There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable ...therapy adherence.
Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed.
Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence <or= 90%; in 12 of these patients (14%), adherence was <or= 80%. There was a strong correlation between adherence rate (<or= 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response MMR) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk RR, 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was <or= 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006).
In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.
Objective
One in three women living with HIV (WLHIV) in the UK is aged 45–56, and therefore of potentially menopausal age. Little is known about the management of menopause in WLHIV in primary care. ...We aim to describe current knowledge and practice in the management of menopause in WLWH among primary care practitioners (PCPs).
Methods
A questionnaire-based study of 88 PCPs attending two sexual and reproductive health conferences.
Results
Almost all respondents (n = 87, 99%) routinely managed women with menopause-related symptoms; however, only 18 (20%) reported having managed menopause in WLHIV. Over 95% (n = 85) reported being confident in managing menopause in general, whereas less than half (n = 40) reported confidence in managing menopause in WLHIV (p < 0.001). The majority of respondents (n = 84) felt that menopause should be routinely managed in primary care, whereas just over half thought that menopause in WLHIV should be managed in primary care (n = 50, p < 0.001). Almost all respondents (n = 85) reported concerns about managing menopause in WLHIV.
Conclusion
PCPs reported limited experience of and low levels of confidence in managing menopause-related symptoms in WLHIV. Nearly all PCPs had concerns about managing menopause-related symptoms in WLHIV, many stating that this should be managed outside primary care. Development of national guidance and specialised training, coupled with good liaison between HIV services and PCPs, may improve confidence in this area.
Increasingly abundant food fraud cases have brought food authenticity and safety into major focus. This study presents a fast and effective way to identify meat products using rapid evaporative ...ionization mass spectrometry (REIMS). The experimental setup was demonstrated to be able to record a mass spectrometric profile of meat specimens in a time frame of <5 s. A multivariate statistical algorithm was developed and successfully tested for the identification of animal tissue with different anatomical origin, breed, and species with 100% accuracy at species and 97% accuracy at breed level. Detection of the presence of meat originating from a different species (horse, cattle, and venison) has also been demonstrated with high accuracy using mixed patties with a 5% detection limit. REIMS technology was found to be a promising tool in food safety applications providing a reliable and simple method for the rapid characterization of food products.
In-community non-invasive identification of asthma-specific volatile organic compounds (VOCs) in exhaled breath presents opportunities to characterize phenotypes, and monitor disease state and ...therapies. The feasibility of breath sampling with children and the preliminary identification of childhood asthma markers were studied.
End-tidal exhaled breath was sampled (2.5 dm³) from 11 children with asthma and 12 healthy children with an adaptive breath sampler. VOCs were collected onto a Tenax®/Carbotrap hydrophobic adsorbent trap, and analyzed by GC-MS. Classification was by retention-index and mass spectra in a 'breath matrix' followed by multivariate analysis.
A panel of eight candidate markers (1-(methylsulfanyl)propane, ethylbenzene, 1,4-dichlorobenzene, 4-isopropenyl-1-methylcyclohexene, 2-octenal, octadecyne, 1-isopropyl-3-methylbenzene and 1,7-dimethylnaphtalene) were found to differentiate between the asthmatic and healthy children in the test cohort with complete separation by 2D principal components analysis (2D PCA). Furthermore, the breath sampling protocol was found to be acceptable to children and young people.
This method was found to be acceptable for children, and healthy and asthmatic individuals were distinguished on the basis of eight VOCs at elevated levels in the breath of asthmatic children.
5-Oxoproline (5-OP; pyroglutamate) is an intermediate in the biosynthesis of the endogenous tripeptide glutathione and has been seen to be elevated in the biofluids and tissues of rats following the ...administration of glutathione-depleting hepatotoxic xenobiotics such as acetaminophen (paracetamol), bromobenzene and ethionine. As 5-OP is a potential biomarker for hepatotoxicity HPLC–MS/MS methods have been developed for its quantification in in vitro cell culture media and rat plasma. For the cell culture media the lower limit of quantification (LLOQ), defined as the lowest concentration on the calibration curve, was 10ng/ml. Minimal carry over was observed for cell culture media between injections (less than 5% at all concentrations examined), precision and accuracy were generally better than 20% for within and between day analyses. For rat plasma a LLOQ of 50ng/ml was obtained. Carry over for plasma was less than 5% for all concentrations, within and between batch accuracy and precision were generally better than 20%. The methods were linear for both sample types from the LLOQ up to 1μg/ml. For samples obtained from rats subjected to chronic administration of the hepatotoxin methapyrilene, concentrations of 5-OP were not observed to increase significantly at any time point compared to controls. 5-OP was also determined in the culture media of human liver epithelial (THLE) cells transfected with cytochrome P450 2E1 (THLE-2E1). Following exposure of THLE-2E1 cells to acetaminophen, large increases in the concentrations of 5-OP were observed, which correlated with reduced cellular glutathione content and with cell toxicity. These results show that LC–MS/MS can be used to perform rapid, sensitive, and quantitative determination of 5-OP in vivo and in vitro and will enable additional investigations into the utility of 5-OP as a biomarker of liver drug-induced liver injury.
A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) ...source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic pre-separation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples.In vitro tests with 5-nonanone indicated an increased sensitivity and a lowered limit-of-detection, both by a factor of ~4, the latter to an on-trap mass of 14.3 ng, equivalent to a sampled breath concentration of 967 pptv. Analysis of the mass spectrometric responses from 20 breath samples acquired sequentially from a single participant indicated enhanced reproducibility (reduced relative standard deviations (RSD) for 5-nonanone, benzaldehyde and 2-butanone were 28 %, 16% and 14% respectively. The corresponding values for an open SESI source were that 5-nonanone was not detected, with %RSD of 39% for benzaldehyde and 31% for 2-butanone).The constrained source with chromatographic pre-separation resulted in an increase in the number of detectable volatile organic compounds (VOCs) from 260 mass spectral peaks with an open SESI source to 541 peaks with the constrained source with pre-separation. Most of the observed VOCs were present at trace levels, at less than 2.5% of the intensity of the base peak.Seventeen 2.5 dm(3) distal breath samples were collected from asthma patients and healthy controls respectively, and subjected to comparative high-throughput screening using thermal desorption/SESI/time-of-flight mass spectrometry (TD-SESI-ToFMS). Breath metabolites were detected by using a background siloxane ion (hexamethylcyclotrisiloxane m/z 223.0642) as an internal lockmass. Eleven breath metabolites were selected from the breath research literature and successfully targeted. These data reinforce the proposition that TD-SESI-MS has potential for development as a rapid screening method for disease stratification and targeted metabolism profiling.
Confounding factors in the analysis of human breath by thermal desorption GC-MS are reviewed, with special emphasis on the high water levels encountered in human breath samples.
Multilinear ...regression optimization of breath sampling factors, along with the selection of ubiquitous sample components used as retention-time standards, enabled data registration based on retention indexing and mass spectral alignment. This was done on a component-by-component basis. The methodology developed reconciled participant safety, artefacts from accelerated hydrolysis of the stationary phase and the destructive nature of thermal desorption. Furthermore, using ubiquitous methylated cyclic-siloxanes in the thermal desorption-GC-MS chromatograms enabled secondary retention indexing for each chromatogram. This methodology enables the creation of a 'breath matrix' that is based on a combination of retention indexing and the mass spectral registration of isolated peaks.
This approach facilitated more efficient data modeling and a case study from a 22-participant (10 male, 12 female) stress-intervention experiment. Principal component analysis of data registered by retention indexing did not classify successfully stressed from unstressed states. By contrast, adoption of a breath matrix approach enabled 95% separation.
To investigate an increase in the number of Salmonella enteritidis isolates detected in a large hospital to ascertain whether it was due to a nosocomial source, to identify the mechanisms of ...transmission, and to institute effective control measures to prevent future episodes.
Observational study, survey of all microbiological samples positive for S. enteritidis detected in the hospital, outbreak investigation, and review of the literature.
A tertiary-care teaching hospital for adults in Barcelona, Spain.
During a 7-month period from May to November 1998, we identified 22 inpatients with S. enteritidis infection for whom nosocomial acquisition was strongly suspected. The attack rate was 0.138 per 1,000 patient-days. All affected patients were immunosuppressed and overall mortality was 41% (9 of 22). A sample of a meal cooked in the kitchen was culture positive for S. enteritidis. All isolates shared the same antibiotic susceptibility pattern and all except one shared the same pulsed-field gel electrophoresis (PFGE) pattern, but PFGE could not differentiate between outbreak-related and control strains. After compliance with kitchen hygiene procedures was emphasized and cleansing was intensified, no more cases were detected.
Apparently, sporadic cases of S. enteritidis may be part of an outbreak with a low attack rate. A small but persistent inoculum affecting only individuals with special predisposition for Salmonella infection might account for this. Suspicion should be raised in hospitals and institutions with a highly susceptible population.
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