Which early ‘red flag’ symptoms identify children with meningococcal disease in primary care?

Background

Symptoms are part of the initial evaluation of children with acute illness, and are often used to help identify those who may have serious infections. Meningococcal disease is a rapidly progressive infection that needs to be recognised early among children presenting to primary care.

Aim

To determine the diagnostic value of presenting symptoms in primary care for meningococcal disease.

Design of study

Data on a series of presenting symptoms were collected using a parental symptoms checklist at point of care for children presenting to a GP with acute infection. Symptom frequencies were compared with existing data on the pre-hospital features of 345 children with meningococcal disease.

Setting

UK primary care.

Method

The study recruited a total of 1212 children aged under 16 years presenting to their GP with an acute illness, of whom 924 had an acute self-limiting infection, including 407 who were reported by parents to be febrile. Symptom frequencies were compared with those reported by parents of 345 children with meningococcal disease. Main outcome measures were diagnostic characteristics of individual symptoms for meningococcal disease.

Results

Five symptoms have clinically useful positive likelihood ratios (LR+) for meningococcal disease: confusion (LR+ = 24.2, 95% confidence interval [CI] = 11.5 to 51.3), leg pain (LR+ = 7.6, 95% CI = 4.9 to 11.9), photophobia (LR+ = 6.5, 95% CI = 3.8 to 11.0), rash (LR+ = 5.5, 95% CI = 4.3 to 7.1), and neck pain/stiffness (LR+ = 5.3, 95% CI = 3.5 to 8.3). Cold hands and feet had limited diagnostic value (LR+ = 2.3, 95% CI = 1.9 to 3.0), while headache (LR+ = 1.0, 95% CI = 0.8 to 1.3), and pale colour (LR+ = 0.3, 95% CI = 0.2 to 0.5) did not discriminate meningococcal disease in children.

Conclusion

This study confirms the diagnostic value of classic ‘red flag’ symptoms of neck stiffness, rash, and photophobia, but also suggests that the presence of confusion or leg pain in a child with an unexplained acute febrile illness should also usually prompt a face-to-face assessment to exclude meningococcal disease. Telephone triage systems and primary care clinicians should consider these as ‘red flags’ for serious infection.     

Effect of hydrogel lens wear on the major tear proteins during extended wear

Purpose: The purpose of the present study was to determine whether contact lens wear disturbed the levels of tear proteins and to further determine whether this was a transient or continuous disruption. Methods: Lactoferrin, lysozyme and albumin were quanti-tated from tears of neophyte patients and were compared with the levels of these proteins in contact lens wearers after one and six nights and 6 months of extended wear The quantitation of these tear proteins was performed by sandwich ELISA and turbidimetric assay. Results: Results showed that there were no statistically significant changes in the concentration of any of the proteins investigated. Conclusions: Extended wear of hydrogel lenses does not appear to alter the concentration of the major tear film proteins, indicating that the tear film is constantly replenished to maintain protein levels, which are depleted due to protein adsorption to the lens surface.     

Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype

This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH- DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis.      

SHOULD WOMEN WITH DIABETES MELLITUS RECEIVE HORMONE REPLACEMENT THERAPY?

The benefits of hormone replacement therapy (HRT) in non-diabetic postmenopausal women are now well established. HRT improves climacteric symptoms and has beneficial effects on the cardiovascular system and the skeleton. In addition, recent studies suggest a reduced risk of Alzheimer's disease and colorectal cancer. Despite these beneficial effects, concerns continue regarding the increased risk of malignancy, thromboembolism and the possible deterioration in blood pressure. There are no long-term studies in women with diabetes who also receive HRT, so we cannot be certain of the benefits and risks in this population. We can postulate, however, and draw some conclusions from current data, which suggest that the risk/benefit ratio is similar to that for the non-diabetic population. Based on present information, postmenopausal diabetic women should be actively considered for HRT provided the physician is aware of the possible problems and the patient is sufficiently counselled to make an informed decision.     

贝母辛的结构修正

从川产家种华西贝母(Fritillaria siechuanica)鳞茎中分出贝母辛(peimisine)(碱Ⅲ)。应用光谱法(¹H—¹H,¹³C—¹H COSY,2D—NOE),对文献报告的贝母辛的结构作了修正,并证明FR—5与贝母辛系同一化合物。指出湖贝辛结构的某些错误以及对松贝辛的结构提出怀疑,认为其可能为贝母辛。     

Pulmonary hamartoma: diagnosis by transthoracic needle-aspiration biopsy

Hamartomas of the lung often present as asymptomatic, noncharacteristic masses that can seldom be differentiated from other lung masses such as primary cancer or metastases by conventional radiography. Transthoracic needle-aspiration biopsy (TNAB) has become a popular and reliable method for the diagnosis of a lung lesion, and it offers a valuable alternative to diagnostic thoracotomy. In our study, TNAB established the diagnosis of pulmonary hamartoma in 12 of 14 (86%) patients. In eight patients, one procedure (using one to three punctures) was sufficient to establish the diagnosis, and, in four patients, two procedures (using one to two punctures) were necessary. In two patients, the lesion was missed on second and/or third biopsy procedures, and the correct diagnosis was obtained at surgery. Cytologic examination of the material was diagnostic in five of the 14 patients. Tissue specimens were sent in 13/14 patients, and findings of histologic examination established the correct diagnosis in 11 of these patients. One of the 12 patients in whom hamartoma was correctly diagnosed by TNAB underwent resection of his lesion, and histologic examination confirmed the diagnosis. In the remaining 11 patients, the lesions have been stable on follow-up chest examinations.     

Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype

Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1- hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.