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PubMed1999

Prospective evaluation of accuracy, precision, and reproducibility of an at-home hemoglobin A1c sampling kit.

BACKGROUND: The measurement of hemoglobin A1c (HbA1c) is critical to the optimal therapeutic management of diabetes. To be most useful, the HbA1c value should be available at the clinical visit. Recently, a number of at-home sampling kits have been developed that facilitate the timely availability of HbA1c results. This is a report of the accuracy, precision (among-subject), and reproducibility (within-subject) of one such kit, B-D A1c, At-Home-Test, which combines a filter paper technique for spotting capillary blood with an immunoturbidometric assay (a variation of the Cobas Integra Hemoglobin A1c method also referred to as Roche Unimate). METHODS: The B-D A1c At-Home test kit was evaluated in a clinical trial using 1625 dried blood spot samples from 59 subjects diagnosed with type 1 or type 2 diabetes collected in an in-clinic setting. Data for replicate samples were compared against those from the standard Cobas Integra Hemoglobin A1c assay and from the BioRad Variant high-performance liquid chromatography [HPLC] assay. The effects of subjecting the dried spotted blood samples to prolonged elevated temperatures was evaluated in a separate laboratory analysis. RESULTS: The B-D A1c At-Home results, which are highly correlated with the standard Cobas Integra Hemoglobin A1c assay, (r2 = 94.7%), demonstrate excellent within-subject reproducibility for 3- to 10-day-old samples (coefficient of variation = 2.7%), and provide a coefficient of variation for among-subjects that is 3.9%. There were no clinically significant differences (i.e., < 0.3 units) in samples aged 3 to 10 days, between venous or capillary blood samples, or from freezing and thawing or prolonged exposure of B-D A1c At-Home dried blood samples to elevated temperatures before assay. CONCLUSIONS: The B-D A1c At-Home kit combines the accuracy, precision, and reproducibility of a clinical laboratory test with the convenience of at-home sample collection. This product may add to the convenience of both patient and health care provider by making it easier for patients to obtain their HbA1c values and have them available at their visit to the clinician.

Adult↗
PubMed2002

The acceptability of self-collected samples for HPV testing vs. the pap test as alternatives in cervical cancer screening.

OBJECTIVE: To explore the acceptability of the self-collection of samples for human papillomavirus (HPV) testing in comparison with that of the Pap test. METHODS: The study population consisted of 1069 women 20 years and older who were eligible for coverage through the Mexican Institute of Social Security (IMSS). These women were randomly selected among participants in a larger study to evaluate the use of HPV testing as an alternative in cervical cancer screening. All participants provided a self-collected vaginal sample for HPV testing according to explicit instructions and underwent a Pap test. Afterwards, each woman was interviewed about her experience and opinion regarding the two procedures. Acceptability was measured by a calculated score based on discomfort, pain, embarrassment, privacy, perception of personal treatment during the Pap test, and understanding of how to perform the self-sampling method. RESULTS: Ninety-three percent of women experienced sufficient privacy with the Pap test, whereas 98% of women reported that privacy with the self-sampling procedure was acceptable. The Pap test consistently provoked more discomfort, pain, and embarrassment than self-sampling. Sixty-eight percent of the women who indicated a test preference chose self-sampling. Preference for this method was positively associated with monthly household income. Women reported a preference for self-sampling because it is more comfortable (71.2%) and causes less embarrassment (55.8%). CONCLUSIONS: Self-sampling is more acceptable than the Pap test and could improve coverage rates of early detection programs. The incorporation of self-collected samples to detect HPV could encourage participation in screening programs among those women who reject the Pap test because of the necessary pelvic examination.

Adult↗
PubMed2004

Problems in isolation of Campylobacter jejuni from frozen-stored raw milk and bovine fecal samples: genetic confirmation using multiplex PCR.

The objectives of this study were to evaluate the use of various protocols for the isolation of Campylobacter jejuni from bulk tank milk and bovine fecal samples that were stored frozen for varying times, and to develop a rapid DNA-based protocol that distinguishes C. jejuni from other thermophilic Campylobacter spp. The pathogen was recovered from fecal samples that had been stored for 96-251 days at -20 degrees C with glycerol as the cryopreservative. In a separate study, C. jejuni-positive bovine fecal samples were stored at 5 degrees C for up to 70 days without compromising subsequent recovery of the pathogen. However, the pathogen could not be recovered from pathogenpositive fecal samples stored with or without glycerol (5 mL/11 g sample) for 21 days at -20 degrees C. Bolton broth (BB) and Bolton broth with 5% blood (BBB), containing BB supplement, were used for enrichment. Bacterial isolation was achieved by streaking from BB and BBB, and filtering from BBB onto blood-free charcoal cefoperazone deoxycholate agar (CCDA). The use of BB for the recovery of Campylobacter was more sensitive than BBB, and streaking achieved better isolation rates than filtration. Multiplex PCR incorporating thermophilic Campylobacter-specific 23S rRNA and C. jejuni-specific hippuricase gene sequences was used to confirm C. jejuni. All 265 bulk tank milk samples analyzed were negative for C. jejuni, whereas five of 411 (1.2%) fecal samples tested positive. This is the first report that has used a combination of sequences of the two genes in a multiplex format to identify C. jejuni to the species level. The method described has potential for routine use in the detection of thermophilic Campylobacter in farm environmental samples as well as other samples.

Animals↗
PubMed1998

High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples.

High-sensitivity immunocytochemistry was used to evaluate the relative frequency of neuroblastoma cells in bone marrow and peripheral blood in patients with neuroblastoma (NB). A total of 51 concomitant paired blood and marrow samples (102 total) from 35 patients with NB (age 4 months-31 years; stage 29 stage IV, 4 stage III, 2 stage IVS; 14 at diagnosis, 18 in relapse, 12 during treatment, and 7 off-therapy) were analyzed. Cytospins containing up to 10(6) cells each were prepared using the mononuclear cell (MNC) fraction. For immunocytologic staining, a primary mouse monoclonal anti-GD2 antibody (3F8), a secondary antimouse biotinylated antibody, and a streptavidin-alkaline phosphatase complex were used. A minimum of two cytospins containing a mean of 1.4 x 10(6) total MNCs was analyzed in addition to a negative and a positive control. No circulating tumor cells were detected when the concomitant marrow samples were negative or had <10 positive cells per 106 MNC (23 of 51 samples). Of the 18 marrow samples positive at 10-10,000 cells per 106 MNC, 6 had detectable NB cells in the corresponding blood sample, whereas for marrow samples with >10,000 NB cells per 10(6) MNC (1%), the concomitant blood sample was positive for 9 of the 10. When both marrow and blood samples were positive (15 BM-PB pairs), NB cell frequency was significantly lower in blood, with a mean difference of 2.14 logs (median 2.22, range -0.16-4.8, standard error 0.38). In patients with NB, circulating tumor cell frequencies seem to be substantially lower than in concomitant marrow samples, with a mean difference of >2 logs.

Adolescent↗
PubMed1995

Manufacturers' distribution of drug samples to a family medicine clinic.

The distribution of drug product samples by pharmaceutical companies to a family medicine clinic was studied. Data on all deliveries of drug samples to the clinic site of a university-affiliated family medicine residency program from November 1992 through December 1993 were collected. In addition, the 11 faculty family physicians were surveyed about their experiences with the deliveries of samples. Forty-three manufacturers delivered samples of 331 drugs during the 14-month study period. There were 366 visits by the drug company representatives, who made 1117 separate deliveries. The total value of the samples, based on the average whole-sale price, was $240,782. Twenty-nine percent of the drugs were nonformulary, and only 49% were stocked by the pharmacy. The physicians surveyed indicated that they were either usually or always asked to sign for samples they did not in fact request, that they usually did not know what was recorded on the receipts for samples that they signed, and that they seldom verified what was actually delivered. Pharmaceutical manufactures delivered large quantities of drug samples during the study period, and many of the drugs were nonformulary or not stocked by the pharmacy. The physicians indicated that they were not well informed about delivered samples for which they signed receipts.

Community Health Centers↗
PubMed1994

Development of the Regular Interlaboratory Counting Exchanges (RICE) scheme to include visual reference counts and samples from asbestos clearance operations.

The RICE proficiency testing scheme for asbestos fibre counting operated until 1992 with industrial samples and with reference counts produced by an image analyser (Magiscan). The visual counts produced in RICE by the participating laboratories have now been used to develop a reliable reference count for these industrial samples. Concurrently with the routine participation in RICE, laboratories also counted samples from asbestos clearance operations; these counts were used to develop suitable reference counts and performance limits for this type of sample. The width of this satisfactory performance interval is proportional to the natural variation in the data on the samples and is therefore a fixed interval on the log scale (of sample density) for high density samples and a fixed interval on the square-root scale for low density samples (where counting normally stops after a fixed number of fields). These developments led to the introduction of visual reference counts and clearance samples into RICE during 1992.

Air↗
PubMed2004

Determination of isocyanates in air using 1-(2-methoxyphenyl)piperazine-impregnated filters: long-term sampling performance and field comparison with impingers with dibutylamine.

Isocyanates may be harmful to workers and methods for monitoring air exposure in the field are necessary. The main aim of this study was to study the field performance of a method using 1-(2-methoxyphenyl)piperazine (2MP)-impregnated filters, by side-by-side comparison of long-term sampling with consecutive short-term samplings and also by short-term comparisons with other methods. Apart from using 2MP-impregnated filters, air monitoring was also performed by a modified 2MP method (FINMP) and by an impinger method using dibutylamine (DBA), which was the reference method. For short-term sampling the compared methods performed equally well for 2,6-toluenediisocyanate (2,6-TDI) and for isocyanic acid. For 2,4-toluenediisocyanate (2,4-TDI), the DBA method gave approximately 10% higher results according to linear regression than the 2MP method and for phenyl isocyanate, the DBA method gave significantly higher results than both the 2MP and FINMP methods. During long-term sampling (2-4 h) of TDI with the 2MP method, significantly lower levels were found compared with parallel sampling with consecutive short-term samplings. A time-dependent correction factor for long-term sampling was calculated to be 1.7 for 2,4-TDI and 1.5 for 2,6-TDI for 4 h sampling. The long-term sampling performance for other isocyanates was not studied. In conclusion, short-term monitoring shows that the 2MP method slightly underestimates the true air concentration for some of the isocyanates studied, but the error is relatively small considering the variation in exposure. For long-term monitoring the 2MP method can be applied for TDI but, since the method underestimates the concentrations, a correction factor is needed which needs to be corroborated further.

Air Pollutants, Occupational↗
PubMed2026

How negative sampling shapes the performance of transcription factor binding site prediction models.

MOTIVATION: Transcription factors (TFs) are key players in gene regulation and development, where they activate and repress gene expression through DNA binding. Predicting transcription factor binding sites (TFBSs) has long been an active area of research, with many deep learning methods developed to tackle this problem. These models are often trained on TF ChIP-seq data, which is generally seen as only providing positive samples. The choice of datasets and negative sampling techniques is a critical yet often overlooked aspect of this work. RESULTS: In this study, we investigate the impact of different negative sampling techniques on TFBS prediction performance. We create high-quality test datasets based on ChIP-seq and ATAC-seq data, where true negatives can be identified as positions that are accessible but not bound by the TF in question. We then train models using various negative sampling techniques, including genomic sampling, shuffling, dinucleotide shuffling, neighborhood sampling, and cell line specific sampling, simulating cases where matching ATAC-seq data is not available. Our results show that, generally, metrics calculated on training datasets give inflated performance scores. Of the tested techniques, genomic sampling of negatives based on similarity to the positives performed by far the best, although still not reaching the performance of baseline models trained on high-quality datasets. Models trained on dinucleotide shuffled negatives performed poorly, despite being a common practice in the field. Our findings highlight the importance of carefully selecting negative sampling techniques for TFBS prediction, as they can significantly impact model performance and the interpretation of results. AVAILABILITY AND IMPLEMENTATION: The code used in this study is available at https://github.com/NatanTourne/TFBS-negatives (DOI: 10.5281/zenodo.18007567).

Binding Sites↗
PubMed1992

Accuracy of coagulation studies performed on blood samples obtained from arterial cannulae.

We have assessed the accuracy of coagulation studies in blood obtained from intra-arterial cannulae. Paired samples were studied in blood from 39 patients receiving intensive care; one sample was obtained by venepuncture and the other from an intra-arterial cannula after the apparatus deadspace plus 5 ml of blood had been discarded. Activated partial thromboplastin time (APTT) (with thromboplastin routinely used in our laboratory), prothrombin time (PT), thrombin time (TT), fibrinogen and heparin assays were measured on each sample. In 37 sample pairs, APTT was measured also using a different thromboplastin. The median difference between the sample pairs was 5.5 s for APTT (P = 0.032) and 1.0 s (P = 0.048) for TT, the times for arterial cannula samples being longer. There was no significant difference between arterial cannula and venepuncture samples for PT or fibrinogen concentration. Heparin assays revealed heparin contamination in samples obtained from arterial cannulae in 15 of 30 patients not receiving heparin. It is concluded that, when coagulation studies are performed using the techniques used routinely in our laboratory, a blood sample from an arterial cannula may give clinically misleading information because of contamination with small amounts of heparin, and that separate venepuncture is recommended.

Blood Coagulation Tests↗
PubMed2000

Solid-phase microextraction and headspace solid-phase microextraction for the determination of high molecular-weight polycyclic aromatic hydrocarbons in water and soil samples.

The feasibility of direct-immersion (DI) solid-phase microextraction (SPME) and headspace (HS) SPME for the determination of high-ring polycyclic aromatic hydrocarbons (PAHs) (4- to 6-ring PAHs) in water and soil samples is studied. Three SPME fibers--100- and 30-microm polydimethylsiloxane (PDMS) and 85-microm polyacrylate (PA) fibers-are compared for the effective extraction of PAHs. Parameters affecting the sorption of PAHs into the fiber such as sampling time, sampling volume, and temperature are also evaluated. The extracted amounts of high-ring PAHs decrease with the decreasing of film thickness, and the 100-microm PDMS has the highest extraction efficiency than 85-microm PA and 30-microm PDMS fibers. Also, the extraction efficiency decreases with the increasing molecular weights of PAHs. Of the 10 high-ring PAHs, only fluoranthene and pyrene can reach equilibrium within 120 min at 25 degrees C for DI-SPME in a water sample. Increasing the temperature to 60 degrees C can increase the sensitivity of PAHs and shorten the equilibrium time. A 0.7- to 25-fold increase in peak area is obtained for DI-SPME when the working temperature is increased to 60 degrees C. For HS-SPME, the extraction efficiency of PAHs decrease when the headspace volume of the sampling system increases. All high-ring PAHs can be detected in a water sample by increasing the temperature to 80 degrees C. However, only 4- and 5-ring PAHs can be quantitated in a CRM soil sample when HS-SPME is used. The addition of a surfactant with high hydrophilic property can effectively enhance the sensitivity of high-ring PAHs. HS-SPME as well as DI-SPME with 100-microm PDMS or 85-microm PA fibers are shown to be suitable methods for analyzing high-ring PAHs in a water sample; however, this technique can only apply in a soil sample for PAHs having up to 5 rings.

Chromatography, Gas↗
PubMed2003

Opportunistic research and sampling combined with fisheries and wildlife management actions or crisis response.

Currently most of the activities of state, federal, first nation, and private conservation agencies, including management of and field research on free-ranging wildlife, are not regulated under the Animal Welfare Act (AWA) and thus not subject to National Institutes of Health guidelines or routine institutional animal care and use committee (IACUC) review. However, every day thousands of fish and wildlife management activities occur across North America that provide an opportunity to take observations, measurements, biological specimens, or samples that may have research value. Most of these opportunities are secondary to ongoing and often mandated wildlife management or conservation actions. Strange as it may seem to the academic and research community, the full research potentials of these opportunities are rarely utilized. IACUCs and research institutions should strive to facilitate such research, which by its very nature is often more opportunistic than designed. They can do this by ensuring that their policies do not unnecessarily impede the rapid research responses needed, or over burden researchers with inappropriate reporting requirements designed for laboratory research. The most prominent reasons for failures to utilize wildlife research opportunities include lack of the following: personnel and expertise to collect and use the information; preparation for inevitable (or predictable) events (e.g., oil spills); resources to preserve and curate specimens; a mandate to conduct research; and recognition of the value in data or sample collection. IACUC support of open protocols and generic sampling plans can go a long way toward improving the development of useful knowledge from animals that will otherwise be lost. Opportunities to sample wildlife are categorized generally as dead sampling (road kill surveys, harvest sampling, lethal collection, and "die-offs"); live sampling (handling for marking, relocation or restocking; and captures for field or biological studies); and crisis response (e.g., population salvage operations or oil spills). Examples of the many unique situations in each category serve to illustrate how valuable research and sampling can be accomplished opportunistically. Several unique limitations of sample collection situation are described. It is recommended that IACUCs have mechanisms in place to facilitate good research in all of these circumstances.

Animal Care Committees↗
PubMed2003

Sequential sampling and biorational chemistries for management of lepidopteran pests of vegetable amaranth in the Caribbean.

Although vegetable amaranth, Amaranthus viridis L. and A. dubius Mart. ex Thell., production and economic importance is increasing in diversified peri-urban farms in Jamaica, lepidopteran herbivory is common even during weekly pyrethroid applications. We developed and validated a sampling plan, and investigated insecticides with new modes of action, for a complex of five species (Pyralidae: Spoladea recurvalis (F.), Herpetogramma bipunctalis (F.), Noctuidae: Spodoptera exigua (Hubner), S. frugiperda (J. E. Smith), and S. eridania Stoll). Significant within-plant variation occurred with H. bipunctalis, and a six-leaf sample unit including leaves from the inner and outer whorl was selected to sample all species. Larval counts best fit a negative binomial distribution. We developed a sequential sampling plan using a threshold of one larva per sample unit and the fitted distribution with a k(c) of 0.645. When compared with a fixed plan of 25 plants, sequential sampling recommended the same management decision on 87.5%, additional samples on 9.4%, and gave inaccurate recommendations on 3.1% of 32 farms, while reducing sample size by 46%. Insecticide frequency was reduced 33-60% when management decisions were based on sampled data compared with grower-standards, with no effect on crop damage. Damage remained high or variable (10-46%) with pyrethroid applications. Lepidopteran control was dramatically improved with ecdysone agonists (tebufenozide) or microbial metabolites (spinosyns and emamectin benzoate). This work facilitates resistance management efforts concurrent with the introduction of newer modes of action for lepidopteran control in leafy vegetable production in the Caribbean.

Amaranthus↗
PubMed2000

Comparison of sample units for estimating population abundance and rates of change of adult horn fly (Diptera: Muscidae).

This study compared the reliability of population estimates of adult horn fly, Haematobia irritans (L.), obtained using different sample units. Mean-variance relationships were similar for abundance estimates obtained by counting flies on the sunny sides of cattle, on the upper body, and on the whole animal. Precision varied among the sample units, and was lowest for estimates obtained using the sunny side. Abundance estimates obtained using the sunny side and upper body sample units were related to estimates obtained using the whole body sample unit. However, the proportion of flies in the upper body and sunny side sample units declined with increasing fly density. Seasonal movement toward the belly accounted for this decline. This movement resulted in bias in estimating rates of change based on counting flies on the sunny side and upper body sample units. Rates of change based on sampling the sunny side were more biased than estimates based on the upper body sampling unit. Bias in estimating rates of change was examined using an analytical model compared with field data, and resulted from changes in the proportion of flies occupying the sample unit. Bias also increased with increasing actual rates of change. The implication of these findings for studying horn fly populations are discussed.

Animal Feed↗
PubMed1993

Effectiveness of the Waksberg telephone sampling method for the selection of population controls.

The effectiveness of the Waksberg telephone sampling method and practical aspects of its implementation were evaluated during the selection of control subjects for a population-based case-control study conducted in Maryland, Virginia, West Virginia, and Washington, DC, in 1991. The first stage of the two-stage sampling procedure was equivalent to simple random sampling. Each telephone number selected was dialed up to 13 times to establish the type of connection. Residential connections were used to generate additional telephone numbers in the second stage by changing the last two digits. Overall, 3,860 telephone numbers yielded 1,311 residences. The proportion of residences was higher in the second stage (54%) than in the first (11%), while that of numbers "not in service" was lower (12% vs. 67%, respectively). Fewer calls (8,735) were made than would have been required by a simple random sampling procedure (up to 18,522). The geographic distribution of residences was similar at both stages of sampling. At the end of enrollment, each sampling unit had yielded 9.8 residences, but only 64% reached 9-11 residences. Compliance rates were 96% for screening (1,259 of 1,311 residences), 90% for interviewing (362 of 403), and 86% overall. Relative to simple random sampling, the Waksberg method considerably reduced the total number of telephone calls, but the sampling process was more complex to manage. This method is particularly suitable for selecting population controls when the density of residential connections is low and variables of interest are not homogeneous within sampling units. Random digit dialing remains an effective method for selecting population controls.

Data Collection↗
PubMed1995

The variability in fallout content of soils and plants and the design of optimum field sampling strategies.

Sampling was carried out at an upland peat site in Ireland to assess the variability in 137Cs deposition to soils and activity concentration in individual vegetation species. A 3,600 m2 quadrat was laid out, and a soil core was extracted within each of sixteen 20 x 20 cm soil monoliths. The coefficient of variation values for 137Cs deposition and activity in individual soil horizons were in all cases greater than 30%, and the relative variability between corresponding horizons tended to increase with depth. Samples of Calluna vulgaris and Juncus squarrosus were taken at each soil sampling location and coefficients of variation for 137Cs activity in these species were 12 and 20%, respectively. The data was used to examine the relationship between the number of samples analyzed in a survey, the variability within those samples, and the way those two factors affect our ability to detect between-site differences in 137Cs contamination levels. A methodology is developed for detection of between-site differences in 137Cs contamination under different experimental criteria. The data show that, of the sample types examined, between-site differences could be detected most efficiently with C. vulgaris. Because of the variability associated with the 137Cs content of each sample type, between-site differences could be detected with fewer plant samples than soil samples. Plant-soil concentration ratios, transfer factors, and plant-plant ratios were calculated from the data, and the variability associated with each parameter was assessed. The variation among values for plant-plant ratios was less than among concentration ratios, and the greatest spread of values was associated with plant-soil transfer factors.

Analysis of Variance↗
PubMed1996

Sample size and statistical power in [15O]H2O studies of human cognition.

Determining the appropriate sample size is a crucial component of positron emission tomography (PET) studies. Power calculations, the traditional method for determining sample size, were developed for hypothesis-testing approaches to data analysis. This method for determining sample size is challenged by the complexities of PET data analysis: use of exploratory analysis strategies, search for multiple correlated nodes on interlinked networks, and analysis of large numbers of pixels that may have correlated values due to both anatomical and functional dependence. We examine the effects of variable sample size in a study of human memory, comparing large (n = 33), medium (n = 16,17), small (n = 11, 11, 11), and very small (n = 6,6,7,7,7) samples. Results from the large sample are assumed to be the "gold standard." The primary criterion for assessing sample size is replicability. This is evaluated using a hierarchically ordered group of parameters: pattern of peaks, location of peaks, number of peaks, size (volume) of peaks, and intensity of the associated t (or z) statistic. As sample size decreases, false negatives begin to appear, with some loss of pattern and peak detection; there is no corresponding increase in false positives. The results suggest that good replicability occurs with a sample size of 10-20 subjects in studies of human cognition that use paired subtraction comparisons of single experimental/baseline conditions with blood flow differences ranging from 4 to 13%.

Adult↗
PubMed2000

Influence of time interval and number of blood samples on the error in renal clearance determination using a mono-exponential model: a Monte Carlo simulation.

Mono-compartmental analysis based on 2- and 4-h blood samples (BS) of 51Cr-EDTA (EDTA, ethylenediaminetetraacetic acid) is commonly used for the calculation of the glomerular filtration rate (GFR). The purposes of this study were to estimate the magnitude of error in clearance induced by errors in the time of sampling and activity measurement; to estimate the impact of changing the interval between the BS; and to assess the influence of a higher number of BS in reducing the error. A model of mono-exponential curves based on a finite number of BS was created. Normally distributed random errors were introduced in the time of sampling and activity measurement. In a first step, three different time intervals were used; in a second step, seven different numbers of BS were used, all taken between 120 and 240 min. For each setting, the random errors were successively introduced 200 times and the coefficients of variation (CV) of the calculated clearances were determined. Variable errors in clearance were induced by errors in the time of sampling and activity measurement. In general, the observed errors were higher for high and low clearance, with lower errors for moderately reduced clearances. The errors in indicating the time of sampling played an important role for high clearance, whereas the errors in activity measurements led to important errors for low clearance. Prolonging the interval from 1 to 2 h resulted generally in an important decrease in error, except in the range 60-100 ml x min(-1). Prolonging the interval from 2 to 3 h resulted in only a small additional decrease in error, except for very low clearance. Errors in indicating the time of sampling and in activity measurements induce errors in clearance determination. These errors cannot be significantly reduced by simply increasing the number of BS or by prolonging the interval between the samples. It is probably better, in most cases, to keep using the 2-4-h method and to take extreme care when indicating the time of sampling and when measuring the activity, instead of increasing the number of samples or lengthening the procedure.

Algorithms↗
PubMed2001

Limited sampling strategies for the estimation of the systemic exposure to the HIV-1 nonnucleoside reverse transcriptase inhibitor nevirapine.

The objective of this study was to develop and validate a limited sampling strategy (LSS) that allows accurate and precise estimation of the area under the plasma concentration versus time curve (AUC) of nevirapine, when used in the licensed dosage of 200 mg twice daily. Because nevirapine has a long plasma elimination half-life and the plasma concentration shows little variation within the 12-hour dosing interval, the authors also wanted to explore whether a time frame exists for which a single-sample LSS can be applied. Twenty HIV-1-infected individuals receiving steady-state treatment with nevirapine (200 mg twice daily) were enrolled. For the development of the LSS, 10 patients were randomly selected from the study population (index set). The pharmacokinetic results from the other 10 patients (validation set) were used for prospective validation of the proposed LSS. Blood samples were obtained before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after ingestion. The relationship between the nevirapine concentration at each of the designated time points and the AUC 12h was evaluated by univariate and multivariate linear regression analysis. At each of the sampling times, a strong correlation was observed between the nevirapine concentration and the corresponding AUC 12h (r > 0.97). This allows for a single-sample LSS, using any time point during the dosing interval. When a single equation is preferred, the concentration of nevirapine in a random sample drawn 2 to 4 hours after ingestion of nevirapine (C 2-4h; in microg/mL) can be used for accurate estimation of the AUC 12h (in h x microg/mL) by using the equation AUC 12h (h x microg/mL) = 11.699 (h) x C 2-4h (microg/mL) - 4.381 (h x microg/mL). Validation of this equation resulted in a predicted AUC 12h that was nonbiased and very precise. These data show that the nevirapine concentration at each time point during the dosing interval can be used for accurate estimation of the AUC 12h. Even more practical, a sample obtained at any time between 2 and 4 hours after ingestion of nevirapine can be used. The authors therefore conclude that less intensive sampling (i.e., a single sample) can readily be used to assess the AUC 12h of nevirapine when used in a dosage of 200 mg twice daily.

Adult↗