A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair.

STUDY OBJECTIVE: To compare the efficacy and complication profile of oral midazolam therapy and continuous-flow 50% nitrous oxide in alleviating anxiety during laceration repair in children 2 to 6 years old. METHODS: We conducted a prospective, randomized clinical trial using 4 study groups who required laceration repair: (1) children who received standard care alone, which included comforting and topical anesthesia augmented with injected lidocaine if needed; (2) children who received standard care and oral midazolam; (3) children who received standard care and nitrous oxide; and (4) children who received standard care, oral midazolam, and nitrous oxide. Videotapes were blindly scored using the Observational Scale of Behavioral Distress-Revised (OSBD-R) to assess distress during baseline, wound cleaning, lidocaine injecting, suturing, and recovery. Adverse effects were noted during suturing and by parent questionnaires completed 24 hours after suturing and at suture removal. OSBD-R data were analyzed using repeated-measures analysis of variance. Adverse effect data were analyzed using categorical models. RESULTS: Two hundred four subjects were enrolled (midazolam plus nitrous oxide 52, midazolam 51, nitrous oxide 51, standard care 50; mean patient age was 4.1 years; 66% were boys). Mean OSBD-R scores were lower for groups that received nitrous oxide during wound cleaning by 2.2 points (95% confidence interval [CI] 1.1 to 3.2), lidocaine injecting by 2.5 points (95% CI 1.4 to 3.5), and suturing by 2.9 (95% CI 1.8 to 3.9). Adverse effects occurred more frequently, and recovery times were longer for groups that received midazolam. CONCLUSION: For facial suturing in 2- to 6-year-old children, regimens including continuous-flow nitrous oxide were more effective in reducing distress, and had fewer adverse effects and shorter recovery times than midazolam.

Nontraumatic atlantoaxial rotary subluxation in the pediatric otolaryngology patient. A report of four cases.

Nontraumatic atlantoaxial rotary subluxation (NAARS) is a relatively uncommon entity, with inconsistent presentations. It most commonly follows infectious processes or operative procedures. We present our experience with 4 pediatric otolaryngology patients with NAARS who were treated at the University of Iowa Hospitals and Clinics during a 2-year period beginning in 1997. A review of the symptoms, physical findings, and radiographic abnormalities is presented. Treatment options, varying from muscle relaxants to surgical fusion, are discussed. A high index of suspicion in evaluating children with a stiff neck or pain on attempted motion is essential in order to facilitate prompt diagnosis and appropriate intervention.

Parents' utilities for outcomes of occult bacteremia.

OBJECTIVE: To describe parents' values for outcomes of occult bacteremia using utility assessment, a quantitative method that incorporates risk preference. DESIGN: Computer-based utility assessment interview. SETTING: Urban children's hospital pediatric emergency department with 50 000 visits annually. PARTICIPANTS: Convenience sample of parents presenting with a child between 3 and 36 months. MAIN OUTCOME MEASURE: Parents' utility values for 8 outcomes from treatment of occult bacteremia: blood drawing, localized infection, hospitalization for antibiotics, meningitis with recovery, meningitis resulting in deafness, minor brain damage, severe brain damage, and death. RESULTS: Ninety-four subjects successfully completed the interview. Mean utilities were 0.9974 for blood drawing, 0.9941 for local infection, 0.9921 for hospitalization, 0.9768 for meningitis with recovery, 0.8611 for deafness, 0.7393 for minor brain damage, 0.3903 for severe brain damage, and 0.0177 for death. All values were significantly different from those that immediately preceded and succeeded (P<.0001), except for local infection vs hospitalization (P = .14). Median utilities for blood drawn, local infection, and hospitalization were 1. There were no significant differences among utilities of parents who presented with a febrile child (temperature > or =39 degrees C), or an afebrile child (temperature <39 degrees C). There were also no significant differences among utilities regardless of whether parents had children with prior experience with the outcomes. CONCLUSIONS: Assessment of utilities for outcomes of occult bacteremia yielded extremely high mean and median values for outcomes without permanent sequelae. This suggests that parents presenting to an emergency department may rationally prefer painful transient experiences, including venipuncture, for their children rather than risk even rare chances of severe outcomes.

Description of Missouri children who suffer burn injuries.

OBJECTIVE: This study uses Missouri's inpatient and outpatient E code data system to describe the demographic characteristics of Missouri children who suffered burn injuries during 1994 and 1995. METHODS: Retrospective review of Missouri E code data. RESULTS: Altogether 8,404 children aged 0-14 years were treated for burn injuries in Missouri hospitals during 1994 and 1995. The rate of burn injury in Missouri children was 339 per 100,000/year. African-American boys 0-4 years living in urban counties were at increased risk. In addition, African-American girls ages 0-4 years living in counties with a high poverty rate had raised burn injury rates. Burns from hot objects and scalds from hot liquids caused more than half of the burns. CONCLUSIONS: Hospital based E coding has proven an invaluable tool for the study of burns and will, no doubt, prove equally useful for other injuries.

Continuous-flow delivery of nitrous oxide and oxygen: a safe and cost-effective technique for inhalation analgesia and sedation of pediatric patients.

Nitrous oxide (N2O) safely and rapidly alleviates the pain and distress of minor procedures in the emergency department (ED). We have found self-administration in children does not consistently achieve acceptable analgesia and sedation. The equipment generally available for ED use is designed for adults and delivers 50% N2O through a demand valve that requires an inspiratory effort of -3 to -5 cm of water to activate gas flow. This is difficult for young children who are crying, have more shallow respirations than adults, or cannot follow instructions. In collaboration with the Departments of Anesthesiology, Dentistry, and Respiratory Therapy, we constructed a continuous-flow system for delivering N2O and oxygen (O2). The following is a description of the components, assembly, and use of a continuous-flow machine that safely and inexpensively delivers N2O and O2 to children.

A tool to organize instructions at discharge after treatment of asthmatic children in an emergency department.

Asthma exacerbations continue to be a major cause of visits to emergency departments (ED). Comprehensive care in the outpatient setting, with planning for early intervention for exacerbations, can reduce emergency visits. Thus, a major goal of ED intervention is to establish a link between the patient and the provider of ongoing asthma care, where complete education can be achieved and reinforced over time. When designing the Asthma 1-2-3 Plan discharge teaching tool for the ED, consideration was given to educational format, readability, patient population, and setting in which education was to be delivered. To evaluate use of the plan, ED records of patients enrolled in a separate asthma study, the Neighborhood Asthma Coalition (NAC), were audited for two 8-month intervals, May-December 1993 (before initiation of the plan) and May December 1994 (starting 1 month after completion of pilot testing on the plan in the ED). To evaluate effectiveness of the plan, records of physicians who cared for children in the NAC were evaluated. The database was reviewed for the date of the first visit for planned review of asthma that occurred after the acute asthma ED visit. After introduction of the plan, the proportion of children told to return to the physician for follow-up increased from 54% to 81%. The proportion of children given advice to return to their physician within the recommended 3 days or less increased from 11% to 54%. Chi2 Analyses showed that these changes were both statistically significant (p<0.0001). The plan was not effective in achieving increased follow-up visits for regular asthma care, in that 7% returned for follow-up within 7 days after an ED visit before the plan and only 6% returned for such a visit after the Plan. Successful initiation of a focused discharge teaching tool into the routine of the ED increased appropriate advice given at time of discharge from the ED. Although unsuccessful in increasing appropriate follow-up, the present intervention uses the ED not as a base for asthma education, but as a point for contacting patients in need of regular care and education, and for promoting access to that regular care.

Effect of intravenous substance P on laryngeal adductor activity in young dogs.

Reflex laryngeal adduction is a component of both the laryngeal chemoreflex and the esophagolaryngeal adductor reflex, two life-threatening reflexes that occur in immature animals. These two reflex responses are also thought to exist in infants and may play a role in causing life-threatening laryngospastic events and perhaps sudden infant death syndrome. Identifying neurotransmitters that mediate laryngeal adduction is important to understanding the mechanism of reflex laryngeal responses and to identifying potential means of pharmacologic prevention. Substance P (SP), a tachykinin, putatively functions as a sensory neurotransmitter and may play a role in mediating laryngeal reflexes. Substance P-immunoreactive-like fibers and receptors are present in the subepithelial tissues of the larynx, the vagus nerves, the nodose and jugular ganglia, and the vagal brain stem nuclei. In this investigation, the effect of SP infusion on laryngeal motor activity in an in vivo model is reported. Substance P was infused intravenously into 8 puppies (20 to 133 days of age, mean 81.2), on a mean of 3.0 occasions (range 1 to 6). Cardiovascular, respiratory, arterial blood gas, and cricothyroid (CT), thyroarytenoid (TA), and genioglossus electromyographic (EMG) responses to infusion of the tachykinin were recorded and subsequently analyzed. The SP infusion induced a marked increase in CT or TA EMG activity in 23 of 24 studies, and the increase was typically apparent within 60 seconds of the infusion. An increase in genioglossus EMG activity did not occur. An immediate, profound decrease in mean arterial pressure and an increase in respiratory rate and depth of chest wall excursion accompanied the laryngeal response. Arterial blood gas values remained unchanged (p > .05). The laryngeal adductor response to SP infusion was blocked when animals were pretreated with a systemic SP antagonist (Pfizer CP-96,345). This study demonstrates that peripheral infusion of the tachykinin SP induces a marked increase in laryngeal adductor activity. The response may be blocked by pretreatment of animals with a systemic SP antagonist. Because SP is thought to act primarily as a sensory neurotransmitter, these findings may be important in understanding the mechanism of reflex laryngeal adductor responses.

Priorities for research in emergency medical services for children: results of a consensus conference.

STUDY OBJECTIVE: To arrive at a consensus on the priorities for future research in emergency medical services for children. METHODS: A consensus group was convened using the Rand-UCLA Consensus Process. The group took part in a 3-phase process. Round 1 involved reviewing a compendium of relevant research articles and answering a mailed questionnaire. Panel members were asked to prioritize topics on the basis of the 1993 Institute of Medicine Report on Emergency Medical Services for Children. Participants were asked to rate each topic based on the significance of the research, and whether the topic would (1) improve general knowledge, (2) change behavior, (3) improve health, (4) decrease the cost of care, or (5) change public policy. A 4-point Likert scale was used. Participants were also asked if the research would require a multicenter study and if the research were feasible. Round 2 of the study involved a meeting of the panel, where the results of Round 1 were discussed and the topics were reprioritized. The topics were given a rank order and a final ranking was done in Round 3. RESULTS: The panel considered a list of 32 topics; these were combined and reworded to give them more precise meaning. Several new topics were also added. Fifteen topics were given a rank order and placed within the 7 broad categories of the Institute of Medicine report. Clinical aspects of emergency care, systems organization, configuration, and operation and injury prevention were given high priority rankings. The first 5 topics were very close in point-rank order. CONCLUSION: The panel was able to develop a list of important topics for future research in emergency medical services for children that can be used by foundations, governmental agencies, and others in setting a research agenda for such services.

Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic emergencies.

OBJECTIVE: Emergency management of pediatric fractures and dislocations requires effective analgesia, yet children's pain is often undertreated. We compared the safety and efficacy of fentanyl- versus ketamine- based protocols. METHODOLOGY: Patients 5 to 15 years of age needing emergency fracture or joint reduction (FR) were randomized to receive intravenous midazolam plus either fentanyl (F/M) or ketamine (K/M). Measures of efficacy were observational distress scores and self- and parental-report. Measures of safety were frequency of abnormalities in and need for support of cardiopulmonary function and other adverse effects. RESULTS: During FR, K/M subjects (n = 130) had lower distress scores and parental ratings of pain and anxiety than did F/M subjects (n = 130). Although both regimens equally facilitated reductions, deep sedation, and procedural amnesia, orthopedists favored K/M. Recovery was 14 minutes longer for K/M. Fewer K/M subjects had hypoxia (6% vs 25%), needed breathing cues (1% vs 12%), or required oxygen (10% vs 20%) than did F/M subjects. Two K/M subjects required assisted ventilation briefly. More K/M subjects vomited. Adverse emergence reactions were rare but equivalent between regimens. CONCLUSIONS: During emergency pediatric orthopedic procedures, K/M is more effective than F/M for pain and anxiety relief. Respiratory complications occurred less frequently with K/M, but respiratory support may be needed with either regimen. Both regimens facilitate reduction, produce amnesia, and rarely cause emergence delirium. Vomiting is more frequent and recovery more prolonged with K/M.

Role of substance P in the laryngeal chemoreflex.

The laryngeal chemoreflex (LCR) is a potentially life-threatening reflex that is elicited in immature animals by the topical application of water to the laryngeal mucosa. The reflex response is characterized by immediate apnea and laryngeal adduction and delayed cardiovascular instability. The cardiorespiratory changes of the LCR may be life-threatening, particularly in very immature animals such as piglets under 2 weeks of age. The afferent and efferent limbs of the LCR are mediated through the vagus nerve, but the neuromediators responsible for the reflex changes have not yet been clearly elucidated. Previous agonist and antagonist studies in immature dogs demonstrated that substance P, a sensory tachykinin, mediates the life-threatening esophagolaryngeal adductor reflex elicited by distal esophageal sensory nerve stimulation. This study was conducted to determine if substance P also plays a role in mediating the LCR. The LCR response was compared before and after treatment with intravenous substance P antagonist (Pfizer CP-96,345-1) in eight piglets (mean 27.7 days of age). The laryngeal and cardiovascular responses of the animals following intravenous administration of the tachykinins substance P, neurokinin A, and neurokinin B were also assessed. Pretreatment with substance P antagonist did not alter the LCR's duration of apnea (p > .10), laryngeal adductor response, or early change in mean arterial pressure (p > .10), although the early maximal heart rate response was significantly altered (p < .01). Intravenous substance P, neurokinin A, and neurokinin B did not reproduce the laryngeal respiratory response of the LCR. We conclude that substance P, neurokinin A, and neurokinin B are not key neurotransmitters of the LCR.

Predictors of occult pneumococcal bacteremia in young febrile children.

STUDY OBJECTIVE: Occult pneumococcal bacteremia (OPB) occurs in 2.5% to 3% of highly febrile children 3 to 36 months of age, and 10% to 25% of untreated patients with OPB experience complications, including 3% to 6% in whom meningitis develops. The purpose of this study was to identify predictors of OPB among a large cohort of young, febrile children treated as outpatients using multivariable statistical methods. METHODS: We derived and validated a logistic regression model for the prediction of OPB. We evaluated 6,579 outpatients 3 to 36 months of age with temperatures of 39 degrees C or higher who previously had been enrolled in a study of young febrile patients at risk of OPB in the emergency departments of 10 hospitals in the United States between 1987 and 1991; 164 patients (2.5%) had OPB. We randomly selected two thirds of this population for the derivation of the model and one third for validation. In the derivation set, we analyzed the univariate relationships of six variables with OPB: age, temperature, clinical score, WBC count, absolute neutrophil count (ANC), and absolute band count (ABC). All six variables were then entered into a logistic regression equation and those retaining statistical significance were considered to have an independent association with OPB. RESULTS: Patients with OPB were younger, more frequently ill-appearing, and had higher temperatures, WBC, ANC, and ABC than patients without bacteremia. Only three variables, however, retained statistically significant associations with OPB in the multivariate analysis: ANC (Adjusted odds ratio [OR] 1.15 for each 1,000 cells/mm3 increase, 95% confidence interval [CI] 1.06, 1.25), temperature (adjusted OR 1.77 for each 1 degree C increase, 95% CI 1.21, 2.58), and age younger than 2 years (adjusted OR 2.43 versus patients 2 to 3 years old, 95% CI interval 1.11, 5.34). In the derivation set, 8.1% of patients with ANCs greater than or equal to 10,000 cell/mm3 had OPB (95% CI 6.3, 10.1%) versus .8% of patients with ANCs less than 10,000 cells/mm3 (95% CI .5, 1.2%). When tested on the validation set, the model performed similarly. CONCLUSION: Independent predictors of OPB in children 3 to 36 months of age with temperatures of 39 degrees C or higher treated as outpatients include ANC, temperature, and age younger than 2 years. These predictors may be used to develop clinical strategies to limit laboratory testing and antibiotic administration to those children at greatest risk of OPB.

Comparison of concentric needle versus hooked-wire electrodes in the canine larynx.

BACKGROUND: The use of a specific electrode type in laryngeal electromyography has not been standardized. Laryngeal electromyography is usually performed with hooked-wire electrodes or concentric needle electrodes. Hooked-wire electrodes have the advantage of allowing laryngeal movement with ease and comfort, whereas the concentric needle electrodes have benefits from a technical aspect and may be advanced, withdrawn, or redirected during attempts to appropriately place the electrode. OBJECTIVES: This study examines whether hooked-wire electrodes permit more stable recordings than standard concentric needle electrodes at rest and after large-scale movements of the larynx and surrounding structures. A histologic comparison of tissue injury resulting from placement and removal of the two electrode types is also made by evaluation of the vocal folds. METHODS: Electrodes were percutaneously placed into the thyroarytenoid muscles of 10 adult canines. Amplitude of electromyographic activity was measured and compared during vagal stimulation before and after large-scale laryngeal movements. Signal consistency over time was examined. Animals were killed and vocal fold injury was graded and compared histologically. RESULTS: Waveform morphology did not consistently differ between electrode types. The variability of electromyographic amplitude was greater for the hooked-wire electrode (p < 0.05), whereas the mean amplitude measures before and after large-scale laryngeal movements did not differ (p > 0.05). Inflammatory responses and hematoma formation were also similar. CONCLUSIONS: Waveform morphology of electromyographic signals registered from both electrode types show similar complex action potentials. There is no difference between the hooked-wire electrode and the concentric needle electrode in terms of electrode stability or vocal fold injury in the thyroarytenoid muscle after large-scale laryngeal movements.

Diagnostic testing for acute head injury in children: when are head computed tomography and skull radiographs indicated?

OBJECTIVE: Despite the frequent occurrence of head injury in children, there is no agreement about clinical screening criteria that indicate the need for imaging studies. This study was undertaken to provide information relevant to the choice of imaging modalities in children with acute head trauma. METHODOLOGY: A prospective cohort of 322 children seeking care consecutively in an urban pediatric emergency department for nontrivial head injury was assembled. Skull radiographs, head computed tomography, and data forms including mechanism of injury, symptoms, and physical findings were completed for each child. RESULTS: Intracranial injury occurred in 27 children (8%), whereas 50 (16%) had skull fractures. Of those with intracranial injury, 16 (59%) had normal mental status and no focal abnormalities, and 1 of those 16 required surgery for evacuation of an epidural hematoma. Six (38%) of the 16 were younger than 1 year, 5 of whom had scalp contusion or hematoma without other symptoms. Findings not significantly associated with intracranial injury were scalp contusion, laceration, hematoma, abrasion, headache, vomiting, seizure, drowsiness, amnesia, and loss of consciousness for less than 5 minutes. Findings associated with intracranial injury were skull fracture, signs of a basilar skull fracture, loss of consciousness for more than 5 minutes, altered mental status, and focal neurologic abnormality. CONCLUSIONS: Intracranial injury may occur with few or subtle signs and symptoms, especially in infants younger than 1 year. The relative risk for intracranial injury is increased almost fourfold in the presence of a skull fracture, although the absence of a skull fracture does not rule out intracranial injury. The significance of nonsurgical intracranial injury in neurologically normal children needs further study.

Case report of metallic mercury injury.

OBJECTIVE: Injury and poisoning from metallic mercury has become a rare event. Review of the literature and a case report of pediatric metallic mercury injury are presented. DESIGN: A case report. SETTING: The Emergency Department at St. Louis Children's Hospital. PATIENTS OR PARTICIPANTS: A 15-year-old boy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: The 15-year-old boy fell on a broken mercury thermometer. A subcutaneous abscess formed on his left forearm during the next five days. He had no signs or symptoms of mercury toxicity. His wound was debrided in the operating room and healed completely after several months. CONCLUSIONS: This case shows elemental mercury from a thermometer as a potential, if unusual, source of mercury toxicity.

Playground injuries in children.

Childhood injuries are a major source of morbidity and mortality in industrialized countries, and many injuries occur on playgrounds. Our purpose was to examine childhood playground injuries in a metropolitan center in Canada. All children injured on playground equipment who were seen in the emergency department (ED) at The Hospital for Sick Children between March 1990 and July 1991 and were entered in the Children's Hospital Injury Research and Prevention Project (CHIRPP) database were included. The type, body part, and mechanism of injury were determined as well as the type of equipment, location, and surface. Among the 289 children injured on playground equipment, the mean age was 5.9 years with 39% < 5 years (range: 1 to 18 years). The most common injuries included fractures (28%), lacerations (24%), and hematomas (14%). The head and neck were injured 43% of the time, the upper extremity 41%, lower extremity 10%, and the trunk 6%. Climbing apparatus injuries occurred in 29% of children < 5 years compared with 47% of those injured who were > or = 5 years (P = 0.002). Injuries related to slides occurred in 40% of children < 5 years compared to 26% of children > or = 5 years (P = 0.033). Of children < 5 years, 58% had head and neck injuries compared to 32% of children > or = 5 years (P = 0.0006). Of children < 5 years, 28% had upper extremity injuries compared to 49% of children > or = 5 years (P = 0.0005). There were no fatalities and the overall hospitalization rate was 18%. Of those children hospitalized, 77% had fractures, compared to 16% of those not hospitalized (P = 0.00001). Of all children hospitalized, 62% were injured on climbing apparatus, compared to 37% of those not hospitalized (P = 0.0004). There were no significant differences between nonprotective and natural protective surfaces with respect to hospitalization. We conclude that: 1) upper extremity injuries, especially fractures, accounted for the majority of hospitalizations resulting from injuries on playground equipment; 2) climbing apparatus-related injuries accounted for nearly two thirds of hospitalizations; 3) older children sustained more injuries on climbing apparatus, where younger children sustained more injuries on slides; and 4) younger children sustained more head injuries on playground equipment than older children, but most of these were minor.

Cervical spine injuries in children.

While cervical spine injuries are unusual in children, when they occur they frequently cause death or life-long disability. The primary care practitioner should be familiar with the signs and symptoms of cervical spine injuries, know the proper techniques of initial management, and engage in anticipatory guidance to prevent these injuries.

Conscious sedation for pediatric orthopaedic emergencies.

The objective of this study was to assess complications and risk factors among children undergoing conscious sedation (CS) with fentanyl (F) and midazolam (M) for reduction of fractures and dislocations. A 22-month retrospective review was made of an urban pediatric emergency department's records after implementing a CS protocol for the administration of F/M. Data collection was facilitated by standard CS forms, and data were analyzed using descriptive statistics, chi 2 analysis, Fisher's exact test, t test, odds ratio, and logistic regression. A total of 339 children (65% boys), mean age of 8.4 years, were enrolled in the study. The mean time to sedation was 11.3 +/- 6.2 minutes and to discharge was 92 +/- 36.3 minutes. The mean total doses of M and F were 0.17 +/- 0.08 mg/kg and 1.5 +/- 0.8 micrograms/kg, respectively. An alteration in respiratory status occurred in 37 (11.0%) patients: 28 (8.3%) had oxygen saturation < 90%; 16 (4.7%) received oxygen; 12 (3.6%) were given verbal breathing reminders, eight (2.4%) received airway positioning maneuvers, and 2 (0.6%) received naloxone. Four patients (1.2%) vomited. None required assisted ventilation, intubation, or admission resulting from complications of CS. Characteristics associated with the respiratory events included female sex (odds ratio = 2.2) and deep sedation (odds ratio = 2.7). We conclude that complications associated with F/M administered by protocol were few, minor, and easily managed. Patients who are female or who enter a state of deep sedation may be at modestly increased risk for alterations in respiratory status. Careful attention to monitoring vital functions on all patients is necessary to provide safe CS.

Intraperitoneal rupture of an infected urachal cyst: a rare cause of peritonitis in children.

Intraperitoneal rupture of an infected urachal cyst is a rare cause of peritonitis in children, and has previously been reported in four children. We report this condition in a 34-month-old toddler who presented with a two-week history of abdominal pain and four days of infraumbilical swelling and erythema. Abdominal ultrasonography (US) and computerized tomography (CT) scan with contrast were helpful in the preoperative evaluation, showing an inflammatory process involving the anterior abdominal wall. The child was treated with intravenous antibiotics, and the infected urachal cyst, other parts of the urachal remnant, and a small portion of the dome of the bladder were excised. The postoperative hospital course was uncomplicated. Because of its rarity and variable manifestations, prompt diagnosis depends on maintaining a high index of suspicion. This diagnosis should be entertained in children with peritonitis in association with umbilical and midline abdominal abnormalities.