Miami Valley Hospital

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article.

OBJECTIVE: To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model. DESIGN: Interventional study. Patient demographic and clinical information for infants with birth weight 501 to 1500 g was collected using the Vermont Oxford Network Database for January 1, 1994 to December 31, 1997. SETTING: Ten self-selected neonatal intensive care units (NICUs) received the intervention. They formed 2 subgroups (6 NICUs working on infection, 4 NICUs working on chronic lung disease). Sixty-six other NICUs served as a contemporaneous comparison group. PATIENTS: Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group (n = 3063) and the 66 comparison NICUs (n = 21 509); infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group (n = 738). INTERVENTIONS: NICUs formed multidisciplinary teams that worked together under the direction of a trained facilitator over a 3-year period beginning in January 1995. They received instruction in quality improvement, reviewed performance data, identified common improvement goals, and implemented "potentially better practices" developed through analysis of the processes of care, literature review, and site visits. MAIN OUTCOME MEASURES: The rates of infection after the third day of life with coagulase-negative staphylococcal or other bacterial pathogens for infants with birth weight 501 to 1500 g, and the rates of oxygen supplementation or death at 36 weeks' adjusted gestational age for infants with birth weight 501 to 1000 g. RESULTS: Between 1994 and 1996, the rate of infection with coagulase-negative staphylococcus decreased from 22.0% to 16.6% at the 6 project NICUs in the infection group; the rate of supplemental oxygen at 36 weeks' adjusted gestational age decreased from 43.5% to 31.5% at the 4 NICUs in the chronic lung disease group. There was heterogeneity in the effects among the NICUs in both project groups. The changes observed at the project NICUs for these outcomes were significantly larger than those observed at the 66 comparison NICUs over the 4-year period from 1994 to 1997. CONCLUSION: We conclude that multidisciplinary collaborative quality improvement has the potential to improve the outcomes of neonatal intensive care.

It is impossible to provide effective dental care without the use of local anesthetics. This drug class has an impressive history of safety and efficacy, but all local anesthetics have the potential to produce significant toxicity if used carelessly. The purpose of this review is to update the practitioner on issues regarding the basic pharmacology and clinical use of local anesthetic formulations.

OBJECTIVE: Although benzodiazepines (BZDs) are commonly used in the treatment of posttraumatic stress disorder (PTSD), no systematic review or meta-analysis has specifically examined this treatment. The goal of this study was to analyze and summarize evidence concerning the efficacy of BZDs in treating PTSD. METHODS: The review protocol was undertaken according to the principles recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and is registered with the PROSPERO international prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42014009318). Two authors independently conducted a search of all relevant articles using multiple electronic databases and independently abstracted information from studies measuring PTSD outcomes in patients using BZDs. Eighteen clinical trials and observational studies were identified, with a total of 5236 participants. Outcomes were assessed using qualitative and quantitative syntheses, including meta-analysis. RESULTS: BZDs are ineffective for PTSD treatment and prevention, and risks associated with their use tend to outweigh potential short-term benefits. In addition to adverse effects in general populations, BZDs are associated with specific problems in patients with PTSD: worse overall severity, significantly increased risk of developing PTSD with use after recent trauma, worse psychotherapy outcomes, aggression, depression, and substance use. Potential biopsychosocial explanations for these results are proposed based on studies that have investigated BZDs, PTSD, and relevant animal models. CONCLUSIONS: The results of this systematic review suggest that BZDs should be considered relatively contraindicated for patients with PTSD or recent trauma. Evidence-based treatments for PTSD should be favored over BZDs.

Mild hypothermia is common during deep sedation or general anesthesia and is frequently associated with patient discomfort and shivering. Greater declines in temperature can produce an even greater number of significant detrimental effects. This article reviews principles of thermoregulation and influences of anesthetic agents. An understanding of these will provide a foundation for strategies to reduce heat loss and better manage patient discomfort when it occurs.

Glucocorticosteroids are a product of the adrenal cortex and perform a staggering number of physiological effects essential for life. Their clinical use is largely predicated on their anti-inflammatory and immunosuppressive properties, but they also have notable efficacy in the prophylaxis of postoperative nausea and vomiting. This article reviews the basic functions of glucocorticoids and their clinical use in dental practice.

Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and is commonly used in emergency centers and ambulatory surgery centers as well. When used alone, it is incapable of producing general anesthesia reliably, but it may be combined with other inhalation and/or intravenous agents in deep sedative/general anesthetic techniques. However, as a single agent, it has impressive safety and is excellent for providing minimal and moderate sedation for apprehensive dental patients. To gain a full appreciation of the pharmacology, physiologic influences, and proper use of nitrous oxide, one must compare it with other inhalation anesthetics. The purpose of this CE article is to provide an overview of inhalation anesthetics in general and to address nitrous oxide more specifically in comparison.

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.

The purpose of this study was to determine the minimum thickness of cortical bone required for the accurate measurement of cortical material density by computed tomography (CT) and to establish normal reference values. A phantom with several wall thicknesses of bone-like material was constructed to simulate various cortical widths. The CT density at each level of thickness was measured on a GE 9800 CT scanner and on the OsteoQuant, a special CT scanner optimized for the measurement of bone in the extremities. The minimum width required to attain the correct material density was determined for each scanner. Additionally, the material density and width of the cortex in the radius and/or femur were measured by CT in 761 healthy subjects, ages 4-84 years. The minimum thickness necessary for an accurate density evaluation of the walls of the phantom by CT was 2-2.5 mm; below these thresholds the values fell in a linear way relative to width. In humans, the material density of cortical bone in the appendicular skeleton was not influenced by height or weight, and the values were similar for all subjects, as long as the cortical width was above 2-2.5 mm. The cortical width increased with age up to 30 years and decreased from 50 years on. We conclude that the material density of cortical bone in the appendicular skeleton can be measured accurately by CT if the thickness of the cortex exceeds 2-2.5 mm.

Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests.

Nausea, vomiting, and hiccups are troubling complications associated with sedation and general anesthesia. This article will review the basic pathophysiology of these events and current recommendations for their prevention and management.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.

PURPOSE: To provide an overview of the appropriate evaluation and management of partial-thickness burns. TARGET AUDIENCE: This continuing-education activity is intended for physicians and nurses with an interest in learning about burn wound care. LEARNING OBJECTIVES: After reading the article and taking the test, the participant will be able to: 1. Describe the classification of burn wounds. 2. Identify characteristics of burn wounds and the clinical techniques for diagnosing burn wound depth. 3. Identify the treatment options for partial-thickness burns.

Previous research on the development of distributive justice decisions, by centering largely on situations in which rewards for work productivity are to be allocated, has shed little light on the child's developing ability to select the justice norm most appropriate to the situation. Children 5, 9, and 13 years of age were asked to allocate resources and judge the fairness of alternative decision rules in situations to which either equity, equality, or need norms were especially applicable. As predicted, young children were insensitive to contextual information, generally preferring to allocate resources equally, whereas older children tailored their decisions appropriately to the situation. The fact that developmental trends differed from situation to situation points to the importance of adopting a contextual perspective on the development of distributive justice orientations.

Safe and effective management of acute dental pain can be accomplished with nonopioid and opioid analgesics. To formulate regimens properly, it is essential to appreciate basic pharmacological principles and appropriate dosage strategies for each of the available analgesic classes. This article will review the basic pharmacology of analgesic drug classes, including their relative efficacy for dental pain, and will suggest appropriate regimens based on pain intensity. Management of chronic pain will be addressed in the second part of this series.

BACKGROUND: There are no clear guidelines for how long a sterile operating-room tray can be exposed to the open environment before the contamination risk becomes unacceptable. The purpose of this study was to determine the time until first contamination and the rate of time-dependent contamination of sterile trays that had been opened in a controlled operating-room environment. We also examined the effect of operating-room traffic on the contamination rate. METHODS: Forty-five sterile trays were opened in a positive-air-flow operating room. The trays were randomly assigned to three groups. All trays were opened with use of sterile technique and were exposed for four hours. Culture specimens were obtained immediately after opening and every thirty minutes thereafter during the study period. Group 1 consisted of fifteen trays that were opened and left uncovered in a locked operating room (i.e., one with no traffic). Group 2 was identical to Group 1 with the addition of single-person traffic flowing in and out of the operating room from a nonsterile corridor every ten minutes. Group 3 included fifteen trays that were opened, immediately covered with a sterile surgical towel, and then left uncovered in a locked operating room (i.e., one with no traffic). RESULTS: Three of the thirty uncovered trays (one left in the operating room with traffic and two left in the room with no traffic) were found to be contaminated immediately after opening. After those three trays were eliminated, the contamination rates recorded for the twenty-seven uncovered trays were 4% (one tray) at thirty minutes, 15% (four) at one hour, 22% (six) at two hours, 26% (seven) at three hours, and 30% (eight) at four hours. There was no difference in survival time (p = 0.47) or contamination rate (p = 0.69) between the uncovered trays in the room with traffic and those in the room without traffic. The covered trays were not contaminated during the testing period. The survival time for those trays was significantly longer (p = 0.03) and the contamination rate was significantly lower (p = 0.02) than those for the uncovered trays. CONCLUSIONS: Culture positivity correlated directly with the duration of open exposure of the uncovered operating-room trays. Light traffic in the operating room appeared to have no impact on the contamination risk. Coverage of surgical trays with a sterile towel significantly reduced the contamination risk.

BACKGROUND: Retained surgical items (RSI) continue to occur. Large RSI studies are few due to low RSI frequency in single institutions and the medicolegal implications. Consequently, RSI risks are not fully defined, with discrepancies persisting among published studies. The goals of this study were to better define risk factors for RSI, to clarify previously discrepant risk factors, and to evaluate other potential contributors to RSI occurrence, such as trainee presence during an operation. STUDY DESIGN: Multicenter case-match study of RSI risk factors was conducted between January 2003 and December 2009. Cases complicated by RSI were identified at participating centers using clinical quality improvement and adverse event reporting data. Case match controls (non-RSI) were selected from same or similar-type cases performed at each respective institution. Retained surgical item risk factors were evaluated by univariate and multivariate conditional logistic regression. RESULTS: Fifty-nine RSIs and 118 matched controls were analyzed (RSI incidence 1 in 6,975 or 59 in 411,526). Retained surgical items occurred despite use of confirmatory x-rays (13 of 27 instances) and/or radiofrequency tagging (2 of 32 instances). Among previously discrepant results, we confirmed that body mass index, unexpected intraoperative events, and procedure duration were associated with increased RSI risk. The occurrence of any safety variance, and specifically an incorrect count at any time during the procedure, was associated with elevated RSI risk. Trainee presence was associated with 70% lower RSI risk compared with trainee absence. CONCLUSIONS: Longer duration of surgery, safety variances, and incorrect counts during the procedure result in elevated RSI risk. The possible positive influence of trainee presence on RSI risk deserves additional study. Our findings highlight the need for zero tolerance for safety omissions, continued study and development of novel approaches to RSI reduction, and establishing anonymous RSI reporting systems to better track both the incidence and risks associated with this problem, which has yet to be solved.

BACKGROUND AND PURPOSE: Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches. METHODS: A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care. RESULTS: A total of 442 consecutive patients of mean age 66 ± 14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008). CONCLUSIONS: Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

BACKGROUND: Fryns syndrome (FS) is the commonest autosomal recessive syndrome in which congenital diaphragmatic hernia (CDH) is a cardinal feature. It has been estimated that 10% of patients with CDH have FS. The autosomal recessive inheritance in FS contrasts with the sporadic inheritance for the majority of patients with CDH and renders the correct diagnosis critical for accurate genetic counselling. The cause of FS is unknown. METHODS: We have used array comparative genomic hybridisation (array CGH) to screen patients who have CDH and additional phenotypic anomalies consistent with FS for cryptic chromosome aberrations. RESULTS: We present three probands who were previously diagnosed with FS who had submicroscopic chromosome deletions detected by array CGH after normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving chromosome band 15q26.2 and one male had a deletion of chromosome band 8p23.1. CONCLUSIONS: We conclude that phenotypes similar to FS can be caused by submicroscopic chromosome deletions and that high resolution karyotyping, including array CGH if possible, should be performed prior to the diagnosis of FS to provide an accurate recurrence risk in patients with CDH and physical anomalies consistent with FS.

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118-29. ©2016 AACR.