Increasing number and shifting demographics of adolescent opioid use disorder presentations to the emergency department.

INTRODUCTION: Opioid use has been increasing in adolescents; however, lacking are data describing sex, ethnicity, and age groups most affected. We identified and characterized the trend in the adolescent population who presented to the emergency departments (ED) of a large hospital system. METHODS: We obtained data directly from the electronic medical record for patients aged 12-21 years from January 2014 to December 2022. We identified opioid-related visits by primary diagnosis. Trends were compared amongst age groups and by sex and reported ethnicity. RESULTS: Opioid-related presentations increased in all age groups and were significantly increased in adolescents aged 13-17 years compared to patients aged 18-21 years (1700% [range: 1000-3300%] v 400% [200-800%]; p = 0.02). Adolescents presenting to the ED with opioid-related primary diagnoses were more likely to be Hispanic and male in our region. DISCUSSION: Over the last two years (2021-22) there was a significant increase in opioid-related presentations to our hospital system amongst adolescents and an acceleration post-COVID. In 2022, emergency department presentations shifted to younger teenagers and from white young adults to Hispanic adolescents. The increased number of cases posed management problems in the ED given the lack of outpatient treatment options. CONCLUSION: Opioid-related ED presentations are increasing in adolescents with post-COVID increases in male, Hispanic, and younger patients in our region. Pathways for outpatient treatment need to be developed for adolescents with OUD.

Expediting Treatment of Trauma Patients in the Emergency Department: Rapid Trauma Evaluation (RTE).

BACKGROUND: Criteria for trauma determination evolves. We developed/evaluated a Rapid Trauma Evaluation (RTE) process for a trauma patient subset not meeting preestablished trauma criteria. METHODS: Retrospective study (July 2019 - May 2020) for patients either > 65 years with ground level fall within 24 hours or in a motorcycle collision (MCC) arriving by EMS not meeting ACS trauma-criteria. RTE process was immediate evaluation by nurse/EMT, room placement, physician notification, undressing/gowning, vital signs, head-to-toe assessment, upgrade trauma status. Number/type of admissions, discharges, trauma upgrades, LOS obtained via trauma-registry and chart-review. For comparison, historic controls (HC) were used [all patients meeting RTE criteria seen in the ED prior to RTE (Apr- June 2019)]. RESULTS: The RTE cohort (n=755) was 77% falls,23% MCCs, median age 82 [IQR 74-88] years; 42% male-Among falls, 3.2% required a modified-upgrade; 0.7% full-upgrade, 55% admitted [29.4% trauma). HC (n=575) was 92.3% falls, 7.7% MCCs, median age 81 (IQR: 67-88) years, 40.5% males-57.4% admitted (22% trauma). RTE MCC median age 42 (IQR:30-49) years, 84.4% male- 21.9% were upgraded [(6 modified-trauma; 1 full-trauma; 43.8% admitted (85.7% trauma)]. HC MCC median age 29 (IQR: 23-41) years, 95.5% male, 54.5% admitted (75% trauma]. No difference on demographics, admissions or discharges between groups (P>0.05) except HC MCC was younger (P<0.005). RTE median LOS was shorter than HC [203 (IQR: 147-278) minutes vs. 286 (IQR: 205-392) minutes, P<0.001]. CONCLUSIONS: Patients > 65 years with a ground level fall or in a MCC arriving via EMS not meeting ACS trauma criteria may benefit from RTE.

Improper defibrillator pad usage by emergency medical care providers for children: an opportunity for reeducation.

PURPOSE: Approximately 14 000 pediatric out-of-hospital arrests occur annually. With this significant number and the diversity in the training backgrounds of medical providers, correct choice and placement of defibrillator pads are imperative to ensure maximum efficacy. METHODS: One hundred fifty-two emergency medical care providers from 6 medical fields were recruited for the study. Each participant answered a series of questions to ascertain baseline knowledge of correct defibrillator pad choice and placement in 2 scenarios with mannequins weighted less than 15 kg and more than 15kg. After the testing, each participant received an educational intervention. Six months after the first phase, participants received a questionnaire to ascertain knowledge retention. RESULTS: In the primary study phase, for correct pad choice for mannequins weighing less than 15 kg and more than 15 kg, overall results were 98% (95% confidence interval [CI], 94.1%-100%) and 38.8% (95% CI, 31.4%-46.8%), respectively. In the second phase, pad choices for mannequins weighing less than 15 kg and more than 15 kg were 77.3% (95% CI, 68.6%-84.2%) and 60% (95% CI, 47.7%-71.1%). The rates of correct pad placement during the initial phase for mannequins weighing less than 15 kg and more than 15 kg were 5.8% (95% CI, 2.8%-11.2%) and 25.7%, respectively (95% CI, 19.4%-35.7%). Rates for correct pad placement (<15-kg and >15-kg mannequins) improved in the second phase to 68.2% (95% CI, 56%-78.4%) and 71.2% (95% CI, 62.8%-81.5%). CONCLUSION: Pediatric emergency providers have poor understanding of pad choice and placement. Emergency medical care providers for children who are educated about the correct defibrillator pad choices and placement have improved knowledge and can retain that knowledge for at least 6months.

Capnometry as a predictor of admission in bronchiolitis.

OBJECTIVES: Bronchiolitis is a dynamic condition, and predicting clinical deterioration can be difficult. The objective of this study was to determine whether capnometry readings among bronchiolitic children admitted to the hospital are significantly different from those discharged from the emergency department. METHODS: We prospectively studied a convenience sample of children younger than 24 months with clinical bronchiolitis. A single end-tidal CO2 (ETCO2) reading was taken before treatment, and a clinical work of breathing score was assigned to each patient. Treating physicians and nurses were blinded to capnometry readings. The decision to admit was based on the judgment of the attending physician. Descriptive statistics and appropriate hypothesis testing were performed. A receiver operating characteristic curve was constructed for the association between admission and capnometry readings. The α was set at 0.05 for all comparisons. RESULTS: One hundred five children with bronchiolitis were included for study. Capnometry readings for admitted (mean, 32.6 mm Hg; 95% confidence interval [CI], 30.3-34.9 mm Hg) and discharged (mean 31.4 mm Hg; 95% CI 29.8-33.0 mm Hg) bronchiolitic children were not significantly different. Capnometry readings for low (mean, 31.7 mm Hg; 95% CI, 29.5-33.8 mm Hg), intermediate (mean, 32.1 mm Hg; 95% CI, 30.1-34.1 mm Hg), and high (mean, 30.5 mm Hg; 95% CI, 19.3-41.7 mm Hg) work of breathing (score) ranges were not significantly different. CONCLUSIONS: Capnometry readings are not useful in predicting admission for children younger than 2 years with clinical bronchiolitis. There are no significant differences in capnometry readings among bronchiolitic children with low, medium, and high work of breathing scores.

Clinical policy: Critical issues in the evaluation and management of emergency department patients with suspected appendicitis.

This clinical policy from the American College of Emergency Physicians is an update of a 2000 clinical policy on the evaluation and management of patients presenting with nontraumatic acute abdominal pain.1 A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1)Can clinical findings be used to guide decision making in the risk stratification of patients with possible appendicitis? (2) In adult patients with suspected acute appendicitis who are undergoing a computed tomography scan, what is the role of contrast? (3) In children with suspected acute appendicitis who undergo diagnostic imaging, what are the roles of computed tomography and ultrasound in diagnosing acute appendicitis?Evidence was graded and recommendations were given based on the strength of the available data in the medical literature.

Sternal tuberculosis.

Tuberculosis is a public health problem worldwide. Between 19% and 43% of the world's population is infected with Mycobacterium tuberculosis. Tubercular sternal osteomyelitis is a rare manifestation of tuberculosis. Tuberculous sternal osteomyelitis manifests with fever, weight loss, and chest wall lesions. Computed tomography (CT) scan defines the extent of the thoracic extension, and standard microbiologic methods diagnose this entity. Four-drug anti-tuberculous therapy is effective. The authors report a case of tuberculous osteomyelitis of the sternum not associated with pulmonary tuberculosis.

Bioterrorism-related inhalational anthrax: can extrapolated adult guidelines be applied to a pediatric population?

OBJECTIVE: Since the 2001 anthrax attacks, an extensive body of literature has evolved, but there has been a limited focus on the management of pediatric-specific issues. We looked at the symptom complexes of all pediatric patients presenting to the emergency department of our hospital during this period and examined whether their presentations would likely allow current guidelines to be used as potential screening criteria to identify children infected with anthrax. METHODS: We retrospectively reviewed emergency department records of all adult and pediatric patients (up to the age of 21 years) at Inova Fairfax Hospital during this time, when a large, and at the time ill-defined, group in the Washington, DC, metropolitan area was at risk for pulmonary anthrax. Two cases of anthrax infection were identified at this hospital in exposed adult postal workers. Screening algorithms (described by Mayer et al. and Hupert et al.) were applied to adult and pediatric patients with the presence of fever (38 degrees C), tachycardia, or other symptoms compatible with pulmonary anthrax. Specifically, the usefulness of these guidelines as potential screening tools to identify possibly infected children was examined. RESULTS: Of 767 pediatric patients seen in the emergency department during the study period, 312 met criteria for review (41%; 95% CI: 37-44%). Four adult patients (0.4%; 95% CI: 0.1-0.9%) had at least five clinical symptoms, fever, and tachycardia; two of them had inhalational anthrax. No pediatric patient presented with five or more clinical symptoms. Twelve children (3.9%; 95% CI: 2-6.6%) presented with four clinical symptoms; five of the 12 had neither fever nor tachycardia. Children, particularly infants and toddlers, presented with nonspecific symptom complexes primarily limited to fever, vomiting, cough, and trouble breathing. CONCLUSIONS: Existing guidelines are likely to be unreliable as a screening tool for inhalational anthrax in children, largely because of the children's inability to adequately communicate a suggestive symptom complex.

A Novel Specialty-Specific, Collaborative Faculty Development Opportunity in Education Research: Program Evaluation at Five Years.

PURPOSE: For the busy clinician-educator, accessing opportunities that develop the skills and knowledge necessary to perform education research can be problematic. The Medical Education Research Certification at Council of Emergency Medicine Residency Directors (MERC at CORD) Scholars' Program is a potential alternative. The current study evaluates the program's outcomes after five years. METHOD: The authors employed a quasi-experimental design in this study. The study population consisted of the initial five MERC at CORD cohorts (2009-2013). Development of a logic model informed Kirkpatrick-level outcomes. Data from annual pre/post surveys, an alumni survey (2014), and tracking of national presentations/peer-reviewed publications resulting from program projects served as outcome measurements. RESULTS: Over the first five years, 149 physicians participated in the program; 97 have completed six MERC workshops, and 63 have authored a national presentation and 30 a peer-reviewed publication based on program projects. Of the 79 participants responding to the pre- and postsurveys from the 2011-2013 cohorts, 65 (82%) reported significant improvement in skills and knowledge related to education research and would recommend the program. Of the 61 graduates completing the alumni survey, 58 (95%) indicated their new knowledge was instrumental beyond educational research, including promotion to new leadership positions, and 28 (47% of the 60 responding) reported initiating a subsequent multi-institutional education study. Of these, 57% (16/28) collaborated with one or more peers/mentors from their original program project. CONCLUSIONS: Kirkpatrick-level outcomes 1, 2, 3, and perhaps 4 demonstrate that the MERC at CORD program is successful in its intended purpose.

Screening for inhalational anthrax due to bioterrorism: evaluating proposed screening protocols.

Eleven known cases of bioterrorism-related inhalational anthrax (IA) were treated in the United States during 2001. We retrospectively compared 2 methods that have been proposed to screen for IA. The 2 screening protocols for IA were applied to the emergency department charts of patients who presented with possible signs or symptoms of IA at Inova Fairfax Hospital (Falls Church, Virginia) from 20 October 2001 through 3 November 2001. The Mayer criteria would have screened 4 patients (0.4%; 95% CI, 0.1%-0.9%) and generated charges of 1900 dollars. If 29 patients (2.6%; 95% CI, 1.7%-3.7%) with >or=5 symptoms (but without fever and tachycardia) were screened, charges were 13,325 dollars. The Hupert criteria would have screened 273 patients (24%; 95% CI, 22%-27%) and generated charges of 126,025 dollars. In this outbreak of bioterrorism-related IA, applying the Mayer criteria would have identified both patients with IA and would have generated fewer charges than applying the Hupert criteria.

Are one or two dangerous? Clonidine and topical imidazolines exposure in toddlers.

Clonidine and the imidazolines, commonly found in topical ophthalmic and nasal decongestants, are chemically related drugs that have been responsible for many pediatric poisonings. These medications can cause significant morbidity in small doses. A review of the available literature reveals that young children have exhibited severe signs and symptoms after ingesting as little as one to two clonidine tablets or 2.5 ml of a topical imidazoline product. Central nervous system depression, respiratory depression, and cardiovascular instability are the most common features of poisoning. Signs and symptoms develop rapidly, within 4-6 h. Care is supportive. Death is rare, but many poisoned patients require monitoring in an intensive care setting.

Council of Emergency Medicine Residency Directors' standardized letter of recommendation: the program director's perspective.

OBJECTIVES: The standardized letter of evaluation (SLOE) was created in 1997 to provide residency program directors (PDs) with a summative evaluation that incorporates normative grading (i.e., comparisons to peers applying to emergency medicine [EM] training). Although the standard letter of recommendation (SLOR) has become increasingly popular and important in decision-making, it has not been studied in the past 12 years. To assess the SLOR's effectiveness and limitations, the perspective of EM PDs was surveyed in this study. METHODS: After validation of the questionnaire by 10 retired PDs, the survey was sent to the PD of each of the 159 EM residencies that existed at that time. The survey was circulated via the Council of Emergency Medicine Residency Directors' (CORD) listserv from January 24, 2013, to February 13, 2013. Weekly e-mail reminders to all PDs served to increase participation. RESULTS: A total of 150 of 159 PDs (94.3%) completed the questionnaire. Nearly all respondents (149 of 150; 99.3%) agreed that the SLOR is an important evaluative tool and should continue to be used. In the application process, 91 of 150 (60.7%) programs require one or more SLORs, and an additional 55 (36.7%) recommend but do not require a SLOR to be considered for interview. When asked to identify the top three factors in deciding who should be interviewed, the SLOR was ranked first (139 of 150; 92.7%), with EM rotation grades ranked second (73 of 150; 48.7%). The factors that were most often identified as the top three that diminish the value of the SLOR in order were 1) "inflated evaluations" (121 of 146; 82.9%), 2) "inconsistency between comments and grades" (106 of 146; 72.6%), and 3) "inadequate perspective on candidate attributes in the written comments" and "inexperienced authors" (60 of 146; 41.1% each). CONCLUSIONS: The SLOR appears to be the most important tool in the EM PD's armamentarium for determining which candidates should be interviewed for residency training. Although valuable, the SLOR's potential utility is hampered by a number of factors, the most important of which is inflated evaluations. Focused changes in the SLOR template should be mindful that it appears, in general, to be successful in its intended purpose.

Are pediatric concussion patients compliant with discharge instructions?

BACKGROUND: Concussions are commonly diagnosed in pediatric patients presenting to the emergency department (ED). The primary objective of this study was to evaluate compliance with ED discharge instructions for concussion management. METHODS: A prospective cohort study was conducted from November 2011 to November 2012 in a pediatric ED at a regional Level 1 trauma center, serving 35,000 pediatric patients per year. Subjects were aged 8 years to 17 years and were discharged from the ED with a diagnosis of concussion. Exclusion criteria included recent (past 3 months) diagnosis of head injury, hospital admission, intracranial injury, skull fracture, suspected nonaccidental trauma, or preexisting neurologic condition. Subjects were administered a baseline survey in the ED and were given standardized discharge instructions for concussion by the treating physician. Telephone follow-up surveys were conducted at 2 weeks and 4 weeks after ED visit. RESULTS: A total of 150 patients were enrolled. The majority (67%) of concussions were sports related. Among sports-related concussions, soccer (30%), football (11%), lacrosse (8%), and basketball (8%) injuries were most common. More than one third (39%) reported return to play (RTP) on the day of the injury. Physician follow-up was equivalent for sport and nonsport concussions (2 weeks, 58%; 4 weeks, 64%). Sports-related concussion patients were more likely to follow up with a trainer (2 weeks, 25% vs. 10%, p = 0.06; 4 weeks, 29% vs. 8%, p < 0.01). Of the patients who did RTP or normal activities at 2 weeks (44%), more than one third (35%) were symptomatic, and most (58%) did not receive medical clearance. Of the patients who had returned to activities at 4 weeks (64%), less than one quarter (23%) were symptomatic, and most (54%) received medical clearance. CONCLUSION: Pediatric patients discharged from the ED are mostly compliant with concussion instructions. However, a significant number of patients RTP on the day of injury, while experiencing symptoms or without medical clearance. LEVEL OF EVIDENCE: Care management, level IV. Epidemiologic study, level III.

Characterization of the Council of Emergency Medicine Residency Directors' standardized letter of recommendation in 2011-2012.

OBJECTIVES: The Council of Emergency Medicine Residency Directors (CORD) introduced the standardized letter of recommendation (SLOR) in 1997, and it has become a critical tool for assessing candidates for emergency medicine (EM) training. It has not itself been evaluated since the initial studies associated with its introduction. This study characterizes current SLOR use to evaluate whether it serves its intended purpose of being standardized, concise, and discriminating. METHODS: This retrospective, multi-institutional study evaluated letters of recommendation from U.S. allopathic applicants to three EM training programs during the 2011-2012 Electronic Residency Application Service (ERAS) application cycle. Distributions of responses to each question on the SLOR were calculated, and the free-text responses were analyzed. Two pilots, performed on five applicants each, assisted in developing a strategy for limiting interrater reliability. RESULTS: Each of the three geographically diverse programs provided a complete list of U.S. allopathic applicants to their program. Upon randomization, each program received a list of coded applicants unique to their program randomly selected for data collection. The number of applicants was selected to reach a goal of approximately 200 SLORs per site (n = 602). Among this group, comprising 278 of 1,498 applicants (18.6%) from U.S. allopathic schools, a total of 1,037 letters of recommendation were written, with 724 (69.8%) written by emergency physicians. SLORs represented 57.9% (602/1037) of all LORs (by any kind of author) and 83.1% (602/724) of letters written by emergency physicians. Three hundred ninety-two of 602 SLORs had a single author (65.1%). For the question on "global assessment," students were scored in the top 10% in 234 of 583 of applications (40.1%; question not answered by some), and 485 of 583 (83.2%) of the applicants were ranked above the level of their peers. Similarly, >95% of all applicants were ranked in the top third compared to peers, for all but one section under "qualifications for emergency medicine." For 405 of 602 of all SLORs (67.2%), one or more questions were left unanswered, while 76 of all SLORs (12.6%) were "customized" or changed from the standard template. Finally, in 291 of 599 of SLORs (48.6%), the word count was greater than the recommended maximum of 200 words. CONCLUSIONS: Grade inflation is marked throughout the SLOR, limiting its ability to be discriminating. Furthermore, template customization and skipped questions work against the intention to standardize the SLOR. Finally, it is not uncommon for comments to be longer than guideline recommendations. As an assessment tool, the SLOR could be more discerning, concise, and standardized to serve its intended purpose.

Factors that influence medical student selection of an emergency medicine residency program: implications for training programs.

OBJECTIVES: An understanding of student decision-making when selecting an emergency medicine (EM) training program is essential for program directors as they enter interview season. To build upon preexisting knowledge, a survey was created to identify and prioritize the factors influencing candidate decision-making of U.S. medical graduates. METHODS: This was a cross-sectional, multi-institutional study that anonymously surveyed U.S. allopathic applicants to EM training programs. It took place in the 3-week period between the 2011 National Residency Matching Program (NRMP) rank list submission deadline and the announcement of match results. RESULTS: Of 1,525 invitations to participate, 870 candidates (57%) completed the survey. Overall, 96% of respondents stated that both geographic location and individual program characteristics were important to decision-making, with approximately equal numbers favoring location when compared to those who favored program characteristics. The most important factors in this regard were preference for a particular geographic location (74.9%, 95% confidence interval [CI] = 72% to 78%) and to be close to spouse, significant other, or family (59.7%, 95% CI = 56% to 63%). Factors pertaining to geographic location tend to be out of the control of the program leadership. The most important program factors include the interview experience (48.9%, 95% CI = 46% to 52%), personal experience with the residents (48.5%, 95% CI = 45% to 52%), and academic reputation (44.9%, 95% CI = 42% to 48%). Unlike location, individual program factors are often either directly or somewhat under the control of the program leadership. Several other factors were ranked as the most important factor a disproportionate number of times, including a rotation in that emergency department (ED), orientation (academic vs. community), and duration of training (3-year vs. 4-year programs). For a subset of applicants, these factors had particular importance in overall decision-making. CONCLUSIONS: The vast majority of applicants to EM residency programs employed a balance of geographic location factors with individual program factors in selecting a residency program. Specific program characteristics represent the greatest opportunity to maximize the success of the immediate interview experience/season, while others provide potential for strategic planning over time. A working knowledge of these results empowers program directors to make informed decisions while providing an appreciation for the limitations in attracting applicants.

Pediatric genitourinary emergencies.

Pediatric medical complaints and differential diagnoses often vary from adults, requiring a specialized knowledge base and behavioral skill set. This article addresses a variety of congenital and acquired pediatric genitourinary disorders. Genitourinary emergencies include paraphismosis, priapism, serious infection, significant traumatic injury and gonadal torsion.

Gingival eruption cysts induced by cyclosporine administration to neonatal dogs.

OBJECTIVES: The purpose of this paper is to report the development of extensive, gingival eruption cyst formation in neonatal dogs during chronic administration of cyclosporine, which regressed after treatment ceased. MATERIALS AND METHODS: As part of an investigation of the efficacy of adenoviral-mediated gene therapy in a canine model of Duchenne Muscular Dystrophy (DMD), 26 Golden retriever pups were given intramuscular injections of adenoviral gene constructs (at 2-5 days old) either with (15 pups) or without (9 pups) concomitant immunosuppression using oral cyclosporine (from 1 to 3 days old). RESULTS: The daily administration of cyclosporine to Golden Retriever pups from 1 to 3 days of age resulted in the formation of eruption cysts over the incisors after approximately 3 weeks of treatment. The gingiva over the remaining teeth became swollen. However unlike the incisors, part of the crown erupted through the gingiva. Continuous treatment for 60-90 days was associated with persistence and expansion of the cysts over the incisor teeth. The cysts resolved within 1 month if cyclosporine administration was discontinued. Movement of incisors within the jaws was not appreciably affected when compared with age-matched controls. CONCLUSION: Chronic cyclosporine administration to neonatal dogs induces the formation of eruption cysts over the incisors, which is reversible once treatment is discontinued and does not affect intraosseous eruption.

Electrocardiographic changes associated with beta-blocker toxicity.

STUDY OBJECTIVE: We sought to characterize the ECG changes associated with symptomatic beta-blocker overdose. METHODS: The study population consisted of a prospective cohort of patients reporting to 2 regional poison centers with beta-blocker overdose. Each patient received an ECG on presentation and a structured follow-up. The inclusion criteria for symptomatic overdose included heart rate of less than 60 beats/min or systolic blood pressure of less than 90 mm Hg; symptoms consistent with decreased end-organ perfusion; therapeutic intervention with cardioactive medication; and corroboration by 2 of the authors that this was a clear-cut case of symptomatic beta-blocker overdose with cardiovascular toxicity. Exclusion criteria included cardioactive coingestants, age younger than 6 years, and no available ECG. RESULTS: Of 167 patients, 13 were determined to have symptomatic exposures. First-degree heart block (>200 ms) was the most common ECG finding (10/12) and also had the greatest likelihood ratio (5.31) when comparing those with symptomatic exposures with those with asymptomatic exposures. Comparing the asymptomatic with the symptomatic groups, the mean PR interval was 167 ms (95% confidence interval [CI] 162 to 171 ms) versus 216 ms (95% CI 193 to 238 ms), the mean QRS interval was 89 ms (95% CI 87 to 91 ms) versus 112 ms (95% CI 92 to 132 ms), the mean QTc interval was 422 ms (95% CI 417 to 428) versus 462 ms (95% CI 434 to 490 ms), and the mean heart rate was 72 beats/min (95% CI 69 to 74 beats/min) versus 66 beats/min (95% CI 59 to 73 beats/min). Two cases of symptomatic acebutolol exposure appeared unique by demonstrating disproportionate prolongation of the QTc interval, an RaVR height of 3 mm or greater, and associated ventricular tachydysrhythmia. CONCLUSION: The majority of clinically significant beta-blocker intoxications demonstrate negative dromotropic effects on ECG. Several ECG differences in acebutolol intoxication might reflect unique pathophysiologic processes relative to other beta-blockers.