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Panic Disorder: Diagnosis and Treatment in Primary Care
JOHN R. VANIN, M.D.
West Virginia University School of Medicine
Morgantown, West Virginia
SANDRA K. VANIN, M.D.
West Virginia University School of Physical Education
Morgantown, West Virginia

Anxiety disorders affect millions of persons in the United States and are among the most common psychiatric disorders. Everyone experiences anxiety at one time or another, especially in situations such as meeting someone new, giving a speech or taking a test. Some individuals, however, have severe disabling panic attacks that significantly interfere with school, work, relationships and overall health status.

Panic disorder, a common, chronic anxiety disorder manifested by recurrent unexpected panic attacks, is potentially debilitating. The intense fear and physical symptoms that accompany panic episodes may lead to repeated visits to the emergency department or the family physician's office because of the fear of having a heart attack or stroke, or the fear of dying.

Individuals who have panic disorder live with a persistent concern about having another attack. This concern is called "anticipatory anxiety." Agoraphobia (phobic avoidance) may also develop. As discussed by Saeed and Bruce in this issue of American Family Physician, agoraphobia usually accompanies panic disorder in clinical populations.¹ Those who are employed may avoid going to work for fear of having a panic attack, and students may not attend classes. The ability to recognize anticipatory anxiety and phobic symptoms can be extremely helpful to the family physician in the evaluation of panic disorder.

Panic disorder may mimic or coexist with other medical problems such as asthma. By definition, however, panic attacks in panic disorder are not caused by the direct physiologic effects of a substance or a general medical condition.²

Panic disorder occurs in approximately 3.5 percent of the population.³ Typical age at onset is in young adulthood, and it occurs twice as frequently in females as it does in males. Estimates of the incidence of panic disorder in primary care settings range between 4 and 10 percent.⁴

See Article in this issue.

The classic presentation of panic disorder may be easily recognized, but it is not uncommon for panic disorder to present atypically and thus go unrecognized. It is important for the family physician to recognize limited-symptom attacks (one or two symptoms), nocturnal panic and non-fearful panic. Non-fearful attacks, consisting primarily of somatic symptoms, may be confused with other medical conditions such as cardiovascular, pulmonary, gastrointestinal and neurologic conditions.^4,5 If no adequate medical explanation can be found in patients with episodes of physical symptoms, panic disorder should be considered even without associated fear and anxiety.⁴

Factors contributing to the cause of panic disorder include serotonin and norepinephrine dysregulation, respiratory control dysfunction and hormonal dysregulation.^4,6 Stress, sudden loss of social supports, separation anxiety and childhood psychologic trauma have been associated with panic disorder.⁶ A comprehensive family, personal and social history is invaluable in the evaluation of panic disorder.

Persons with panic disorder often have comorbid psychiatric disorders. Depressions develops in at least 30 to 50 percent of patients with panic disorder.⁶ The Epidemiological Catchment Area Survey found that 20 percent of patients with panic disorder made at least one suicide attempt.⁶

Panic disorder may cause impaired quality of life and increased utilization of health care resources. Patients ultimately diagnosed with panic disorder often have been seen by many primary care practitioners and consultants, and often have undergone costly diagnostic tests. Patients with panic disorder are more likely than others to seek general medical care, visit the emergency department and take prescription tranquilizers.⁷

A careful history and brief physical examination with a few screening tests are important in the evaluation of panic disorder. Medical diagnoses such as thyroid dysfunction, mitral valve prolapse and asthma must be considered. The physician should inquire about caffeine, alcohol and over-the-counter cold medication use that may cause or aggravate particular symptoms. A concern is the potential for substance abuse in a patient who tries to self-medicate to relieve the intense, uncomfortable anxiety symptoms.

The treatment of panic disorder includes medications (antidepressants and benzodiazepine anxiolytics) and cognitive-behavioral therapy. In patients with panic disorder, it is wise to start antidepressants at low doses and carefully titrate upward to minimize the risk of activating symptoms. Saeed and Bruce give very practical recommendations for starting and titrating antidepressants in patients with panic disorder. The doses of antidepressants required in the treatment of panic disorder may ultimately be similar to those used in the treatment of depression. Benzodiazepines are especially useful for the highly distressing anticipatory anxiety⁴--however, they are not useful for treating comorbid depression. Cognitive-behavioral approaches include supportive measures, education (e.g., brochures), breathing retraining and helping the patient restructure distorted thinking patterns. A trusting relationship with the family physician is vital. An integrated treatment approach is recommended by the Anxiety Disorders Association of America.⁸

Individuals with panic disorder may require repeated reassurance and explanation about the disorder, especially regarding the physical symptoms. Frequent contact with the physician, either by telephone or in the office, is helpful, particularly during the initial treatment phase. Several medication adjustments are not uncommon.

Panic disorder is a legitimate disorder that may present with medically unexplainable symptoms that may go unrecognized for a long time. Early recognition allows for effective treatment by the family physician, with mental health consultation as necessary. The improvement in the patient's quality of life and the satisfaction of both the patient and the physician is most rewarding.

REFERENCES

1. Saeed SA, Bruce TJ. Panic disorder: evidence-based treatment options. Am Fam Physician 1998;57 2405-20.
2. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington, D.C., American Psychiatric Association, 1994:393-405.
3. Hirschfield RM. Panic disorder: diagnosis, epidemiology, and clinical course. J Clin Psychiatry 1996; 57(Suppl 10):3-8.
4. Elliot R. Panic disorder in primary care. Primary Psychiatry 1995;2:52-9.
5. Roy-Bryne P, Cowley D. Assessment and treatment of panic disorder. In: Dunner DL, ed. Current psychiatric therapy. 2d ed. Philadelphia: Saunders, 1997:309-16.
6. Gorman J. Recent developments in understanding panic disorder leading to improved treatment strategies. Primary Psychiatry 1996;3:31-8.
7. Rosenbaum JF. Panic disorder in the emergency department. Emerg Med 1996;28:54-69.
8. Ballenger J, Pollack M, Ross J. Practical approaches to the treatment of panic disorder. J Clin Psychiatry 1996;57:45-52.

Dr. John Vanin is professor of behavioral medicine and psychiatry/community medicine at West Virginia University School of Medicine. He is also director for Mental Health Services/Health Education at the West Virginia University Health Service, Robert C. Byrd Health Sciences Center. Dr. Sandra Vanin is assistant professor of adapted physical education, School of Physical Education, West Virginia University. See article on page 2405.

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Diagnosis of Urinary Tract Infection in Children
ALEJANDRO HOBERMAN, M.D.
ELLEN R. WALD, M.D.
Children's Hospital
Pittsburgh, Pennsylvania

The article by Hellerstein¹ in this issue focuses on risk factors for urinary tract infection in children and reviews methods of prevention. Leaving aside the issue of circumcision and abnormal voiding patterns, this commentary will focus on the diagnosis of urinary tract infection in children and the selection of imaging procedures after diagnosis.

See Article in this issue.

Infant girls are at a particularly high risk of urinary tract infection. The incidence of urinary tract infection is higher during the first year of life than at any other age in childhood.² Our initial study investigated the prevalence of urinary tract infections in febrile infants, with and without an apparent source of fever, who presented to the emergency department. Urine cultures obtained by catheter were positive in 5.3 percent of 945 infants with fever. The prevalence did not vary with age but was higher in girls than in boys (8.8 percent versus 2.5 percent; P< 0.0001) and was higher in white infants than in black infants (6.6 percent versus 3.6 percent; P< 0.05). When sex, race and degree of temperature were combined as risk factors, white females whose highest temperature had been at least 102.2°F (39°C) were found to be at particularly high risk of urinary tract infection (prevalence of 17 percent).³

Diagnosis of urinary tract infection is a major issue, and it should be based on both the results of urinalysis and the results of culture of a properly collected urine specimen. In older, toilet-trained children, a midstream clean-catch specimen is appropriate. Suprapubic aspiration may be necessary for preterm infants, girls who cannot be catheterized because of labial adhesions, uncircumcised boys with tight foreskins and children with various anatomic abnormalities. In most other situations, a catheterized specimen is usually obtained.

Bacteria grown from a urine culture may arise from the following sources: (1) contamination outside of the urinary tract, (2) colonization of the distal urethra (contamination from within the urinary tract), (3) asymptomatic colonization of the bladder urine or (4) true urinary tract infection. The "enhanced urinalysis" has been a useful screening test to distinguish these conditions.

During the past years, we have evaluated uncentrifuged urine specimens obtained by catheter from young febrile children, and enumerated white blood cells per mm³ using a Neubauer hemocytometer. Of 3,257 cultures of urine, most (2,983 or 92 percent) showed no growth. Specimens with counts of bacteria between one and 49,000 colony-forming units (CFU) per mL were more likely to yield nonpathogens or mixed organisms than single pathogens. Specimens with counts of at least 50,000 CFU were most likely to yield single pathogens. Of all of the specimens in which there was a sterile culture, 97 percent had fewer than 10 white blood cells per mm³, and only 89 specimens or 3 percent had more than 10 white blood cells per mm³. In contrast, 90 percent of the urine specimens with more than 50,000 CFU per mL had at least 10 white blood cells per mm³.

Therefore, urinary tract infection is best defined by the presence of at least 10 white blood cells per mm³ on hemocytometer and cultures with growth of at least 50,000 CFU per mL on specimens obtained by catheter from young febrile children.⁴ For midstream clean-voided specimens, at least 10⁵ CFU per mL of a single urinary pathogen is usually regarded as a positive urine culture. These definitions will almost always discriminate true urinary tract infections from bacteriuria associated with contamination or colonization of the urinary tract (asymptomatic bacteriuria). It is important to recognize that, occasionally, low colony counts of bacteria in urine may be significant.

When urine specimens are obtained by suprapubic aspiration, growth of urinary pathogens in any number is considered significant (with the exception of 20,000 to 30,000 CFU per mL of coagulase-negative staphylococci). Even with catheterized specimens, the repeated recovery of a single species of bacteria in specimens with colony counts lower than 50,000 CFU per mL (especially in a symptomatic patient) should be regarded as representative of true infection. Colony counts of bacteria may fall below the range that is characteristic of infection when one of the following factors is present: (1) a bacteriostatic agent is present in the urine; (2) there is a rapid rate of urine flow with reduced incubation time; (3) there is an obstruction of the ureter that interferes with discharge of bacteria into the bladder; or (4) the infection is limited to areas of the kidney not directly accessible to renal tubules.

Imaging studies are part of the standard care after diagnosis of a first urinary tract infection in young children. As part of a recently completed clinical trial,⁵ 179 children aged one to 24 months with fever (higher than 100.9°F [38.2°C]) had a renal ultrasound examination and a renal scan with dimercaptosuccinic acid labeled with technetium 99m (DMSA scan) performed within 48 hours of diagnosis, a voiding cystourethrogram performed one month following diagnosis, and a repeat DMSA scan performed six months later. Results of renal ultrasound examination and DMSA scan at the time of presentation with urinary tract infection did not modify management in any patient.

Current widespread use of prenatal ultrasonography leads to identification of obstruction of the urinary tract in utero. Accordingly, selective rather than routine performance of ultrasound is recommended (i.e., in patients with persistent fever or abdominal findings and in those who have not had a prenatal ultrasound examination). In the study described above,⁵ a voiding cystourethrogram at one month and a DMSA scan six months later were useful for identifying patients with vesicoureteral reflux who required prophylactic antimicrobial therapy and patients with renal scarring. Patients with renal scarring may benefit from the early performance of urine culture during subsequent episodes of fever.

REFERENCES

1. Hellerstein S. Urinary tract infections in children. Am Fam Physician 1998;57:2440-54.
2. Winberg J, Andersen HJ, Bergstrom T, Jacobsson B, Larson H, Lincoln K. Epidemiology of symptomatic urinary tract infection in childhood. Acta Paediatr Scand Suppl 1974:1-20.
3. Hoberman A, Chao HP, Keller DM, Hickey R, Davis HW, Ellis D. Prevalence of urinary tract infection in febrile infants. J Pediatr 1993;123:17-23.
4. Hoberman A, Wald ER, Reynolds EA, Penchansky L, Charron M. Pyuria and bacteriuria in urine specimens obtained by catheter from young children with. J Pediatr 1994;124:513-9.
5. Hoberman A, Charron M, Wald ER, Reynolds EA. Imaging studies in the follow-up of children with first diagnosed urinary tract infection: what's needed? Pediatric Research 1996; 39:133A.

Dr. Hoberman is an associate professor of pediatrics at the University of Pittsburgh School of Medicine. He is a member of the Division of General Academic Peditrics, Children's Hospital of Pittsburgh. Dr. Wald is a professor of pediatrics and otolaryngology at the University of Pittsburgh School of Medicine. She is the chief of the Division of Allergy, Immunology and Infectious Diseases, Children's Hospital of Pittsburgh, and vice chairman of the Department of Pediatrics.

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