Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety of adalimumab in global clinical trials and postmarketing surveillance among patients with rheumatoid arthritis (RA). METHODS: Safety data for adalimumab treated patients from randomised controlled trials, open label extensions, and two phase IIIb open label trials were analysed. In addition, postmarketing spontaneous reports of adverse events in the United States were collected following Food and Drug Administration approval of adalimumab on 31 December 2002. RESULTS: As of 15 April 2005, the RA clinical trial safety database analysed covered 10,050 patients, representing 12,506 patient-years (PYs) of adalimumab exposure. The rate of serious infections, 5.1/100 PYs, was comparable to that reported on 31 August 2002 (4.9/100 PYs), and to published reports of RA populations naive to anti-tumour necrosis factor (TNF) therapy. Following implementation of tuberculosis (TB) screening in clinical trials, the rate of TB decreased. There were 34 cases of TB as of this analysis (0.27/100 PYs). The standardised incidence ratio for lymphoma was 3.19 (95% CI 1.78 to 5.26), consistent with the observed increased incidence in the general RA population. As of 30 June 2005, there were an estimated 78 522 PYs of exposure to adalimumab in the US postmarketing period. Seventeen TB cases were spontaneously reported (0.02/100 PYs) from the US. Rates of other postmarketing events of interest, such as congestive heart failure, systemic lupus erythematosus, opportunistic infections, blood dyscrasias, lymphomas, and demyelinating disease, support observations from clinical trials. CONCLUSION: Analyses of these data demonstrate that long term adalimumab treatment is generally safe and well tolerated in patients with RA.

Medical students' experiences with and perceptions of chronic illness prior to medical school.

Concerns have been expressed about the failure of the medical curriculum to address the health-care needs of the chronically ill. It has been shown in the literature that medical students develop cynicism and negative feelings towards chronic illness as they progress through their training, perhaps as a result of the attitudes and frustrations of their teachers. What has been inadequately addressed are the experiences with and perceptions about chronic illness that medical students have before entering medical school. Some recommendations are made for curriculum changes based on the findings reported.

A novel asthma camp intervention for childhood asthma among urban blacks. The Pediatric Lung Committee of the American Lung Association of the District of Columbia (ALADC) Washington, DC.

Following a needs assessment, the American Lung Association of the District of Columbia (ALADC) began a 3-year pilot program (1986 to 1989) to improve the health status of 5- to 10-year-old urban black asthmatic children. The authors hypothesized that participation in a 1-day asthma camp curriculum, using a collaborative multidisciplinary team approach between university and community-based staff, would provide an effective educational intervention to teach children and their families daily management strategies for asthma. The 84 participants (mean age: 9.6 years) were predominantly black (93%), male (73%), and from single-parent or single-guardian homes (52.7%). Follow-up interviews suggested that a high percentage of the children were using new techniques such as aerosol/inhalers (78%) and breathing/warm-up exercises (55%). Overall, participation in this novel program was associated with a clinically significant, 36% to 69% reduction in school absences, emergency room visits, and hospitalizations.

Bronchoalveolar lavage for pneumocystis pneumonia in HIV-infected children.

Bronchoalveolar lavage (BAL) by flexible fiberoptic bronchoscopy is useful in the diagnosis of Pneumocystis carinii pneumonia (PCP) in adults with acquired immunodeficiency syndrome. To evaluate the safety and efficacy of this procedure in children with human immunodeficiency virus in whom PCP was considered, we reviewed the records of 15 consecutive procedures performed on eight patients by a pediatric pulmonologist during a 19-month period. Pneumocystis carinii pneumonia was identified after five of 15 BAL procedures. Other pathogens or multiple pathogens were found in some cases. A specific infectious diagnosis was obtained in ten of 15 procedures. No patient required subsequent open lung biopsy. Follow-up for a minimum of 6 weeks and response to therapy did not suggest PCP in any case where BAL failed to establish its diagnosis. No major complication was attributed to BAL. We conclude that BAL is safe and effective in the diagnosis of PCP in children with HIV infection. Guidelines are suggested to optimize its safety and utility.

Do health care needs of indigent Mexican-American, black, and white adolescents differ?

Few studies have addressed the specific health care needs of Mexican-American adolescents. This 2-year study assessed the routine health care needs and incidence of chronic illness among 279 Mexican-American, 233 white, and 333 black indigent adolescents enrolled in a vocational training program. Mexican-Americans were more likely to have a positive purified protein derivative tuberculin test and acne/eczema requiring treatment. Blacks were more likely to have incomplete immunizations and thyroid disorders, while whites were more likely to have musculoskeletal conditions and require family planning services and psychiatric intervention for mental health disorders. Although no difference in incidence of chronic illness was noted, our data suggests that routine health care needs may differ among indigent Mexican-American, white, and black adolescents.

Cystic fibrosis in blacks in Washington, DC: fifteen years' experience.

Controversies exist regarding the clinical presentation and characteristics of cystic fibrosis (CF) in American blacks. Between 1971 and 1986, 188 patients with CF (165 whites, 20 blacks, and 3 others) seen at Children's Hospital National Medical Center, Washington, DC, were evaluated for age at diagnosis, duration of symptoms prior to diagnosis, clinical presentations, initial sputum culture results, and weight and height at diagnosis. Comparisons between black and white patients revealed no statistically significant differences in average age at diagnosis, average duration of symptoms prior to diagnosis, average sweat electrolyte concentrations, or sputum culture results. A breakdown of presenting symptoms by race showed some points of disparity. About twice as many black patients as white patients (40% v 22%) presented with only pulmonary symptoms, whereas slightly more whites presented with only gastrointestinal symptoms (46% v 35%). Those patients presenting with a combination of symptomatology were equally distributed by race (25% black, 21% white). At diagnosis, age-adjusted weight percentiles were significantly lower for black patients than for white patients (chi 2 = 9.60, P less than or equal to 0.05). Although the authors agree that CF is relatively rare among blacks, a high index of suspicion is essential for early diagnosis.

Coccidioidomycosis in adolescents presenting as chest pain.

Chest pain is a relatively common complaint in adolescents and is most often attributed to anxiety or musculoskeletal conditions. Pleuritic chest pain in association with fever and cough are frequently reported in adults with primary pulmonary coccidioidomycosis. We describe three cases in which chest pain mimicking costochondritis was the predominant initial presenting symptom of pulmonary coccidioidomycosis. In addition, in each case, recent tuberculin skin test reactivity complicated the diagnostic assessment and treatment. We conclude that, in endemic areas, coccidioidomycosis should be considered in the differential diagnosis of acute chest pain in teenagers as well as in adults.

Caring for an adolescent with a chronic illness.

Although early, mid, and late adolescence are transient psychological periods, the teenager must master these three phases to complete the psychological stages and tasks of adolescence. Because chronic disease delays or alters these phases, it becomes imperative for the primary care physician to reassess psychological development periodically for appropriate and intensive counseling. With the advantage of continuous contact with the family and the understanding of the family's structure and interpersonal relationships, the primary care physician may be able to: alleviate struggles for control that may seriously impede care, encourage the teenager to accomplish the psychological tasks of adolescence, both during hospitalization and in follow-up outpatient care visits, promote the adolescent's participation in his or her own health care, and ultimately enhance both the family's and the teenager's adaptation to a chronic illness. Finally, during the terminal phase of an illness, the primary care physician will be able to help the adolescent find meaning in his or her short life, provide the support to help the teenager to disengage from life with dignity, and provide a supportive relationship to the parents and siblings.

Diagnosis of cystic fibrosis during adolescence.

The manifestations of cystic fibrosis (CF) may be minimal, absent, or overlooked during childhood, thus 8-10% of cases are diagnosed during adolescence. Between 1970 and 1982, 14/157 (8.9%) patients were diagnosed as having CF as teenagers, based on clinical findings and elevated sweat electrolyte levels. Of these 14 patients (means = 15 years, range = 12-20 years), 50% had pulmonary and gastrointestinal symptoms dating from childhood; 50% became symptomatic during adolescence (primarily with pulmonary manifestations). None had a family history of CF. Four had false-negative sweat tests resulting in a mean diagnostic delay of 7.3 years. Because of the potential long-term complications of CF on physical maturation, completion of the psychosocial tasks of adolescence, adaptation to a chronic illness, and issues of sexuality and fertility, consideration of this diagnosis is crucial.

Transbronchial lung biopsy in pediatric and adolescent patients.

Since data are unavailable on the role of transbronchial lung biopsy (TBB) in pediatric and adolescent patients, we reviewed our two-year experience in 12 patients (median age, 14.5 years). In all 12, the indication for TBB was a persistently abnormal chest roentgenogram (nine with multilobar infiltrates, two with unilateral infiltrates, and one with a cavitary lesion). Overall, a specific diagnosis was made by TBB in six patients, including three patients with sarcoidosis, one with lymphoma, and two with eosinophilic granuloma. In three additional patients, nonspecific histologic findings on TBB combined with clinical findings, roentgenographic patterns, and supplemental laboratory data helped support a diagnosis. Although the need for general anesthesia and the small size of the biopsy specimens may limit the usefulness of TBB in most pediatric patients, TBB may be a useful alternative in carefully selected patients.

Use of oral contraceptives in women with cystic fibrosis.

Oral contraceptive pills (OCP) represent the most common contraceptive method among teenagers and young adults. Because many women with cystic fibrosis (CF) are now surviving into childbearing age and are at risk for the complications of pregnancy in CF, oral contraceptive use may be indicated. However, it has been suggested that OCP use by CF patients may be associated with deterioration in pulmonary function. Ten adolescent and young adult women with CF and moderate-to-severe obstructive lung disease were studied while taking a combination oral contraceptive pill (Ovral 28). No significant deterioration was found in clinical status or pulmonary function. Careful follow-up should nevertheless be continued to monitor for other adverse effects of oral contraceptive use in CF, such as cholelithiasis.

Iron deficiency in black females during late adolescence.

The role of serum ferritin (SF) in detecting early iron deficiency and the associated risk factors in black adolescent females are evaluated. SF less than or equal to 12 ng/mL indicated low iron stores and a Hb less than or equal to 11.3 g/dL (5% ile for black females-Hanes Survey) anemia. Of the 103 females (means = 16.8 yr) screened in a Family Planning Clinic (FPC), 20.4% (21/103) had a low SF. Of these 21, 72% had a Hb greater than 11.3 g/dL. Chronologic age, gynecologic age, history of pregnancy, Tanner stage IV and V, and birth control method did not appear to be risk factors. However, longer rather than shorter use of oral contraceptives appeared to protect against iron deficiency. This study suggests that routine screening of iron status by hemoglobin and serum ferritin is warranted during annual FPC visits.

PIP: The role of serum ferritin (SF) in detecting earlyiron deficiency and the associated risk factors in black adolescent females are evaluated. SF or=12 ng/mL indicated low iron stores and a Hb or= 11.3 g/dL (5%ile for black females--Hanes Survey) anemia. Of the 103 females (chisquare=16.8 years) screened in a Family Planning Clinic (FPC), 20.4% (21/103) had a low SF. Of these 21, 72% had an Hb 11.3 g/dL. Chronologic age, gynecologic age, history of pregnancy, Tanner 4 and 5, and birth control method did not appear to be risk factors. However, longer rather than shorter use of oral contraceptives appeared to protect against iron deficiency. This study suggests that routine screening of iron status by hemoglobin and SF iss warranted during annual FPC visits.

Serological response to rubella revaccination in adolescent females.

The study's purpose was to utilize ELISA in determining rubella susceptibility in teenagers who are seronegative by HI. Ten previously vaccinated, seronegative adolescent females were revaccinated with RA 27/3 and their IgG and IgM responses measured by ELISA. Before revaccination, all 10 were seronegative for rubella by HI (less than 1:10). However, by ELISA, six showed an IgG and no IgM levels. After reimmunization, three showed a significant IgM response by day 6, indicating primary rubella exposure. The remaining seven females failed to demonstrate an IgM response; however, the failure was consistent with a history of prior rubella vaccination. Peak IgG responses were noted by day 12 in nine of the females. The remaining teenager failed to show an IgG response and was considered a vaccine failure. This study confirms the superiority of ELISA as compared to HI titers in determining rubella susceptibility.

Moxalactam-tobramycin-resistant Pseudomonas aeruginosa isolates in patients with cystic fibrosis.

In vitro studies have shown synergistic killing activity against Pseudomonas aeruginosa (PA) with the combination of an aminoglycoside and moxalactam, a new beta-lactam agent. We describe three patients with cystic fibrosis (CF) with PA isolates that were resistant to all single-agent antibiotics, but sensitive to the combination of moxalactam-tobramycin. Initially, all patients had a good clinical response to this combination. However, during a second course of therapy, there was clinical deterioration coincident with the rapid emergence of moxalactam-tobramycin-resistant PA isolates.

Indications for flexible fiberoptic bronchoscopy in pediatric patients.

Although the availability of flexible fiberoptic bronchoscopy (FFB) has been a major advance in adult pulmonary medicine, the role of FFB in pediatrics has remained less well defined. Therefore, a two-year retrospective study was undertaken to determine the indications for FFB in 95 pediatric patients (mean age, 6.9 years) who underwent 129 FFB procedures. Indications for FFB included stridor (41/129), abnormal chest roentgenogram (38/129), airway evaluation in patients with tracheostomy (13/129), airway obstruction (11/129), hoarseness (9/129), recurrent pneumonia (7/129), chronic cough (4/129), failed extubation (3/129), tracheal injury (2/129), and hemoptysis (1/129). Overall, a specific diagnosis was made in 88% of cases, of which 48% involved a lower airway disorder. A minor complication rate of 2% was observed with no major complications.