Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)     

Health outcomes in offspring of mothers with breast implants

OBJECTIVE: To examine the occurrence of esophageal disorders, connective tissue diseases, and congenital malformations in children of mothers with breast implants. METHODS: Nationwide register-based follow-up study of all offspring born during 1977 to 1992 to a cohort of 1135 women with breast implants for cosmetic reasons and to a comparison cohort of 7071 women who underwent breast reduction surgery. Cause-specific hospi-talization rates among offspring, relative to those of the general population, were calculated from the Danish National Registry of Patients. RESULTS: Among the 939 children of mothers with breast implants, higher rates of esophageal disorders were observed, but the excess was similar for those born before versus after the implant surgery. Higher than expected hospitalization rates for these conditions were also observed among 3906 children of women who underwent breast reduction surgery. No significant increases in connective tissue diseases or congenital malformations were observed in either the breast implant or breast reduction cohorts. CONCLUSIONS: This first epidemiologic cohort study provides no evidence that silicone breast implants affect risks of esophageal or other disorders in children of the implantees. Rather, the observed risk pattern suggests that a lower threshold exists among both groups of women who have undergone cosmetic breast surgery in seeking professional medical care for problems normally solved outside the hospital.     

Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG)

OBJECTIVE: To describe the clinical and microbiological characteristics of infants and children with bone and joint infections caused by penicillin-susceptible and penicillin-nonsusceptible strains of Streptococcus pneumoniae. DESIGN: Multicenter, prospective patient accrual; retrospective chart review of identified patients. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Forty-two children with bone and/or joint infections prospectively enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Data were collected on multiple variables, including age, gender, race, days of symptoms before and during hospitalization, antibiotic and surgical therapy, laboratory and imaging studies. RESULTS: Of the 42 children enrolled (21 bone, 21 joint infections), 14 had isolates that were not susceptible to penicillin. Eight of 16 (50%) strains isolated from children who received antibiotics within 4 weeks before hospitalization were not susceptible to penicillin, compared with 4 of 15 (27%) strains isolated from children without previous antibiotic exposure. Clinical response to therapy was similar between children infected by penicillin-susceptible strains compared with those infected by penicillin-nonsusceptible strains, including duration of hospitalization (9.1 days vs 11.2 days), days of intravenous antibiotic therapy (25.3 days vs 24.6 days), days of fever (3.6 days vs 3.1 days), and sequelae (14% vs 7%). The most commonly prescribed single agents for parenteral therapy in definitive treatment were ceftriaxone (36%), penicillin (15%), and clindamycin (15%). Oral therapy followed parenteral therapy in 56% of children. The mean (+/- standard deviation) duration of total antibiotic therapy in children with osteomyelitis was 57.5 +/- 48.6 days (range, 23-196 days) and 29.2 +/- 11.8 days (range, 12-67 days) for arthritis. Late sequelae (long-term destructive changes of the bone or joint) were documented in 5 (12%) children, 4 with osteomyelitis, and 1 with arthritis. Sequelae occurred in 30% of children with long bone osteomyelitis associated with infection in the adjacent joint. The age of children with sequelae was younger than those without sequelae (6.4 months vs 18.6 months). CONCLUSIONS: The demographic characteristics and anatomic sites of infection in our patients were similar to previously published series collected from single institutions before the emergence of significant antibiotic resistance in S pneumoniae. Our analysis suggests that children infected by penicillin-nonsusceptible strains have a similar clinical response to therapy when compared with children infected by penicillin-susceptible strains.     

Initial qualitative evaluation of computed radiography in an intensive care unit

The first computed radiography (CR) unit in Australia was installed at St Vincent's Hospital, Melbourne, in February 1994. An initial qualitative evaluation of the attitude of the intensive care unit (ICU) physicians to the CR unit was conducted in June 1994 by use of a survey. The results of the survey of ICU physicians indicated that images were available faster than under the previous system and that the use of the CR system was preferred to evaluate chest tubes and line placements. While it is recognized that a further detailed radiological evaluation of the CR system is required to establish the diagnostic performance of CR compared with conventional film, some comments on the implementation of the system and ICU physician attitudes to the CR system are put forward for consideration by other hospitals examining the possible use of CR systems.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Comparison of Gemcitabine and the Gemcitabine Analog 1-(2′-deoxy-2′-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models

Purpose

Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2′-deoxy-2′-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug.

Procedures

[¹⁸F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [¹⁴C]gemcitabine and [¹⁸F]FAC were mapped with autoradiography. The inter-tumor correlation between [¹⁴C]gemcitabine and [¹⁸F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [³H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays.The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [¹⁸F]FAC and [¹⁴C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [¹⁴C]gemcitabine and [¹⁸F]FAC were largely co-localized.

Conclusions

In the lines examined here, [¹⁸F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [¹⁸F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors.

     

高效液相色谱法同时测定苯巴比妥、苯妥英钠和卡马西平血药浓度

目的：建立同时测定血清中苯巴比妥,苯妥英钠和卡马西平的浓度的高效液相色谱（ＨＰＬＣ）,方法：血清乙酸乙酯提取浓集后进样,采用Ｃ１８柱,以甲醇－水（５０：５０）为流动相,苯乙酮为内标物,在波长２１０ｎｍ处测定。     

Off-Campus Residence as a Risk Factor for Heavy Drinking Among College Students

Background: College student alcohol use is a public health problem. Objectives: The aim of this study was to examine associations between residence and drinking behaviors among college students. We hypothesized that living off-campus independently or with peers would be associated with riskier drinking than living on-campus, and living with parents would be associated with less risky drinking than living on-campus. Methods: We analyzed data from two separate studies conducted at two four-year universities in the Northeast. Study 1 examined data from 1286 students (57% female) attending a private university. In Study 2, analyses were replicated and extended with 2408 students (67% female) from a public university. We conducted regression analyses that controlled for age, race, gender, and class year to determine the unique association of residence on typical and peak drinking, frequency of heavy drinking, and alcohol-related consequences. Results: In both samples, students living off-campus without parents reported more frequent alcohol consumption, larger drinking quantities, more frequent heavy drinking, and a greater number of alcohol-related consequences than students living on-campus (ps <.001). In Study 2, students living off-campus with their parents exhibited significantly fewer risky drinking behaviors than those living on-campus (ps <.001). Conclusions: Living off-campus – either independently or with peers – is a risk factor for heavy drinking and consequences. This group exhibits more risky drinking behaviors and alcohol-related consequences than students living on-campus, independent of age and class year. Therefore, students moving off-campus may be appropriate targets for alcohol misuse prevention programs.     

Community-based surveillance of maternal deaths in rural Ghana

Objective

To examine the feasibility and effectiveness of community-based maternal mortality surveillance in rural Ghana, where most information on maternal deaths usually comes from retrospective surveys and hospital records.

Methods

In 2013, community-based surveillance volunteers used a modified reproductive age mortality survey (RAMOS 4+2) to interview family members of women of reproductive age (13–49 years) who died in Bosomtwe district in the previous five years. The survey comprised four yes–no questions and two supplementary questions. Verbal autopsies were done if there was a positive answer to at least one yes–no question. A mortality review committee established the cause of death.

Findings

Survey results were available for 357 women of reproductive age who died in the district. A positive response to at least one yes–no question was recorded for respondents reporting on the deaths of 132 women. These women had either a maternal death or died within one year of termination of pregnancy. Review of 108 available verbal autopsies found that 64 women had a maternal or late maternal death and 36 died of causes unrelated to childbearing. The most common causes of death were haemorrhage (15) and abortion (14). The resulting maternal mortality ratio was 357 per 100 000 live births, compared with 128 per 100 000 live births derived from hospital records.

Conclusion

The community-based mortality survey was effective for ascertaining maternal deaths and identified many deaths not included in hospital records. National surveys could provide the information needed to end preventable maternal mortality by 2030.