Prospective diagnostic test accuracy of transvaginal ultrasound posterior approach for uterosacral ligament and torus uterinus deep endometriosis.

OBJECTIVE: To determine the diagnostic test accuracy of transvaginal ultrasound (TVS) using a standardized technique for the diagnosis of deep endometriosis (DE) of the uterosacral ligaments (USLs) and adjacent torus uterinus (TU). METHODS: This was a prospective diagnostic test accuracy study conducted at the McMaster University Medical Center Tertiary Endometriosis Clinic, Hamilton, ON, Canada. Consecutive participants were enrolled if they successfully underwent TVS and surgery by our team from 10 August 2020 to 31 October 2021. The index test was TVS using a standardized posterior approach performed and interpreted by an expert sonologist. The reference standard included direct surgical visualization on laparoscopy by the same person who performed and interpreted the ultrasound scans. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios were calculated for the TVS posterior approach for each location using the reference standard. RESULTS: There were 54 consecutive participants included upon completion of laparoscopy and histological assessment. The prevalence of DE for the left USL, right USL and TU was 42.6%, 22.2% and 14.8%, respectively. Based on surgical visualization as the reference standard, TVS demonstrated an accuracy of 92.6% (95% CI, 82.1-97.9%), sensitivity of 82.6% (95% CI, 61.2-95.1%), specificity of 100% (95% CI, 88.8-100%), PPV of 100% and NPV of 88.6% (95% CI, 76.1-95.0%) for diagnosing DE in the left USL. For DE of the right USL, TVS demonstrated an accuracy of 94.4% (95% CI, 84.6-98.8%), sensitivity of 75.0% (95% CI, 42.8-94.5%), specificity of 100% (95% CI, 91.6-100%), PPV of 100% and NPV of 93.3% (95% CI, 84.0-97.4%). For DE of the TU, TVS demonstrated an accuracy of 100% (95% CI, 93.4-100%), sensitivity of 100% (95% CI, 63.1-100%), specificity of 100% (95% CI, 92.3-100%), PPV of 100% and NPV of 100%. CONCLUSIONS: We observed high diagnostic test accuracy of the evaluated standardized TVS technique for assessing DE of the USLs and TU. Further studies evaluating this technique should be performed, particularly with less experienced observers, before considering this technique as the standard approach. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dental referrals for patients with diabetes: survey of barriers and enablers for medical and health professionals.

BACKGROUND: Oral health care improves diabetes management; however, medical and other health practitioners do not commonly refer their patients with diabetes for oral health care. This study aimed to understand barriers to and enablers of dental referrals for patients with diabetes. METHODS: Quantitative data were collected from a cross-sectional survey of health care providers attending a virtual Grand Rounds on the relationship between oral health and diabetes. Attendees were invited to complete and share a Forms survey. Barriers to and enablers of dental referrals were compared for 18 health professionals working in inpatient/ward settings to 23 working in community/primary care settings using the chi-square test. RESULTS: Across both work settings, only 12% of respondents often or always discussed the importance of oral health and only 8% often or always referred their patients with diabetes for dental care. Time barriers, awareness and knowledge of how/where to send dental referrals were significant barriers, while online referral pathways, more education and availability of brochures for the patient to take home were identified as key enablers for dental referrals. CONCLUSIONS: Online referral pathways, targeted oral health education and resources for medical and health professionals caring for patients with diabetes may increase the number of patients being referred for dental care as part of their diabetes managements. © 2023 Australian Dental Association.

Developing a prototype for integrated dental and diabetes care: understanding needs and priorities.

BACKGROUND: Periodontal treatment may be a useful adjunct to medical management of diabetes; however, oral health has not been integrated into multidisciplinary diabetes care in Australia. This study aimed to understand the needs of patients and staff at a diabetes clinic to inform a prototype of integrated dental and diabetes care. METHODS: Quantitative and qualitative data were collected from patients and staff at West Moreton Diabetes Clinic (WMDC) between September-October 2019. Clinical information, survey responses and dental screening results were analysed for 41 patients. Semi-structured interviews were held with six patients and a focus group with seven staff. RESULTS: Most patients (83%) had not seen a dentist in the previous year. Of the 37 patients with remaining natural teeth, 84% required periodontal assessment and 46% had multiple carious lesions. Unmet treatment needs and rates of access were similar for private and public dental patients. Staff and patients reported high levels of support for incorporation of dental care at WMDC. CONCLUSIONS: Integrating oral health into diabetes management is well-supported by patients and staff to address significant unmet dental needs for both public and private dental patients. Incorporating dental screening/services within diabetes clinics may increase uptake and improve awareness of its importance in diabetes management.

Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management.

Odontogenic infections can become life-threatening if not managed in a timely manner, and they increase the physical cost of treatment to the patient and the financial cost to the public health system. We investigated the number of admissions to a Queensland tertiary hospital within a decade, and differences in the patients' characteristics, severity at presentation, and clinical outcomes. We compared patients with odontogenic infections who were taken to theatre at the Royal Brisbane & Women's Hospital (RBWH) between January 2003 and December 2004 with those treated between January 2013 and December 2014, a total of 292. Data on demographics, presentation, previous history, antimicrobial treatment, and admissions, were collated and analysed. There were no significant differences in demographics. In the 2013/2014 group there was a two-fold increase in infections related to lower third molars (p=0.001), a 50% increase in trismus (p=0.001), and a 20% increase in submandibular swelling (p=0.010). The percentage of patients admitted to the intensive care unit (ICU) was three and a half times higher in the 2013/2014 group (p=0.001). The presentation of odontogenic infections has increased in the decade from 2003/2004 to 2013/2014. Measures of the severity of disease have increased, while the basic characteristics of the patients have remained constant. Improved primary preventative measures and early interventions are therefore needed to alleviate the burden that these infections place on the public health system.

Osteonecrosis of the jaws: a 14-year retrospective survey of hospital admissions.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a serious complication of both radiation and antiresorptive therapies. This study aimed to determine how many patients have been treated for medication-related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis (ORN), and whether the number of diagnoses has decreased over time with improved awareness and preventative measures. METHODS: Medical records at the Royal Brisbane and Women's Hospital, Gold Coast University Hospital and Robina Hospital were reviewed to identify patients diagnosed with MRONJ and ORN between January 2003 and May 2017. Data on patient demographics, year of admission and primary disease were analysed. RESULTS: Two hundred and thirty-eight patients were diagnosed with ONJ, of which 74.4% were ORN and 25.6% were MRONJ. Tongue (24.6%), floor of mouth (17.3%) and tonsillar (15.1%) squamous cell carcinomas were the most common primary diseases associated with ORN, with a strong male predominance (80%). Of patients diagnosed with MRONJ, 52.5% were taking low-dose antiresorptives for osteoporosis (44.2%), rheumatoid arthritis (4.6%) or Paget's disease (3.3%), while 47.5% were oncology patients receiving high-dose antiresorptives. CONCLUSIONS: The number of patients diagnosed with MRONJ and ORN has trended upwards since 2003. ORN affected three times more patients than MRONJ, and patients on low-dose antiresorptives accounted for over half of the MRONJ cases.

Risk factors for medication-related osteonecrosis of the jaws: A systematic review.

The purpose of this study was to identify the patient populations at risk of medication-related osteonecrosis of the jaw (MRONJ) and determine which medical and dental comorbidities are significant risk factors for this disease. An electronic search of Embase, MEDLINE, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform and ProQuest Dissertations and Theses Global was conducted to identify all human studies that reported risk factors for MRONJ. Only a qualitative analysis was performed due to significant heterogeneity in the collected data. The search strategy identified 2872 records, of which 219 studies were eligible for inclusion. A total of 4106 patients with MRONJ were identified, 39 different systemic diseases were implicated, and 14 medical and 11 dental risk factors were reported, although no statistical analysis of the significance of each of these factors was possible. The clinical reach of MRONJ may be wider than anticipated, and more data on the significance of each potential risk factor are needed to guide the identification and management of at-risk patients.

Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality.

Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC). Using short hairpin RNA (shRNA)-mediated suppression of NRP1, we demonstrate that NRP1 regulates the mesenchymal phenotype of mCRPC cell models and the invasive and metastatic dissemination of tumor cells in vivo. In patients, immunohistochemical staining of tissue microarrays and mRNA expression analyses revealed a positive association between NRP1 expression and increasing Gleason grade, pathological T score, positive lymph node status and primary therapy failure. Furthermore, multivariate analysis of several large clinical prostate cancer (PCa) cohorts identified NRP1 expression at radical prostatectomy as an independent prognostic biomarker of biochemical recurrence after radiation therapy, metastasis and cancer-specific mortality. This study identifies NRP1 for the first time as a novel androgen-suppressed gene upregulated during the adaptive response of prostate tumors to ATTs and a prognostic biomarker of clinical metastasis and lethal PCa.

A multigene array for measurable residual disease detection in AML patients undergoing SCT.

AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ-PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994-2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ-PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection.

Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.

REASONS FOR PERFORMING STUDY: Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals. OBJECTIVES: To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose-dependent manner in both neonatal and older pony foals. METHODS: Seven healthy neonatal pony foals (age 1-2 weeks), and 11 healthy older pony foals (age 4-8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2-way repeated measures ANOVA, followed by a Holm-Sidak multiple comparison procedure if warranted. RESULTS: There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups. CONCLUSIONS: Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects. POTENTIAL RELEVANCE: Butorphanol shows analgesic potential in foals for management of somatic painful conditions.

Capturing cold-stress-related sequence diversity from a wild relative of common bean (Phaseolus angustissimus).

One restriction to the cultivation of common bean, Phaseolus vulgaris L., is its limited tolerance to low temperatures. In the present study, subtraction suppression hybridization was employed to enrich for stress responsive genes in both a chilling-susceptible common bean and a relatively more chilling-tolerant wild bean species, Phaseolus angustissimus. For each species, approximately 11 000 expressed sequence tags were generated. Comparative sequence analysis of the EST collection with the available annotated genome sequences of the model Fabaceae species Medicago truncatula and Glycine max identified protein homologues for approximately 65% and 80% of the Phaseolus sequences, respectively. This difference reflects the closer phylogenetic relationship between the genera Phaseolus and Glycine compared with Medicago. Annotation of the Phaseolus sequences was facilitated through this comparative analysis and indicated that several heat shock proteins, cytochrome P450s, and DNA binding factors were uniquely found among the sequences from the wild species P. angustissimus. The Phaseolus sequences have been made available on a GBrowse implementation using M. truncatula as the reference genome, providing rapid access to the sequence data and associated comparative genome data.

The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories.

Massively parallel pyrosequencing allows sensitive deep sequencing to detect molecular aberrations. Thus far, data are limited on the technical performance in a clinical diagnostic setting. Here, we investigated as an international consortium the robustness, precision and reproducibility of amplicon next-generation deep sequencing across 10 laboratories in eight countries. In a cohort of 18 chronic myelomonocytic leukemia patients, mutational analyses were performed on TET2, a frequently mutated gene in myeloproliferative neoplasms. Additionally, hotspot regions of CBL and KRAS were investigated. The study was executed using GS FLX sequencing instruments and the small volume 454 Life Sciences Titanium emulsion PCR setup. We report a high concordance in mutation detection across all laboratories, including a robust detection of novel variants, which were undetected by standard Sanger sequencing. The sensitivity to detect low-level variants present with as low as 1-2% frequency, compared with the 20% threshold for Sanger-based sequencing is increased. Together with the output of high-quality long reads and fast run time, we demonstrate the utility of deep sequencing in clinical applications. In conclusion, this multicenter analysis demonstrated that amplicon-based deep sequencing is technically feasible, achieves high concordance across multiple laboratories and allows a broad and in-depth molecular characterization of cancer specimens with high diagnostic sensitivity.

Factors associated with the risk of West Nile virus among crows in New York State.

West Nile virus (WNV) is transmitted between avian hosts in enzootic cycles by a mosquito vector. The virus has significant disease effects on humans and equines when it bridges into an epizootic cycle. As the initial epidemic of WNV in 1999, perennial outbreaks in New York State suggest the local establishment of natural foci with perpetuation of the virus among susceptible hosts rather than reintroduction of the virus. The factors that play a role in the perpetuation of the virus are not fully understood. American crows (Corvus brachyrhynchos) are known to be highly susceptible to infection with the virus. We investigate the factors that put crows at risk of infection in Tompkins County, New York during the period of 2000-2008 in a case-control study. Cases were crow carcasses that were found dead and tested positive for WNV using real time reverse transcription or VecTest. Data on putative risk factors were collected and assessed for significance of association with the presence of WNV using logistic regression analysis to evaluate the significance of each factor while simultaneously controlling for the effect of others. The risk of a crow carcass testing WNV positive varied with age, season of the year and ecological area where the carcass was found. Crows that were more than 1-year-old were four times more likely to be WNV positive in comparison to birds that were less than 1 year of age. It was three times more likely to find WNV positive carcasses in residential areas in comparison to rural areas. The risk of testing WNV positive did not vary by sex of the crow carcasses.

Suitability of an automated nucleic acid extractor (easyMAG) for use with hepatitis C virus and human immunodeficiency virus type 1 nucleic acid amplification testing.

Serological screening assays have greatly reduced, but not eliminated, the risk of transmission of viral infections by transfusion of blood and blood products. In addition, the 1999 regulation of the European Agency for the Evaluation of Medicinal Products requiring all plasma for fractionation to have tested negative for hepatitis C virus (HCV) RNA (CPMP/BWP/390/97, 1998) led many blood transfusion services to introduce nucleic acid amplification technology (NAT) to screen blood donations for HCV, and in some services for human immunodeficiency virus (HIV) and hepatitis B virus (HBV). BioMérieux's second-generation system, the NucliSENS easyMAG, was evaluated as a suitable platform for the automated extraction of nucleic acids for use with the existing SNBTS NAT assays. Two nucleic acid extraction protocols were examined, either lysis on the easyMAG (on board) or a 30-min pre-incubation of the sample with lysis buffer at 37 °C (off board). Off board lysis was found to extract nucleic acid more efficiently for both HCV and HIV NAT assays although the improvement was more marked with HIV. The 95% limit of detections (LODs) were 10.11 IU/ml (on board) and 7.21 IU/ml (off board) for HCV and 55.11 IU/ml (on board) and 34.13 (off board) for HIV. Using the more sensitive off board lysis, nucleic acid extraction specificity, robustness and reliability of the easyMAG were examined and over 10,000 Scottish blood donations (in 107 pools of 95 donations) were tested for HCV and HIV in parallel with the existing assay. The results indicate that the easyMAG is a suitable and flexible nucleic acid extraction system, providing high quality nucleic acids and a rapid response alternative to commercial, fully automated, approved blood screening platforms.

Antifungal susceptibility against yeasts isolated from pediatric oncology patients.

Yeast infections cause morbidity in children with cancer and we evaluated species distribution and antifungal susceptibilities of the etiologic agents in this group. Specimens from 58 children yielded 64 cultures positive for yeasts. Central venous catheters were present in 56 (97%) of the children and neutrophil counts were <500 cells/ml3 in 34% of the patients. Twenty-two (38%) had received recent antifungal treatment, with 15 (25%) receiving fluconazole (FLU) prophylaxis. The Candida isolates recovered from four (27%) of the children on FLU prophylaxis, were resistant to this drug. Candida albicans isolates were susceptible to 100% of antifungals tested, whereas non-C. albicans Candida spp. were variable in their susceptibility patterns. FLU prophylaxis minimally affected susceptibility.

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Kinetics of collagen crosslinking in adult bovine articular cartilage.

OBJECTIVE: Determine the kinetics of collagen crosslinking in adult bovine articular cartilage explants using radiolabel pulse-chase studies. METHODS: Explant cultures of adult bovine articular cartilage were radiolabeled with [14C]lysine in medium including fetal bovine serum and ascorbate, and then maintained for chase periods up to 28 days. In some samples, beta-aminopropionitrile (BAPN) was included during chase to inhibit lysyl oxidase-mediated collagen crosslinking. Tissue was hydrolyzed and analyzed for [14C]metabolites in the forms of lysine, hydroxylysine, dehydrodihydroxylysinonorleucine (DeltaDHLNL), and hydroxylysyl pyridinoline (HP). RESULTS: Explant cultures of adult bovine articular cartilage metabolized lysine into hydroxylysine and the collagen crosslinks, DeltaDHLNL and HP. During chase, [14C]hydroxylysine maintained steady-state levels, [14C]DHLNL rose to a plateau, and [14C]HP increased gradually. Addition of BAPN inhibited formation of [14C]DHLNL. Analysis of raw data and that normalized to [14C]hydroxylysine gave characteristic time constants for formation of DeltaDHLNL and HP crosslinks of 1-2 and 7-30 days, respectively. The distribution of [14C]lysine metabolites in collagen crosslinks was described by peak values in [14C]DHLNL/[14C]hydroxylysine of 0.047-0.064 and in [14C]HP/[14C]hydroxylysine of 0.03. CONCLUSION: Collagen crosslinks form in cartilage explants in vitro according to the classical lysyl oxidase-mediated pathway.

A link between prompt optical and prompt gamma-ray emission in gamma-ray bursts.

The prompt optical emission that arrives with the gamma-rays from a cosmic gamma-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt gamma-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt gamma-rays, indicating a common origin for the optical light and the gamma-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium.

Biochemical quantification of DNA in human articular and septal cartilage using PicoGreen and Hoechst 33258.

OBJECTIVE: To compare two fluorometric assays, utilizing (1) the bisbenzimidazole Hoechst 33258 and (2) PicoGreen, for determining DNA content in human cartilage. METHODS: Human articular and nasal septal cartilage explants were digested using proteinase K. Portions of sample digest were analysed for intrinsic and dye-enhanced fluorescence with either Hoechst 33258 or PicoGreen. RESULTS: Intrinsic tissue fluorescence in both articular and septal cartilage increased with age and was prominent at wavelengths used for Hoechst 33258 but relatively low at wavelengths used for PicoGreen. The relative contribution of intrinsic fluorescence to total dye-enhanced fluorescence of human cartilage was markedly greater for Hoechst 33258 (19-57%) than for PicoGreen (2-7%). Thus, in many situations, DNA in human cartilage can be assayed using PicoGreen without the need to correct for intrinsic cartilage fluorescence. The enhancement of fluorescence by each dye was found to be specific for DNA, as shown by fluorescence spectra, >90% sensitivity to DNase, and resistance to RNase. In addition, little or no interference was caused by non-DNA tissue components, since DNA caused an equal enhancement in the absence or presence of proteinase K digested human cartilage, once intrinsic cartilage fluorescence was subtracted. PicoGreen was more sensitive for assaying DNA (0.9ng DNA/ml) than Hoechst 33258 (6ng DNA/ml) and can also be used in a microplate reader. CONCLUSION: PicoGreen can be used in a rapid and sensitive assay to quantify DNA in small samples of human cartilage.

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.

Detection of enterovirus viraemia in blood donors.

BACKGROUND AND OBJECTIVES: The infrastructure established for screening blood donations for hepatitis C virus has enabled large-scale population testing for other viruses which are potentially transmissible by transfusion of blood components and plasma-derived blood products. We have measured the frequency of viraemia of enteroviruses and parechoviruses in 83 600 Scottish blood donors to allow an initial assessment of their risk to blood safety. MATERIALS AND METHODS: Plasma samples collected from blood donors over 7 calendar months were tested anonymously in mini-pools of 95 donations, by polymerase chain reaction (PCR) for human enterovirus and parechovirus sequences. RESULTS: A total of 19 mini-pools, from the 880 that were tested, were PCR-positive for enterovirus RNA, predicting a donor prevalence of 0.023%. Enterovirus sequences were not detected in factor VIII or IX clotting factor concentrates. None of the 230 mini-pools or concentrates contained detectable parechovirus RNA. CONCLUSIONS: The prevalence of enterovirus viraemia detected in this study predicts that at least 1000 enterovirus-contaminated blood components are transfused per year in the UK. The frequency of transmission and clinical outcome after exposure to enterovirus-contaminated blood components in recipients is unknown.