bluuebunny/crossref_metadata_2025_split huggingface dataset:
REASSESSING THE THERAPEUTIC RANGE FOR THEOPHYLLINE ON LABORATORY REPORT FORMS: ANOTHER PERSPECTIVE
Authors: Kamada Alan K. 
Published: December 2021

The therapeutic utility of theophylline and the recommended range for serum concentrations are debated in a series of three editorials by noted contributors in this area. In the first, it is pointed out that the role of theophylline has evolved into an "adjunctive" therapy for asthma and chronic obstructive pulmonary disease. Serum concentrations of 10 to 15 µg/mL do not sacrifice significant clinical benefit, whereas there is increased risk for adverse effects at higher concentrations. Changing laboratry report forms to designate a lower therapeutic range of 5 to 15 µg/mL for an increased margin of safety (with &gt;20 µg/mL continuing as the lower limit of the toxic range) is advocated and a stepwise approach for implementing this change is proposed.
The second paper supports the view that theophylline remains more important than a third- or fourth-line agent in the treatment of asthma, particularly in selected patients. A higher target serum concentration range of 10 to 15 µg/mL may be desirable in more severe asthmatics (requiring oral steroids despite treatment with inhaled steroid), those with nocturnal symptoms, acute exacerbations requiring hospitalization and mechanical ventilation, and in patients for whom this is a more economical or preferable therapy. In these patients a serum concentration of 5 µg/mL may be too low to achieve sufficient benefit. Designation of "10 to 15 µg/mL (5 to 20)" as the therapeutic range is suggested to emphasize the midrange as the target while indicating that levels between 5 and 20 µg/mL are acceptable, although not ideal from either an efficacy or safety standpoint.
In the third and final viewpoint presented, much data supporting the efficacy of theophylline in the treatment of chronic asthma and its relationship to serum concentrations are presented. Evidence for potential anti-inflammatory effects of theophylline is also reviewed. Severe toxicity, a rare event, is noted to be not a result of serum concentrations slightly above the therapeutic range, but from massive overdosage and/or drug interactions or concomitant illnesses that alter elimination of the drug. No changes in the recommended therapeutic range of theopylline, which might alter its effectiveness, are proposed. Rather, more careful use and monitoring through education of prescribers is advocated.
EFFICACY OF CROMOGLYCATE IN PERSISTENTLY WHEEZING INFANTS
Authors: Joos Thad H. 
Published: December 2021

Purpose of the Study. To evaluate the effectiveness of sodium cromoglycate in the treatment of persistent wheezing in children ages 4 to 12 months.
Study Population. Thirty-one asthmatic infants without such complicating factors as gastroesophageal reflux, cystic fibrosis, bronchopulmonary dysplasia, etc, were enrollled. Sixteen received active medication and 15 received placebo.
Methods. All 31 infants were observed for 3 weeks before the final enrollment with symptom scores recorded based on cough, wheeze, thoracic indrawing, and sleep pattern. Any noticeable problems were treated with albuterol delivered by a nebulizen and tightly fitting face mask.
Pulmonary function parameters were determined by the "squeeze technique" on all enrollees.
For the next 6 weeks, 16 infants received 40 mg of sodium cromoglycate in 4 mL solution via the nebulizer three times a day and 15 infants received 4 mL of normal saline three times a day.
Symptom scores were meticulously recorded and again pulmonary function studies were performed.
Findings. There were no significant differences noted between the sodium cnomoglycate group or the placebo group that led the investigators to conclude that sodium cromoglycate was not an effective agent in controlling asthma in very young infants.
Reviewer's Comments. This appeared to be a very well done investigation and employed twice the dose of sodium cromoglycate e.g. 40 mgm tid, than most of us would use. It certainly makes one wonder especially in view of Dr. Shirley Murphy's similar results with sodium cromoglycate in premature newborns and its failure to prevent BPD.
The use of inhaled corticosteroids to manage asthma in this young group of patients deserves such a carefully conducted study.
EFFECTS OF REDUCING OR DISCONTINUING INHALED BUDESONIDE IN PATIENTS WITH MILD ASTHMA
Authors: Chipps Bradley E. 
Published: December 2021

Purpose of the Study. To determine the effect of decreasing the dose of inhaled steroid and delayed introduction of inhaled steroid on symptomatic control, pulmonary function, and bronchial hyperresponsiveness in new onset asthma.
Study Population. Thirty-seven asthmatics treated for 2 years with budesonide (1200 µg/day) were randomized to receive either placebo or budesonide (400 µg/day) in a double-blind continuation study for 1 additional year. Also 37 patients who had received inhaled terbutaline only during the initial 2 years of the study were crossed over and given budesonide 1200 µg/day for the subsequent year.
Methods. The drugs were delivered in a multi-dose powder inhaler. Histamine challenge studies were performed with six doubling step doses (1 to 32 mg/mL). A drop in forced expiratory volume in 1 second (FEV1) of 15% (PC15) was viewed as a positive test. Asthma symptom scores, home peak-flow recordings, and pulmonary function tests were recorded at regular intervals. If inadequate control was achieved with the study drugs, then sustained release theophylline was added and short courses (6 days) of oral corticosteroids were prescribed for acute exacerbations.
Findings. Pulmonary function studies and histamine challenge results did not change significantly at either budesonide dose. In the placebo group, the FEV1 decreased by 250 mL (P = .01) and PCI5 increased by 1.5 steps (P = .037). Likewise, asthma symptoms scores deteriorated as did morning peak flows in the group only treated with terbutaline. Early institution of inhaled steroid in newly diagnosed asthmatics lead to more rapid improvement in pulmonary function, decreased supplemental β-agonist usage, and improved symptom scores.
Epiglottitis and Haemophilus influenzae Immunization: The Pittsburgh Experience–A Five-Year Review
Authors: Valdepeña Hugo González , Wald Ellen R. , Rose Elizabeth , Ungkanont Kitirat , Casselbrant Margaretha L. 
Published: December 2021

Objective. Current trends in the clinical presentation and management of children with epiglottitis at Children's Hospital of Pittsburgh were reviewed for the years 1988 to 1993.
Methodology. The medical records of all patients diagnosed as having epiglottitis between July 1988 and June 1993 at the Children's Hospital of Pittsburgh were reviewed. An additional telephone survey was conducted among the primary care physicians of those patients to collect information regarding administration of Haemophilus influenzae type b (HIB) vaccines.
Results. During the study period 28 children (age range, 11 months to 11 years, 10 months) were admitted with the diagnosis of epiglottitis. Cases declined remarkably in 1991. Fever, sore throat, and stridor were the usual symptoms. HIB was the most common cause of epiglottitis accounting for 21 cases. Candida albicans was recovered from the surface culture of the epiglottis in two patients. At least 11 children experienced vaccine failure: nine with polysaccharide vaccine and two with the conjugate vaccine for HIB.
Conclusion. Cases of epiglottitis have declined dramatically since licensure of HIB conjugate vaccines for use in early infancy. At least 52% of the reported cases represent vaccine failures with the purified polysaccharide vaccine.
Group A β-Hemolytic Streptococcal Bacteremia: Historical Overview, Changing Incidence, and Recent Association With Varicella
Authors: Doctor Allan , Harper Marvin B. , Fleisher Gary R. 
Published: December 2021

Objective. To quantitate the increase in invasive group A β-hemolytic streptococcal (GABHS) infections and to define a possible association between GABHS bacteremia and primary varicella zoster virus (VZV) infections.
Methods. This was a retrospective chart review conducted at Children's Hospital. Participants were patients with documented GABHS bacteremia occurring from January 1977 through December 1993.
Measurements/Main Results. We identified 63 episodes of GABHS bacteremia in 62 patients. From 1977 to 1992, a mean of 3.2 ± 2 cases occurred per year (range, 0 to 6), increasing by a factor of 3 (10 cases) in 1993. The median age was 4 years (range, 1 day to 20 years; mean, 8 years ± 3 months); 36 were male; five children were immunocompromised. One child was dead on arrival and one had a cardiac arrest during evaluation in the emergency department. Primary sites of infection (oropharynx, skin, or middle ear) were identified in 40 (75%) of the cases; in addition, 10 cases occurred in patients with primary VZV. From 1977 to 1992, we identified five VZV-associated cases; an average of 7 ± 11.5% of the patients with GABHS had concurrent VZV infection annually, with no more than one case per year. In 1993, 50% of the 10 new GABHS cases were in children with VZV infection (P = .003, Fisher's exact test). The diagnosis of invasive GABHS infection in patients with VZV was not readily recognized, requiring a median of two (range, one to four) physician visits before admission and the administration of antibiotics. All 10 children were diagnosed on the fourth or fifth day of the exanthem and were febrile (39.6 ± 1.1°C, range, 38.3 to 40.8°C), with a mean white blood cell count (WBC) of 11 500 ± 8 400/mm3 (8 of 10 cases had a WBC less than 15 000/mm3). None of the five VZV-associated cases in 1993 had signs of cutaneous bacterial superinfection; among these were two cases of streptococcal toxic shock syndrome (one death), one case of osteomyelitis, and two cases of occult bacteremia. Of the five VZV-associated cases before 1993, one patient was diagnosed with supraglottitis, one with septic arthritis, one with orbital cellulitis, and two solely with impetiginized or cellulitic lesions.
Conclusions. We found that the incidence of invasive GABHS infections has risen dramatically, increasing by a factor of 3 over the past year. In 1993, 50% of new cases of invasive GABHS disease were associated with VZV infection. Invasive GABHS should be considered in children with VZV who manifest fever on or beyond the fourth day of the exanthem. The absence of an elevated WBC and impetiginized or cellulitic lesions should not eliminate this diagnosis from consideration.
Pediatrician Involvement in Breast-Feeding Promotion: A National Study of Residents and Practitioners
Authors: Freed Gary L. , Clark Sarah J. , Lohr Jacob A. , Sorenson James R. 
Published: December 2021

Objective. Physician support for breast-feedings mothers has been shown to improve breast-feeding rates, but no evaluation of the adequacy of physicians' breast-feeding-related training has been conducted. This study was designed to assess pediatricians' knowledge, attitudes, training, and activities related to breast-feeding promotion.
Methods. Surveys were mailed to a national random sample of pediatric residents (n = 999) and practitioners (n = 610) who were board certified within the previous 3 to 5 years.
Results. Response rates were 74% for residents and 69% for practitioners. Although more than 90% of respondents agreed that pediatricians should be involved in breast-feeding promotion, their clinical knowledge and experience did not suggest a high degree of competency. For example, practitioners were only slightly more aware of breast-feeding's protective effect against otitis media (71% vs 60%), and more than one quarter of both groups did not agree that exclusive breast-feeding is the most beneficial form of infant nutrition. Clinical advice often included inappropriate recommendations for breast-feeding termination or formula supplementation; only 64% of practitioners and 52% of residents knew that supplementing during the first few weeks of life may cause breast-feeding failure. For both groups, prior personal breast-feeding experience (ie, respondent or spouse had breast-fed an infant for 2 or more weeks) was a major determinant of improved clinical knowledge, more frequent activity, and greater self-confidence and perceived effectiveness in the area of breast-feeding promotion. Residents reported that the breast-feeding instruction provided during training was primarily in lecture format, with limited clinical opportunities to practice skills needed to assist breast-feeding mothers. Reflecting on their own training, more than 70% of practitioners recommended that more time be devoted to direct patient interaction and practice of counseling and problem-solving skills.
Conclusions. These results indicate that residency training does not adequately prepare pediatricians for their role in breast-feeding promotion. Improvements in residency training and innovative continuing education programs should be implemented to help pediatricians meet the needs of their breast-feeding patients.
Growth of Breast-Fed Infants Deviates From Current Reference Data: A Pooled Analysis of US, Canadian, and European Data Sets
Authors: Dewey Kathryn G. , Peerson Janet M. , Brown Kenneth H. , Krebs Nancy F. , Michaelsen Kim F. , Persson Lars A. , Salmenpera Leena , Whitehead Roger G. , Yeung David L. ,   World Health Organization Working Group on Infant Growth
Published: December 2021

The sample sizes of infants from the selected studies are shown in Tables 2-4, categorized by duration of breast-feeding, timing of introduction of solid foods, and use of infant formula or other milks. Table 5 shows the cross-tabulation by duration of breast-feeding and age of introduction of supplemental milk or formula. In total, 453 infants were included, of whom 226 were breast-fed for at least 12 months. Of these 226, 141 were not regularly given other milks or formula during the first year of life. Of the total sample, solid foods were introduced at 4 to 5 months to 42% (Table 3), at 6 to 7 months to 38%, at 8 to 9 months at 17%, and after 9 months to 2%.
The samples were relatively homogeneous with respect to average maternal weight, height, and age. Mean pregnancy weight gain in the three studies reporting this ranged from 12.7 to 15.0 kg. Maternal educational levels were generally high: in the studies reporting this as a continuous variable, the overall mean was 15.4 ± 2.4 years of education. Mean birth weight ranged from 3414 to 3605 g. Characteristics of infants categorized by breast-feeding duration are shown in Table 6 (the group breast-fed for 4 to 5 month is not shown, because there were only 10 infants in this category). Mothers who breast-fed for 12 or more months were older and had higher parity and educational levels than mothers who breast-fed for less than 12 months, but birth weight did not differ significantly among groups.
Scopolamine Patch-Induced Unilateral Mydriasis
Authors: Thiele Elizabeth A. , Riviello James J. 
Published: December 2021

Tnansderm Scōl patches, containing scopolamine, have become a very popular and effective treatment for nausea and vomiting accompanying chemotherapy. We report two patients in whom unilateral fixed and dilated pupils related to scopolamine developed while undergoing chemotherapeutic protocols for bone marrow transplant (BMT). Both patients had neurologic consultations and neuroimaging as a result of the mydriatic pupils.
CASE REPORTS
Patient 1, a 20-year-old woman, was undergoing allogenic BMT for acute lymphocytic leukemia. She had a history of common migraine but had never experienced visual symptoms with her migraine. On the day before receiving her BMT, she had a headache and blurred vision and was found to have a fixed and dilated pupil on the left.
Multicenter Acellular Pertussis Vaccine Trial: A National Institutes of Health Perspective
Authors: Klein David L. 
Published: December 2021

The Pertussis Program within the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, is responsible for the development, management, and monitoring of several research and training initiatives in the field of pertussis. As directed by Congress through the National Childhood Injury Act, and with support by the National Vaccine Program Office, the NIAID has a mandate to accelerate scientifically and systematically the development and clinical testing of new candidate acellular pertussis vaccines, with the goal of licensure of an improved product that is less reactogenic than, and equally effective as, conventional whole-cell vaccine. A major portion of this activity is done through contracted Vaccine Treatment and Evaluation Units (VTEUs) in the form of phase I and II clinical trials. Much of this effort involves close collaboration with vaccine manufacturers and the US Food and Drug Administration (FDA). The success of the NIAID's vaccine evaluation program has relied heavily on this unique interaction with industry during the past 14 years, which has proved beneficial for all parties. Furthermore, this interaction has provided vaccines and antigens for use in the clinical setting and the laboratory, respectively, promoting the rapid evaluation and testing of many of these products.
Although the conventional whole-cell pertussis vaccine used in the United States is efficacious in preventing disease, there is concern about its safety. Recent advances in the characterization of the antigenic and biologically active components of Bordetella pertussis have allowed for the development and production of a new generation of more highly purified acellular vaccines, which we hope will prove to be much safer.
Comparison of 13 Acellular Pertussis Vaccines: Adverse Reactions
Authors: Decker Michael D. , Edwards Kathryn M. , Steinhoff Mark C. , Rennels Margaret B. , Pichichero Michael E. , Englund Janet A. , Anderson Edwin L. , Deloria Maria A. , Reed George F. 
Published: December 2021

Objective. To compare the reactogenicity of a licensed conventional whole-cell (WCL) and 13 acellular pertussis vaccines that differed in the source, manufacture, and quantity of included antigens; all vaccines included diphtheria and tetanus toxoids.
Methods. Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Parents recorded the occurrence of fever, redness, swelling, pain, fussiness, drowsiness, anorexia, and use of antipyretics for 2 weeks after each inoculation; nurses interviewed parents on the third day and at each succeeding visit; long-term follow-up information was collected from parents and medical records 1 year after the third immunization.
Results. Of 2200 vaccinated infants, 2189 contributed reaction data after 6375 vaccinations. For every acellular vaccine, every monitored reaction except vomiting occurred at a significantly lower frequency and severity than was seen with WCL. The groups receiving acellular pertussis vaccines differed significantly with respect to redness, swelling, pain, and vomiting, but not with respect to fussiness, antipyretic use, drowsiness, or anorexia.
Conclusion. Although there were differences among the acellular vaccines, none was consistently the most or least reactogenic; all were associated with substantially fewer and less severe adverse reactions than a standard commercial whole-cell vaccine. Selection of acellular vaccines for further development and for introduction into efficacy trials can give priority to assessments of immunogenicity and purity, with comparative reactogenicity a secondary consideration.
Gastrostomy Tube Supplementation for HIV-infected Children
Authors: Miller Tracie L. , Awnetwant Ester L. , Evans Sylvia , Morris Vivien M. , Vazquez Isabel M. , McIntosh Kenneth 
Published: December 2021

Objective. Malnutrition is common in pediatric human immunodeficiency virus (HIV) infection, and little is known of effective nutritional interventions. We sought to determine whether enteral supplementation with gastrostomy tube feedings would provide improvements in weight, height, body composition, immune parameters, morbidity, and mortality.
Methods. We collected clinical data on 23 HIV-in-fected children who were fed chronically by gastrostomy tube. The main outcome measures included weight, height, triceps skinfold thickness (TSF), arm-muscle circumference (AMC), hospital days, caloric intake, and CD4-positive T-lymphocyte count. Each of these parameters was measured or evaluated at four points: 6 months before nasogastric tube feeding, at the time nasogastric tube feeding was initiated, at the time gastrostomy tube feeding was initiated, and 6 months after gastrostomy tube feedings began.
Results. Weight z score [-2.1 (0.14) to -1.58 (0.14)] and weight-for-height z score [-0.98 (0.16) to -0.15 (0.17)] improved with gastrostomy tube feedings. There was a trend toward improvement in weight z score with nasogastric tube feedings. Caloric intakes increased progressively with nasogastric and gastrostomy tube feedings. No improvement in height, TSF, AMC, hospital days, or CD4 counts was seen in the follow-up period. However, children who had the greatest increase in weight had the most improvement in fat stores (TSF) (r = .65, P = .002) and a decrease in hospital days after the gastrostomy tube was placed (r = -.48, P = .025). Higher age-adjusted CD4 counts and lower weight-for-height z scores at the time of enteral supplementation were significant predictors of a positive response to gastrostomy tube feedings(r = .85, P = .0001). Children who responded favorably had a 2.8-fold reduction in the risk of dying for every positive unit change in weight z score (P = .005).
Conclusion. Gastrostomy tube supplementation for HIV-infected children can improve weight and fat mass when other oral methods fail. Weight gain is coincident with greater caloric intakes. HIV-infected children with higher CD4 counts and lower weight-for-height z scores are likely to respond favorably to gastrostomy tube feedings. Early nutritional intervention is indicated for HIV-infected children.
Parental Stress and Growth Outcome in Growth-deficient Children
Authors: Bithoney William G. , Van Sciver Margaret M. , Foster Susan , Corso Stephen , Tentindo Christine 
Published: December 2021

Objective. In order to examine the relationship between parental stress, child psychosocial factors, anemia, lead poisoning, and growth deficiency (GD), 48 children attending a GD referral program were recruited consecutively and matched with 50 comparison subjects from a primary care program.
Method. Parents completed the Parenting Stress Index (PSI) with subscales and provided demographic data. Children received developmental screening, hemoglobin levels, Pb levels, and growth evaluation. They also received medical evaluation for GD. T tests were used to evaluate group differences. Spearman Rho correlation analyses were computed between group coefficients and PSI scales, Pb, and hemoglobin levels.
Results. No differences were found on the PSI with regard to overall parental stress. GD parents perceived themselves as less competent (P &lt; .001), and their children as less adaptable (P &lt; .006). They also reported more social isolation (P &lt; .05). The GD group had more anemia and Pb poisoning (P &lt; .002 and P &lt; .001, respectively); however, these variables were not related to differences in child adaptability or growth outcome. A high sense of parental competence and high child adaptability were associated with improved growth outcomes (P &lt; .001 and P &lt; .02, respectively).
Conclusions. We conclude that parents of GD children seen in an outpatient referral setting show no difference in overall perceived stress levels versus comparison subjects. Increased parental competence and child adaptability are strongly associated with improved growth outcome. Decreased child adaptability may contribute to GD pathology. These findings challenge the traditional view of GD etiology.