COVID-19 stressors, wellbeing and health behaviours: a cross-sectional study.

BACKGROUND: Following the implementation of pandemic response measures, concerns arose regarding the impact for population health and wellbeing. METHODS: This study reports findings from a survey (N = 2510) conducted in Warwickshire (UK) during August and September 2020, and for the first time investigates behaviours which may worsen or mitigate the association between COVID-19-related stressors and wellbeing. RESULTS: Increased stressors were associated with lower mental wellbeing and higher loneliness. Participants with a mental health condition reported lower wellbeing, as did younger groups, women and participants not in employment. To cope with restrictions, more participants engaged in healthier behaviours over unhealthy behaviours, and relaxing reduced the association between stressors and poor wellbeing. Some participants reported increasing alcohol and unhealthy dietary behaviours to cope with restrictions, however, these behaviours did not mitigate the impact of COVID-19 stressors and were instead negatively associated with wellbeing. Around half of participants helped neighbours during the pandemic, a behaviour positively associated with wellbeing particularly among older adults. CONCLUSION: These findings contribute understanding about how various positive and negative health behaviours may mitigate or worsen the impact of COVID-19 on wellbeing, and how public health interventions may effectively target behaviours and groups in similar populations.

Site of PGF2α injection does not alter effectiveness of the Select Synch + controlled internal drug release and timed artificial insemination protocol.

Beef Quality Assurance programs have contributed to significant improvements in the wholesomeness of beef available for consumption. Injection site blemishes in the round have declined since the promotion of administering intramuscular injections in the neck. Unfortunately, many producers continue to administer estrus synchronization (ES) drugs in the rump. The objective of this study was to compare the effectiveness of injection site of PGF2α, in ES protocols, on steroid hormone concentrations and pregnancy rates. A Select Synch + 7-day controlled internal drug release ES protocol was conducted with the site of PGF2α injection alternated between neck and rump in beef cattle (n = 312) at the Ohio State University Agricultural Technical Institute and North Carolina State University. Blood samples (n = 75) were collected at controlled internal drug release insertion and at the time of artificial insemination (AI) to determine if progesterone (P4) and estrogen (E2) concentrations varied due to PGF2α injection site. All cattle were confirmed pregnant by ultrasonography at approximately 30 and 90 days after insemination in North Carolina and approximately 70 days after insemination in Ohio. Data were analyzed as randomized complete block designs in PROC GLIMMIX with animal as the experimental unit. Differences were declared significant at P < 0.05. Site of PGF2α injection, in either the neck or rump, did not affect (P > 0.05) overall conception rates in response to AI (58.4% and 55.6%, respectively). Altering PGF2α injection site did not impact P4, E2 concentrations, or the P4:E2 ratio at AI (P > 0.05). However, cattle inseminated after displaying estrus had greater (P < 0.05) pregnancy rates than timed AI (67.8 vs. 47.5%, respectively). First service conception rates and pregnancy rates were consistent with previous reports. Overall, altering the location of the PGF2α injection during ES did not change circulating hormone concentrations at AI or pregnancy rates; therefore, cattle producers should follow Beef Quality Assurance guidelines when administering ES protocols.

Divergent regulation of hypothalamic neuropeptide Y and agouti-related protein by photoperiod in F344 rats with differential food intake and growth.

Hypothalamic genes involved in food intake and growth regulation were studied in F344 rats in response to photoperiod. Two sub-strains were identified: F344/NHsd (F344/N) and F344/NCrHsd (F344/NCr); sensitive and relatively insensitive to photoperiod respectively. In F344/N rats, marked, but opposite, changes in the genes for neuropeptide Y (NPY) (+97.5%) and agouti-related protein (AgRP) (-39.3%) expression in the arcuate nucleus were observed in response to short (8 : 16 h light/dark cycle, SD) relative to long (16 : 8 h light/dark cycle, LD) day photoperiods. Changes were associated with both reduced food intake and growth. Expression of the genes for cocaine and amphetamine-regulated transcript (CART) and pro-opiomelanocortin (POMC) in the arcuate nucleus was unchanged by photoperiod. POMC in the ependymal layer around the third ventricle was markedly inhibited by SD. Parallel decreases in the genes for growth hormone-releasing hormone (GHRH) and somatostatin (Somatostatin) mRNA in the arcuate nucleus and Somatostatin in the periventricular nucleus were observed in SD. Serum levels of insulin-like growth factor (IGF)-1 and insulin were lower in F344/N rats in SD, whereas neither leptin nor corticosterone levels were affected. By contrast, F344/NCr rats that show only minor food intake and growth rate changes showed minimal responses in these genes and hormones. Thus, NPY/AgRP neurones may be pivotal to the photoperiodic regulation of food intake and growth. Potentially, the SD increase in NPY expression may inhibit growth by decreasing GHRH and Somatostatin expression, whereas the decrease in AgRP expression probably leads to reduced food intake. The present study reveals an atypical and divergent regulation of NPY and AgRP, which may relate to their separate roles with respect to growth and food intake, respectively.

Altered expression of SOCS3 in the hypothalamic arcuate nucleus during seasonal body mass changes in the field vole, Microtus agrestis.

We have previously shown that cold-acclimated (8 degrees C) male field voles (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity.

Having it all: historical energy intakes do not generate the anticipated trade-offs in fecundity.

An axiom of life-history theory, and fundamental to our understanding of ageing, is that animals must trade-off their allocation of resources since energy and nutrients are limited. Therefore, animals cannot "have it all"--combine high rates of fecundity with extended lifespans. The idea of life-history trade-offs was recently challenged by the discovery that ageing may be governed by a small subset of molecular processes independent of fitness. We tested the "trade-off" and "having it all" theories by examining the fecundities of C57BL/6J mice placed onto four different dietary treatments that generated caloric intakes from -21 to +8.6% of controls. We predicted body fat would be deposited in relation to caloric intake. Excessive body fat is known to cause co-morbidities that shorten lifespan, while caloric restriction enhances somatic protection and increases longevity. The trade-off model predicts that increased fat would be tolerated because reproductive gain offsets shortened longevity, while animals on a restricted intake would sacrifice reproduction for lifespan extension. The responses of body fat to treatments followed our expectations, however, there was a negative relationship between reproductive performance (fecundity, litter mass) and historical intake/body fat. Our dietary restricted animals had lower protein oxidative damage and appeared able to combine life-history traits in a manner contrary to traditional expectations by having increased fecundity with the potential to have extended lifespans.

Introduction of a high-energy diet acutely up-regulates hypothalamic cocaine and amphetamine-regulated transcript, Mc4R and brown adipose tissue uncoupling protein-1 gene expression in male Sprague-Dawley rats.

Obesity is an escalating problem in Western societies. Susceptibility to weight gain within an obesogenic environment is variable. It remains unclear how the range of weight gain responses are generated. It is possible that an individual's immediate and/or sustained appetite for apparently palatable foods, or metabolic adaptations to a new diet could be important. The present study therefore examined the short- to medium-term effects of a high-energy (HE) diet on bodyweight, food intake, and energy balance-related signalling systems. Sprague-Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 (UCP-1) and hypothalamic energy-balance related genes were determined by Northern blotting or in situ hybridisation, respectively. Short-term exposure (12 h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but caloric intake was increased. Exposure to HE diet for 14 days (medium term) established a bodyweight differential of 7.7 g, and animals exhibited a transient increase in caloric intake of 5 days duration. Terminal levels of leptin, insulin, glucose and non-esterified fatty acids (NEFAs) were all increased in HE-fed animals. UCP-1 mRNA was elevated in interscapular brown adipose tissue from HE-fed rats only at 12 h. Cocaine and amphetamine-regulated transcript (CART) and Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an HE diet, respectively. The rats appear to passively over-consume calories as a result of consuming a similar weight of a more energy dense food. This evokes physiological responses, which adjust caloric intake over several days. Circulating NEFA and insulin concentrations, UCP-1, Mc4R and CART gene expression are increased as an immediate consequence of consuming HE diet, and may be involved in countering hypercaloric intake. Circulating leptin is increased in the HE-fed animals after 48 h, reflecting their increasing adiposity.

Serotype prevalence of occult pneumococcal bacteremia.

OBJECTIVE: The licensure and use of a pneumococcal conjugate vaccine that is immunogenic in children who are younger than 2 years may affect the epidemiology of occult bacteremia. This study was conducted to determine the serotype prevalence of Streptococcus pneumoniae isolates from children with occult bacteremia and to document the proportion that would be covered by the recently licensed heptavalent pneumococcal conjugate vaccine. METHODS: A cohort of 5901 children who were 2 to 24 months of age and had a temperature of >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department was studied to determine the prevalence of S pneumoniae serotypes. Patients were excluded if their immune system was suppressed, they had a diagnosis of a focal infection, they were evaluated by lumbar puncture, they were admitted to the hospital, or they died during initial evaluation. Blood cultures were inoculated into pediatric blood culture bottles and processed using an automated carbon dioxide monitoring system. All pneumococcal isolates were serotyped on the basis of capsular swelling with type-specific antisera (Quellung reaction). RESULTS: The study population consisted of 5901 patients. The overall rate of occult bacteremia was 1.9% (95% confidence interval [CI]: 1.5-2.3). S pneumoniae accounted for 92 of 111 isolates (82.9%; 95% CI: 74.6-89.4) in children with occult bacteremia. Eight pneumococcal serotypes were represented: 6A (2%), 9V (6%), 19F (6%), 18C (8%), 4 (9%), 6B (13%), 23F (15%), and 14 (42%). Serotypes 14, 6B, and 23F accounted for 69.3% (95% CI: 58.6-78.7) of typed isolates. In the cohort, 97.7% (95% CI: 92-99.7) of isolated serotypes are represented in the newly licensed heptavalent pneumococcal conjugate vaccine. The single isolated serotype that would not have been covered by the currently licensed heptavalent pneumococcal conjugate vaccine was 6A. CONCLUSIONS: S pneumoniae accounts for the vast majority of bacterial pathogens in children with occult bacteremia. As indicated by the results of this study, the heptavalent pneumococcal conjugate vaccine may prevent the majority of occult pneumococcal bacteremia episodes. The 2 cases of bacteremia with a serotype that would not have been included in the vaccine both were due to serotype 6A. It has been noted that there is potential nonvaccine serotype and subgroup cross-protection (6A from 6B) afforded to children who are immunized with the heptavalent vaccine. The high potential efficacy of the heptavalent pneumococcal conjugate vaccine for strains that cause occult bacteremia in our population may have a profound effect on the treatment of children with fever without a source. There has been an alarming and rapid emergence of antibiotic-resistant pneumococcal strains. Less pressure to use broad-spectrum antibiotics, which in turn causes further antibiotic resistance, should result. Laboratory testing and hospitalization also should be reduced. The prevalence rates determined by this study may be used as baseline data for comparison of serotype rates of occult pneumococcal bacteremia after widespread use of the heptavalent vaccine.

Effects of medicaid managed care on quality: childhood immunizations.

BACKGROUND: Underimmunization is distributed unevenly across populations, concentrated among the impoverished. Managed care has stimulated the development of quality indicators such as immunization rates to assess health status of populations. OBJECTIVE: To determine if enrollment in Medicaid managed care (MMC) improves quality of health care as reflected by immunization rates when compared with fee-for-service Medicaid (FFSM). DESIGN. Prospective cohort study of infants born between May 1994 and April 1995 with a 24-month follow-up period. SETTING: Urban teaching hospital and surrounding ambulatory settings. PARTICIPANTS: Consecutive sample of infants (n = 644) enrolled in MMC or FFSM. Ninety-two percent of eligible patients were enrolled, and 87% completed follow-up. MAIN OUTCOME MEASURE: Up-to-date immunization status. RESULTS: Seventy-three percent of the MMC and 72.4% of the FFSM patients were up-to-date on their immunizations: relative risk 1.01, (95% confidence interval [CI] 0.87, 1.17). No differences were found in age at immunization between the MMC and FFSM groups. After adjusting for other factors in multivariate analysis, insurance status remained unassociated with immunization status: adjusted odds ratio (OR) 1.04, (95% CI: 0.90, 1.10). Factors associated with up-to-date immunization included firstborn child, OR 2.28 (95% CI: 1.45, 3.60) and adequate maternal prenatal care, OR 2.24 (95% CI: 1.44, 3.48). Variables characterizing children less likely to be adequately immunized included father living in home with child, OR 0.53 (95% CI: 0.33, 0.85) and using private office-based primary care, OR 0.39 (95% CI: 0.23, 0.63). CONCLUSIONS: Enrollment in MMC did not improve rates of immunizations when compared with FFSM.

Serratia marcescens transmission in a pediatric intensive care unit: a multifactorial occurrence.

BACKGROUND: Fourteen patients in the pediatric cardiac intensive care unit (CICU) had > or =1 positive culture for a single strain of Serratia marcescens from April through December 1995 (study period). OBJECTIVES: To identify risk factors for S marcescens infection or colonization in a pediatric CICU. METHODS: Retrospective case-control study. Assessment of CICU infection control practices and patient exposure to CICU health care workers (HCWs). Epidemiologic-directed cultures of the environment and HCWs' hands were obtained. SETTING: Pediatric CICU. PATIENTS: Fourteen patients in the pediatric CICU had > or =1 positive culture for a single strain of S marcescens from April through December 1995 (study period). CICU patients who did not have S marcescens infection or colonization during the study period were randomly selected as controls. RESULTS: A case patient was more likely than a noncase patient to have exposure to a single HCW (odds ratio [OR], 19.5; 95% CI, 2.6-416; P<.003); however, this association was not adequately explained by epidemiologic or microbiologic studies. Interviews suggested that during the outbreak period, handwashing frequency among HCWs might have been reduced because of severe hand dermatitis. CONCLUSIONS: A combination of factors, including breaks in aseptic technique, reduced frequency of handwashing among HCWs before and between caring for patients, decreased attention to infection control practices, and environmental contamination may have indirectly contributed to this S marcescens infections outbreak.

Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome.

OBJECTIVE: To evaluate selected characteristics of occult bacteremia in the post-Haemophilus influenzae type b (HIB) vaccine era. METHODS: A retrospective cohort study was performed involving 5901 children 2 to 24 months old with fever >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department (ED) between February 1993 and June 1996. Patients were excluded if immune-suppressed, diagnosed with a focal infection, evaluated by lumbar puncture, or admitted to the hospital during initial evaluation. Prevalence of occult bacteremia, distribution of current pathogenic organisms, and time to positive culture in a continuously monitored system were determined. All patients with cultures positive for pathogenic bacteria were reevaluated and serious adverse outcomes were documented. RESULTS: The prevalence of occult bacteremia was 1.9% (95% confidence interval: 1.5%-2.3%). Streptococcus pneumoniae accounted for 82.9% of all pathogens and H influenzae was not a causative organism in this cohort. The mean time to positive culture was significantly shorter for pathogens compared with contaminants (14.9 hours vs 31.1 hours). A culture that was positive in

Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control.

OBJECTIVE: To determine the cost-effectiveness and cost-benefit of an infection control program to reduce nosocomial respiratory syncytial virus (RSV) transmission in a large pediatric hospital. DESIGN: RSV nosocomial infection (NI) was studied for 8 years, before and after intervention with a targeted infection control program. The cost-effectiveness of the intervention was calculated, and cost-benefit was estimated by a case-control comparison. SETTING: Children's Hospital of Philadelphia, a 304-bed pediatric hospital. PATIENTS: All inpatients with RSV infection, both community- and hospital-acquired. INTERVENTION: Consisted of early recognition of patients with respiratory symptoms, confirmation of RSV infection by laboratory testing, establishing cohorts of patients and nursing staff, gown and glove barrier precautions, and monitoring and education of staff. OUTCOME MEASURES: The incidence density of RSV NI before and after the intervention was calculated as the rate per 1000 patient days-at-risk for infection. Intervention costs included laboratory testing, isolation, and administration of the program. The cost of RSV NI was estimated by comparing hospital charges for 30 cases and matched uninfected controls. RESULTS: A total of 148 patients acquired NI (88 before and 60 after the intervention). The Mantel-Haenszel stratified relative risk for NI in the period before the infection control program, compared with the postintervention period, was.61 (95% confidence interval:.53-.69). By applying the preintervention stratum-specific rates of infection to the days-at-risk in the postintervention period, an estimated 100 NIs would have been expected, which in comparison to the 60 NIs observed, yielded an estimated program effectiveness of 10 RSV NIs prevented per season. The total cost of the program per season was $15 627 or $1,563/NI prevented. In comparison, the mean cost to the hospital was $9,419/case of RSV NI, resulting in a cost-benefit ratio of 1:6. CONCLUSIONS: A targeted infection control intervention was cost-effective in reducing the rate of RSV NI. For every dollar spent on the program, approximately $6 was saved.

Hyperosmotic stress stimulates promoter activity and regulates cellular utilization of the serum- and glucocorticoid-inducible protein kinase (Sgk) by a p38 MAPK-dependent pathway.

We have established that the serum- and glucocorticoid-inducible protein kinase (Sgk) is a new component of the hyperosmotic stress response. Treatment of NMuMg mammary epithelial cells with the organic osmolyte, sorbitol, caused the stable accumulation of Sgk transcripts and protein after an approximately 4-h lag. Transient transfection of a series of sgk-CAT reporter plasmids containing either 5' deletions or continuous 6-base pair substitutions identified a hyperosmotic stress-regulated element that is GC-rich and is necessary for the sorbitol stimulation of sgk gene promoter activity. Gel shift analysis identified four major DNA-protein complexes in the hyperosmotic stress-regulated element that, by competition with excess consensus wild type and mutant oligonucleotides and by antibody supershifts, contains the Sp1 transcription factor. Several lines of evidence suggest that the p38 MAPK signaling pathway mediates the hyperosmotic stress stimulation of sgk gene expression. Treatment with pharmacological inhibitors of p38 MAPK or with a dominant negative form of MKK3, an upstream regulator of p38 MAPK, significantly reduced or ablated the sorbitol induction of sgk promoter activity or protein production. Using an in vitro peptide transphosphorylation assay, sorbitol treatment activates either endogenous or exogenous Sgk that is localized to the cytoplasmic compartment. Thus, we propose that the stimulated expression of enzymatically active Sgk after sorbitol treatment is a newly defined component of the p38 MAPK-mediated response to hyperosmotic stress.

The judicious use of antibiotic agents in common childhood respiratory illness.

Increased bacterial resistance is caused most frequently by the widespread use of antimicrobial agents. Antimicrobial agents are often used inappropriately to treat common respiratory illnesses in children. This article discusses the judicious use of antimicrobials in the common cold, otitis media, acute sinusitis, pharyngitis, and bronchitis.

Phorbol ester induced MDR1 expression in K562 cells occurs independently of mitogen-activated protein kinase signaling pathways.

The MDR1 gene encoding the multidrug pump P-glycoprotein is transcriptionally activated in response to diverse extracellular stimuli, including the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the signal transduction pathway responsible is unknown. Downstream of protein kinase C (PKC), the effects of TPA are often mediated by the Raf-1/MEK/ERK mitogen-activated protein kinase (MAPK) cascade, and Raf-1 has been implicated in MDR1 induction by serum and mitogens. Therefore, we examined the potential role of MAPK activation in TPA-mediated MDR1 induction in human leukemia K562 cells. MDR1 mRNA expression was significantly increased by TPA in the concentration range of 4 - 100 nM, with a maximal response 5 - 10 h after TPA addition. TPA-mediated MDR1 induction was inhibited by several PKC inhibitors including staurosporine, H7 and calphostin C. TPA stimulated the subcellular translocation of PKCalpha from the cytosol to the membrane and nucleus but did not affect other PKC isozymes. TPA also activated the Raf1/MEK/ERK cascade and activated another MAPK member, p38, but not JNK. In order to determine the potential role of MAPKs in MDR1 induction by TPA, specific inhibitors were utilized. The MEK inhibitor PD 098059, as well as the PKC inhibitors, completely blocked TPA-mediated ERK activation. However, under identical conditions, MDR1 induction by TPA was completely unaffected by PD 098059. Furthermore, SB 202190, which effectively inhibited TPA-mediated p38 activation, failed to inhibit TPA-induced MDR1 mRNA expression. These data demonstrate that MDR1 induction by TPA occurs via a PKC-dependent mechanism that operates independently of ERK, p38 or JNK pathways, and thus have important implications for understanding the mechanisms of MDR1 induction by extracellular stimuli.

Pharmacokinetics of single daily dose gentamicin in children with cancer.

PURPOSE: To study the pharmacokinetics of single daily dose (SDD) gentamicin in children with cancer. METHODS: Serum concentrations of gentamicin were prospectively measured at 0.5, 8, 16, and 24 hours after a single daily dose of gentamicin 6 mg/kg, given as a 30-minute infusion in 18 febrile children with cancer and a central venous catheter. Then the peak (0.5-hour) and 12-hour serum concentrations of gentamicin were prospectively measured after a SDD of 7 mg/kg during 73 febrile episodes in 54 pediatric cancer patients with suspected infections. The aim was to achieve a peak serum concentration of 15 to 20 microg/mL 10 times the minimum inhibitory concentration (MIC) for sensitive Pseudomonas strains, resulting in good bactericidal activity and a long post-antibiotic effect (PAE) after a SDD of gentamicin. RESULTS: The mean serum peak gentamicin concentration 30 minutes after the end of the infusion of 6 mg/kg was 13.3 +/- 4.0 microg/mL. The mean serum concentration 16 hours after the infusion was 0.3 +/- 0.2 microg/mL. The mean peak and 12-hour serum concentration after SDD of 7 mg/kg was 17.2 +/- 3.9 microg/mL and 0.9 +/- 0.7 microg/mL, respectively. The mean peak serum concentration after SDD of 7 mg/kg in children younger than 5 years of age (16.1 +/- 3.5 microg/mL ) was significantly lower than that of children over 5 years of age (18.2 +/- 3.9 microg/mL; P = 0.02). The desired peak serum concentration was achieved in 67% of children younger and 84% of those older than 5 years of age. CONCLUSION: Adequate peak serum concentrations of gentamicin in children may be obtained with a SDD of 7 mg/kg. Children younger than 5 years of age achieve lower peak serum gentamicin concentration after SDD of 7 mg/kg than those older than 5 years.

Unpredictability of serious bacterial illness in febrile infants from birth to 1 month of age.

BACKGROUND: A prior study (N Engl J Med. 1993; 329: 1437-1441) produced an effective screen to identify 1-to 2-month-old febrile infants (FIs) who are at low risk of having a serious bacterial illness (SBI). Because of anticipated differences in the epidemiological features of febrile illnesses, that Philadelphia protocol was not applied to FIs younger than 1 month. OBJECTIVES: To describe the epidemiological features of febrile illness in neonates from birth to 1 month of age and to determine the applicability to this population of the Philadelphia screen for identifying FIs at low risk for SBI. DESIGN: A 36-month consecutive cohort study. SETTING: An urban pediatric emergency department. PARTICIPANTS: Infants aged from 3 to 28 days old with temperatures of 38 degrees C or higher. INTERVENTIONS: Following full evaluation for SBI, all FIs, pending results of bacterial cultures, were admitted to the hospital and empirically administered antibiotics. After their illnesses resolved, the medical records of all FIs were reviewed. At that time, the Philadelphia protocol (originally developed for 1- to 2-month-old FIs) was applied and retrospectively judged for safety and efficacy. RESULTS: Of the 254 FIs enrolled, 32 (12.6%) had an SBI. The spectrum of bacterial and nonbacterial diseases closely approximated that described in 1- to 2-month-old FIs. When the Philadelphia protocol was applied to all 254 FIs, 109 (42.9%) would have been identified as at low risk for bacterial disease. Included in that group are 2 FIs with bacterial urinary tract infection, 2 FIs with bacteremia, and 1 FI with bacterial gastroenteritis. CONCLUSIONS: The cause of febrile illnesses in neonates (infants younger than 1 month) approximates that of FIs 1 to 2 months of age. Unlike that for older 1- to 2-month-old FIs, however, the Philadelphia protocol lacks the sensitivity and negative predictive value to identify neonates at low risk for SBI.

The efficacy of routine outpatient management without antibiotics of fever in selected infants.

BACKGROUND: A previous study produced a protocol for outpatient management of febrile infants (FIs) judged to be at low risk for serious bacterial illness (SBI). This Philadelphia protocol demonstrated that 40% of FIs seen in the emergency department could be safely managed without antibiotics at home; and it was established by the emergency department staff as the standard of care at our institution. OBJECTIVE: To determine 1) the actual practices of management of FIs 18 months after establishment of the Philadelphia protocol as the standard of care, and 2) the continued efficacy of noninvasive outpatient management of fever in FIs who, using the Philadelphia protocol, were identified as low risk for SBI. DESIGN: Thirty-six-month consecutive cohort study. SETTING: Urban pediatric emergency department. PARTICIPANTS: Four hundred twenty-two infants, 29 to 60 days of age, with rectal temperatures >/=38.0 degrees C. Interventions. After a complete history taking, physical examination, and workup for SBI, infants were managed at the discretion of the attending physician in the emergency department. Subsequently, those management practices were reviewed and compliance with the Philadelphia protocol was evaluated. In addition, the overall efficacy and safety of that standard during 8 years of use was assessed. RESULTS: Of the 422 FIs enrolled, 101 (24%) were prospectively identified as low risk for SBI, and safe for management without antibiotics. Twenty-eight (6%) FIs were managed out of accordance with the Philadelphia protocol. Seven were admitted out of accordance, 10 (2 with UTI) were discharged out of accordance, and 11 inpatients (1 with bacterial gastroenteritis) initially received no antibiotics out of accordance with the protocol. Physician failure to consider the results of the complete blood count or urinalysis accounted for errors involving FIs with SBI. None of the 43 FIs with SBI were identified by the Philadelphia protocol to be at low risk for SBI. CONCLUSIONS: The Philadelphia protocol for outpatient management without antibiotics of FIs at low risk for SBI remains practical, reliable, and safe. Because breaches do occur, physicians must carefully scrutinize protocol compliance, especially with regard to the complete blood count and urinalysis.

Preschoolers with syphilis.

Syphilis in preschoolers is rarely described in current medical literature, despite the rise in syphilis in both the adult and the pediatric populations during the past decade. Since that time, 3 children between 3 and 4 years of age have been diagnosed with syphilis at the Children's Hospital of Philadelphia. The presentations and clinical manifestations of syphilis in these 3 children are described, and the difficulty in identifying the source of infection is discussed. The presentations of these children included nephrosis and secondary syphilis, the corymbiform and palmar rash of syphilis, and subtle signs of late congenital infection in an otherwise asymptomatic child. One child had documented congenital infection, 1 had probable congenital infection that went untreated, and 1 did not have appropriate neonatal testing documented. None of the children gave a verbal history of sexual abuse, although it is likely that all three cases resulted from sexual abuse. The evaluation of preschool children with syphilis is confounded by the interpretation of acquired infection in consideration of a history of possible or documented congenital disease. The assessment is complicated further by problems with recognition of clinical disease, the inability of young children to provide a history, prenatal and neonatal testing methods used, changes in treatment recommendations made during the past decade, and inadequate follow-up to document cure of congenitally infected infants. With the increase in syphilis seen in recent years, physicians are more likely to encounter preschoolers with syphilis. Our ability to document acquired infection, however, is hampered by the difficulties encountered in following recommended guidelines for evaluation and follow-up and by limitations in interviewing young victims of sexual abuse, which may impair our ability to protect children from additional harm. Understanding the pathophysiology and progression of this disease remains challenging even in this modern era.

Effectiveness of intramuscular penicillin versus oral amoxicillin in the early treatment of outpatient pediatric pneumonia.

OBJECTIVE: To determine if intramuscular (IM) penicillin is more effective than oral (PO) amoxicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia. METHODS: Prospective, randomized, evaluator-blinded, clinical trial. SETTING: Pediatric emergency department (ED) of an urban children's hospital. PATIENTS: ED patients with radiographically confirmed pneumonias managed as outpatients. Patients with chronic illnesses, wheezing, allergy to amoxicillin or penicillin, recent antibiotic therapy, or concurrent diagnosis of another febrile illness were excluded. INTERVENTIONS: Patients received either a two-day supply of PO amoxicillin (50 mg/kg/day divided tid), or an IM injection of procaine penicillin G (PPG) (50,000 units/kg). They had a complete blood count (CBC), blood culture, and nasopharyngeal swab for viral culture done at initial visit. They returned in 24 to 36 hours for reevaluation. OUTCOME MEASURES: The main measures were temperature, respiratory rate, and general appearance score; additional measures were accessory muscle use, pulse oximetry, parental report of activity/oral intake. RESULTS: One hundred seventy patients were enrolled. There were no significant differences between the two groups at initial or follow-up visits with respect to temperature, respiratory rate, accessory muscle use, pulse oximetry, or parental reports of activity level and oral intake. Only in the general appearance of children less than two years of age did there appear to be a difference (P = 0.03). When subanalysis excluded patients with positive viral studies (n = 17) or chest x-rays "reread" by an attending pediatric radiologist as "no infiltrate" (n = 29), this difference disappeared (P = 0.10). Three patients in the PO group, and five in the IM group failed by all three main outcome measures (P = 1.00). Four patients in the PO group, and five in the IM group were hospitalized at the follow-up visit (P = 1.00). CONCLUSION: There does not appear to be a significant difference between PO amoxicillin and IM penicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia.