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Personnel requirements for an outpatient chemotherapy admixture service.

Chemotherapy preparation times and personnel requirements for an outpatient chemotherapy admixture service (CAS) were determined in this study. CAS activities and time measurement endpoints were identified by process analysis. Direct time studies were performed over a 2-month period on approximately 400 variable (chemotherapy admixture) activities and on their related fixed (auxiliary) activities. Variable activities were divided into four distinct categories based upon the original formulation of the antineoplastic agent and its complexity of admixture. All CAS activities were performed by a pharmacy technician under the supervision of a pharmacist. Mean preparation times for the different categories of variable and fixed activities were determined. Variable, fixed, and estimated nonproductive time were combined with 8 months retrospective output data to determine total weakly CAS service hours and personnel requirements. Variable activity time varied widely among the four categories of admixtures and had an aggregate mean time of 9.7 minutes per admixture. Variable and fixed activity time comprised 13.5 and 4.5 mean weekly service hours, respectively. Total weekly service time was 18 hours or 0.48 full-time equivalents. These results on elemental times and personnel requirements are similar to those obtained in previous studies.

Ambulatory Care↗

Syringes versus minibags as an intravenous admixture system: a comparison of cost and nursing preference.

The implementation of centralized intravenous admixture programs in Canadian hospitals has been hindered by the high costs associated with such programs. The most popular system uses minibags as an admixture base but other less expensive alternatives are being investigated. This study examines the material and labour costs associated with preparing admixtures in either minibags or polypropylene syringes. The minibag admixtures were administered by nursing staff using secondary medication administration sets. Standard volume-control sets were used for diluting and administering the intravenous admixtures supplied in syringes. The results indicated a major cost advantage for the syringe-based program. Furthermore, evaluation of the two systems by nursing staff indicated a strong preference for the syringe-based system.

Attitude of Health Personnel↗

Admixture studies in Latin America: from the 20th to the 21st century.

The present study is a review of admixture studies in Latin America, an interesting subject because of the unique history of the area, in which populations from 3 different origins had contact and intercrossed. The most often used methods of analysis of admixture in Latin America and some problems related to them, such as the determination of the parental populations and selection of genetic markers, are briefly reviewed. Several sources of data for admixture studies (surnames, quantitative traits, proteins, and molecular information) are summarized. The results obtained using protein systems and blood groups, the most often used markers in Latin America, are considered. They are classified according to their application in 3 groups of populations: urban centers, native Americans, and African-descended subjects. The data show that almost every population is dihybrid or trihybrid, and when African influence is not detected, it is probably due more to the method than to an absence of that contribution. A special section is dedicated to the direction of gene flow, and results about directional mating based on mtDNA, Y-chromosome, and nuclear DNA or proteins are also given. From these studies it is possible to conclude that Amerindian admixture came mainly from female lineages, but it is difficult to establish what happened with the African contribution. A last subject considered is the relation between interethnic crosses and diseases; it is easy to analyze that relation when the pathological condition is related to a unique allele, but when complex diseases are considered, the results are not as clear because of the influence of nongenetic factors. Finally, the perspectives for admixture studies in the 21st century are considered, and some attempts to predict their future in Latin America are made.

Africa↗

The impact of population admixture on traditional linkage analysis.

INTRODUCTION: Families of admixed ancestry are routinely excluded from traditional (Log of the Odds [LOD] score) linkage analysis or are analyzed as being derived from a homogeneous population using the proband's ethnicity. Using traditional linkage analysis with these families can cause complications due to the mixing of different disease rates and allele frequencies that occurs. The presence of admixture violates the key assumptions of Hardy-Weinberg Equilibrium (HWE) and Linkage Equilibrium (LE) invoked in the current methods of linkage analysis. If one or more of these assumptions are violated, incorrect inference for linkage could result. DESIGN AND METHODS: Through simulation, we investigated the effect of admixture of two populations on the LOD score under various conditions, using prostate cancer as our underlying disease model. Four-generation homogeneous and admixed families were simulated with 27 markers and two linked, bi-allelic disease loci. Two different types of admixture were tested: admixture within a family unit and a mixture of homogeneous families within a data set. All mixing was done at the founder level in three different proportions: 30/70, 50/50 and 70/30. RESULTS AND CONCLUSIONS: We observed that the LOD scores under both models of admixture were closest to the homogeneous family scores of the population having the highest mixing proportion. Random sampling of families or ascertainment of families with disease affection status did not affect this observation, nor did the mode of inheritance (dominant/recessive) or sample size. Thus, the presence of families of mixed population ancestry impacts linkage analysis in terms of the LOD score and the estimate of the recombination fraction.

Alleles↗

Dyslipidemia and insulin resistance in relation to genetic admixture among Hispanics and non-Hispanic blacks of Caribbean origin.

The tendency to develop insulin resistance and dyslipidemia varies between black Africans, white Europeans, and Amerindian racial groups. Genetic admixture of these three racial groups has resulted in hybrid populations of Hispanics and non-Hispanic blacks. The current study was undertaken to examine the relationship of white European admixture to insulin resistance and dyslipidemia among Hispanics and non-Hispanic blacks of Caribbean origin. The study population included 224 Hispanics and 684 non-Hispanic blacks without a history of diabetes who were recruited between 1995 and 1999 on the island of St. Croix in the U.S. Virgin Islands. For each participant, anthropometric measurements were performed, and a fasting blood sample was analyzed for glucose, insulin, and serum lipids (triglycerides, HDL cholesterol). Genetic admixture was determined from grandparent race data. Hispanics were more likely than non-Hispanic blacks to have dyslipidemia and insulin resistance (measured by HOMA-IR method). White European admixture was significantly and inversely associated with insulin resistance among Hispanics. There was no significant relationship between white European admixture and insulin resistance or dyslipidemia among non-Hispanic blacks. Individuals who classified themselves as Hispanic blacks appeared to have a greater risk for cardiovascular disease than Hispanic whites or non-Hispanic blacks.

Black People↗

Informativeness of the CODIS STR loci for admixture analysis.

Population admixture (or ancestry) is used as an approach to gene discovery in complex diseases, particularly when the disease prevalence varies widely across geographic populations. Admixture analysis could be useful for forensics because an indication of a perpetrator's ancestry would narrow the pool of suspects for a particular crime. The purpose of this study was to use Fisher's information to identify informative sets of markers for admixture analysis. Using published founding population allele frequencies we test three marker sets for efficacy for estimating admixture: the FBI CODIS Core STR loci, the HGDP-CEPH Human Genome Diversity Cell Line Panel and the set of 39 ancestry informative SNPS from the Shriver lab at Pennsylvania State University. We conclude that the FBI CODIS Core STR set is valid for admixture analysis, but not the most precise. We recommend using a combination of the most informative markers from the HGDP-CEPH and Shriver loci sets.

Databases as Topic↗

Osmolality of small-volume i.v. admixtures for pediatric patients.

The osmolalities of pediatric i.v. admixtures were measured to identify drug concentrations in selected vehicles that would conserve fluid while maintaining osmolality values of 400 mOsm/kg or less. Test solutions were prepared by diluting appropriate volumes of freshly reconstituted powdered drug products or commercially diluted drug products with 5% dextrose injection, 0.9% sodium chloride injection, or both to provide 5 mL of each admixture at desired drug concentrations. To reduce their osmolalities, trimethoprim-sulfamethoxazole and ampicillin sodium were also diluted in 0.45% sodium chloride injection; ticarcillin disodium was diluted only in 0.45% sodium chloride injection. A vapor pressure osmometer was used to measure osmolalities in triplicate for three solutions prepared for each admixture. Of the 63 different admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection or both, 47 (75%) had osmolalities of 400 mOsm/kg or less. At least one concentration of each selected drug diluted in these vehicles had an osmolality of less than 425 mOsm/kg, except for trimethoprim-sulfamethoxazole and ampicillin sodium. Selected concentrations of the latter two drugs and ticarcillin disodium in 0.45% sodium chloride injection resulted in acceptable osmolalities. For most drugs diluted to the same concentration in 5% dextrose injection and 0.9% sodium chloride injection, osmolalities were lower in the dextrose solutions. Selection of an appropriate vehicle and drug concentration can control the osmolality of i.v. admixtures when the volume of fluid must be minimized, as for pediatric patients.

Anti-Bacterial Agents↗

Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture.

In a sample of 4,920 Native Americans of the Pima and Papago tribes, there is a very strong negative association between the Gm haplotype Gm3;5,13,14 and type 2--or non-insulin-dependent--diabetes mellitus (prevalence ratio = 0.27, 95% confidence interval 0.18-0.40). One might conclude from this observation that the absence of this haplotype--or the presence of a closely linked gene--is a causal risk factor for the disease. It is shown that Gm3;5,13,14 is a marker for Caucasian admixture, and it is most likely the presence of Caucasian alleles and the concomitant decrease of Indian alleles that lowers the risk for diabetes, rather than the direct action of the haplotype or of a closely linked locus. This study demonstrates both the potential confounding effect of admixture on the interpretation of disease association studies and the importance of considering genetic admixture (or excluding individuals with genetic admixture) in studies of genetic markers of disease. The relationship between this admixture marker and the prevalence of diabetes also suggests a strong genetic component in the susceptibility to type 2 diabetes in Pima and Papago Indians.

Arizona↗

Stability of amiodarone hydrochloride in admixtures with other injectable drugs.

The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.

Amiodarone↗

Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures.

The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied. Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags. Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively. All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C). Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags. No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions. Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours.

Cefotaxime↗

Stability of intravenous admixtures of aztreonam and clindamycin phosphate.

The stability of aztreonam and clindamycin phosphate in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 20 mg/mL and clindamycin phosphate 6 mg/mL; aztreonam 20 mg/mL and clindamycin phosphate 3 mg/mL; aztreonam 10 mg/mL and clindamycin phosphate 6 mg/mL; and aztreonam 10 mg/mL and clindamycin phosphate 3 mg/mL. One of each of these admixtures was stored at 22-23 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 1-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed using high-performance liquid chromatography. No visual changes were observed. The pH of admixtures decreased only slightly during storage. Concentrations of aztreonam and clindamycin phosphate under both storage conditions decreased by less than 10%. Intravenous admixtures of aztreonam and clindamycin phosphate at the concentrations studied are stable for at least 48 hours at 22-23 degrees C and at least seven days at 4 degrees C.

Ampicillin↗

Stability of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate admixtures.

A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate, and the stability of the three drugs mixed together in four infusion fluids was assessed. Solutions were prepared with two concentrations of the three drugs similar to those administered intrathecally. Admixtures were prepared in Elliott's B solution, 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection. and lactated Ringer's injection. Solutions were filtered and kept in a disposable syringe in a 25 degrees C water bath for 24 hours. An HPLC assay capable of separating the three drugs and their degradation products was developed and validated. With one exception, all three drugs were stable in all four solutions for 24 hours. Hydrocortisone sodium succinate concentrations decreased to less than 90% of initial concentration in one of the admixtures with Elliott's B solution. No precipitation was noted in any admixture during the first eight hours of storage, but longer storage led to precipitation of unknown substances in some solutions. Admixtures of these three drugs in the four solutions tested are stable for at least 10 hours at 25 degrees C. However, intrathecal and administration of such admixtures within several hours of preparation is encouraged since none contains antibacterial preservatives.

Chemistry, Pharmaceutical↗

Inexpensive microcomputer for intravenous admixture service applications.

A microcomputer system for maintaining data on intravenous piggyback (IVPB) admixture use and for generating labels for IVPB admixtures is described. The system was developed in a 558-bed hospital where the pharmacy compounds 500-800 i.v. admixtures daily. The objectives were to (1) provide an electronic profile with quick patient-search capabilities, (2) reduce time spent and errors occurring in labeling, (3) decrease duplication and consequent waste of admixtures, and (4) improve collection of drug-use statistics. Software was developed by the pharmacist to achieve these objectives. When a drug order is entered, files are automatically searched for duplication. Every 24 hours, labels for the entire patient profile are printed and statistics are generated on types of drugs used, number of each type of drug, total number of patients on IVPBs, and total number of IVPBs. A user's manual was developed and staff-training sessions were held before the system was implemented. In the first 24 months of operation, most computer downtime was caused by hardware problems. Four man-hours per day were saved in typing time (+7000 annual cost reduction). Waste of approximately six admixtures daily was prevented (+5000 annual savings). Total software development and implementation cost +5000, and hardware cost +4200. The total cost of the system was thus realized during the first year of operation.

Computers↗

Method for testing aseptic technique of intravenous admixture personnel.

A method of checking the aseptic technique of personnel that prepare i.v. admixtures is described. The following sterile dosage forms of trypticase soy broth (TSB) were prepared: (1) single-strength ampuls 5 ml, (2) six-times (6X) concentrated broth ampuls 10 ml, (3) lyophilized broth sufficient to make 5 ml single-strength broth in 10-ml vials, and lyophilized broth sufficient to make 10.6 ml 6X concentrated broth in 20-ml vials. Admixture personnel were told these were investigational products, and they were given simulated orders to prepare syringes and 50-ml piggyback admixtures of the products. The specimens containing the broth were intercepted by an investigator, incubated for seven days at 37 degree C, and observed for turbidity on days 2 and 7. To verify that the broth supported the growth of bacteria, two common contaminants were inoculated into the broth in the syringes and admixtures to serve as positive controls. At least 100 samples from each of four procedures were processed during the three-month study period. A total of 405 samples prepared by 13 individuals were tested. None of the samples became turbid; hence, the bacterial contamination rate was 0%. Among the positive controls, 98% inoculated with one species and 100% inoculated with the other became turbid. This method is now used for monitoring the aseptic technique of new admixture personnel. This unique method of checking the aseptic technique of personnel is accurate and cost effective, and it avoids the risk of adventitious contamination.

Antisepsis↗

Prediction of phenytoin solubility in intravenous admixtures: physicochemical theory.

The application of basic scientific principles to the practical problem of phenytoin precipitation in large volume parenteral solutions is reviewed. The solubility of phenytoin in i.v. admixtures depends on phenytoin's pKa and the i.v. solution pH as well as the admixture volume and the solubility of undissociated phenytoin in that admixture. Equations are derived that predict the solubility of phenytoin in i.v. admixtures, and illustrative examples are presented using the formulas. The effect of storage time on phenytoin solubility is discussed, and the effects of hydroalcoholic solvents (present in commercially available sodium phenytoin injection) and their dilution in aqueous admixtures are considered. Although simple equations can be used to predict the solubility of phenytoin sodium injection in i.v. fluids, the time required for a precipitate to develop cannot be predicted because of the variability in published studies.

Chemical Phenomena↗

Pneumoperitoneum for laparoscopic surgery does not increase venous admixture.

Venous admixture as a measure of pulmonary gas exchange was studied before and during laparascopic cholecystectomy in 12 patients with normal healthy cardio-pulmonary function. After induction of anaesthesia the patients were studied by radial and pulmonary arterial catheterization and simultaneous arterial and mixed venous blood gas sampling in the horizontal, 15-20 degrees head-down and 15-20 degrees head-up tilt positions. After establishing the pneumoperitoneum (PP) by insufflation of carbon dioxide to an intraabdominal pressure level of 11-12 mmHg, the measurements were repeated in the same positions. The laparoscopic cholecystectomy then started and measurements were repeated every 30 min during surgery. The venous admixture was 4 +/- 0.6% (range 2-6%) in the horizontal position and was not influenced by altered body position. Immediately after establishment of PP, there was a 31 +/- 5% (P < 0.05) reduction of venous admixture and a 15 +/- 3% (P < 0.01) elevation of PaO2 compared with the control situation without PP. These changes were maintained during pneumoperitoneum and were not influenced by posture. It is suggested that alterations in the distribution of ventilation and/or lung perfusion results in a reduced venous admixture during PP without surgery. In addition, there was no indication that venous admixture is elevated as a result of laparoscopic surgery in the reversed Trendelenburg position.

Adolescent↗

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-&#x3b1;-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage↗

Sex-Biased Admixture Followed by Isolation and Adaptive Evolution Shaped the Genomic and Blood Pressure Diversity of the LopNur People.

The LopNur people are an ethnic group living on the edge of the Taklamakan Desert, and they are believed to demonstrate a unique genetic makeup due to their isolation and limited contact with neighboring populations. However, a lack of genetic studies on the LopNur people has resulted in limited knowledge about their ancestral origins and demographic history. Here, we conducted the first whole-genome sequencing study of 164 LopNur individuals (LOP) to gain insight into their genetic history and adaptive evolution in an isolated desert area. Our analysis revealed that the present-day LOP have experienced a complex history of admixture followed by long-term isolation, with their ancestry derived from East Asia (&#x223c;41.46%), West Eurasia (&#x223c;26.43%), Siberia (&#x223c;24.27%), and South Asia (&#x223c;7.82%). Notably, a remarkable sex-biased admixture occurred between Western males and Eastern females. In addition to complex admixture followed by long-term geographic isolation and further recent migrations, adaptive evolution jointly formed the gene pool and phenotypic diversity of the present-day LOP. Intriguingly, our analysis suggests that the USP35-GAB2 region may be correlated with blood pressure in LOP, based on a joint analysis of genomics and blood pressure data. Moreover, we identified two variants, rs7387065, and rs2229437, located on CSMD1 and PRCP, respectively. These variants exhibited frequency differences between Asian and European populations and were reported to be associated with antihypertensive drug absorption. Our results provide new insight into the complex history of the LOP, an admixed and isolated ethnic group residing at the crossroads of East and West, a case with ancient admixture, long-term isolation, adaptive evolution, and sex-biased gene flow.

Female↗