infirmary, the 22 year old patient felt sharp pain and a burning sensation in the neck area. The pain occurred as a result of being stung by an insect, probably a hornet. The physical examination found him to be mildly disoriented, dyspneic, afebrile, sweaty and tachycardic, with pale skin and mucous membranes. His eyelids, lips, tongue and uvula were swollen. At the site of the sting (the back side of the neck) a nodus had developed measuring 3x3cm surrounded with a skin edema measuring 10x10cm and erythema. The skin of both upper and lower extremities, as well as the torso, was covered with generalized urticaria. Based on patient's history and physical findings, the diagnosis of anaphylactic reaction was made. As the first line of therapy, the patient received an intramuscular injection of Adrenalin 500μg (0,5ml diluted to the ratio of 1:1000) in the anteromedial region of his thigh. He was given oxygen by mask (6l/min) and 1000ml of Ringer's solution. After initial stabilization, the patient received the second line of therapy: antihistamines (H1 and H2 antagonists) and a slow i.v. injection of Methylprednisolone. The patient's vital signs had stabilized after the initial treatment and he was transferred by ambulance, while being constantly monitored, to the Emergency Center where he was kept under close observation for the next six hours. He was then discharged in good health, with the advice to submit to additional allergology testing. Conclusion: This case study of an all too common situation in prehospital settings accentuates the need to be familiar with protocols for anaphylactic reaction treatment and their implementation in every day work.
Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic ...media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.
Anaphylaxis is a serious disease that can be encountered in all medical departments. Although the onset mayoccur in unforeseen circumstances, it is necessary that the initial response be as efficient ...as possible. This articleoutlines the initial response and preventive measures based on the guidelines published by the Allergy Society in2014. In the future, with the development of new drugs such as anti-tumor drugs, monoclonal antibodies, and biologics, dealing with atypical symptoms will become an issue. In order to deepen the understanding of anaphylaxis,it is important to understand the disease state, including the phenotype, end type, and biomarkers.
The renin-angiotensin-aldosterone system (RAAS) plays a relevant role in regulating blood pressure and thus maintaining cardiovascular homeostasis. Although it was recently shown that RAAS parameters ...are responsive to acute psychosocial stress, the psychobiological determinants of the acute stress-induced RAAS activation have not yet been investigated. In a randomized placebo-controlled design, we investigated potential psychological and physiological determinants of the RAAS response and underlying mechanisms.
Fifty-seven young healthy male participants underwent either an acute standardized psychosocial stress test or a nonstress placebo task. We measured aldosterone in plasma and saliva, as well as renin, and the stress-reactive endocrine measures adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine in plasma at rest, immediately after the task and several times up to 3 hours thereafter. Moreover, we assessed stress-reactive psychological (anticipatory cognitive stress appraisal, mood, physical discomfort) and basal demographic-physiological measures (age, body mass index, blood pressure).
Acute psychosocial stress elicited changes in all assessed endocrine (p values ≤ .028, ηp2 values ≥ 0.07) and stress-reactive psychological measures (p values ≤ .003, ηp2 values ≥ 0.15). The basal parameter body mass index, the stress-reactive endocrine parameters ACTH and norepinephrine, and the psychological parameter anticipatory stress appraisal were identified as determinants of higher RAAS parameter reactivity to acute psychosocial stress. The association between anticipatory cognitive stress appraisal and plasma RAAS measures was fully mediated by ACTH increases (p values ≤ .044, ηp2 values ≥ 0.05).
Cognitive stress appraisal processes seem to modulate RAAS stress reactivity. This points to potential clinical implications for psychoeducative therapeutical interventions targeting stress appraisal processes to reduce endocrine stress reactivity.
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