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With the expanding list of prenatally detectable disorders, increasing numbers of patients are presented with the option of invasive prenatal diagnosis. Care providers need to address questions regarding the safety and accuracy of these procedures, as well as the indication. This article reviews these issues for genetic amniocentesis and chorionic villus sampling.
BACKGROUND: The systematic screening for several blood-borne viral genomes in blood donations is a complementary safety measure planned or discussed by the national authorities of several countries. STUDY DESIGN AND METHODS: To appreciate the feasibility of such screening using pooled samples, a multicenter study of real-time simulation has been performed on the model of hepatitis C virus (HCV) infection. Four blood transfusion center laboratories and two research and diagnosis laboratories simultaneously screened, by several HCV RNA polymerase chain reaction assays, a panel of plasma sample pools of different sizes (500, 100, and 10 samples), collected from HCV-infected or HCV-uninfected blood donors. One viremic plasma was introduced in each pool. HCV RNA was detected by in-house polymerase chain reaction procedures or by standardized manual or semi-automated polymerase chain reaction assays. RESULTS: The results indicate the feasibility of sample pooling, which renders the screening for viral genomes by molecular biology techniques applicable in the short term and the importance of the experience of laboratory personnel in the use of molecular biology tools. CONCLUSION: The improvement of standardized assays needs to be continued, and training of laboratory staff members appears to be a crucial step before systematic screening of blood donations for viral genomes by molecular biology techniques can occur.
The implementation of nucleic acid amplification technology (NAT) for detection of HCV, HIV-1 and HBV has undoubtedly contributed to the viral safety of blood, reducing the window period. One important matter related to the stability of RNA/DNA is the effect of the storage conditions on samples. In a previous work, we studied the stability of HCV RNA in plasma samples after storage at different temperatures. This work is an update on the follow-up of a sample containing 100 IU/ml HCV RNA for 5 years at -20 degrees C, showing no decrease in the initial titre. The nucleic acid stability of other viruses, such as HIV-1 and HBV, has also been studied. At -20 degrees C, samples containing HIV-1 were followed up for approximately 3 years and the results obtained show no decay in HIV-1 RNA detectability. Regardless of the HIV-1 RNA concentration, samples stored at 5 degrees C maintain their titre for at least 14 days. At 25 degrees C, the HIV-1 RNA half-life was determined at nearly 7 days. The HBV DNA, at 5 degrees C and 25 degrees C, is stable for at least 28 days, regardless of the initial titre.
BACKGROUND: Home human immunodeficiency virus (HIV) testing has been proposed as an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV-1) home test systems, these concerns have not to our knowledge been previously studied. OBJECTIVE: To evaluate the safety and efficacy of the Home Access Health Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1 testing with venous blood. METHODS: A total of 1255 subjects were studied prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics using intent-to-treat analysis. Subjects were provided a home collection kit (Home Access Health Corp) to collect their own finger-stick blood spot samples for laboratory analysis. Subjects received pretest counseling by telephone and their comprehension was subsequently assessed. Subject-collected blood spot samples were compared with professionally drawn blood spot samples for adequacy (sufficient for completing the Food and Drug Administration-endorsed testing) and with venous samples for accuracy. Subjects called 3 days later for anonymous results and posttest counseling. Device safety was evaluated based on adverse events incidence. Subject comprehension of HIV information was measured. RESULTS: Subject-collected blood spot sample results were in complete agreement with venous blood sample results, demonstrating 100% sensitivity and 100% specificity compared with venous controls. Ninety-eight percent of subjects obtained testable blood spot specimens compared with phlebotomists. Following pretest counseling, subjects answered 96% of HIV risk questions correctly. There were no significant adverse events. CONCLUSION: Anonymous HIV-1 home collection kits with pretest and posttest telephone counseling can provide a safe and effective alternative to conventional venous HIV-1 antibody testing.
Isotope ratio mass spectrometry (IRMS) was used to assess what contribution the technique could make towards the comparative analysis of matchstick samples within the 'normal' framework of a forensic investigation. A method was developed to allow the comparison of samples submitted as a result of an investigation, with the added advantage of rapid sample turn-around expected within this field. To the best of our knowledge this is the first time that wooden safety matches have been analysed using IRMS. In this particular case, bulk stable isotope analysis carrried out on a 'like-for-like' basis could demonstrate conclusively that matches seized from a suspect were different from those collected at the scene of crime. The maximum delta13C variability observed within one box was 2.5 per thousand, which, in conjunction with the error of measurement, was regarded to yield too wide an error margin as to permit differentiation of matchsticks based on 13C isotopic composition alone given that the 'natural' 13C abundance in wood ranges from -20 to -30 per thousand. However, from the delta2H values obtained for crime scene matches and seized matches of -114.5 per thousand and -65 per thousand, respectively, it was concluded that the matches seized were distinctly different from those collected at the crime scene.
Sirolimus (Rapamune, rapamycin) has been shown to be an effective and safe immunosuppressive drug in adult kidney transplant patients when administered concomitantly with cyclosporine (CsA) and steroids. This study reports on a phase 1 assessment of the drug's tolerance, safety, and pharmacokinetic parameters in pediatric patients. The safety and pharmacokinetic profiles of ascending single doses of sirolimus oral solution were investigated in 32 clinically stable pediatric patients on chronic hemodialysis (n = 26) or peritoneal dialysis (n = 6). Patients were divided into two age groups (5-11 and 12-18 yr), and each patient received either a single dose of sirolimus (1, 3, 9, or 15 mg/m(2)) or placebo. Whole blood and plasma samples were collected from each patient for the determination of sirolimus pharmacokinetic parameters. Safety assessments were based on reports of adverse events and results of scheduled physical examinations, vital sign measurements and clinical laboratory tests. The younger patients (5-11 yr) showed statistically significant increases in whole blood sirolimus t(max) (p < or = 0.05) and weight-normalized CL/F (p<0.05) when compared with older patients (12-18 yr). There were no differences in terminal t(1/2), V(ss)/F, dose-normalized peak concentration (C(max)) and AUC, or the B/P. The whole blood sirolimus mean t(max) and weight-normalized CL/F in younger patients were increased by approximately 41.5% and 30%, respectively. Whole blood sirolimus concentrations exhibited less than proportional increases with ascending doses, which may have been caused by the large inter-subject variability in CL/F, small number of subjects, and a potentially inherent decrease in sirolimus bioavailability in younger pediatric patients. Adverse events occurred in all dose and age groups, with headache and stomach pain being the most frequently observed events. No deaths or serious adverse events were reported, and no patient withdrew from the study because of an adverse event. Based on an inter-study analysis, weight-normalized CL/F in the current population of younger pediatric dialysis patients (5-11 yr, 544 +/- 463 mL/h/kg, n = 7) was increased by 90% (p < or = 0.05) compared with healthy adults (19-36 yr, 287 +/- 111 mL/h/kg, n = 25). These results suggest that younger pediatric patients might require an increased maintenance dose of sirolimus to achieve whole blood exposures similar to those in healthy adults. Sirolimus is well tolerated as a single dose of 1, 3, 9, or 15 mg/m(2).
Fluorouracil content was studied in air samples from a hospital pharmacy work area where a vertical laminar-airflow biological safety cabinet (BSC) vented into the work area was used for the preparation of antineoplastic drugs. The BSC was run 24 hours per day and used approximately 6 hours per day. During one 56-hour period and one 95-hour period, a portable pump delivering room air at 2 L/min was positioned 12 inches outside the BSC. Fluorouracil content in extracts from 0.5-micron Teflon filters housed in the pump was assayed by high-performance liquid chromatography. The assay's lower limit of fluorouracil detection was 0.2 ng/cu m air. In the 56-hour sampling period and the 96-hour sampling periods, 25.4 g and 25 g, respectively, of fluorouracil were prepared. No fluorouracil was detectable in the filter extracts. Use of an appropriate biological safety cabinet in conjunction with good aseptic technique and the recommended procedures for safe handling of antineoplastic drugs may reduce the potential for dispersal of drug into the pharmacy workroom environment.
"Troo, the Traumaroo" bicycle and playground safety education program created for kindergarten, first, and second grade students, was provided to a convenience sample of seven elementary schools in a Southwestern city. Favorable principal, classroom teacher, and school nurse evaluations indicated that the "Troo, the Traumaroo" program was successful in providing young children with bicycle and playground safety in a fun and entertaining way. Results of this pilot study indicated that kindergarten children pre-tested for bicycle safety knowledge prior to participating in the program, had significantly higher bicycle safety knowledge scores 30 days after participating in the program (p < .0001).
The Microbiological Criteria (MC) is a set of parameters used to determine whether a specific lot of food is acceptable or not. These parameters are the microbial test protocol and its sensitivity, the confidence level that an unacceptable lot will be detected, the number of samples to be taken and the number of positive samples that are allowed before rejecting the lot. Determining the microbiological criteria begins with knowledge of the distribution of contamination from samples within a lot, particularly within a lot that is just at the unacceptable level of the microbial hazard. The just unacceptable lot can be defined by the Food Safety Objective (FSO) or Performance Objectives (PO), the small fraction of samples that can exceed these values and the standard deviation of the samples from the lot. With this information, a microbial test protocol is chosen to have a sensitivity level that would detect between approximately 15% and 45% of the samples. A confidence level for the MC and the number of positive samples that would be acceptable (c value which is usually zero) are also chosen. With this information the number of samples (n) required can be calculated. A critical factor in setting the microbiological criteria is the sensitivity of the microbiological test (m value). The sample size (weight) and sampling procedure can affect the standard deviation of the samples, particularly foods with non-homogeneous distribution and low numbers of microorganisms. Sampling, sample preparation and analytical procedures that reduce the variation between the samples will affect the choice of m value and maximum lot mean that meets the MC.
OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of twice-daily indinavir + ritonavir regimens DESIGN: A cohort-based survey of HIV-infected patients who either used indinavir 800 mg + ritonavir 100 mg twice daily or indinavir 400 mg + ritonavir 400 mg twice daily. METHODS: Data were extracted from a database of samples sent to our laboratory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retrospective chart review. RESULTS: 100 Patients using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400-mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6 and 0.45 mg/L in the 400/400 group. The most frequently found side effects were nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 groups, respectively. Viral load data were analyzed for patients who switched from 800-mg indinavir three times daily to one of the indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100 group) and 60% (400/400 group) had an undetectable viral load and this increased to 77% and 70%, respectively, during follow-up. Patients who switched to the 400/400 group discontinued treatment more frequently than patients who switched to the 800/100 group (70% vs. 26%, p =.008). CONCLUSIONS: Indinavir + ritonavir regimens show improved pharmacokinetic properties, allowing twice-daily dosing with food. Clinical data suggest that safety and efficacy is at least as good as with indinavir three-times-daily regimens without ritonavir. Prospective, comparative trials are needed to properly assess the role in HIV therapy of these twice-daily indinavir + ritonavir regimens.
This trial was aimed to estimate the pharmacokinetic interaction between voriconazole and methadone at steady state in male patients on methadone therapy and to characterize the safety and tolerability profile during the coadministration. Twenty-three patients on individualized methadone therapy (30 to 100 mg once daily) were enrolled into this randomized, patient- and investigator-blind, placebo-controlled, parallel-group study. Methadone pharmacokinetic samples were collected from patients receiving methadone alone as the baseline before they were randomized to coadminister either 200 mg voriconazole twice daily (BID) (400-mg BID loading doses on the first day) (n = 16) or matching placebo (n = 7) for the next 5 days. Pharmacokinetic samples for methadone and voriconazole were collected on the last day of voriconazole dosing. The safety data were collected throughout the study. Voriconazole increased the steady-state exposure of pharmacologically active enantiomer (R)-methadone: the mean area under the concentration-time curve from 0 to 24 h (AUC(0-24)) was increased by 47.2% (90% confidence intervals [CI]: 37.7%, 57.4%), and the mean peak concentration (C(max)) was increased by 30.7% (90% CI: 22.2%, 39.8%). The magnitude of increase in (S)-methadone exposure was greater than that of (R)-methadone: the AUC(0-24) was increased by 103.4% (90% CI: 85.0%, 123.6%), and the C(max) was increased by 65.4% (90% CI: 52.6%, 79.2%). Methadone appeared to have no effect on the steady-state voriconazole pharmacokinetics compared to the historical data for voriconazole alone. Methadone patients receiving voriconazole showed no signs or symptoms of significant opioid withdrawal or overdose. Coadministration of 200 mg voriconazole BID with methadone was generally safe and well tolerated. Nevertheless, caution should be exercised when voriconazole is coadministered with methadone due to the increase in (R)-methadone exposure, which in turn may require a dose reduction of methadone.
A simple and specific liquid chromatographic method was developed for determination of clopidol in chicken tissues. Samples were extracted with acetonitrile. The extracts were cleaned up on an alumina column and an anion exchange column. The clopidol was separated on a column (30 cm x 3.9 mm) of microBondapak C18 (10 microm) by using acetonitrile-water (20 + 80, v/v) as mobile phase, and determined quantitatively at 270 nm. Recoveries were 86.0-97.6%, with relative standard deviations of 2.14-9.42% at 0.010-2.0 mg/kg from 4 spiked matrixes of chicken muscle, egg, liver, and kidney. The limit of detection was 0.005 mg/kg. Compared with the modified AOAC gas chromatographic method, the present method is simple and fast to operate. Its results are accurate and reliable, making it favorable for environmental protection and meeting requirements for human safety. Thus, it is suitable for routine analysis of large quantities of samples.
A 12-month open-label clinical trial was conducted to evaluate patient acceptance and safety of venlafaxine, a novel antidepressant, in ambulatory geriatric depressed patients. The sample consisted of 58 depressed patients aged 65 years and older who needed long-term antidepressant treatment. The setting was multiple study sites in California, Florida, New York, Utah, and Washington. All patients took venlafaxine; 52 qualified for the intent-to-treat analysis, and 24 completed 12 months of treatment. Repeated-measures analysis of variance within subjects showed significant improvements in Clinical Global Impressions severity and improvement, Modified Symptom Checklist, and Quality of Life Questionnaire scores. One patient developed a rash that was judged to be a serious drug-related side effect. The most common side effects were headache (n = 25), nausea (n = 21), insomnia (n = 18), dry mouth (n = 18), and sweating (n = 18). The results demonstrate the safety and patient acceptance of venlafaxine in depressed geriatric outpatients for acute and maintenance treatment.
Results of a comparative field study on the performance of 25-mm inhalable samplers (Institute of Occupational Medicine [IOM]) and midget impingers for the collection of total isocyanates in air using the 1-(9-anthracenylmethyl)piperazine (MAP) reagent are presented. Air sampling and analysis was performed according to the National Institute for Occupational Safety and Health MAP draft method 5525. Midget impingers filled with 15 mL of 1 x 10(-4) M MAP in butyl benzoate were operated at 1 L/min. IOM cassettes loaded with 25-mm quartz fiber filters impregnated with 500 microg MAP, were operated at 2 L/min. Filters were field extracted with 10 mL of 1 x 10(-4) M MAP in acetonitrile. Thirty-four impinger-IOM pairs were collected in three autobody shops during spray painting tasks. Regression analysis [Ln (IOM) = 1.0 Ln (impinger), R2 = 0.98] and a paired t-test (Pr > 0.9) demonstrated that impingers and IOMs perform equally in their collection efficiency for the monomer and total oligomeric hexamethylene diisocyanate (HDI). IOM performance did not deteriorate at longer sampling times compared with the impinger performance. Within-sampler variability was calculated from the individual coefficients of variation (CV) of the 17 pairs of like samplers. The mean of CVs (SD)% for the monomer and total oligomeric HDI was approximately 12 (12)% and 15 (13)% for the IOM and the impinger sampler, respectively. Poor correlation (Pearson correlation coefficient < 0.3) and statistically nonsignificant differences (P > 0.74 two-sided) were found for the between-sampler CVs. Factors that might have influenced the observed sampler agreement are also discussed. It is concluded that MAP impregnated filters can be successfully used for sampling of slow curing total aliphatic isocyanates in air.
BACKGROUND: The provision of free prescription medicine samples is a common and traditional marketing strategy used by pharmaceutical companies, but concerns have been raised about their influence on physician prescribing behavior and patient safety. OBJECTIVE: We sought to investigate the knowledge, attitudes, and behaviors of Australian family physicians regarding the use of sample prescription medications. METHODS: Qualitative and quantitative techniques were used, including (1) mailed questionnaires to family physicians, (2) semistructured interviews with family physicians, and (3) sample cupboard inventories. RESULTS: A number of issues about samples were identified by the questionnaires (208) and interviews (17 doctors), including insufficient labeling, poor record keeping, diversion of stock (personal use by doctors, their families, practice staff and pharmaceutical representatives), and wasting of expired stock. Prescription medicine samples also influenced prescribing behavior. Australian doctors were less likely to provide samples to patients on financial grounds compared with a previous study in the United States on medical residents. Six sample cupboards were inventoried. Median wholesale value of sample cupboards was AUD Dollars 4959 (range Dollars 2395-Dollars 8709), with 6% of stock expired. Very little generic medicine was included in the sample cupboards. CONCLUSIONS: Better methods are needed to meet legislative requirements and to ensure quality use of medicines (and optimal public health) with respect to prescription medicine samples. Doctors and practice staff require training on the appropriate handling and storage of prescription medications. Alternative ways for distribution of sample medications need to be investigated.
We tested a kiosk-based tailoring intervention with a sample of 144 parents of young children using a two-group randomized controlled design to evaluate the kiosk. Intervention group parents (n = 70) answered 50 questions at a practice-based kiosk and they and their child's physician received immediate feedback reports of their injury prevention needs. Four weeks later, both control (n = 74) and intervention parents completed a telephone interview. Safety knowledge, beliefs, and practices were compared at follow-up. Compared to control group parents, intervention group parents were more knowledgeable about the inappropriateness of young children riding in the front seat of a car (16% versus 5%, p < 0.05), less likely to believe that teaching a child to mind you is the best way to prevent injuries (64% versus 86%, p < 0.05), and more likely to report that they "have syrup of ipecac" (34% versus 9%, p < 0.001) and "know how to use" it (24% versus 4%, p < 0.002). This study provides further support for the use of tailored communication to address the prevention of injuries to young children but calls for continued investigation in the area.
The pharmacokinetics, safety, and tolerability of four topical lidocaine patches 5% continuously applied for 72 hours and changed every 12 or 24 hours were examined. In this randomized, prospective, multiple-dose, open-label pharmacokinetic study, lidocaine patches were applied to healthy men and women for three consecutive days. Ten subjects received four lidocaine patches every 24 hours (group 1), and 10 subjects received four patches every 12 hours (group 2). Serial samples of venous blood were obtained to determine pharmacokinetic data. Overall tolerability and safety were assessed, and skin sensory testing was conducted to determine whether local anesthetic activity was produced. The mean maximum plasma lidocaine concentrations at steady state with lidocaine patches applied in groups 1 and 2 were 186 and 225 ng/mL, respectively, compared with the reported mean maximum plasma concentration of 130 ng/ml. with the labeled dosage (12 hr/day). The area under the concentration-time curve for one dosage interval at steady state was 3550 and 4506 ng.hr/mL for groups 1 and 2, respectively. No loss in sensation at the application site was reported. No patient had edema, and most cases of erythema were very slight. No systemic adverse events were judged to be related to the patches. Continuous application for 72 hours of four lidocaine patches 5%, changed every 12 or 24 hours, produced plasma lidocaine concentrations that remained well below those that typically produce antiarrhythmic effects or toxicity. Mild application-site erythema occurred in most patients, but no systemic adverse reactions were judged to be related to the patches. No loss in sensation at the application site was reported.
BACKGROUND: Behavioural and psychiatric disturbances affect at least 50% of people with Alzheimer's disease and other dementias. Neuroleptic drugs are extensively prescribed to treat behavioural manifestations of dementia in spite of only modest efficacy and a high frequency of adverse effects. There is clearly a need for safer and more effective remedies. Trazodone is a psychoactive compound with sedative and antidepressant properties, and with mixed serotonin agonist and antagonist effects. Functional serotonergic deficits may be related to the genesis of behavioural disturbances in dementia. OBJECTIVES: To determine the clinical efficacy and safety of trazodone, for any type of behavioural or psychological cognition in people with dementia without an additional diagnosis of depression. SEARCH STRATEGY: Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 1 June 2004 using the terms trazodon*, beneficat, desirel, sideril, trazodil, trazalon. This register contains records from all major health care databases and many ongoing trials databases, and is updated regularly. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials, comparing trazodone with placebo in managing behavioural and psychiatric symptoms (except depression) in any type of dementia. DATA COLLECTION AND ANALYSIS: Available data for this analysis were extracted from the two included studies and odds ratios or average differences, with 95% confidence intervals, calculated. Intention-to-treat analysis was undertaken where possible. MAIN RESULTS: Two studies were included, comprising 104 participants with dementia. The trials differed in design - one being a parallel-group study of patients with Alzheimer's disease (Teri 2000) and one being a cross-over study of patients with frontotemporal dementia (Lebert 2004). It was not possible to pool the data. The studies were respectively of 16 and 6 weeks duration, using trazodone from 50 to 300mg daily. Both trials examined global clinical state, behavioural disturbances and cognitive function. Teri 2000 also assessed activities of daily living and caregiver burden. Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales (ABID, CERAD-BRSD,CMAI, NPI). Analysis of changes from baseline for clinical impression of change and for cognitive function did not produce statistically significant results in favour of trazodone. A variety of adverse effects were recorded with no significant differences between trazodone and placebo. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia. In order to assess effectiveness and safety of trazodone, longer-term trials are needed, involving larger samples of participants with a wider variety of types and severities of dementia.