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Biomedical subjects

Elizabeth Johnson

Publications and source records attributed to Elizabeth Johnson.

At least 19 recordsLinked to original sources
PubMed2026

Diagnostic performance of panfungal PCR on tissue specimens for the diagnosis of invasive fungal diseases: a systematic review and meta-analysis of the Fungal PCR Initiative (FPCRI).

UNLABELLED: Invasive fungal diseases are difficult to diagnose because of the limited sensitivity of culture. Panfungal PCR amplicon sequencing assays (targeting ribosomal RNA, such as 18S, 28S, ITS) are recommended for fungal identification in histopathology samples showing fungal elements. However, data describing its overall performance and consistency are lacking. This systematic literature review and meta-analysis assessed the performance of panfungal PCR on formalin-fixed paraffin-embedded (FFPE) and non-fixed (fresh or frozen) tissue samples. A systematic literature search was performed to include studies reporting the use of panfungal PCR for fungal identification in FFPE or non-fixed tissue samples. PCR sensitivity and specificity were assessed using the reference standard of histopathology showing fungal elements. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled estimates were obtained using random-effects meta-analysis. Twenty-eight studies were included. In FFPE samples (18 studies, 852 samples), sensitivity and specificity were 75.4% (95% confidence interval [CI], 59.2-86.6) and 93.5% (70.2-98.9), respectively. Sensitivity in non-fixed samples (13 studies, 207 samples) was 86.5% (74.7-93.3), while specificity could not be assessed (insufficient data). Comparative analyses showed a significantly higher sensitivity of panfungal PCR over culture (88.2%; 76-94.7 vs 52.2%; 39-65, P = 0.001). Sub-analyses could not demonstrate the superiority of one PCR target over another due to limited data. Panfungal PCR exhibited adequate sensitivity and good specificity in FFPE samples. Sensitivity was even higher in non-fixed samples and largely superior to culture. Nevertheless, large interstudy variability was observed, warranting interlaboratory studies to define the optimal PCR target and standardized protocols. IMPORTANCE: Invasive fungal diseases are difficult to diagnose because of the low sensitivity of culture. Panfungal PCRs are widely used for fungal identification in tissue specimens but suffer from heterogeneous procedures and performance. This meta-analysis shows an acceptable sensitivity (75.4% and 86.5% in fixed and non-fixed samples, respectively) and good specificity (93.5%) of panfungal PCR, supporting its use, not only on histopathology-positive fixed samples but also in non-fixed samples concomitantly with other diagnostic tools (cultures and fungal-specific PCRs if available). These results provide a strong basis for further standardization of panfungal PCR techniques via interlaboratory assays to assess reproducibility and optimize analytical protocols. CLINICAL TRIALS: This study is registered with PROSPERO as CRD42023461148.

Humans↗
PubMed2006

Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis.

In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.

Administration, Oral↗
PubMed2006

Risk factors for brachial plexus injury with and without shoulder dystocia.

OBJECTIVE: To ascertain whether brachial plexus palsy (BPP) that occurs without shoulder dystocia (SD) represents a traction injury during unrecognized SD or a natural phenomenon with a different mechanism of injury, we compared risk factors and outcomes between SD-associated and non-SD-associated BPP. STUDY DESIGN: Neonates with BPP after cephalic vaginal delivery were pooled from all deliveries at Johns Hopkins (June, 1993-December, 2004) and a dataset of litigated permanent BPP from multiple institutions (1986-2003), grouped by SD association based on clinician documentation and compared by using Fisher exact and t tests. RESULTS: Thirty percent of 49 non-SD-BPP and 11% of 280 SD-BPP lacked all risk factors for SD (P = .002). Compared with SD-BPP infants, non-SD-BPP infants were average weight (P < .001) and had cord pH less than 7.10 (P = .01) more commonly and exhibited a trend toward posterior shoulder involvement (P = .06). Nearly all non-SD-BPP were temporary, whereas more than 90% of permanent BPP were associated with SD (odds ratio 17, 7.3-39.6). CONCLUSION: Non-SD-BPP is uncommon and likely mechanistically distinct from SD-BPP. Risk factors, birth weight, fetal acidosis, posterior arm involvement, and injury severity distinguish between shoulder dystocia-related brachial plexus injuries and those not recorded as such.

Brachial Plexus↗
PubMed2006

Schizophyllum commune associated with bronchogenous cyst.

Previous TBC lesions, diabetes and use of corticosteroids are recognised as risk factors for developing long-standing disease caused by Schizophyllum commune. In the case report presented in this work, S. commune was isolated from an inflamed bronchogenous cyst of previously immunocompetent patient. The isolated mould failed to sporulate and identification was achieved by nucleotide sequencing.

Bronchogenic Cyst↗
PubMed2006

A consensus on fungal polymerase chain reaction diagnosis?: a United Kingdom-Ireland evaluation of polymerase chain reaction methods for detection of systemic fungal infections.

The limitations of classical diagnostic methods for invasive fungal infections (IFIs) have led to the development of molecular techniques to aid in the detection of IFIs. Despite good published performance, interlaboratory reproduction of these assays is variable, and no consensus has been reached for an optimal method. This publication describes the first multicenter study of polymerase chain reaction methods, for the detection of Aspergillus and Candida species, currently used in the UK and Ireland by distribution and analysis of multiple specimen control panels. All three Candida methods were comparable, achieving a satisfactory level of detection (10 cfu), and the method of preference was dependent on the requirements of the particular laboratory. The results for the five Aspergillus assays were more variable, but two methods (2Asp and 4Asp) were superior (10(1) conidia). Formally, the overall performances of the two Aspergillus assays were comparable (kappa statistic = 0.77). However, on the Roche LightCycler, there was a clear sample-type effect that greatly reduced the detection limit of the 4Asp method when testing whole blood samples. Therefore, the preferred Aspergillus method relied on the amplification platform available to the user. This study represents the initial process to achieve a consensus method for the diagnosis of IFIs.

Aspergillosis↗
PubMed2005

Low effective dispersal of asexual genotypes in heterogeneous landscapes by the endemic pathogen Penicillium marneffei.

Long-distance dispersal in microbial eukaryotes has been shown to result in the establishment of populations on continental and global scales. Such "ubiquitous dispersal" has been claimed to be a general feature of microbial eukaryotes, homogenising populations over large scales. However, the unprecedented sampling of opportunistic infectious pathogens created by the global AIDS pandemic has revealed that a number of important species exhibit geographic endemicity despite long-distance migration via aerially dispersed spores. One mechanism that might tend to drive such endemicity in the face of aerial dispersal is the evolution of niche-adapted genotypes when sexual reproduction is rare. Dispersal of such asexual physiological "species" will be restricted when natural habitats are heterogeneous, as a consequence of reduced adaptive variation. Using the HIV-associated endemic fungus Penicillium marneffei as our model, we measured the distribution of genetic variation over a variety of spatial scales in two host species, humans and bamboo rats. Our results show that, despite widespread aerial dispersal, isolates of P. marneffei show extensive spatial genetic structure in both host species at local and country-wide scales. We show that the evolution of the P. marneffei genome is overwhelmingly clonal, and that this is perhaps the most asexual fungus yet found. We show that clusters of genotypes are specific to discrete ecological zones and argue that asexuality has led to the evolution of niche-adapted genotypes, and is driving endemicity, by reducing this pathogen's potential to diversify in nature.

Journal Article↗
PubMed2005

BRCA1/2 testing in hereditary breast and ovarian cancer families II: impact on relationships.

Members of hereditary breast and ovarian cancer (HBOC) families often express concern during genetic counseling about the impact of BRCA1/2 testing on close relatives. Yet whether there are likely to be adverse effects of either the decision to undergo genetic testing or the results of testing on family relationships is unknown. One purpose of this study was to assess the impact on close family relationships. Within a randomized trial of breast cancer genetic counseling methods, members of 13 HBOC families were offered BRCA1/2 testing for a known family mutation. The Family Relationship Index (FRI) of the Family Environment Scale (FES) was used to measure perceived family cohesion, conflict, and expressiveness at baseline and again 6-9 months following the receipt of test results, or at the equivalent time for those who declined testing. Participants (n = 212) completed baseline and follow-up questionnaires. Comparisons were made between testers and non-testers as well as between those who tested positive and negative for the family mutation. One hundred eighty-one participants elected to undergo genetic testing (85%) and 47 (26%) were identified to have a mutation. After adjusting for baseline family relationship scores, counseling intervention, gender and marital status, non-testers reported a greater increase in expressiveness (P = 0.006) and cohesion (P = 0.04) than testers. Individuals who tested positive reported a decrease in expressiveness (P = 0.07), although as a trend. Regardless of test decision or test result, those who were randomized to a client-centered counseling intervention reported a decrease in conflict (P = 0.006). Overall, study results suggest that undergoing genetic testing and learning ones BRCA1/2 status may affect family relationships. Those individuals who declined testing reported feeling closer to family members and more encouraged to express emotions to other family members demonstrating potential benefit from the offer of testing. Since those who tested positive reported feeling less encouraged to express their emotions within the family, we recommend helping clients to identify others with whom they feel comfortable sharing their thoughts and feelings about their positive gene status and increased cancer risk.

BRCA1 Protein↗
PubMed2005

Modelling the incubation period of anthrax.

Models of the incubation period of anthrax are important to public health planners because they can be used to predict the delay before outbreaks are detected, the size of an outbreak and the duration of time that persons should remain on antibiotics to prevent disease. The difficulty is that there is little direct data about the incubation period in humans. The objective of this paper is to develop and apply models for the incubation period of anthrax. Mechanistic models that account for the biology of spore clearance and germination are developed based on a competing risks formulation. The models predict that the incubation period distribution depends critically on the rate that spores are cleared from the lung and to a lesser extent on the dose of inhaled spores. The models are used in a statistical analysis of data from an anthrax outbreak that occurred in Sverdlovsk, Russia. The analysis suggests that spores are cleared from the lung at a rate between 8 per cent per day and 14 per cent per day, which is in good agreement with experimental studies of animals. The analysis suggests that at low doses, the overall median incubation period time is about 10 days, which includes a median lag of about 2 days between spore germination and onset of symptoms. Male gender and younger ages were associated with longer incubation periods as was lower dose of inhaled spores.

Adult↗
PubMed2005

Chart documentation by general physicians of the glaucoma medications taken by their patients.

PURPOSE: To estimate the frequency of documentation of glaucoma medications by primary care physicians. DESIGN: Cross-sectional, observational study. METHODS: The general medical records of 100 patients of one glaucoma specialist were reviewed. We recorded whether the mention of eyedrops appeared in the medical record. RESULTS: The median number of glaucoma medications used was 2.5 (range 1 to 5). Fifty-five (55%, 95% confidence interval: 45%-65%) of the medical records of the primary physicians mentioned eyedrops. Alpha-agonists were statistically less frequently documented (13%) in the general medical record than beta-adrenergic blockers (47%) and prostaglandins (44%). CONCLUSION: Almost half of the charts of these primary physicians had no documentation of any eyedrop use by their patients with glaucoma. An important step in reducing drug-induced side effects and interactions with other medications would be better recognition by primary physicians of the ophthalmic drugs used by their patients.

Adult↗
PubMed2005

Perioperative nurses and patient outcomes--mortality, complications, and length of stay.

THE PURPOSE OF THE STUDY described in this article was to identify the relationship between RN staffing factors in the OR and surgical patient outcomes. THE STUDY ADDRESSED two main questions: whether the level of RN staffing in the OR is related to postoperative complications, mortality, and length of stay (LOS) and whether certification, RN agency use, 24-hour staffing, and the performance of multidisciplinary code drills are related to complications, mortality, and LOS. ACCORDING TO THIS STUDY, selected organizational factors in ORs had a significant influence on patient outcomes.

Aged↗
PubMed2005

Phenotypic identification of Candida albicans by growth on chocolate agar.

In this study, we describe a simple method for the identification of Candida albicans in clinical samples. A total of 383 clinical isolates of Candida species were streaked onto chocolate agar and incubated for 48 h at 37 degrees C in the presence of an atmosphere of 6% CO2. All 208 of the C. albicans isolates tested, developed an easy to identify filamentous colony morphology. Of 175 other Candida species tested, 172 (98.3%) were distinguishable from C. albicans by their smooth colony morphology. Three isolates (1.7%) exhibited weak filamentation after prolonged incubation. Although not a routine medium in medical mycology a significant advantage of using chocolate agar lies in its use in clinical bacteriology laboratories for the isolation of fastidious bacteria. Implementation of the proposed method is applicable across a range of specimen types, thus allowing the direct identification of C. albicans in clinical samples. This simple method may allow a quicker entry into directed treatment.

Candida albicans↗
PubMed2005

Preferences for eye drop characteristics among glaucoma specialists: a willingness-to-pay analysis.

PURPOSE: To determine the importance that US glaucoma specialists place on attributes of eye drops for lowering intraocular pressure. MATERIALS AND METHODS: We performed a cross-sectional survey by conducting a telephone interview with 113 members of the American Glaucoma Society. We administered a willingness-to-pay (WTP) instrument asking glaucoma specialists how much they would pay to obtain particular characteristics in an eye drop. Demographic data were correlated with the WTP responses. We compared the glaucoma specialists' responses to those previously obtained from patients. The main outcome measure was willingness-to-pay more (in US dollars). RESULTS: Almost all respondents were willing to pay extra to reduce the frequency of administration of eye drops from 3 times a day to once a day, and to avoid blurred vision, drowsiness, or inhibition of sexual performance. Only 54 (48%) were willing to pay more to avoid iris darkening. The mean amount that respondents were willing to pay (relative to US 50 dollars) differed significantly across eye drop characteristics (P < 0.001). The mean amount that the respondents were willing to pay was highest for avoidance of inhibition of sexual performance (US 105 dollars), blurred vision (US 92 dollars), and drowsiness (US 92 dollars). When compared with glaucoma and glaucoma suspect patients, more ophthalmologists were likely to pay extra for desirable eye drop attributes. However, the magnitude of the extra amount was similar between ophthalmologists and patients. CONCLUSIONS: Glaucoma specialists place differing value on various eye drop characteristics. Although the proportion of glaucoma specialists willing to pay more is generally greater than the proportion of patients, the preferences of glaucoma specialists and patients are alike.

Adult↗
PubMed2005

Disparities in osteoporosis screening between at-risk African-American and white women.

BACKGROUND: Despite a lower prevalence of osteoporosis in African-American women, they remain at risk and experience a greater mortality than white women after sustaining a hip fracture. Lack of recognition of risk factors may occur in African-American women, raising the possibility that disparities in screening practices may exist. OBJECTIVE: To determine whether there is a difference in physician screening for osteoporosis in postmenopausal, at-risk African-American and white women. METHODS: We conducted a retrospective chart review at an urban academic hospital and a suburban community hospital. Subjects included 205 African-American and white women, age > or = 65 years and weight < or = 127 pounds, who were seen in Internal Medicine clinics. The main outcome was dual-energy x-ray absorptiometry (DXA) scan referral. We investigated physician and patient factors associated with referral. Secondary outcomes included evidence of discussion of osteoporosis and prescription of medications to prevent osteoporosis. RESULTS: Significantly fewer African-American than white women were referred for a DXA scan (OR 0.39%, 95% confidence interval (CI): 0.22 to 0.68). Physicians were also less likely to mention consideration of osteoporosis in medical records (0.27, 0.15 to 0.48) and to recommend calcium and vitamin D supplementation for this population (0.21, 0.11 to 0.37). If referred, African-American women had comparable DXA completion rates when compared with white women. No physician characteristics were significantly associated with DXA referral patterns. CONCLUSIONS: Our study found a significant disparity in the recommendation for osteoporosis screening for African-American versus white women of similar risk, as well as evidence of disparate osteoporosis prevention and treatment, confirming results of other studies. Future educational and research initiatives should target this inequality.

Absorptiometry, Photon↗
PubMed2005

A randomized trial of an intervention to increase fruit and vegetable intake in curatively treated patients with early-stage head and neck cancer.

The leading cause of death in patients who have had curatively treated early-stage head and neck cancer is a second primary cancer of the upper aerodigestive tract (lung, esophagus, larynx, pharynx, and oral cavity cancers). Low fruit and vegetable intake has been associated with increased risk of primary head and neck cancer and the available data suggest that increasing intake following diagnosis may reduce the risk of a second primary cancer. The goal of this study was to develop and test an easily administered intervention to increase fruit and vegetable intake in these patients following diagnosis and treatment. The 6-month intervention was based on the Stage of Change model. Seventy-five early-stage head and neck cancer patients were randomized to either the intervention group or to the "blinded" control group, with diet change data available on 65 patients. Fruit and vegetable intake, assessed using a food frequency questionnaire, and plasma carotenoid concentrations were measured at baseline and at the end of the study period. The change in self-reported intake of fruit and vegetables (servings per day) over the study period was significantly greater (P = 0.009) in the intervention group (n = 35; +2.1) compared with the control group (n = 30; +0.5). Total plasma carotenoids, a biomarker of fruit and vegetable intake, increased by 70 nmol/L in the intervention group as compared with a reduction of 42 nmol/L in the control group, a relative difference of 12% (nonsignificant). An intervention that can be delivered in a physician's office resulted in a significant increase in intake of fruit and vegetables in early-stage head and neck cancer patients.

Carotenoids↗
PubMed2005

Fluoroquinolone-resistant Campylobacter isolates from conventional and antibiotic-free chicken products.

The use of fluoroquinolones (FQs) in poultry production is an important issue in public health today. In February 2002, two prominent U.S. poultry companies pledged to stop using FQs for flock-wide treatment. One year later, we began a survey of Campylobacter isolates on chicken products from these two companies and from two producers claiming total abstention from antibiotic use. Using both standard isolation methods and new methods modified to enhance detection of FQ-resistant Campylobacter, we compared rates of FQ-resistant Campylobacter among these products. Four major findings were drawn from this study: a) antibiotic-free brands were not more likely to be contaminated with Campylobacter; b) a high percentage of products from the two conventional brands were contaminated with FQ-resistant Campylobacter (43 and 96%); c) these conventional brands had significantly higher odds of carrying resistant strains compared with antibiotic-free products; and d) supplementing media with FQs increased the sensitivity of detecting FQ-resistant strains among mixed populations of Campylobacter, thus reducing a bias toward underestimating the prevalence of FQ-resistant Campylobacter on samples. These results suggest that FQ resistance may persist in the commercial poultry environment in the absence of FQ-selective pressure and that these strains contaminate a larger proportion of foods than reported previously.

Animal Husbandry↗
PubMed2004

Public health vaccination policies for containing an anthrax outbreak.

Concern about biological weapons has raised questions about the most effective public health policies to contain an anthrax outbreak. We developed a probability model to predict the impact of different anthrax antibiotic and vaccination policies. An anthrax outbreak can be significantly contained by minimizing the delay until initiation of antibiotic prophylaxis. However, even if mass distribution of antibiotics is completed within six days of the initial exposure, then at most about 70% of cases can be prevented. Post-exposure vaccination will not significantly increase that prevention rate if adherence to antibiotic regimens is similar or higher than that attained in the 2001 US outbreak. However, post-exposure vaccination can be useful either in shortening the duration of a prolonged antibiotic regimen, in the event of an antibiotic-resistant strain, or if antibiotic adherence rates are very low. Here we show that a mass pre-exposure vaccination programme for the general population would require very high population coverage rates to significantly increase prevention rates from that achieved with targeted and rapid post-exposure prophylaxis programmes.

Anthrax↗