Dental anaesthesia for children - effects of a computer-controlled delivery system on pain and heart rate: a randomised clinical trial.

Local anaesthesia in dentistry is usually given by conventional injection through a syringe. In this randomised, single-blind, split-mouth clinical study we evaluated the perception of pain and changes in heart rate in children being given dental local anaesthesia using a computer-controlled device compared with that given using a traditional syringe. Participants were in good general health with no contraindications to local anaesthetics. One half of each maxilla was anaesthetised using each technique, the order having been randomly selected according to a computer-generated sequence. The hypothesis was that the controlled anaesthetic flow rate results in virtually imperceptible injections. The outcomes were the perception of pain and the heart rate. Seventy-six children aged from 5-12 years old participated in this study. The mean (SD) pain score of the conventional injection was 5.51 (2.46) and the mean (SD) heart rate was 2.72 (6.76), which were significantly higher than those of the computerised delivery system, which were 4.74 (2.8) and 0.34 (7.3) (p=0.04). More patients anaesthetised with the traditional syringe technique required a second injection (n=21). These results suggest that dental anaesthesia given to children with a computer-controlled delivery system reduced pain better than that given with a conventional syringe.

Pharmacokinetic and pharmacodynamic interaction of hydroalcoholic extract of Ocimum sanctum with valproate.

For effective control of seizures, antiepileptic drugs (AEDs) are administered at higher dose which is associated with several adverse effects. This study envisaged antiepileptic and neuroprotective potential of Tulsi, a commonly used herb for its immunomodulatory property. The optimal dose of Ocimum sanctum hydroalcoholic extract (OSHE) was determined using maximal electroshock seizure (MES)- and pentylenetetrazol (PTZ)-induced seizure models in Wistar rats (200-250g) after administering OSHE (200-1000mg/kg) orally for 14days. For interaction study, OSHE optimal dose in combination with maximum and submaximal therapeutic doses of valproate was administered for 14days. Serum levels of valproate were estimated using HPLC for pharmacokinetic study. For pharmacodynamic interaction, antiepileptic effect on above seizure models, neurobehavioral effect using Morris water maze, passive avoidance and elevated plus maze tests, and antioxidant capacity were assessed. Ocimum sanctum hydroalcoholic extract 1000mg/kg was found to be optimal providing 50% protection against both MES- and PTZ-induced seizures. Combination of OSHE with valproate did not alter antiepileptic efficacy of valproate significantly. However, the combination showed better memory retention potential in neurobehavioral tests and protection against oxidative stress compared with valproate-alone-treated groups. Pharmacokinetic parameters did not reveal any significant change in combination group compared with valproate alone. Ocimum, although having per se antiepileptic action, did not affect antiepileptic action of valproate in combination. However, combination treatment has an edge over valproate alone-better neurobehavioral function and reduced oxidative stress-predicting adjuvant potential of Ocimum in epilepsy treatment.

Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations.

Pain Experience and Behavior Management in Pediatric Dentistry: A Comparison between Traditional Local Anesthesia and the Wand Computerized Delivery System.

Aim. To evaluate the pain experience and behavior during dental injection, using the Wand computerized delivery system versus conventional local anesthesia in children and adolescents. Methods. An observational crossover split mouth study was performed on 67 patients (aged 7 to 15 years), requiring local anesthesia for dental treatments in both sides of the dental arch. Patients received both types of injections in two separate appointments, one with the use of a Computer Delivery System (the Wand STA system) and one with the traditional syringe. The following data were recorded: pain rating; changes in heart rate; level of collaboration; patient satisfaction. The data were analyzed using ANOVA for quantitative outcomes and nonparametric analysis (Kruskal-Wallis) for qualitative parameters. Results. The use of the Wand system determined significantly lower pain ratings and lower increase of heart rate than the traditional syringe. During injection, the number of patients showing a relaxed behavior was higher with the Wand than with the traditional local anesthesia. The patient level of satisfaction was higher with the Wand compared to the conventional local anesthesia. Conclusions. The Wand system may provide a less painful injection when compared to the conventional local anesthesia and it seemed to be better tolerated with respect to a traditional syringe.

Prescription Errors with Chemotherapy: Quality Improvement through Standardized Order Templates.

BACKGROUND: Despite the existence of established guidelines advocating the use and value of chemotherapy order templates, chemotherapy orders are still handwritten in many hospitals in Lebanon. This manuscript describes the implementation of standardized chemotherapy order templates (COT) in a Lebanese tertiary teaching hospital through multiple steps. INITIAL ASSESSMENT: An initial assessment was conducted through a retrospective appraisal of completeness of handwritten chemotherapy orders for 100 adult patients to serve as a baseline for the project and identify parameters that might afford improvement. CHOICE OF SOLUTION: Development of over 300 standardized pre-printed COTs based on the National Comprehensive Cancer Network templates and adapted to the practice culture and patient population. IMPLEMENTATION: The COTs were implemented, using Kotter's 8-step model for leading change, by engaging health care providers, and identifying and removing barriers. EVALUATION: Assessment of physicians' compliance with the new practice (122 orders assessed) was completed through two phases and allowed for the identification of areas of improvement. LESSONS LEARNED: Overall, COT implementation showed an average improvement in order completion from 49.5% (handwritten orders) to 77.6% (phase 1-COT) to 87.6% (phase 2-COT) reflecting an increase of 38.1% between baseline and phase 2 and demonstrating that chemotherapy orders completeness was improved by pre-printed COT. As many of the hospitals in Lebanon are moving towards standardized COTs and computerized physician order entry (CPOE) in the next few years, this study provides a prototype for the successful implementation of COT and demonstrates their role in promoting quality improvement of cancer care.

Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease.

Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences) with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.

Systems Pharmacology and Rational Polypharmacy: Nitric Oxide-Cyclic GMP Signaling Pathway as an Illustrative Example and Derivation of the General Case.

Impaired nitric oxide (NO˙)-cyclic guanosine 3', 5'-monophosphate (cGMP) signaling has been observed in many cardiovascular disorders, including heart failure and pulmonary arterial hypertension. There are several enzymatic determinants of cGMP levels in this pathway, including soluble guanylyl cyclase (sGC) itself, the NO˙-activated form of sGC, and phosphodiesterase(s) (PDE). Therapies for some of these disorders with PDE inhibitors have been successful at increasing cGMP levels in both cardiac and vascular tissues. However, at the systems level, it is not clear whether perturbation of PDE alone, under oxidative stress, is the best approach for increasing cGMP levels as compared with perturbation of other potential pathway targets, either alone or in combination. Here, we develop a model-based approach to perturbing this pathway, focusing on single reactions, pairs of reactions, or trios of reactions as targets, then monitoring the theoretical effects of these interventions on cGMP levels. Single perturbations of all reaction steps within this pathway demonstrated that three reaction steps, including the oxidation of sGC, NO˙ dissociation from sGC, and cGMP degradation by PDE, exerted a dominant influence on cGMP accumulation relative to other reaction steps. Furthermore, among all possible single, paired, and triple perturbations of this pathway, the combined perturbations of these three reaction steps had the greatest impact on cGMP accumulation. These computational findings were confirmed in cell-based experiments. We conclude that a combined perturbation of the oxidatively-impaired NO˙-cGMP signaling pathway is a better approach to the restoration of cGMP levels as compared with corresponding individual perturbations. This approach may also yield improved therapeutic responses in other complex pharmacologically amenable pathways.

Relief of Injection Pain During Delivery of Local Anesthesia by Computer-Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial.

BACKGROUND: Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). METHODS: Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). RESULTS: DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. CONCLUSION: Within the limitations of the present study, relief from injection pain is observed using CNR.

Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase.

Behavioral response and pain perception to computer controlled local anesthetic delivery system and cartridge syringe.

AIM: The present study evaluated and compared the pain perception, behavioral response, physiological parameters, and the role of topical anesthetic administration during local anesthetic administration with cartridge syringe and computer controlled local anesthetic delivery system (CCLAD). DESIGN: A randomized controlled crossover study was carried out with 120 children aged 7-11 years. They were randomly divided into Group A: Receiving injection with CCLAD during first visit; Group B: Receiving injection with cartridge syringe during first visit. They were further subdivided into three subgroups based on the topical application used: (a) 20% benzocaine; (b) pressure with cotton applicator; (c) no topical application. Pulse rate and blood pressure were recorded before and during injection procedure. Objective evaluation of disruptive behavior and subjective evaluation of pain were done using face legs activity cry consolability scale and modified facial image scale, respectively. The washout period between the two visits was 1-week. RESULTS: Injections with CCLAD produced significantly lesser pain response, disruptive behavior (P < 0.001), and pulse rate (P < 0.05) when compared to cartridge syringe injections. Application of benzocaine produced lesser pain response and disruptive behavior when compared to the other two subgroups, although the result was not significant. CONCLUSION: Usage of techniques which enhance behavioral response in children like injections with CCLAD can be considered as a possible step toward achieving a pain-free pediatric dental practice.

Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients.

BACKGROUND: We evaluated the effectiveness of a computer clinical decision support system (CDSS) for reducing the risk of QT interval prolongation in hospitalized patients. METHODS AND RESULTS: We evaluated 2400 patients admitted to cardiac care units at an urban academic medical center. A CDSS incorporating a validated risk score for QTc prolongation was developed and implemented using information extracted from patients' electronic medical records. When a drug associated with torsades de pointes was prescribed to a patient at moderate or high risk for QTc interval prolongation, a computer alert appeared on the screen to the pharmacist entering the order, who could then consult the prescriber on alternative therapies and implement more intensive monitoring. QTc interval prolongation was defined as QTc interval >500 ms or increase in QTc of ≥60 ms from baseline; for patients who presented with QTc >500 ms, QTc prolongation was defined solely as increase in QTc ≥60 ms from baseline. End points were assessed before (n=1200) and after (n=1200) implementation of the CDSS. CDSS implementation was independently associated with a reduced risk of QTc prolongation (adjusted odds ratio, 0.65; 95% confidence interval, 0.56-0.89; P<0.0001). Furthermore, CDSS implementation reduced the prescribing of noncardiac medications known to cause torsades de pointes, including fluoroquinolones and intravenous haloperidol (adjusted odds ratio, 0.79; 95% confidence interval, 0.63-0.91; P=0.03). CONCLUSIONS: A computer CDSS incorporating a validated risk score for QTc prolongation influences the prescribing of QT-prolonging drugs and reduces the risk of QTc interval prolongation in hospitalized patients with torsades de pointes risk factors.

Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy.

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r(2) of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

[Medicine from the computer]. / Medizin aus dem Computer.

Small molecules can have a significant effect on human metabolic processes. Computational drug design aims at constructing specialized small molecules that selectively and efficiently address specific proteins. The basic ideas of computational molecular design are presented and it will be shown how a virtual protein can be computer designed. This virtual protein can be used to predict the binding affinity of given small molecules without having to synthesize them in a laboratory. Modern computational drug design goes far beyond the lock and key principle. Possible future developments are discussed and a current successful example of computational drug design in the field of painkiller medication is demonstrated.

Advancing medication infusion safety through the clinical integration of technology.

Adverse drug events resulting from errors in prescribing or administering medications are preventable. Within a hospital system, numerous technologies are employed to address the common sources of medication error, including the use of electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. Infusion safety is inherently risky because of the high-risk medications administered and the lack of integration among the stand-alone systems in most institutions. Intravenous clinical integration (IVCI) is a technology that connects electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. It combines the safety features of an automatically programmed infusion pump (drug, concentration, infusion rate, and patient weight, all auto-programmed into the device) with software that provides visibility to real-time clinical infusion data. Our article describes the characteristics of IVCI at WellSpan Health and its impact on patient safety. The integrated infusion system has the capability of reducing medication errors, improving patient care, reducing in-facility costs, and supporting asset management. It can enhance continuous quality improvement efforts and efficiency of clinical work flow. After implementing IVCI, the institution realized a safer patient environment and a more streamlined work flow for pharmacy and nursing.

Automated synthesis and visualization of a chemotherapy treatment regimen network.

Cytotoxic treatments for cancer remain highly toxic, expensive, and variably efficacious. Many chemotherapy regimens are never directly compared in randomized clinical trials (RCTs); as a result, the vast majority of guideline recommendations are ultimately derived from human expert opinion. We introduce an automated network meta-analytic approach to this clinical problem, with nodes representing regimens and edges direct comparison via RCT(s). A chemotherapy regimen network is visualized for the primary treatment of chronic myelogenous leukemia (CML). Node and edge color, size, and opacity are all utilized to provide additional information about the quality and strength of the depicted evidence. Historical versions of the network are also created. With this approach, we were able to compactly compare the results of 17 CML regimens involving RCTs of 9700 patients, representing the accumulation of 45 years of evidence. Our results closely parallel the recommendations issued by a professional guidelines organization, the National Comprehensive Cancer Network (NCCN). This approach offers a novel method for interpreting complex clinical data, with potential implications for future objective guideline development.

Comparative evaluation of different medication safety measures for the emergency department: physicians' usage and acceptance of training, poster, checklist and computerized decision support.

BACKGROUND: Although usage and acceptance are important factors for a successful implementation of clinical decision support systems for medication, most studies only concentrate on their design and outcome. Our objective was to comparatively investigate a set of traditional medication safety measures such as medication safety training for physicians, paper-based posters and checklists concerning potential medication problems versus the additional benefit of a computer-assisted medication check. We concentrated on usage, acceptance and suitability of such interventions in a busy emergency department (ED) of a 749 bed acute tertiary care hospital. METHODS: A retrospective, qualitative evaluation study was conducted using a field observation and a questionnaire-based survey. Six physicians were observed while treating 20 patient cases; the questionnaire, based on the Technology Acceptance Model 2 (TAM2), has been answered by nine ED physicians. RESULTS: During field observations, we did not observe direct use of any of the implemented interventions for medication safety (paper-based and electronic). Questionnaire results indicated that the electronic medication safety check was the most frequently used intervention, followed by checklist and posters. However, despite their positive attitude, physicians most often stated that they use the interventions in only up to ten percent for subjectively "critical" orders. Main reasons behind the low usage were deficits in ease-of-use and fit to the workflow. The intention to use the interventions was rather high after overcoming these barriers. CONCLUSIONS: Methodologically, the study contributes to Technology Acceptance Model (TAM) research in an ED setting and confirms TAM2 as a helpful diagnostic tool in identifying barriers for a successful implementation of medication safety interventions. In our case, identified barriers explaining the low utilization of the implemented medication safety interventions - despite their positive reception - include deficits in accessibility, briefing for the physicians about the interventions, ease-of-use and compatibility to the working environment.

Drugs don't work in patients who don't take them: Dr. Drin, the new ICT paradigm for chronic therapies.

Poor adherence to drug therapies still represents an unsolved problem. In order to provide a useful solution to chronic patients of all ages--with particular attention to the elderly--who are subjected to complex therapeutic regimen, an innovative ICT solution, called Dr.Drin, has been designed and tested. The aim of the developed framework is to assist the patient during the therapy and to enable and support a bidirectional communication between all healthcare stakeholders (doctors, caregivers and family members) and the patient. During the screening phase, patients were interviewed to understand what are the common practices they usually adopt to remember when and how to take a drug. The solutions which they rely the most on are the list of drugs, writing on the packaging, and setting up alarms. Patients who complained about difficulties of adherence and who had a smartphone were subsequently recruited to test Dr.Drin over a three-months period. In the following, preliminary results from the first twelve patients are presented and analyzed to prove the effectiveness of Dr.Drin in supporting patients adherence to therapies.

Clinical decision support for monitoring drug-drug-interactions and potassium-increasing drug combinations: need for specific alerts.

Computer-triggered reminders alerting physicians on every potentially harmful drug-drug-interaction (DDI) induce alert fatigue due to frequent messages of limited clinical relevance. On demand DDI-checks, however, are not commonly used by physicians. Optimal strategies for sustained quality assurance have to consider patients' risk factors and focus on the most significant DDIs only. An approach is proposed based on the analysis of concurrent prescription of potassium-sparing diuretics and potassium supplements (CPPP), which are the most frequent DDIs classified as contraindicated. Although the frequency of monitoring potassium serum levels declined during prolonged periods of CPPP, the likelihood of observing a hyperkalaemia increased. The median treatment period of CPPP was 3.3 days, whereas hyperkalaemia occurred after a median observation time of 4.5 days of CPPP. Thus, computer-triggered reminders for ordering potassium serum levels may be indicated if monitoring has been discontinued after 48h of CPPP.

An implantable closedloop asynchronous drug delivery system for the treatment of refractory epilepsy.

In this paper, we present an implantable device for intra-cerebral electroencephalography (icEEG) data acquisition and real-time epileptic seizure detection with simultaneous focal antiepileptic drug injection feedback. This implantable device includes a neural signal amplifier, an asynchronous seizure detector, a drug delivery system (DDS) including a micropump, and a hybrid subdural electrode (HSE). The asynchronous detection algorithm is based on data-dependent analysis and validated with Matlab tools. The detector and DDS have a power saving mode. The HSE contacts are made of Platinum (Pt) encapsulated with polydimethylsiloxane (PDMS). Given the heterogeneity of electrographic seizure signals and seizure suppression threshold, the implantable device provides tunable parameters facility through an external transmitter to adapt to each individual's neurophysiology prior to clinical deployment. The proposed detector and DDS were assembled in Ø 50 mm and Ø 30 mm circular printed circuit boards, respectively. The detector was validated using icEEG recordings of seven patients who had previously undergone an intracranial investigation for epilepsy surgery. The triggering of the DDS was tested and a predefined seizure suppression dose was delivered ~16 s after electrographical seizure onsets. The device's power consumption was reduced by 12% in active mode and 49% in power saving mode compared to similar seizure detection algorithms implemented with synchronous architecture.