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PubMed1993

[Possibilities for psychological intervention in persistent delusions and persistent acoustic hallucinations in schizophrenic patients].

In practice the therapy of treatment resistant psychotic symptomatology (delusions and hallucinations) is a difficult and up to now unsolved problem. This overview presents and discusses behaviour therapy oriented studies (in the main part single case studies). The majority of studies show that it is in principle possible to influence this symptomatology. Because of methodological limitations of many studies finally some proposals for future research are discussed.

Adaptation, Psychological↗
PubMed1999

Developmental aspects of delinquency and internalizing problems and their association with persistent juvenile substance use between ages 7 and 18.

Analyzed longitudinal data from 3 samples of the Pittsburgh Youth Study on boys ages 7 to 18 to examine the co-occurrence of persistent substance use with other problem behaviors, including attention deficit hyperactivity disorder (ADHD), persistent delinquency, and persistent internalizing problems (i.e., depressed mood, anxiety, shy or withdrawn behavior). In preadolescence, persistent substance users also tended to be persistent delinquents, and half of this group displayed persistent internalizing problems as well. In adolescence, a third of the persistent substance users did not manifest other persistent problems. Across the samples, the least common substance users were those who manifested persistent internalizing problems only. Logistic regression analyses showed that persistent substance use in preadolescence was predicted by persistent delinquency and internalizing problems and in adolescence by persistent delinquency only. The combination of persistent substance use and delinquency was predicted by oppositional defiant disorder in middle childhood and by persistent internalizing problems in middle to late childhood. ADHD was not a predictor of persistent substance use (and delinquency) in any of the analyses. Results are discussed in terms of developmental models of multiproblem youth with an eye on improving early interventions.

Adolescent↗
PubMed2003

Identifying factors that predict persistent driving after drinking, unsafe driving after drinking, and driving after using cannabis among young adults.

UNLABELLED: The main aim of this study was to identify adolescent/young adulthood factors that predicted persistent driving after drinking, persistent unsafe driving after drinking, and persistent cannabis use and driving among young adults. It was a longitudinal study of a birth cohort (n=933, 474 males and 459 females) and was based on data collected at ages 15, 18, 21 and 26 years. At each of these ages members of the cohort attended the research unit for a personal interview by a trained interviewer, using a standardised questionnaire. For this study, the data for the outcome measures (persistent driving after drinking, persistent unsafe driving after drinking, and persistent driving after using cannabis) were obtained at ages 21 and 26 years. The main explanatory measures were collected at ages 15, 18, 21 years and included demographic factors (academic qualifications, employment, parenting); personality measures; mental health measures (substance use, cannabis dependence, alcohol dependence, depression); anti-social behaviour (juvenile arrest, aggressive behaviour, court convictions); early driving behaviour and experiences (car and motorcycle licences, traffic crashes). The analyses were conducted by gender. The results showed that females who persisted in driving after drinking (13%, n=61) were more likely than the others to have a motorcycle licence at 18. The males who persisted in driving after drinking (28%, n=135) were more likely than the other males to have some school academic qualifications and to be employed at age 26. Compared to the other males, those who persisted in unsafe driving after drinking (4%, n=17) were more likely to be aggressive at 18 and alcohol dependent at 21. Only six (1%) females persisted in unsafe driving after drinking so regression analyses were not conducted for this group. For persistent driving after using cannabis, the univariate analyses showed that females who persisted with this behaviour tended to have high substance use at 18, cannabis dependence at 21, police contact as a juvenile, and to be a parent at 21. For this group, because of the small numbers (3%, n=13) multivariate analyses were not appropriate. For the males who persisted in driving after using cannabis (14%, n=68) a wide range of variables were significant at the univariate stage. The multivariate analysis showed that the most important factors were dependence on cannabis at 21, at least one traffic conviction before 21, a non traffic conviction before 18, and low constraint at 18. CONCLUSION: These results show different characteristics were associated with persistence in each of these outcome behaviours. This indicates that different approaches would be required if intervention programmes were to be developed to target these behaviours.

Adolescent↗
PubMed1998

Small bowel and fecal microbiology in children suffering from persistent diarrhea in Bangladesh.

BACKGROUND: The etiology of persistent diarrhea in children is multifactorial. The objective of the current study was to ascertain the role of microorganisms in the etiology and pathogenesis of persistent diarrhea in a group of children in Bangladesh. METHODS: Enteric pathogens and total aerobic microflora were studied in the duodenal aspirates of 100 children with persistent diarrhea and compared with those in aspirates of 30 children with acute diarrhea, and those in aspirates of 15 healthy control children. The enteric pathogens in the stools of these children and in stools of an additional 38 patients with persistent diarrhea and 12 with acute diarrhea were also studied. RESULTS: Approximately two thirds of the patients with acute diarrhea and persistent diarrhea, and half of the control subjects had more than 10(5) organisms per milliliter of duodenal fluid. Significantly, more patients with persistent diarrhea had a greater variety of flora than did patients with acute diarrhea and control subjects. The predominant organisms in patients with acute diarrhea and in those with persistent diarrhea were Gram-negative rods, whereas those in control subjects were Gram-positive cocci. Significantly more acute diarrhea patients and persistent diarrhea patients had enteric pathogens isolated from stool than did control subjects. Diarrheagenic Escherichia coli, as a whole, were present in significantly more persistent diarrhea patients than in acute diarrhea patients and control subjects. Among diarrheagenic E. coli, enteroaggregative E. coli were significantly associated only with persistent diarrhea. Other organisms significantly associated with persistent diarrhea were Aeromonas spp. and Klebsiella spp. Some patients in the acute diarrhea and the persistent diarrhea groups had the same pathogens isolated from both the duodenal fluid and stool. CONCLUSIONS: In accordance with results of other studies, an association between enteroaggregative E. coli and persistent diarrhea was found in the present study. This suggests that therapy directed against enteroaggregative E. coli can be evaluated for management of some cases of persistent diarrhea.

Acute Disease↗
PubMed2000

Trends in persistent proteinuria in adult-onset diabetes: a population-based study.

OBJECTIVE: This study investigates temporal trends in the prevalence and incidence of persistent proteinuria among people with adult-onset diabetes (age > or =40 years). RESEARCH DESIGN AND METHODS: The complete community-based medical records of all Rochester, Minnesota, residents with a diagnosis of diabetes or diabetes-like condition from 1945 through 1989 were reviewed to determine whether they met National Diabetes Data Group (NDDG) criteria. All confirmed diabetes cases residing in Rochester on 1 January 1970 (n = 446), 1980 (n = 647), and/or 1990 (n = 940) were identified. The medical records of these prevalence cases were reviewed from the time of the first laboratory urinalysis value to the last visit, death, or 1 April 1992 (whichever came first) for evidence of persistent proteinuria (two consecutive urinalyses positive for protein, with no subsequent negative values). Similarly, the medical records of all 1970-1989 diabetes incidence cases (n = 1,252) were reviewed to investigate temporal changes in 1) the likelihood of having persistent proteinuria before the date NDDG criteria was met, i.e., baseline; 2) the risk of persistent proteinuria after baseline; and 3) the relative risk of mortality associated with persistent proteinuria. RESULTS: The proportion of diabetes prevalence cases with persistent proteinuria on or before the prevalence date declined from 20% in 1970 to 11% in 1980 and 8% in 1990. Among the 1970-1989 diabetes incidence cases, 77 (6%) had persistent proteinuria on or before baseline; the adjusted odds declined by 50% with each 10-year increase in baseline calendar year (P<0.001). Among individuals free of persistent proteinuria at baseline, 136 subsequently developed persistent proteinuria; the estimated 20-year cumulative incidence was 41% (95% CI 31-59); the adjusted risk did not differ as a function of baseline calendar year. Survival of individuals with persistent proteinuria relative to those without was reduced but did not differ by baseline calendar year. CONCLUSIONS: The prevalence of persistent proteinuria among people with adult-onset diabetes in Rochester, Minnesota, declined 60% between 1970 and 1990. The decline appears because of a decrease in the proportion of diabetes incidence cases with persistent proteinuria before baseline rather than secular declines in the risk of persistent proteinuria after baseline or secular increases in the risk of mortality associated with persistent proteinuria. Similarity over time in age and fasting glucose at baseline, and at prevalence dates, is evidence that earlier detection of diabetes is not the sole explanation for the decline.

Blood Glucose↗
PubMed2006

Candida albicans biofilms produce antifungal-tolerant persister cells.

Fungal pathogens form biofilms that are highly recalcitrant to antimicrobial therapy. The expression of multidrug resistance pumps in young biofilms has been linked to increased resistance to azoles, but this mechanism does not seem to underlie the resistance of mature biofilms that is a model of in vivo infection. The mechanism of drug resistance of mature biofilms remains largely unknown. We report that biofilms formed by the major human pathogen Candida albicans exhibited a strikingly biphasic killing pattern in response to two microbicidal agents, amphotericin B, a polyene antifungal, and chlorhexidine, an antiseptic, indicating that a subpopulation of highly tolerant cells, termed persisters, existed. The extent of killing with a combination of amphotericin B and chlorhexidine was similar to that observed with individually added antimicrobials. Thus, surviving persisters form a multidrug-tolerant subpopulation. Interestingly, surviving C. albicans persisters were detected only in biofilms and not in exponentially growing or stationary-phase planktonic populations. Reinoculation of cells that survived killing of the biofilm by amphotericin B produced a new biofilm with a new subpopulation of persisters. This suggests that C. albicans persisters are not mutants but phenotypic variants of the wild type. Using a stain for dead cells, rare dark cells were visible in a biofilm after amphotericin B treatment, and a bright and a dim population were physically sorted from this biofilm. Only the dim cells produced colonies, showing that this method allows the isolation of yeast persisters. Given that persisters formed only in biofilms, mutants defective in biofilm formation were examined for tolerance of amphotericin B. All of the known mutants affected in biofilm formation were able to produce normal levels of persisters. This finding indicates that attachment rather than formation of a complex biofilm architecture initiates persister formation. Bacteria produce multidrug-tolerant persister cells in both planktonic and biofilm populations, and it appears that yeasts and bacteria have evolved analogous strategies that assign the function of survival to a small part of the population. In bacteria, persisters are dormant cells. It remains to be seen whether attachment initiates dormancy that leads to the formation of fungal persisters. This study suggests that persisters may be largely responsible for the multidrug tolerance of fungal biofilms.

Antifungal Agents↗
PubMed2004

The persistence of ripe fleshy fruits in the presence and absence of frugivores.

A trade-off between antimicrobial defences and palatability to dispersers may place limits on fruit persistence in nature. The retention times of ripe fruits on 34 wild plant species under natural conditions (unbagged persistence) and when fruits had been bagged with nylon mesh to exclude frugivores (bagged persistence) were compared in Hong Kong, China (22 degrees N). Bagged persistence is a measure of the effectiveness of fruit defence while unbagged persistence is an inverse measure of attractiveness to vertebrate frugivores. Bagged fruits persisted significantly longer than unbagged fruits in 30 species, with half the species tested persisting for more than 2 months. There was a significant positive relationship between the median persistence times of bagged and unbagged fruits, suggesting that species with a high resistance to microbial infection are also less attractive to frugivores. Both bagged and unbagged fruits persisted significantly longer at lower temperatures. There was a significant positive relationship between bagged persistence time and fibre content of the fruit pulp, but no significant relationships between unbagged persistence and the six fruit traits tested (diameter, pulp as a percentage of fruit fresh weight, and lipid, total soluble carbohydrate, nitrogen and fibre as percentages of pulp dry weight). Mechanical damage significantly decreased the bagged persistence time for half of the species. Although some fruits decayed or dried up while attached to the plant, fruits of 53% of the species remained visually attractive until they fell off.

Animals↗
PubMed1985

Spatial-frequency-dependent visible persistence and specific reading disability.

Visible persistence duration for sine-wave gratings was measured in 9-year-old normal and specific-reading-disabled children. Experiment 1 investigated the influence of stimulus duration on visible persistence. The results demonstrated a Reading Group X Spatial Frequency interaction with disabled readers showing a smaller increase in persistence duration with increasing spatial frequency than controls. This interaction was greatest with stimulus durations longer than 80 msec. In Experiments 2a and 2b persistence was measured across a range of contrasts from .1 to .5. The stimulus durations employed were 100 msec in Experiment 2a and 300 msec in Experiment 2b. In both experiments, increasing contrast decreased persistence duration at 2 and 12 cycles per degree (c/deg) for the control group. In the specific-reading-disabled group, however, contrast had little effect on the persistence of 2-c/deg gratings in either experiment. In Experiment 2a the persistence of the 12-c/deg grating decreased with increasing contrast for both groups. In Experiment 2b contrast had significantly less effect on persistence duration in the specific-reading-disabled group, however, contrast had little effect on the persistence of 2-c/deg ratings in either experiment. In Experiment 2b contrast had significantly less effect on persistence duration in the specific-reading-disabled group than in the control group at 12 c/deg. Consequently, contrast had less effect on persistence in specific-reading-disabled children than in normal readers, especially at durations longer than the "critical duration" for each spatial frequency. Experiment 3 extended this finding to gratings with spatial frequencies of 4 and 8 c/deg. These results indicate a difference between normal and specific-reading-disabled children in cortical visible persistence. Two scores of visual processing were derived from the above experiments. On these scores the reading-disabled children were divided into Visual Disabled Readers (approximately 70%--eight subjects) and Nonvisual Disabled Readers (approximately 30%--four subjects). The percentages of disabled readers in each category remained constant when the sample size was increased to 61 normal and disabled readers.

Attention↗
PubMed2006

Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis.

BACKGROUND: Although bisphosphonates are useful in the management of osteoporosis, patients often discontinue treatment. OBJECTIVES: The aims of this study were to investigate persistence with bisphosphonates, and to assess whether the dose interval influenced persistence, among women with postmenopausal osteoporosis. METHODS: Data were obtained from the PHARMO Record Linkage System, which includes, among other databases, drug-dispensing records from community pharmacies linked to hospital discharge records of > 1 million subjects in defined areas in The Netherlands. Women who were new users of alendronate (daily or weekly), etidronate (daily), or risedronate (daily) during the period from January 2000 through September 2003 were eligible for inclusion in the study if they were aged > or = 55 years or had been hospitalized for a menopausal disorder. One-year rates of persistence with treatment (defined as the percentage of patients who used the drug for > or = 365 days without failure to continue renewals) were determined by using episodes of bisphosphonate treatment. The association between persistence and dose intervals, type of bisphosphonate, and other determinants (including age, occurrence of gastrointestinal adverse events as measured by use of concomitant medications [eg, antacids, proton pump inhibitors, histamine2 (H2)-receptor antagonists, misoprostol, laxatives, antidiarrheals, bowel motility enhancers] and fractures) was assessed. To study whether persistence with bisphosphonates was associated with the former use of other antiosteoporosis medication or the presence of drug-induced osteoporosis, the use of hormone replacement therapy, raloxifene, and systemic corticosteroids in the 6 months before the index date were included as determinants. RESULTS: The study sample included 2124 women who were new users of bisphosphonates. The mean (SD) age of the study population was 71.6 (8.7) years. After 1 year, 51.9% of weekly alendronate users and 30.1% to 42.2% of daily bisphosphonate users were persistent. In the multivariate analysis (which included age, concomitant medication, and fractures), patients using alendronate weekly were significantly more likely to persist than those using alendronate daily (relative risk [RR], 1.56 [95% CI, 1.32-1.85]). The likelihood of persistence was similar among those who used the daily regimens of risedronate, etidronate, and alendronate. The occurrence of gastrointestinal adverse events was associated with decreased persistence with bisphosphonates (H2)-receptor antagonists: RR, 0.71 [95% CI, 0.53-0.94]; bowel motility enhancers: RR, 0.78 [95% CI, 0.65-0.94]). CONCLUSIONS: In this study, dose interval and the occurrence of gastrointestinal adverse events were independent determinants of persistence with bisphosphonate therapy. Although the likelihood of persistence with bisphosphonate use was significantly higher among those who used a less frequently administered regimen, persistence rates were still suboptimal.

Age Factors↗
PubMed2006

Toward a standard definition and measurement of persistence with drug therapy: Examples from research on statin and antihypertensive utilization.

BACKGROUND: Long-term utilization of prescription drugs for chronic conditions such as hypertension and/or hypercholesterolemia is a reality for millions of individuals, yet therapies may be discontinued before they can exert their beneficial effect. Several studies have measured the mean duration of therapy (ie, persistence) using administrative health databases. However, the terminology and methodology used for measuring persistence varied across studies, making it difficult to compare persistence rates. OBJECTIVES: The objectives of this study were to identify currently used measures of persistence and to propose a standard operational definition for use in administrative database analyses of drug utilization. METHODS: MEDLINE was searched for English-language articles published between January 1997 and June 2005 that quantified the concepts of persistence, adherence, compliance, or continuity with statin or antihypertensive therapy using administrative prescription claims databases. The conceptual and operational definitions of persistence used in the identified studies were categorized and applied to prescription-refill data for a hypothetical patient to compare the durations of persistence resulting from each method. RESULTS: Thirty-one articles were identified and reviewed. Few of the studies explicitly stated the conceptual definition of persistence used. Five methods of measuring persistence were identified: anniversary models, minimum-refills models, refill-sequence models, proportion-of-days-covered models, and hybrid models. When these models were applied to data for the hypothetical patient, total persistence with drug therapy ranged from 7 days to >1 year. CONCLUSIONS: There continue to be inconsistencies in the definition of persistence and the methods by which it is measured. A standard operational definition of persistence should be 2-dimensional, quantifying not only the total duration of therapy, but also the intensity of medication-taking within this interval.

Antihypertensive Agents↗
PubMed2026

Selective context, rather than persister cycling alone, drives resistance fixation in Escherichia coli.

Whether persister cells contribute to the evolution of antibiotic resistance and, if so, under what selective conditions this occurs, remain unresolved. Here, we examined whether repeated persister cycling itself promotes resistance evolution and how persister-associated minor variants are retained, lost, or fixed under distinct selective contexts. We compared five Escherichia coli cellular states: mutation-induced cells (M), persister-Amp cycling cells (A), persister cycling cells without selection (R), stationary-phase cells (S), and NaCl-stored persisters (P), using state-resolved whole-genome sequencing and phenotypic assays. Persister cycling without selection, stationary-phase cells, and NaCl-stored persisters maintained baseline MICs and showed no detectable high-frequency variant fixation. In contrast, mutation-induced cells fixed efflux-regulatory mutations in marR, acrR, and acrB, increasing MIC to 32&#x2009;&#x3bc;g/mL. Persister-Amp cycling cells showed an intermediate MIC increase to 16&#x2009;&#x3bc;g/mL without detectable quality-filtered genetic fixation, distinguishing this state from mutation-induced resistance. The stfE/stfP prophage background further shaped adaptive routes under mutation-inducing conditions. Exploratory analysis revealed sub-threshold low-frequency variant signals during persister cycling, but lineage tracking showed that these variants were not stage-specifically fixed and were instead stochastically retained or lost. These findings support a model in which persister cycling can reveal low-frequency genetic heterogeneity, but fixed resistance evolution requires selection that promotes variant retention and clonal expansion. Thus, resistance fixation was governed primarily by selective context during regrowth rather than by the persister state itself.

Journal Article↗
PubMed2000

A model for persistency of egg production.

The objectives of our study were to propose a new definition for persistency of egg production and to develop a mathematical model to describe the egg production curve, one that includes a new measure for persistency, based on the proposed definition, for use as a selection criterion to improve total egg production. Persistency of egg production is an important determining factor for total egg production. Hens with the same total production, however, can exhibit different egg production curves because of differences in persistency. We propose a new definition for persistency of egg production: the number of weeks during which a level of constant production is maintained. No egg production model exists that includes a measure of persistency in terms of duration of time or that allows this measure of persistency to be derived from model parameters. It was necessary, therefore, to develop a new model to describe an egg production curve for a flock: equation [see text] and for an individual: equation [see text] where y(t) = egg production at time t, t1 and t2 = times at transition, r = duration of transition, y(p) = level of constant production, b4 = rate of decline in production, and P = persistency of constant production. These parameters measure directly the important biological characteristics of an egg production curve. To illustrate the model, six data sets were used: two from flocks (one pullet flock and one hen flock) and four from two pairs of individuals. The proposed definition of persistency should be important for genetic selection because it might be desirable to select for increased persistency. The novel approach to the definition and measure of persistency presented here should provide a better understanding of the relationship between the new measure of persistency and other characteristics of egg production.

Animals↗
PubMed2005

Modelling protection from antimicrobial agents in biofilms through the formation of persister cells.

A mathematical model of biofilm dynamics was used to investigate the protection from antimicrobial killing that could be afforded to micro-organisms in biofilms based on a mechanism of 'persister' cell or phenotypic variant formation. The persister state is a hypothetical, highly protected state adopted by a small fraction of the cells in a biofilm. Persisters were assumed to be generated at a fixed rate, independent of the presence of substrate or antimicrobial agent. Cells were assumed to revert from the persister state when exposed to the growth substrate. Persister cells were assumed to be incapable of growth. The model predicted that persister cells increased in numbers in the biofilm, even though they were unable to grow, accumulating in regions of substrate limitation. In these regions, normal cells failed to grow, but did slowly convert to the persister state. Calculations of persister formation in planktonic cultures predicted that persisters would be present in low numbers in growing cultures, but should accumulate under conditions of slow growth, e.g. very low dilution rates in continuous culture or stationary phase in batch culture. When antibiotic treatment was simulated, bacteria near the biofilm surface were killed, but persisters in the depth of the biofilm were poorly killed. After antibiotic treatment ceased, surviving persister cells quickly reverted and allowed the biofilm to regrow. This modelling study provides motivation for further investigation of the hypothetical persister cell state as an explanation for biofilm resistance to antimicrobial agents.

Anti-Bacterial Agents↗