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Persistence, switching, and discontinuation rates among patients receiving sertraline, paroxetine, and citalopram.

STUDY OBJECTIVE: To compare persistence, switching, and discontinuation rates among patients taking brand-name selective serotonin reuptake inhibitors (SSRIs). DESIGN: Retrospective cohort study. Data Source. Protocare Sciences managed care database. PATIENTS: A total of 14,933 patients with depression, posttraumatic stress disorder, or social anxiety disorder whose prescriptions for brand-name SSRIs were filled from January 1, 1999-June 30, 2002. MEASUREMENTS AND MAIN RESULTS: A total of 5598 patients received sertraline, 4131 citalopram, and 5204 paroxetine. Adherence status was categorized as persistence, switching (from one SSRI to another SSRI), and discontinuation. Persistence was determined based on the number of days' supply of the prescribed drug, with a minimum of 15 days to refill. Survival analyses using life-table survival curves and Cox proportional hazard models were conducted. Age, sex, and copayment were covariates in the Cox proportional models. Sensitivity analysis with a longer time to refill was performed to determine whether the results were sensitive to the algorithm for determining adherence. Compared with patients receiving sertraline and citalopram, those receiving paroxetine had lower rates of persistence (23.79% vs 25.96% for sertraline [p = 0.0093] and 26.56% for citalopram [p = 0.0022]) and higher rates of switching (3.55% vs 3.32% for sertraline [p = 0.5076] and 2.78% for citalopram [p = 0.0359]) and discontinuation (72.66% vs 70.72% for sertraline [p = 0.0258] and 70.66% for citalopram [p = 0.0334]). Survival curves showed that persistence rates with sertraline and citalopram were significantly greater than with paroxetine (p<0.05, log-rank and Wilcoxon tests). Age was an independent predictor of persistence; male sex and copayment were not. The comparisons across SSRIs were robust in the sensitivity analysis that varied the time to refill allowed. CONCLUSION: Differences in the persistence rates were noted among patients receiving three brand-name SSRIs, with patients receiving paroxetine having lower persistence than those receiving sertraline and citalopram. Observed differences in persistence across SSRIs were not sensitive to model specifications. Prescription of SSRIs that demonstrate better adherence would benefit both the patient and the health care system.

Adolescent↗

Maximization of lactation milk production without decreasing persistency.

This study treats each daily estimated breeding value (EBV) of the lactation as a separate trait to modify the lactation curve on a daily basis. Six selection strategies for improving lactation milk without decreasing persistency were compared: 1) index I(R1), subject to the restriction of equal genetic gains at days in milk (DIM) 60 and 280, 2) I(R2), subject to the restriction of zero gain at DIM 60, 3) desired gains index I(d), designed to increase lactation milk without altering the lactation curve, 4) index I(u), comprising lactation EBV and persistency without standardization, 5) index I(w), consisting of lactation EBV (EBV(L)) and persistency with standardization, and 6) conventional selection on EBV(L) and used as a basis for comparison. Of the 6 selection strategies compared, I(R2) yielded the greatest persistency, but achieved the smallest response in EBV(L), suggesting that it is impractical to increase persistency by inhibiting change in the peak yield. Index I(u) showed the same response in lactation milk as conventional selection on EBV(L), but resulted in the same decreased persistency. Although both I(R1) and I(d) achieved constant persistency, the former produced a greater lactation response (669 kg EBV) than the latter (560 kg EBV). Thus, I(R1) is a viable strategy for improving EBV(L) while holding persistency constant. None of the 6 selection strategies excelled in both lactation milk and persistency. Index I(w) appears to be a reasonable choice for improving both traits, although responses would depend on the relative economic importance of the 2 traits. Differential responses between I(u) and I(w) emphasize the need to weight the EBV of different traits by the inverse of their standard deviations in index construction when the EBV vary widely in variance. The general formula developed here provides a useful genetic means of modifying the lactation curve by restricting differential genetic gains among different days of the lactation.

Animal Nutritional Physiological Phenomena↗

Persistency of lactation yield: a novel approach.

The objectives of our study were to propose a new, simple, and easy-to-understand definition for persistency of lactation yield and to develop a new mathematical model to describe a lactation curve, one that includes a measure for persistency of lactation yield according to the proposed definition. Our definition of persistency is the number of days during which the level of constant yield is maintained. No lactation 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 the lactation curve: [formula: see text] where yt = yield at time t, t1 = time at transition from increased yield to constant yield, yP = level of constant yield, b3 = rate of decline in yield from the end of constant yield to the end of lactation, and P = persistency of constant yield. These four parameters measured directly the important biological characteristics of a lactation curve. Two test day data sets, one for individual records from a high-producing cow and one for average records from 17,607 cows, were used to illustrate the model and to estimate persistency. The proposed measure of persistency should be important for genetic selection because it might be desirable to select for increased persistency (e.g., for extended lactations) without increasing peak yield and, hence, subjecting the cow to undesirable stress.

Animals↗

Visible persistence and form correspondence in Ternus apparent motion.

Visual stimuli remain visible for some time after their physical offset (visible persistence). Visible persistence has been hypothesized to play an important role in determining the pattern of correspondence matching in the Ternus apparent-motion display. In this display, one or more elements reappears in overlapping locations at different times, whereas another element appears alternately to the right or the left of these elements. Usually either the elements are perceived to move coherently as a group (group motion), or one element may be perceived to hop over one or more other elements (element motion). According to the visible-persistence account of the perceptual organization of the Ternus display, element motion is seen when the temporal gap between elements in overlapping locations is small enough to be bridged by visible persistence; if it is not, group motion is seen. We conducted four experiments to test this visible-persistence account. In Experiments 1 and 2, a form correspondence cue (line length) was introduced to bias the visual system toward the element-motion interpretation, while visible persistence was either reduced or eliminated. The element-motion percept dominated despite the elimination of visible persistence. In Experiments 3 and 4, we found that Ternus elements presented without interruption, and thus presumably persisting over time, can be perceived in group motion. Together, the results indicate that visible persistence is neither necessary nor sufficient to account for the pattern of correspondence matches in the Ternus display.

Form Perception↗

Selection of CD8+ T cells with highly focused specificity during viral persistence in the central nervous system.

The relationships between T cell populations during primary viral infection and persistence are poorly understood. Mice infected with the neurotropic JHMV strain of mouse hepatitis virus mount potent regional CTL responses that effectively reduce infectious virus; nevertheless, viral RNA persists in the central nervous system (CNS). To evaluate whether persistence influences Ag-specific CD8+ T cells, functional TCR diversity was studied in spleen and CNS-derived CTL populations based on differential recognition of variant peptides for the dominant nucleocapsid epitope. Increased specificity of peripheral CTL from persistently infected mice for the index epitope compared with immunized mice suggested T cell selection during persistence. This was confirmed with CD8+ T cell clones derived from the CNS of either acutely (CTLac) or persistently (CTLper) infected mice. Whereas CTLac clones recognized a broad diversity of amino acid substitutions, CTLper clones exhibited exquisite specificity for the wild-type sequence. Highly focused specificity was CD8 independent but correlated with longer complementarity-determining regions 3 characteristic of CTLper clonotypes despite limited TCR alpha/beta-chain heterogeneity. Direct ex vivo analysis of CNS-derived mononuclear cells by IFN-gamma enzyme-linked immunospot assay confirmed the selection of T cells with narrow Ag specificity during persistence at the population level. These data suggest that broadly reactive CTL during primary infection are capable of controlling potentially emerging mutations. By contrast, the predominance of CD8+ T cells with dramatically focused specificity during persistence at the site of infection and in the periphery supports selective pressure driven by persisting Ag.

Amino Acid Sequence↗

[Bronchiolitis and persistent wheezing. Is eosinophilia a risk factor?].

OBJECTIVES: To investigate the final outcome of infants presenting an episode of bronchiolitis and to analyze the risk factors for the development of persistent wheezing, with special attention paid to the presence of eosinophilia during the acute episode. PATIENTS AND METHODS: We studied all the children aged less than 2 years who required hospitalization for bronchiolitis between 1990 and 1993. Eosinophil values during the acute phase were collected. Clinical evolution and outcome were classified in three groups: short-term persistent wheezing (if resolved before the child reached the age of 5 years), long-term persistent wheezing (if the child remained symptomatic after the age of 5 years) and no wheezing. Other risk factors for asthma such as familial history, passive smoking and respiratory syncytial virus isolation were also studied. RESULTS: We analyzed 170 patients (100 boys and 70 girls) aged 7.15 6 0.78 years who suffered an episode of acute bronchiolitis at the age of 5.4 4.2 months. One hundred thirteen patients (66.5 %) developed short-term persistent wheezing and 60 (35.3 %) developed long-term persistent wheezing. Fifty-six patients presented no wheezing. The number of patients with eosinophils > 1 % was significantly different in the three groups of patients (p 5 0.029). A Eosinophil values of > 1 % was associated with short-term persistent wheezing (p 5 0.013). Mean eosinophil values were higher in patients who developed wheezing at some time during evolution (p 0.028). A familial history of asthma was associated with the development of long-term persistent wheezing (p 0.033). CONCLUSIONS: In the population studied, eosinophil values of > 1 % during an episode of acute bronchiolitis in infancy was associated with a higher risk of developing persistent wheezing in the first 5 years of life. A familial history of asthma was associated with a higher risk of developing long-term persistent wheezing.

Asthma↗

Antihypertensive persistence and drug class.

BACKGROUND: Noncompliance with antihypertensive therapy is a major problem that hinders successful hypertension management. OBJECTIVE: To study antihypertensive drug persistence for hypertensive patients in routine clinical settings. METHODS: Hypertensive patients were retrospectively studied (1994 through 1998) using databases managed by Saskatchewan Health. The study population (46,458 people) included all patients with an International Classification of Diseases-9 code of 401, 402, 403 or 404, or any four-digit code included in these categories, who received at least one antihypertensive therapy prescription during the first 4.5 years of the study and received no antihypertensive therapy 12 months before the dispensing of the first therapy. Prescriptions were placed into the following drug classes: angiotensin II antagonists, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers and diuretics. Persistence was determined for four intervals in the patient's therapy at 180, 360, 540 and 720 days. RESULTS: Drug class had a statistically significant (P<0.001) effect on persistence. Angiotensin II antagonists had the highest persistence followed by angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers and diuretics. Persistence decreased as the time interval increased. Females were significantly more persistent than males (P<0.005), and elderly patients were significantly more persistent than younger patients (P<0.001) at each of the four time intervals. For angiotensin II antagonists, age and sex did not affect persistence. CONCLUSIONS: The consistently higher persistence associated with the use of angiotensin II antagonists may improve the management of hypertension.

Adolescent↗

Soil persistence of 4-HPPD-inhibitors in different soil types.

In field experiments carried out during the 1997-2001 period on four different soil types (sand, sandy loam, heavy sandy loam and clay) in Flanders (Belgium), the persistence of the three 4-HPPD inhibiting maize herbicides mesotrione (100 and 150 g ha-1), sulcotrione (300 and 450 g ha-1) and isoxaflutole (75 and 125 g ha-1) was studied. Therefore, soil samples were taken at regular intervals from application in spring and frozen. When all samples had been taken, greenhouse bioassays were set up to detect herbicide residues in the different soil types. Therefore, two extremely sensitive test plants, sugarbeet (Beta vulgaris L. spp. altissima Doell. var. saccharifera Deck.-Dill) and red clover (Trifolium pratense L.) were sown in the soil samples. Test plants were harvested after 2 (sugarbeet) and 3 (red clover) weeks and foliage fresh weight per plant was determined. This parameter was expressed relatively to the average fresh weight per plant of the plants sown in the control soil samples taken at each sampling date. The bioassays revealed several factors that influence the persistence of the herbicide tested. First, there is a remarkable influence of the experimental year due to variation in weather conditions (especially rainfall and temperature during the first weeks after spraying). Secondly, a different soil texture results in a highly different persistence: the shortest biological persistence was noticed each year in clay, followed by heavy sandy loam; the longest persistence was recorded in sandy and sandy loam soil types. Thirdly, there are important differences between the three herbicides tested: isoxaflutole (a member of the isoxazole chemical family) was shown to be less persistent than sulcotrione and mesotrione (both members of the triketone family). Remarkably, this was not the case in clay, where a longer persistence could be seen for isoxaflutole compared to sulcotrione and mesotrione. This study also revealed that applying a low rate results in a shorter persistence period compared to the higher rate. All these factors work together in a complex way which determines the persistence of the three herbicides tested.

4-Hydroxyphenylpyruvate Dioxygenase↗

Serum zinc status of children with persistent diarrhoea admitted to the diarrhoea management unit of Mulago Hospital, Uganda.

INTRODUCTION: Despite great advances in the management of diarrhoeal diseases, persistent diarrhoea remains a major problem in developing countries due to its syndromic nature. Zinc depletion ranks high among the factors contributing to the detrimental effects of persistent diarrhoea on the human body. This however, has not been investigated in the Ugandan population. OBJECTIVE: To determine the serum zinc status of children with persistent diarrhoea. DESIGN: Cross-sectional descriptive study. METHODS: Children aged 6-36 months with persistent diarrhoea were enrolled from the diarrhoea management unit of Mulago hospital. Socio-demographic and morbidity data were collected, and laboratory investigations were carried out after recruitment. Healthy children of similar age and sex were recruited to determine reference levels of serum zinc for comparison. RESULTS: The mean serum zinc level in the children with persistent diarrhoea was 5.83 mol/l while that of children without diarrhoea was 8.99 mol/l with no age or sex difference. The serum zinc concentration of children with persistent diarrhoea was significantly lower than that of children without diarrhoea (p<0.001). The prevalence of zinc deficiency in children with persistent diarrhoea was 47.9%. Of the children with persistent diarrhoea, 64 (66.7%) were stunted, wasted or both. However no significant association was observed between nutritional status and serum zinc levels. Only hypoproteinaemia was significantly associated with serum zinc levels in these children (p=0.03). CONCLUSION: There is a high prevalence of zinc deficiency and malnutrition among Ugandan children with persistent diarrhoea.

Age Factors↗

Investigation of the predictors of transition to persistent atrial fibrillation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Until now, no clinically useful indicators have existed that predict the transition from paroxysmal to persistent atrial fibrillation (AF). HYPOTHESIS: The current prospective study was conducted for identifying predictors of progression to persistent AF over the long term. METHODS: We studied 102 consecutive patients (mean age: 55 +/- 10 years: 75 men and 27 women) diagnosed with paroxysmal AF. Standard 12-lead electrocardiography, echocardiography, and P-wave-triggered signal-averaged electrocardiography (P-SAECG) were performed on all patients at the time of their entry into the study. RESULTS: The mean follow-up period was 61 +/- 13 months. Group 1 (n = 66) comprised patients in whom paroxysmal AF did not progress to persistent AF, and Group 2 (n = 36) comprised those who developed persistent AF. In Group 2 the patients were significantly older, and P-wave dispersion, filtered P-wave duration (FPD), and left atrial dimension were significantly higher than in Group 1 (p < 0.05). The root mean square voltage for the last 30 ms of the filtered P-wave was also significantly lower in Group 2 (p < 0.05). Multivariate logistic regression analysis using these five factors identified left atrial dimension (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.16-4.54; p = 0.02) and FPD (OR 2.71; 95% CI 1.78-4.13; p < 0.01) as independent predictors of transition to persistent AF. Left atrial dimension > or = 40 mm predicted progression to persistent AF with a sensitivity of 64%, specificity of 76%, positive predictive value of 59%, negative predictive value of 79%, and an accuracy of 71%. An FPD > or = 150 ms predicted persistent AF with a sensitivity of 81%, specificity of 91%, positive predictive value of 88%, negative predictive value of 90%, and an accuracy of 87%. Filtered P-wave duration was a significantly more sensitive and specific predictor than left atrial dimension (p < 0.05). CONCLUSION: We conclude that FPD is a clinically useful predictor of progression from paroxysmal to persistent AF over the long term.

Aged↗

Characterization of the induction of persistence of major histocompatibility complex class II by hybrids of macrophages from bacillus Calmette Guerin-resistant mice.

Peritoneal macrophages (M phi) from mice that are resistant to infection by Mycobacterium bovis (strain BCG) (Bcgr) can be induced to express major histocompatibility complex (MHC) class II glycoproteins (I-A) continuously upon treatment with 100 units of recombinant interferon-gamma (rIFN-gamma). In contrast, M phi from mice that are susceptible to BCG (Bcgs) express I-A transiently. Persistent expression of I-A does not require the continued synthesis of the glycoprotein. Thus, treatment with cycloheximide (CHX) reduces I-A expression by M phi that express I-A transiently but does not affect the expression of I-A that is persistently expressed. It was not possible, in these studies, to characterize the induction of persistence independent of MHC class II expression because of the 24-48 h required for MHC class II synthesis and cycling to the cell surface. During this time, persistence was also induced. To characterize persistence independent of MHC class II induction we have produced M phi-M phi somatic cell hybrids that express I-A constitutively by fusing cells from a Bcgs M phi cell line with M phi from Bcgr mice. Treatment of some of the hybrids with CHX reduced MHC class II expression. The M phi hybrids required treatment with high doses of rIFN-gamma to induce CHX-resistant I-A expression. The induction of the persistence of I-A, following the addition of rIFN-gamma, required a short burst of protein synthesis as well as the presence of rIFN-gamma for at least 3 h. The addition of actinomycin D simultaneously with rIFN-gamma did not prevent the induction of the persistence of I-A expression by one of the M phi hybrids (F6.4). In contrast, the induction of persistence of I-A expression required a longer period of induction than was observed for hybrid F6.4, which was attributed to the requirement for new RNA and protein synthesis by the A1.8 hybridoma.

Animals↗

Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the Southwestern United States.

Approximately one third of patients with chronic hepatitis C virus (HCV) infection have normal alanine transaminase (ALT) levels. We studied the clinical, biochemical, virological, and histological features in patients with persistently normal ALT. A case-control study was conducted on 275 patients with chronic HCV infection, including 75 patients with persistently normal ALT and 200 patients with abnormal ALT. Persistently normal ALT was defined as 4 consecutive ALT values in each patient within a period of 12 months. The average age of the patients was 44 years (range 18 to 69 years). More non-Hispanic whites had persistently normal ALT. The mean serum ferritin level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (128 +/- 92 ng/mL and 224 +/- 128 ng/mL), respectively (P =.017). The mean HCV-RNA level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (12 x 10(5) +/- 2.8 x 10(6) copies/mL and 33 x 10(5) +/- 8.0 x 10(6)), respectively (P =.02). Histologically, patients with persistently normal ALT had less severe portal inflammation (P <.05), lobular inflammation (P =.003), piecemeal necrosis (P =.002), fibrosis (P <.05), lower prevalence of cirrhosis (P =.007), as well as a slower fibrosis progression rate (P <.001). Chronic hepatitis C patients with persistently normal ALT have low-activity grade and stage on liver biopsy. In these patients the hepatitis C RNA level was lower compared with abnormal ALT patients, which may explain the slower fibrosis progression rate.

Adult↗

Chlamydia trachomatis infection and persistence of human papillomavirus.

Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection.

Adult↗

Associations between serum carotenoids and tocopherols and type-specific HPV persistence: the Ludwig-McGill cohort study.

Although oncogenic HPV infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to cervical lesions. Current research is focused on identifying factors associated with viral persistence and clearance, such as nutritional status. We evaluated the association between serum antioxidant nutrients (retinol, 10 carotenoids and 3 tocopherols) and type-specific HPV persistence over 4 visits among 405 women participating in the Ludwig-McGill cohort study. We measured circulating carotenoids and tocopherol at 4 different clinical visits for each woman. We report the results from different analytic approaches (a case-control approach at both the woman and viral level, and a prospective approach based on persistent events) that examined the association between these micronutrients and type-specific oncogenic and nononcogenic HPV persistence. In the case-control analysis at the viral level, midcirculating levels of alpha-tocopherol were inversely associated with nononcogenic HPV persistent infection (adjusted odds ratio (AOR) = 0.28, 95% CI 0.14-0.57), while high levels were marginally associated (AOR = 0.59, 95% CI 0.28-1.19). Similarly, utilizing generalized estimating equation models, circulating levels of alpha- and delta-tocopherol in the middle or upper tertiles were inversely associated with type-specific nononcogenic HPV persistence (AOR = 0.44, 95% CI 0.19-0.97 and AOR = 0.46, 95% CI 0.19-1.11, respectively). Our study among Brazilian women suggests that serum levels of tocopherols may be protective against nononcogenic HPV persistence. However, we did not find a strong protective effect (as hypothesized) of other serum antioxidant nutrients and type-specific oncogenic HPV persistence measured over 4 clinical visits.

Adult↗

The effects of carbon monoxide on persistent changes in young rat heart: cardiomegaly, tachycardia and altered DNA content.

Newborn rat pups that inhale 500 ppm carbon monoxide (CO) for 32 days and develop increased heart mass (i.e. cardiomegaly) show persistent cardiomegaly and elevated resting heart rate as adults. Studies were carried out to explore the relationship of these phenomena to CO concentration and initial cardiomegaly using exposures of 350, 500 and 700 ppm CO. Initial cardiomegaly was greater in the right ventricle free wall (RV) than in the left ventricle plus interventricular septum (LV + S) at all three CO concentrations, and RV mass excess increased with CO concentration. Initial RV cardiomegaly was greater at 350 and 700 ppm CO in females than in males. Persistent cardiomegaly in the RV also increased with CO concentration, and was significantly greater in the females. Persistent cardiomegaly in the RV increased with initial cardiomegaly but at a decreasing rate at the higher CO concentrations, and when expressed as a percentage of initial cardiomegaly (i.e. 'efficiency'), the relative response was greatest at 500 ppm CO. For LV + S, efficiency of development of persistent cardiomegaly was greatest at 350 ppm CO. Persistent tachycardia increased with CO concentration in males but failed to do so in females, and was only weakly correlated with degree of persistent cardiomegaly. Thus, persistent cardiomegaly and persistent tachycardia (in males) are related to CO concentration. Myocardial DNA content of 32-day-old juveniles was significantly increased at 350 and 700 ppm CO. Adult DNA content of the RV was significantly elevated at 350 ppm CO (females) and continued to rise with CO concentration. DNA concentrations of the RV and LV were increased at 700 ppm CO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Persistence of Japanese encephalitis virus is associated with abnormal expression of the nonstructural protein NS1 in host cells.

Persistent infection with Japanese encephalitis virus (JEV) was established in murine neuroblastoma N18 cells, and the persistency has been maintained in cell culture for over 6 months. From the persistently infected cells, a clone named C2-2 was selected and expanded to form a stable cell line. The vast majority of C2-2 cells showed viral protein staining by immunofluorescence and continuously produced low levels of virus (10(3) to 10(4) PFU/ml) without marked cytopathic effects or cyclic variations. In addition to the wild-type viral proteins, truncated forms of the viral nonstructural protein 1 (NS1) as well as its derivative NS1' were produced in C2-2 cells. Both truncated NS1 and NS1' contain deletions at their N-termini; however, the analyses by RT-PCR and direct sequencing of the viral RNA failed to detect any truncations or mutations within the NS1 region, suggesting that NS1 truncation was a result of a unique posttranslational proteolytic cleavage of NS1 in the persistently infected cells. Similar but not identical truncation of NS1 was also observed in two other persistently infected cell lines established in Vero and DBT (murine astrocytoma) cells. However, viruses released from C2-2 cells did not produce truncated NS1 upon infection of N18 cells, suggesting that NS1 truncations were the result of virus-cell interaction in persistently infected cells. These data indicate a strong association between abnormal NS1 expression and JEV persistency. A probable involvement of dysfunctional NS1 in the establishment and/or maintenance of JEV persistency in tissue culture is discussed.

Amino Acid Sequence↗

Persistence and determinants of statin therapy among middle-aged patients free of cardiovascular disease.

AIM: Statins have been shown to significantly reduce morbidity and mortality both in patients with coronary artery disease and in those with dyslipidemia when they are taken regularly. Middle-aged patients have the highest level of forecasting benefit, and little is known about the persistence rate of these therapies in a real-life setting.Objective. To evaluate the persistence rate of middle-aged patients initiating statin therapy as well as its relation to patients' demographic and clinical characteristics. METHODS: A cohort of 25,733 patients was reconstructed from prescription data recorded in the Régie de l'assurance maladie du Québec administrative database. All patients aged 50-64 years old who received at least one statin prescription between January 1, 1998 and December 31, 2000 for a new intention of treatment for dyslipidemia were included in the cohort and followed up until June 30, 2001. The date of the first prescription of statin was defined as the index date. The cumulative persistence rate was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of ceasing statins after adjustment. RESULTS: Mean age of patients initiating statin agents was 58 years; 39%were male, 24% received social assistance, 19% had diabetes, 30% had hypertension and 11% had a respiratory disease at cohort entry. Persistence with statin therapy fell to 67% in the first 6 months after treatment and continued to decline over the next 3 years to 39%. At 3 years, persistence varied significantly with statin agents. After controlling for individual patients' demographic and clinical characteristics, we found that patients who were prescribed fluvastatin, lovastatin and atorvastatin had a higher rate of cessation than those on simvastatin and pravastatin. The adjusted rate ratio of ceasing statin agents in patients with other risk factors of cardiovascular disease, such as diabetes (HR: 0.78; 0.75-0.82) or hypertension (HR: 0.72; 0.69-0.74), demonstrated a lower cessation rate. We observed lower persistence in patients who used the greatest number of pharmacies and prescribing physicians. CONCLUSION: This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, particularly among patients with few other cardiovascular risk factors.

Atorvastatin↗

Long-term evaluation of persistent supraventricular tachycardia in children: clinical and electrocardiographic features.

Although the long-term prognosis of children with persistent supraventricular tachycardia (SVT) has been generally considered benign, recent reports have suggested that some of these patients may develop cardiac dysfunction secondary to their persistent SVT. The clinical course of six children demonstrating ECG criteria of persistent SVT are presented herein with follow-up data for 5 to 20 years. Persistent SVT was present in each patient from 2 to 19 years. Two patients had transient congestive heart failure early in their course of persistent SVT, and two others demonstrated continued roentgenographic evidence of mild cardiomegaly without associated symptomatology. Conventional antiarrhythmics administered briefly in five patients and chronically in two were without effect on their arrhythmias. Persistent SVT remains in three patients and a fourth continues to exhibit intermittent episodes of SVT; however, all six patients are currently asymptomatic with two in stable normal sinus rhythm. This investigation indicates that the persistent form of SVT (lasting more than 1 year) is uncommon among children with paroxysmal SVT, and long-term observation of the consequences of persistent SVT supports the view that this rhythm disturbance is generally well tolerated in such patients.

Adolescent↗