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PubMed1985

Hydergine pharmacokinetics in the elderly.

The pharmacokinetics of Hydergine was studied following intramuscular administration in a group of 6 subjects aged 76-86 and following oral administration in 6 subjects aged 66-86. Comparison with a control group of healthy volunteers (average age of 25) showed: --a marked reduction (- 50%) in renal clearance (p less than 0.001), related to the decrease in creatinine clearance in this population; --a lowering (- 30%) in metabolic clearance (p less than 0.02) in elderly subjects probably related to the decrease in hepatic blood flow observed with age; --a marked increase in bioavailability (X 2.5) following oral administration in elderly subjects, due either to increased absorption, or to a decreased hepatic first-pass effect. These results underline the value of studying the kinetics of geriatric drugs in the target population.

Administration, Oral↗
PubMed1998

Vancomycin resistant enterococcus in a hospital-based dialysis unit.

OBJECTIVE: The emergence of vancomycin resistant enterococcus (VRE) poses a serious threat to the health care community. Reservoirs of VRE are thought to exist in certain high-risk patient groups who reintroduce the organism into the hospital environment. The frequent use of vancomycin in dialysis patients may place this population at higher risk of developing VRE. This article describes the development of VRE and a point prevalence study conducted in a hospital-based dialysis unit. SETTING/SAMPLE: A dialysis unit of a tertiary care center in the eastern United States was selected as the study site. Patients who agreed to participate in the study after giving informed consent were included. Of the 85 members of this target population 33 (38.8%) agreed to participate in the study. The duration of the study was 30 days. DESIGN: After the literature was reviewed, a point prevalence study was completed at the study site. Stool samples or rectal swabs were collected from the study participants and analyzed for the presence of VRE. A chart review of patient demographic and prior treatment information was completed in order to help identify factors that correlate to the presence of VRE. METHODS: Stool or rectal swab samples were cultured on selective media and sensitivity to vancomycin was measured. RESULTS: A 9.1% prevalence of VRE was detected within the study group. The number of VRE positive subjects (3) did not allow statistically significant correlation with the demographic and prior treatment data collected. CONCLUSION: Although VRE remains a serious threat to the health care community, the prevalence of VRE within the study group does not vary markedly from rates previously reported.

Adult↗
PubMed1999

Bruton's tyrosine kinase controls a sustained calcium signal essential for B lineage development and function.

Genetic data support a role for Btk during the B lineage development transitions regulated by signaling through both the pre-B and the B cell antigen receptors. Dysregulated signaling at each of these transitions can result in failure of these cell populations to proliferate and subsequent cell death. Btk-dependent IP3 production is crucial for maintaining the sustained calcium signal in response to BCR engagement and is likely to regulate a subset of transcriptional events essential for B lineage growth or survival. Identification of these Btk-dependent signals will be important in understanding B cell activation, differentiation, and cell death. This information may lead to therapies specifically targeting these events in B cell autoimmunity or malignancy and provide a fuller understanding of the appropriate target populations and potential negative consequences of Btk gene therapy in XLA. Identification of Btk/Tec family kinases in an increasing number of vertebrate and invertebrate cell lineages suggests that the link between Btk and the PLC gamma/IP3/calcium signaling pathways may be broadly conserved.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2005

Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae.

BACKGROUND: There is a lack of evidence documenting the impact of optimized antibiotic use on the rates of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) in children. This study evaluates the effect of community-based intervention strategies on the prevalence of pnsp colonization. METHODS: A controlled, population-based pharmacoepidemiological trial was conducted from January through May 2000. Three French geographic areas were selected on the basis of demographic similarities. Two intervention strategies were implemented: (1) reduced antibiotic use, which was achieved by not prescribing antibiotics for presumed viral respiratory tract infections (the prescription-reduction group); and (2) better adaptation of dose and duration (the dose/duration group). A control group received no intervention. The target population was children aged 3-6 years who were attending kindergarten. Oropharyngeal pneumococcus colonization and antibiotic use were monitored throughout the 5-month study. RESULTS: The prescription-reduction, dose/duration, and control groups included 601, 483, and 405 children, respectively. The interventions induced significantly larger decreases in antibiotic use in the prescription-reduction group (-18.8%) and dose/duration group (-17.1%) than in the control group (-3.8%), and the rates of PNSP colonization were initially similar for the 3 groups (52.5%, 55.1%, and 50.0%, respectively). At the end of the 5-month study, the rates of PNSP colonization were 34.5% for the prescription-reduction group (P=.05) and 44.3% for the dose/duration group (P=.8), compared with 46.2% for the control group. CONCLUSIONS: Intensive educational strategies aimed at optimizing antibiotic use can significantly reduce the rate of PNSP colonization in areas with high resistance rates.

Anti-Bacterial Agents↗
PubMed1981

The effect of response bias on the odds ratio.

The effect of response bias on odds ratio results was determined based on data from a population-based cardiovascular disease survey. The study subjects consisted of 5000 adult residents of a predominantly white, upper-middle class community. Information from 60% of the 1100 non-respondents was obtained by telephone. Consistent patterns of participation associated with risk factors and diseases under study were found. A simple error term was developed to convert the odds ratio for respondents to the odds ratio for the target population using individual cell response rates. This error term demonstrates that the response patterns found tended to minimize the error in odds ratio calculations for respondents. Only by obtaining relevant information on non-respondents can investigators accurately estimate response bias and its effects on the odds ratio.

Adult↗
PubMed1997

The incidence of delirium in psychiatric inpatient units.

OBJECTIVES: To estimate prospectively the incidence of delirium in psychiatric inpatients and to identify risk factors for delirium in this population. METHOD: The subjects were nondelirious patients newly admitted to the Calgary General Hospital. The Delirium Symptom Interview (DSI), the Confusion Assessment Method (CAM), and the Mini-Mental State Examination (MMSE) were used to identify incident cases of delirium. In order to evaluate the potential impact of selection bias, we conducted a supplementary analysis using record linkage to an electronic administrative data base with coverage of the target population. RESULTS: Of 420 admissions to the hospital, 401 subjects provided informed consent and were not delirious at the time of admission. There were 9 incident cases of delirium. The cumulative incidence rate was, therefore, 2.14 per 100 admissions. The record linkage analysis did not uncover evidence of selection bias. Delirium was associated with a significantly increased length of stay in hospital. CONCLUSIONS: Delirium is an uncommon incident event in the psychiatric inpatient population. The incidence rate reported here may be useful as a benchmark for the identification of excessive rates in other inpatient settings. Since delirium is sometimes related to modifiable therapeutic factors, an excessive rate should prompt a search for its causes.

Adolescent↗
PubMed2002

Erythrocyte-rosetting properties of feline blood lymphocytes and their relationship to monoclonal antibodies to T lymphocytes.

Rosette formation of feline peripheral blood leukocytes with guinea pig (GP) and gerbil (G) erythrocytes (E) has been shown in an earlier study to identify T lymphocytes expressing helper and suppressor cell activity, respectively. This T lymphocyte distinction was based on the removal of the E-rosetting populations from peripheral blood leukocytes (PBL) and the subsequent functional evaluation of the remaining cells in a pokeweed mitogen (PWM)-induced synthesis of immunoglobulin (Ig). In the present study, we demonstrate a direct helper and suppressor function of GPE- and GE-rosetted cells, respectively, wherein the induction of Ig synthesis is altered in a positive or negative way by the addition of the cells to a control target population. A pan-T monoclonal antibody (mAb), CT843, and mAbs to the CD4 (CT248) and CD8 (CT87) subsets are also described; their specificities are established in functional assays, the PWM-induced Ig synthesis and the production of interleukin-2 following Concanavalin A stimulation of PBL, and a biochemical analysis of the surface membrane antigens detected by the mAbs. Immunoprecipitation and SDS-PAGE analyses showed CT248 to react with a approximately 60-kDa protein under both reducing and nonreducing conditions. Under reducing conditions, CT87 reacted with one subunit at approximately 35 kDa; a second faint band at approximately 39 kDa was poorly resolved. mAb CT843 detected a heterodimer of approximately 70 and approximately 60 kDa under both reducing and nonreducing conditions. The relationship of the mAbs to E-rosetting was examined in FACScan analyses and rosette inhibition studies. The percentage of GE-rosetting cells agreed with the percentage of cells stained with the CD8 mAb, whereas a comparison of GPE-rosetting and staining with the CD4 mAb showed variability. The binding of GE to PBL was blocked by pretreatment of PBL with the CD8 mAb, whereas no inhibition of GPE rosettes was observed with any of the mAbs. In a previous study, we had shown that an overnight culture of feline PBL at 37 degrees C leads to the development of a second population of GPE-rosetting cells, also having a helper function. The relationship of the two GPE-rosetting populations to the CD4 mAb, CT248, was examined in rosette depletion studies and FACScan analyses. It was found that depletion of the GPE-rosetting cells from fresh, i.e., Day 0 cells, removed only a small percentage of cells reactive with the CD4 mAb, whereas GPE-rosette depletions performed on Day 1 PBL, which contained both populations of GPE-rosetting cells, removed almost all cells reactive with this antibody. The latter study suggests that the GPE-rosetting phenomenon is detecting two subsets of CD4 cells with T helper function, those present in fresh blood and those acquiring the GPE receptor after an overnight culture.

Animals↗
PubMed2004

[Survey on injury in four rural communities in China].

OBJECTIVE: To understand the incidence and prevalence by causes of injury, and the proportion of different causes of deaths, as well as occurrence of disability due to injuries. METHODS: 200,000 families were randomly sampled in 4 rural communities. Questionnaire on occurrence, disability, death of injury and related risk factors for all family members living at home from Feb. 12, 2002 to Aug. 12, 2002 were studied. RESULTS: The incidence rate and prevalence rate in the observed population were 65.1/1000 and 69.2/1000, respectively. In every 100 cases of injury there were one death and 6 disabled. Fall, animal bites, striking or crushing, cutting and piercing, road accidents, fire and poisoning were the common causes in injury. Animal bites was the leading cause while drawing appeared the highest in children aged 0 - 14. Rate of road accident was the highest in adults aged 15 - 34, while falls causing higher proportion of disability in population aged over 60. CONCLUSIONS: Based on the report of National Disease Surveillance Points System, there were 592,000 death cases of injury in Chinese rural areas every year, meaning 59.2 million cases of injury and 3,490,000 disabled cases every year. Since injury causes serious social and economic loss with different orders of incidence and mortality, it is necessary to develop different preventive strategies on different target populations and different causes accordingly.

Age Factors↗
PubMed1994

The risk of endometrial cancer in diabetic and hypertensive patients: a nationwide record-linkage study in Finland.

The risk of endometrial cancer (EC) in diabetics and hypertensives was studied as part of the planning of a trial of the efficacy of screening for EC. Two nationwide registers, the Finnish Cancer Registry and the Social Insurance Institution's (SII) population register, were linked to obtain 1715 EC patients diagnosed during 1970-1974 with individually matched controls. Data on the right for state-reimbursed medication for diabetes or hypertension prior to the case's cancer diagnosis was obtained from the SII's population register and was used as indicator of the diseases in question. Diabetes was a strong and hypertension a relatively weak risk factor for EC. The relative risk for the association of EC with diabetes was 4.1 (95% confidence limits 2.7 and 6.9) and with hypertension 1.6 (95% confidence limits 1.3 and 2.1). Diabetics and hypertensives are identifiable risk groups for EC in Finland. Diabetics form a suitable target population for a trial of the efficacy of screening for EC.

Adult↗
PubMed2004

An active transposable element, Herves, from the African malaria mosquito Anopheles gambiae.

Transposable elements have proven to be invaluable tools for genetically manipulating a wide variety of plants, animals, and microbes. Some have suggested that they could be used to spread desirable genes, such as refractoriness to Plasmodium infection, through target populations of Anopheles gambiae, thereby disabling the mosquito's ability to transmit malaria. To achieve this, a transposon must remain mobile and intact after the initial introduction into the genome. Endogenous, active class II transposable elements from An. gambiae have not been exploited as gene vectors/drivers because none have been isolated. We report the discovery of an active class II transposable element, Herves, from the mosquito An. gambiae. Herves is a member of a distinct subfamily of hAT elements that includes the hopper-we element from Bactrocera dorsalis and B. cucurbitae. Herves was transpositionally active in mobility assays performed in Drosophila melanogaster S2 cells and developing embryos and was used as a germ-line transformation vector in D. melanogaster. Herves displays an altered target-site preference from the distantly related hAT elements, Hermes and hobo. Herves is also present in An. arabiensis and An. merus with copy numbers similar to that found in An. gambiae. Preliminary data from an East African population are consistent with the element being transpositionally active in mosquitoes.

Africa↗
PubMedDate not supplied

Vaginal dilation associated with pelvic radiotherapy: a UK survey of current practice.

This paper presents results from the first UK national survey of patient information and interventions related to vaginal dilation in pelvic radiotherapy (RT). The aim was to elicit current practice with regard to the target population, content/process of patient education, and the evaluation of compliance in relation to this intervention. A 38-item questionnaire was sent to all RT departments (n= 65) and a convenience sample of specialist gynecological oncology nurses (n= 166), with response rates of 62% (n= 40) and 31% (n= 52), respectively. Data analysis (via SPSS v11) used both descriptive and inferential statistics. Divergence of opinion was evident regarding the specific target audience for dilator education, and only a limited number of elements of vaginal dilator technique achieved consensus. Sixty-seven percent of respondents stated they carried out a wider sexual health assessment associated with the provision of dilator information, although its content varied considerably. Results suggest the provision of vaginal dilation advice may benefit from being placed in the wider context of assessing treatment impact on women's sexual health, raising the profile of appropriate psychosexual assessment, and intervention in clinical oncology practice. Further research could determine the efficacy of vaginal dilation in preventing development of vaginal stenosis among women receiving pelvic RT.

Constriction, Pathologic↗
PubMed2004

Development of a monoclonal antibody based competitive-ELISA for detection and titration of antibodies to peste des petits ruminants (PPR) virus.

Peste des petits ruminants (PPR) is an acute febrile, viral, disease of small ruminants with great economic importance. A competitive-ELISA (c-ELISA) test was developed for detection of antibodies to PPR virus in the sera samples of goats and sheep. The test uses monoclonal antibody to a neutralizing epitope of haemagglutinin protein of the virus. Based on the distribution of known negative sera samples (n=933) in respect of PPR virus antibodies in the test, a cut-off value was set as 38%. This value was the result of mean of negative population added with two times the standard deviations. A total of 1668 sera samples from goat and sheep and 32 sera from cattle were screened by c-ELISA and virus neutralization test (VNT). Efficacy of c-ELISA compared very well with VNT having high relative specificity (98.4%) and sensitivity (92.4%). The sensitivity of c-ELISA for PPR sero-surveillance could further be increased (95.4%), if the target population is non-vaccinated. c-ELISA test correlated well with VNT (r=0.845) for end-point titration of PPR virus antibody in 64 goat sera samples. It could clearly separate infected population from uninfected in field sera. Using c-ELISA test paired sera samples from 13 goats provided a clear diagnosis of PPR virus infection. Furthermore, antibodies to PPR virus could be successfully detected during 1 year after vaccination in four goats inoculated with an experimental PPR vaccine. Findings suggest that the c-ELISA test developed can easily replace VNT for sero-surveillance, sero-monitoring, diagnosis from paired sera samples and end-point titration of PPR virus antibodies.

Animals↗
PubMed2006

Population pharmacokinetics of atazanavir in patients with human immunodeficiency virus infection.

Atazanavir (ATV) is a new azapeptide protease inhibitor recently approved and currently used at a fixed dose of either 300 mg once per day (q.d.) in combination with 100 mg ritonavir (RTV) or 400 mg q.d. without boosting. ATV is highly bound to plasma proteins and extensively metabolized by CYP3A4. Since ATV plasma levels are highly variable and seem to be correlated with both viral response and toxicity, dosage individualization based on plasma concentration monitoring might be indicated. This study aimed to assess the ATV pharmacokinetic profile in a target population of HIV patients, to characterize interpatient and intrapatient variability, and to identify covariates that might influence ATV disposition. A population analysis was performed with NONMEM with 574 plasma samples from a cohort of 214 randomly selected patients receiving ATV. A total of 346 randomly collected ATV plasma levels and 19 full concentration-time profiles at steady state were available. The pharmacokinetic parameter estimates were an oral clearance (CL) of 12.9 liters/h (coefficient of variation [CV], 26%), a volume of distribution of 88.3 liters (CV, 29%), an absorption rate constant of 0.405 h(-1) (CV, 122%), and a lag time of 0.88 h. A relative bioavailability value was introduced to account for undercompliance due to infrequent follow-ups (0.81; CV, 45%). Among the covariates tested, only RTV significantly reduced CL by 46%, thereby increasing the ATV elimination half-life from 4.6 h to 8.8 h. The pharmacokinetic parameters of ATV were adequately described by a one-compartment population model. The concomitant use of RTV improved the pharmacokinetic profile. However, the remaining high interpatient variability suggests the possibility of an impact of unmeasured covariates, such as genetic traits or environmental influences. This population pharmacokinetic model, together with therapeutic drug monitoring and Bayesian dosage adaptation, can be helpful in the selection and adaptation of ATV doses.

Adult↗
PubMed1996

[Myocardial infarction--risks and procedures. Longitudinal observation of a population of 280,000 women and men--Project POL-MONI CA Krakow. III: Epidemiology and treatment of myocardial infarction].

There has been a large amount of progress in the methods of prevention and treatment of ischaemic heart disease (IHD), but the effect of these changes on mortality due to IHD has not been assessed. This paper presents the complex analysis of 10-year trends of incidence, case fatality and mortality due to myocardial infarction (MI) and changes in medical care in the acute phase of MI in residents of one province of Poland-Tarnobrzeg Voivodship, which was the target population of the POL-MONICA Kraków Project (over 280,000 men and women at age 25-64 years). In men, the incidence of MI, which was 335/100,000 in 1984, increased in 1986 to 463/1,000,000 and then was stable until 1993 when it felt to 362/100,000. Mortality from MI, which was 149/100,000 in 1984, increased to 212/100,000 in 1986 and then was stable until 1992, before falling to 173/100,000 in 1993. There were large fluctuations in the incidence and mortality from MI in women i.e. from 58/100,000 to 116/100,000 and from 21/100,000 to 55/100,000 respectively. In 1993 the incidence was 82/100,000 and mortality was 32/100,000. After adding sudden deaths and other fatal events attributed to IHD the mortality figures increased over the ten years of observation by an average of 29% in men and by 28% in women. The average total MI case fatality was 47% in men and 40% in women, with 86% of all deaths due to MI occurring out of hospital. Case-fatality of MI managed in hospital was 11% on average.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Outcome effectiveness of community health workers: an integrative literature review.

Community health workers (CHWs) are promoted as a mechanism to increase community involvement in health promotion efforts, despite little consensus about the role and its effectiveness. This article reviews the databased literature on CHW effectiveness, which indicates preliminary support for CHWs in increasing access to care, particularly in underserved populations. There are a smaller number of studies documenting outcomes in the areas of increased health knowledge, improved health status outcomes, and behavioral changes, with inconclusive results. Although CHWs show some promise as an intervention, the role can be doomed by overly high expectations, lack of a clear focus, and lack of documentation. Further research is required with an emphasis on stronger study design, documentation of CHW activities, and carefully defined target populations.

Behavior Therapy↗
PubMed2006

Structured diabetes therapy and education improves the outcome of patients with insulin treated diabetes mellitus. The 10 year follow-up of a prospective, population-based survey on the quality of diabetes care (the JEVIN Trial).

AIMS/HYPOTHESIS: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year follow-up, population-based survey of all insulin treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of implementation of the St. Vincent Declaration and to evaluate the effect of recent changes in the health care system and new treatment strategies. PATIENTS AND METHODS: 190 patients (83% of the target population), 244 patients (90%) and 261 patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively. RESULTS: Up to 1994/95, the HbA1c of patients with type 1 diabetes mellitus increased (1994/95: 8.50+/-1.80% versus 1989/90: 7.83+/-1.60%, p=0.002). For patients with type 2 diabetes mellitus, it remained constant (9.01+/-2.06% versus 9.17+/-1.60%, n. s.). During the period from 1994/95 to 1999/2000, there was a substantial improvement in the relative HbA1c of both, patients with type 1 (7.62+/-1.55%, p<0.0001), and with type 2 diabetes (7.57+/-1.29%, p<0.0001). Up to 1999/2000, 87.7% of the patients with type 1 (1989/90: 0%, 1994/95: 73.2%) and 96.6% of the patients with type 2 diabetes (1989/90: 0%, 1994/95: 89.7%) participated in TTP's. The incidence of acute and the prevalence of long-term complications remained constant. CONCLUSIONS: Results of the population-based, prospective trial to optimise patients' quality of diabetic control suggest: For patients with insulin treated type 2 diabetes mellitus, excellent treatment can be available by primary care physicians interested, educated and highly engaged in diabetes therapy. Moreover, structured diabetes therapy consisting of treatment and teaching programmes, regular self-monitoring, patients' insulin dose adjustment and patients' empowerment, should be offered to all patients with diabetes mellitus.

Adolescent↗
PubMed2003

Carrier testing for autosomal-recessive disorders.

The aim of carrier testing is to identify carrier couples at risk of having offspring with a serious genetic (autosomal recessive) disorder. Carrier couples are offered genetic consultation where their reproductive options, including prenatal diagnosis, are explained. The Ashkenazi Jewish population is at increased risk for several recessively inherited disorders (Tay-Sachs disease, Cystic fibrosis, Canavan disease, Gaucher disease, Familial Dysautonomia, Niemann-Pick disease, Fanconi anemia, and Bloom syndrome). Unlike Tay-Sachs disease, there is no simple biochemical or enzymatic test to detect carriers for these other disorders. However, with the rapid identification of disease-causing genes in recent years, DNA-based assays are increasingly available for carrier detection. Approximately 5% of the world's population carries a mutation affecting the globin chains of the hemoglobin molecule. Among the most common of these disorders are the thalassemias. The global birth rate of affected infants is at least 2 per 1000 (in unscreened populations), with the greatest incidence in Southeast Asian, Indian, Mediterranean, and Middle Eastern ethnic groups. Carriers are detected by evaluation of red cell indices and morphology, followed by more sophisticated hematological testing and molecular analyses. The following issues need to be considered in the development of a carrier screening program: (1) test selection based on disease severity and test accuracy; (2) funding for testing and genetic counselling; (3) definition of the target population to be screened; (4) development of a public and professional education program; (5) informed consent for screening; and (6) awareness of community needs.

Bloom Syndrome↗
PubMed2003

A historical aspect of lysinuric protein intolerance in a northern part of Iwate, Japan.

Historical aspects of a local cluster of individuals with lysinuric protein intolerance (LPI) were studied in a sample of patients and in a mass-screened population in a northern area of Japan. The historical aspects were investigated by estimating the mutation age and analyses of haplotype diversity of the chromosome carrying the R410X mutation. This mutation occurred over 1000 years ago, and its fixation in the local cluster suggests that LPI had been a nearly neutral phenotype. The present results also give an estimate of the geographical distribution of the R410X mutation, providing a basis for targeting populations for mass screening for LPI.

Alleles↗