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PubMed2005

Molecular characterization of Jurkat cells persistently infected with vaccinia virus mutant vp811.

Previous reports from this laboratory demonstrated that persistent infections could be established in Jurkat cells with wild-type vaccinia virus (Jvac). The infected cells elicit increased expression of IL-2, IL-2Ralpha and IL-6 but not of IL-1beta nor of interferon-gamma. The persistently infected cells are also capable to transactivate the LTR gene of HIV-1 virus (HIV-1LTR). In addition, NFkappabeta and NFAT are found activated in Jvac. To find out whether the gene(s) responsible for establishment, maintenance and molecular characteristics of persistently infected cells are located in the terminal ends of the molecule, Jurkat cells were infected with a deletion mutant Vp811 that lacks 32.7 and 14.9 kb at the left and right terminal, respectively. The results indicate that the deletion mutant is capable of establishing persistent infections. The persistently infected cells show a similar pattern of expression to that observed in Jvac cells. It is concluded that the viral gene(s) involved in persistence and molecular cellular changes is (are) present in the mutant.

DNA, Viral↗
PubMed1990

IgA antigliadin antibodies and persistence of jejunal lesions in adult coeliac disease.

In 46 adult patients with coeliac disease, 41 (89%) of whom were positive for IgA and/or IgG antigliadin antibodies (AGA) when untreated, we investigated after a gluten-free diet the relationship between the persistence of AGA, the persistence of jejunal lesions, and the duration and compliance with the diet. IgG AGA were positive in 21 coeliac patients (46%) after variable periods of gluten-free diet and were associated with IgA positivity only in 4 cases (9%). Both IgA and IgG AGA positivity appeared to be more related to the lack of improvement of the jejunal lesions than to the strictness and duration of gluten withdrawal. Nine coeliacs showed no improvement of jejunal lesions after the gluten-free diet. Of these 9, 4 showed persistent IgA AGA, while the remaining 5 resulted IgAAGA-negative as before when untreated. Though intestinal biopsy remains the best means of determining the positive effect of gluten withdrawal, the persistence of IgA AGA in treated coeliacs is always predictive of the persistence of severe jejunal lesions. The persistence of IgG AGA, on the contrary, should be regarded as an immunological memory.

Adult↗
PubMed2004

Endothelium-dependent flow-mediated vasodilation of systemic arteries is impaired in patients with myocardial virus persistence.

BACKGROUND: Myocardial virus persistence is frequently observed in patients with cardiomyopathy. Endothelial dysfunction in patients with cardiomyopathy is associated with inflammatory immunoresponses in myocardial biopsies. The aim of this study was to investigate the impact of myocardial virus persistence on endothelial function. METHODS AND RESULTS: In 124 patients with suspected cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology). Endothelial function of the radial artery was examined by high-resolution ultrasound. Diameter changes in response to reactive hyperemia (flow-mediated dilation [FMD]) compared with glycerol trinitrate (GTN-MD) were measured. Mean age of the patients (55 men, 69 women) was 45+/-13 years; ejection fraction was 57+/-17%. In 73 patients, adenovirus, enterovirus, parvovirus, or HHV6 virus (V) was detected; in 51, no virus was detected. FMD was significantly impaired in patients with myocardial virus persistence compared with control subjects (Co): FMD-V, 3.38+/-2.67%; FMD-Co, 7.34+/-3.44 (P<0.001). In 86 patients, myocardial inflammation was confirmed (Inf). Of those, 57 had virus, and 29 did not. FMD was significantly impaired in patients with virus compared with controls: FMD-Inf-V, 3.24+/-2.66%; FMD-Inf-Co, 6.07+/-3.00 (P<0.001). In 38 patients, immunohistology of the myocardial biopsies was normal (Co); of those, 16 had virus, and 22 did not. FMD was impaired in patients with virus compared with control subjects: FMD-Co-V, 3.88+/-2.72%; FMD-Co-Co, 9.00+/-3.32% (P<0.001). Endothelium-independent vasodilation (GTN-MD) was not significantly affected. CONCLUSIONS: Myocardial virus persistence is associated with endothelial dysfunction. Endothelial dysfunction in patients with myocardial virus persistence can occur independently of endothelial activation or myocardial inflammation but is more pronounced in patients with concurrent inflammation.

Adenovirus Infections, Human↗
PubMed2005

Differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence, endothelial activation, and myocardial leukocyte infiltrates.

BACKGROUND: Viral cardiomyopathy resulting from myocardial virus persistence can be associated with inflammatory immune responses that involve the myocardium and coronary blood vessels. The aim of this study was to investigate the differential impact of myocardial virus persistence and inflammation on endothelial function of the coronary microcirculation. METHODS AND RESULTS: In 71 patients with nonischemic cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology). Endothelial function of the coronary microcirculation was examined during heart catheterization by measuring diameter (by quantitative coronary angiography) and velocity changes (by intracoronary Doppler) of the left anterior descending artery in response to acetylcholine. Coronary blood flow (CBF) was calculated. Endothelium-independent vasoreactivity to adenosine was assessed. Mean age of the patients (37 men, 34 women) was 43+/-13 years; mean ejection fraction was 64+/-11%. In 43 patients, adenovirus, enterovirus, parvovirus, or HHV-6 was detected; 28 had no virus. Endothelial function of the coronary microcirculation was significantly impaired in patients with myocardial virus persistence (V) compared with patients without virus (Co) (DeltaCBF-V, 22+/-86%; DeltaCBF-Co, 110+/-113%; P=0.001), which was confirmed in 51 patients with myocardial inflammation (MC) (32 with virus, 19 with no virus) (DeltaCBF-MC-V, 12+/-89%; DeltaCBF-MC-Co, 81+/-109%; P=0.034) and in 20 patients with normal immunohistology of the myocardial biopsies (Co) (11 with virus, 9 with no virus) (DeltaCBF-Co-V, 51+/-72%; DeltaCBF-Co-Co, 175+/-97%; P=0.006). Endothelial function of the coronary microcirculation was also significantly impaired in patients with myocardial inflammation/endothelial activation compared with patients without inflammatory immune response. Endothelium-independent vasodilation was not influenced significantly. CONCLUSIONS: Myocardial virus persistence and myocardial inflammation/endothelial activation are associated with endothelial dysfunction of the coronary microcirculation. Endothelial dysfunction in patients with myocardial virus persistence can occur independently of myocardial inflammation/endothelial activation but is more pronounced in patients with concurrent inflammation.

Adult↗
PubMed2003

Transplantation of enalapril-treated kidneys confers persistent lowering of arterial pressure in SHR.

The kidney plays a critical role in regulating the level of arterial pressure and in the pathogenesis of hypertension. Important evidence has come from studies in which hypertension is generated by transplanting kidneys from genetically hypertensive rats into normotensive recipients, suggesting that the level of blood pressure is strongly influenced by the genetic background of the kidney. We hypothesized that pharmacotherapy could modify specific properties intrinsic to the kidney such that after transplantation, there would be persistent changes in the level of arterial pressure. We determined that angiotensin-converting enzyme inhibitor treatment (enalapril) in spontaneously hypertensive rats induced both a persistent 17% reduction of mean arterial pressure and a persistent change in the kidney. This persistent change in the circulation could be completely transferred to untreated spontaneously hypertensive rats by kidney transplantation; ie, mean arterial pressure in untreated spontaneously hypertensive rat recipients was persistently lowered after transplantation of a kidney from a previously treated spontaneously hypertensive rat donor. In addition, the persistent lowering of mean arterial pressure after enalapril treatment could be completely abolished by implanting an untreated kidney, thereby revealing the importance of the kidney-specific changes. Furthermore, after within-group transplantations, there were no changes in the level of arterial pressure; ie, a 16% difference in mean arterial pressure remained between the 2 groups. The findings revealed that drug-induced changes specific to the kidney determined the level of arterial pressure, thereby suggesting the kidney should be a key therapeutic target for pharmacotherapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Persistence of Pneumocystis carinii in patients with AIDS receiving chemoprophylaxis.

Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP). This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens. Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP. Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining. There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients. The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP. One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL. We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts. These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Airway inflammation in mild intermittent and in persistent asthma.

The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, and 18 patients with mild-to-moderate persistent asthma. Epithelial shedding, eosinophil (EG2-positive cells), and activated T-cell (UCHL1) counts in biopsies, and ECP levels in BAL fluids were significantly increased in patients with intermittent asthma by comparison with control subjects and this increase was significantly greater for patients with persistent asthma. Alveolar macrophage activation (percentage of hypodense cells) and the thickness of the basement membrane were significantly increased in asthmatic subjects as compared with controls but there was no difference between the two asthmatic groups. Hyaluronic acid levels in BAL fluids were significantly increased in patients with persistent asthma by comparison with control subjects and patients with intermittent asthma. Mast cell numbers (toluidine blue) in biopsies and histamine or levels in BAL fluids were similar in the three groups. This study shows that airways inflammation is present in patients with intermittent asthma but to a lesser extent than in patients with persistent asthma.

Adult↗
PubMed2005

Peritraumatic and persistent dissociation in the presumed etiology of PTSD.

OBJECTIVE: Dissociative responses that occur at the time of a trauma (peritraumatic dissociation) have been described as a major risk factor for subsequent posttraumatic stress disorder (PTSD). The current study evaluated peritraumatic dissociation and PTSD from a multivariate perspective, along with a less-investigated phenomenon: trauma-specific dissociation that begins during or after an event and continues until the time of assessment (persistent dissociation). METHOD: In two studies, 52 local community participants and 386 participants from the general population with histories of exposure to at least one traumatic event were assessed for the presence of PTSD and were administered measures of dissociation and peritraumatic distress. RESULTS: In both studies, peritraumatic dissociation, persistent dissociation, peritraumatic distress, and generalized dissociative symptoms were associated with PTSD by univariate analyses. However, multivariate analyses in both studies indicated that PTSD status was no longer related to peritraumatic dissociation once other variables (especially persistent and generalized dissociation) were taken into account. In contrast, persistent dissociation was a strong predictor at univariate and multivariate levels. CONCLUSIONS: Trauma-related persistent dissociation is a substantial predictor of PTSD, whereas peritraumatic dissociation ceases to predict PTSD at the multivariate level. These findings suggest that it is less what happens at the time of a trauma (e.g., disrupted encoding) that predicts PTSD than what occurs thereafter (i.e., persistent avoidance).

Adult↗
PubMed1998

Changes in levels of viremia in cattle persistently infected with bovine viral diarrhea virus.

Virus isolation and serum neutralizing antibody titers were determined over a period of time from samples collected from animals persistently infected with bovine viral diarrhea virus (BVDV). To evaluate over time the ability to detect BVDV by virus isolation from serum or white blood cell preparations, 4 persistently infected calves were monitored from birth until 70 days of age. In 3 of 4 persistently infected calves, virus isolation from serum and white blood cells was negative until approximately 42 days of age, when colostral antibody had declined. The level of viremia in 7 adult (> 12 months) persistently infected animals decreased by 1 10-fold dilution over at least a 2-year period. The level of viremia became undetectable by virus isolation from serum in 1 of the 7 animals examined. This decline was associated with the development of virus neutralizing antibody. Although the level of viremia is fairly stable within persistently infected animals, the presence of specific neutralizing antibody may affect the ability to isolate BVDV. These findings are important when considering diagnostic testing to identify persistently infected animals by virus isolation.

Animals↗
PubMed2005

Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus.

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.

Adolescent↗
PubMed2026

CSNK1E sustains stemlike drug persistence in diffuse large B-cell lymphoma.

Relapsed or refractory (R/R) disease occurs in up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) following first-line immunochemotherapy. However, the molecular mechanisms underlying drug persistence remain incompletely defined. In this study, we performed single-cell RNA and B-cell receptor sequencing on paired diagnostic and R/R samples from 8 patients who were either treatment-refractory or relapsed after remission, and validated our findings in 3 independent patient cohorts. We found that drug-persistent cells exhibited a transcriptional profile indicative of a less-differentiated state and adopted a memory B-cell-like program with enhanced stemlike properties, which correlated with unfavorable clinical outcomes across multiple DLBCL cohorts. Functionally, drug-persistent cells showed significantly increased in vitro clonogenicity and in vivo tumor-initiating capacity. Mechanistically, the WNT signaling regulator casein kinase 1&#x25b; (CSNK1E) was upregulated in these stemlike drug-persistent cells, in part through the activation of the A proliferation-inducing ligand (APRIL)-TNFRSF13B axis. Notably, CSNK1E inhibition impaired the growth and tumor-initiating capacity of drug-persistent cells and potentiated the efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based treatment, both in vitro and in vivo. Together, our study reveals the stemlike transcriptional and functional properties of drug-persistent cells, and identifies CSNK1E as a critical mediator and therapeutic vulnerability that may improve the efficacy of standard immunochemotherapy in DLBCL.

Lymphoma, Large B-Cell, Diffuse↗
PubMed2002

Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia.

We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P <.001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.

Blast Crisis↗
PubMed2006

Persisters: a distinct physiological state of E. coli.

BACKGROUND: Bacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944. RESULTS: We hypothesized that persisters are dormant cells with a low level of translation, and used this to physically sort dim E. coli cells which do not contain sufficient amounts of unstable GFP expressed from a promoter whose activity depends on the growth rate. The dim cells were tolerant to antibiotics and exhibited a gene expression profile distinctly different from those observed for cells in exponential or stationary phases. Genes coding for toxin-antitoxin module proteins were expressed in persisters and are likely contributors to this condition. CONCLUSION: We report a method for persister isolation and conclude that these cells represent a distinct state of bacterial physiology.

Anti-Bacterial Agents↗
PubMed2005

Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey.

BACKGROUND: Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population. METHODS: Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months. RESULTS: After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target < or = 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan. CONCLUSION: The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence.

Aged↗
PubMed2004

The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial.

Long-term adherence and persistence with any therapy are very poor ( approximately 50%). Adherence to therapy is defined as the percentage of prescribed medication taken, and persistence is defined as continuing to take prescribed medication. We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit. In addition we evaluated the impact of monitoring on treatment efficacy. Seventy-five postmenopausal women with osteopenia were randomized to 1) no monitoring, 2) nurse-monitoring, or 3) marker-monitoring. All subjects were prescribed raloxifene. At 12, 24, and 36 wk, the nursing staff reviewed subjects in the monitored (nurse-monitoring or marker-monitoring) groups using a predefined protocol. The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen (uNTX), a bone resorption marker, at each visit. Biological response to therapy at 1 yr was determined using the percent change in bone mineral density (BMD) and uNTX. Treatment adherence and persistence were assessed using electronic monitoring devices. Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57% compared with no monitoring (P = 0.04). There was a trend for the monitored group to persist with therapy for 25% longer compared with no monitoring (P = 0.07). Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone. Adherence at 1 yr was correlated with percent change in hip (BMD) (r = 0.28; P = 0.01) and percent change in uNTX (r = -0.36; P = 0.002). In conclusion, monitoring of patients increased adherence to therapy by 57% at 1 yr. Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points.

Aged↗
PubMed1982

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗
PubMedDate not supplied

Self-reported nonadherence with antiretroviral drugs predicts persistent condition.

PURPOSE: To assess variables predictive of nonadherence persisting over time in HIV-infected people treated with highly active antiretroviral therapy. METHOD: Prospective study of consecutive HIV-infected patients who were prescribed ritonavir- or indinavir-containing regimens in a university-based HIV clinic in Rome. A patient questionnaire assessing knowledge of treatment regimen, adherence behavior, reasons for taking and missing therapy, factors influencing adherence, and health behaviors was administered at baseline and 1 year later. A predose protease inhibitor plasma level was measured concurrently. Persistent nonadherence was defined as patient self-reported nonadherence both at enrollment and at follow-up questionnaires. RESULTS: From April 1998 to July 1998, 140 patients were enrolled into the study. At follow-up, 10% remained persistently nonadherent, and 15% of the previously adherent patients became nonadherent. On bivariate analysis, being less than 35 years old (odds ratio [OR] 8.9; 95% CI 1.8-43.1; p =.002), self-reporting nonadherence at enrollment (OR 14.5; 95% CI 3.5-5.8; p <.001), and having experienced "a fair amount" or "a lot" of vomiting (OR 11.1;95% CI 1.6-74.7; p =.02) or pruritus (OR 16.4; 95% CI 2.6-102.8; p =.004) during the 4 weeks before enrollment were significantly correlated to persistent nonadherence. CONCLUSION: Previous self-reported nonadherence was a strong predictor of persistent nonadherence during follow-up. Moreover, being of younger age and self-reporting vomiting or pruritus were also associated with a higher risk of nonadherence persisting over time.

Adult↗
PubMed2006

Adherence and persistence with single-dosage form extended-release niacin/lovastatin compared with statins alone or in combination with extended-release niacin.

BACKGROUND: Lipid-lowering therapies have been shown to reduce cardiovascular events and mortality; patient cooperation with therapy varies. A fixed-dose combination product, extended-release niacin/lovastatin (ERNL), has been shown to be beneficial in lipid management; however, little is known regarding patient behavior with ERNL therapy. OBJECTIVE: To evaluate patient adherence and persistence with ERNL, statin monotherapy (SM), extended-release niacin (ERN) monotherapy, and ERN plus a statin (ERN-S). METHODS: Prescription claims for lipid-lowering therapies were obtained from a pharmacy benefits manager between 2002 and 2003. Claims for a total of 2389 patients were analyzed for adherence and persistence, using medication possession ratios (MPRs) and proportions of days covered (PDCs). Adherence and persistence were defined, respectively, as an MPR or PDC greater than or equal to 0.80. Logistic regression was conducted to detect differences among groups. Covariates included age, gender, copay, and number of lipid-lowering therapies, a surrogate for disease severity. RESULTS: Average MPR scores were relatively high in all groups at 0.88, 0.81, 0.89, and 0.90 for ERNL, SM, ERN, and ERN-S, respectively. The adjusted odds ratio for adherence was lowest for SM (0.69), which was statistically significant compared with ERN-S (1.43), but not ERNL (1.00) or ERN (0.74). Persistence outcomes were poor in all groups. By the fourth quarter, patients receiving ERN-S (OR 1.31) had significantly greater persistence than those receiving ERN (OR 0.41) and SM (0.61), but not those receiving ERNL (OR 1.00). CONCLUSIONS: Managed care patients tended to be adherent to chronic lipid-lowering therapies, based on a mean MPR greater than 0.8. However, most patients failed to persist for at least 6 months.

Delayed-Action Preparations↗