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PubMed2006

Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial.

CONTEXT: Poor medication adherence diminishes the health benefits of pharmacotherapies. Elderly patients with coronary risk factors frequently require treatment with multiple medications, placing them at increased risk for nonadherence. OBJECTIVE: To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, AND PATIENTS: A multiphase, prospective study with an observational phase and a randomized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications. The study was conducted from June 2004 to August 2006. INTERVENTION: After a 2-month run-in phase (measurement of baseline adherence, BP, and LDL-C), patients entered a 6-month intervention phase (standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific packs). Following the intervention phase, patients were randomized to continued pharmacy care vs usual care for an additional 6 months. MAIN OUTCOME MEASURES: Primary end point of the observation phase was change in the proportion of pills taken vs baseline; secondary end points were the associated changes in BP and LDL-C. Primary end point of the randomization phase was the between-group comparison of medication persistence. RESULTS: A total of 200 elderly patients (77.1% men; mean [SD] age, 78 [8.3] years), taking a mean (SD) of 9 (3) chronic medications were enrolled. Coronary risk factors included drug-treated hypertension in 184 patients (91.5%) and drug-treated hyperlipidemia in 162 (80.6%). Mean (SD) baseline medication adherence was 61.2% (13.5%). After 6 months of intervention, medication adherence increased to 96.9% (5.2%; P<.001) and was associated with significant improvements in systolic BP (133.2 [14.9] to 129.9 [16.0] mm Hg; P = .02) and LDL-C (91.7 [26.1] to 86.8 [23.4] mg/dL; P = .001). Six months after randomization, the persistence of medication adherence decreased to 69.1% (16.4%) among those patients assigned to usual care, whereas it was sustained at 95.5% (7.7%) in pharmacy care (P<.001). This was associated with significant reductions in systolic BP in the pharmacy care group (-6.9 mm Hg; 95% CI, -10.7 to -3.1 mm Hg) vs the usual care group (-1.0 mm Hg; 95% CI, -5.9 to 3.9 mm Hg; P = .04), but no significant between-group differences in LDL-C levels or reductions. CONCLUSIONS: A pharmacy care program led to increases in medication adherence, medication persistence, and clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased medication adherence and persistence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00393419

Aged↗
PubMed1996

Persistence of human papillomavirus (HPV) infections preceding cervical carcinoma.

BACKGROUND: A persistent genital infection with an oncogene-type of human papillomavirus (HPV) is considered to be essential for the development of most cervical carcinomas. Therefore, HPV analysis has been proposed as a possible complementary cytological screening program. The authors have developed a technique to analyze archival Pap smears, which has enabled them to study the relation between persistent HPV infection and the development of cervical cancer. METHODS: Nested polymerase chain reaction was used to demonstrate the presence of HPV DNA, and sequencing of the obtained amplimer was performed to establish HPV type. The authors analyzed a series of 88 smears taken 1.5 to 7 years prior to the diagnosis of an HPV-containing cervical carcinoma (12 invasive adenocarcinomas, 18 invasive squamous carcinomas, and 58 squamous carcinoma in situ), which were compared with age-matched controls with no tumor development. RESULTS: HPV DNA was present in a majority of the smears preceding a cancer, with an odds ratio of around 15 for all tumor groups. Infections with a persisting HPV type were demonstrated in most samples from a series of eight patients, from who multiple smears were available, covering the 7-year period preceding the cancer diagnosis. CONCLUSIONS: Persisting infection can be demonstrated in exfoliated cells many years before cancer is diagnosed. The results are complementary to those obtained with cytology, that is, HPV is detected also in those at-risk patients whose Pap smears are morphologically normal. However, the results are still insufficient to justify a general recommendation to use HPV testing for health control purposes.

Adenocarcinoma↗
PubMed1997

Persistence of radiation-induced translocations in rat peripheral blood determined by chromosome painting.

In this article, we address the issue of persistence of chromosome exchanges following acute in vitro exposure of rat peripheral blood to 137Cs. Irradiation occurred 24 hr after culture initiation, and metaphase chromosomes were prepared 2, 3, 4, and 5 days later. Chromosomes 1, 2, and 4 were painted in unique colors and scored for structural aberrations. Dicentric chromosomes and acentric fragments diminished rapidly with time, as expected. Translocations exhibited greater persistence, but still showed a reduction in frequency, reaching a plateau of approximately 65 and 55% of their initial values, 4 days after exposure to 1 and 2 Gy, respectively. An exponentially declining model was fit to the combined dicentric, acentric fragment, and translocation frequencies, which showed that all three aberration types declined at equivalent rates. The frequencies of dicentrics and fragments declined to a plateau of zero, while translocations reached a plateau at frequencies significantly greater than zero. The decline in translocations with time is inconsistent with prevailing theoretical expectations, but is consistent with a model where some translocations are fully stable (persistent) and some are unstable (not persistent) through cell division. These results may have implications for radiation biodosimetry in humans.

Animals↗
PubMed2000

Donor cell persistence and activation-induced unresponsiveness of peripheral CD8+ T cells.

We studied the impact of the duration of donor cell persistence on CD8+ T cell responsiveness after adoptive transfer of antigen-expressing lymphoid cells. Naive or immunized female mice were treated by adoptive transfer of spleen cells from mice ubiquitously expressing a lymphocytic choriomeningitis virus-derived cytotoxic T lymphocyte (CTL) epitope (gp33-41) either alone or in combination with the male H-Y antigen providing additional antigenic CTL and T helper cell determinants. Low doses of male spleen cells (or sorted B cells) primed CTL, while high doses of the same cells rendered them unresponsive. CTL unresponsiveness induced by high numbers of male spleen cells was dependent upon prolonged persistence of antigen-expressing donor cells. Unresponsive CTL reverted to a state of activation when the duration of donor cell chimerism was limited. Memory CTL could be rendered unresponsive if antigen-expressing donor cells were allowed to persist. These results suggest that, irrespective of the type of antigen-presenting cell and the functional state of the responding T cell, activation and unresponsiveness can represent two different outcomes critically determined by quantitative and kinetic differences of antigen persistence.

Adoptive Transfer↗
PubMedDate not supplied

Significance of persisting serologic abnormalities in SLE.

The significance of abnormal serum anti-DNA and complement levels persisting in SLE patients on treatment has been explored. Instances when serologic abnormalities returned to normal were followed by a significantly longer mean duration of remission. When anti-DNA persisted at abnormal levels, a more severe exacerbation was likely to follow, although this result was not the case for persisting hypocomplementemia. These data did not result from two variants of SLE, one mild and one severe, because druation of remission correlated directly with dosage of steroid. Randomly discovered abnormalities in anti-DNA and complement levels were of limited predictive value, because they frequently persisted for over 1 year before exacerbations occurred. Hypocomplementemia resolved spontaneously without recognizable exacerbation in nearly half the observed instances.

Adult↗
PubMed2006

Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication.

BACKGROUND: Combined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events. It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring. METHOD: A prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal reflux disease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients who had undergone fundoplication at this institution. Follow-up after fundoplication was by periodic telephone interview and review of clinical records. RESULTS: Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7-78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow-up of 14 (range 7-25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow-up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months. CONCLUSION: Patients with a positive symptom index resistant to PPIs with non-acid or acid reflux demonstrated by MII-pH monitoring can be treated successfully by laparoscopic Nissen fundoplication.

Adolescent↗
PubMed2002

A question for DSM-V: which better predicts persistent conduct disorder--delinquent acts or conduct symptoms?

BACKGROUND: Conduct disorder (CD), a psychiatric index of antisocial behaviour, shares similarities with delinquency, a criminological index. This study sought to examine which factors in childhood predict a repeated diagnosis of CD in adolescence, and whether self-reported delinquent acts enhance the utility of symptoms of CD in predicting later persistent CD. METHOD: Longitudinal data used in this paper come from a clinic-referred sample of 177 boys, along with their parents and teachers, who were assessed using a structured clinical interview. The boys also reported on their delinquent behaviours, as well as a broad range of other family and life events. RESULTS: Before age 13, 77 boys met criteria for CD according to their parent, 69 according to their own report, and 36 reported three or more delinquent acts. Forty-eight boys (29%) met criteria for CD three or more times between 13 and 17. In childhood, delinquency overlapped, but was distinct from CD. Both were present in 28 cases, while 41 cases had CD without delinquency, and eight had delinquency without CD. When tested as predictors of later persistent CD, child-reported CD was the strongest predictor of later persistent CD, but self-reported delinquency was stronger than parent-reported CD. A final model of significant predictors included child-reported CD, delinquency, poor child communication with parents, and maternal prenatal smoking. CONCLUSIONS: It appears that delinquency does add uniquely to the prediction of persistent CD. It may be useful to expand the diagnostic criteria for CD accordingly.

Adolescent↗
PubMed2002

Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone.

BACKGROUND: Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS: Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29-77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30-70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS: Median follow-up was 7.8 years (range, 1.0-25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS: Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level.

Adult↗
PubMed2005

Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation.

Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent antigen suppressed IL-7Ralpha expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7Ralpha expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Ralpha expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.

Animals↗
PubMed2006

Long-term persistence of hepatitis B surface antigen and antibody induced by DNA-mediated immunization results in liver and kidney lesions in mice.

DNA-mediated immunization has been recognized as a new approach for prevention and treatment of hepatitis B virus (HBV) infection. However, the side effects of this approach have not been well described. Here we report that DNA-mediated immunization by intramuscular injection of plasmid DNA encoding HBV surface antigen (HBsAg) induced long-term persistence of HBsAg and HBsAg-specific antibody (anti-HBs) in the sera of the immunized BALB/c mice and resulted in liver and kidney lesions. The lesions persisted for 6 months after injection. Lesions were also found in normal mice injected with the sera from immunized mice, and in HBV-transgenic mice injected with anti-HBs antibody, or sera from immunized mice. Furthermore, lesions were accompanied by deposition of circulating immune complex (CIC) of HBsAg and anti-HBs antibody in the damaged organs. These results indicate that long-term persistence of HBsAg and anti-HBs in the immunized mice can result in deposited CIC in liver and kidney, and in development of lesions. The use of DNA containing mammalian replication origins, such as the plasmids used in this study, is not appropriate for human vaccines due to safety concerns relating to persistence of DNA; nevertheless, the safety of DNA-mediated immunization protocols still needs to be carefully evaluated before practical application.

Animals↗
PubMedDate not supplied

Evolution of coxsackie B virus during in vitro persistent infection: detection of protein mutations using two-dimensional polyacrylamide gel electrophoresis.

Serotype 5 coxsackie B virus (CBV5) can establish in vitro persistent infections in human rhabdomyosarcoma (RD) cells. This paper describes the characterisation of the virus released from the persistently infected RD cell line designated piRD-3673. Although infectious virus was released for 42 sequential passages of piRD-3673 cells, no gross virus-specific cytopathic effect was detected when the cells were examined by light microscopy. Two-dimensional polyacrylamide gel electrophoresis was used to compare the virus released from piRD-3673 cells with the CBV5 isolate (CBV-3673) used to initiate the persistent virus infection. Two of the virus intracellular proteins (apparent molecular weights 33,000 and 39,000, designated p33 and p39, respectively) increased in their net basic charge for the virus released from piRD-3673 cells compared to CBV-3673; a reduction in the apparent molecular weights of p33 and p39 was also observed. The charge alteration for both p33 and p39 was a two-stage process, the accumulative effect of which resulted in p33 increasing in pI from 6.14 to 6.53 and p39 increasing in pI from 6.29 to 6.63. The first mutation of p33 and p39 occurred between passages 7 and 10 of piRD-3673 cells and affected both the charge and apparent molecular weight of these two proteins. The second mutation at passage 15 of piRD-3673 cells caused only a change in the charge of p33 and p39. Two other virus proteins (p54 and p75) showed no evidence of mutation over the same passage history of piRD-3673 cells. The virus released from piRD-3673 cells also differed from CBV-3673 by two further criteria, a reduction in plaque-forming efficiency in HEp-2 cells and increased virus replication in RD cells. These data on virus evolution are discussed in relation to the maintenance of persistent CBV infections and the presence of naturally occurring CBV variants.

Coxsackievirus Infections↗
PubMedDate not supplied

Persistence of chromosome aberrations following acute radiation: I, PAINT translocations, dicentrics, rings, fragments, and insertions.

Chromosome translocations are used to estimate the doses of radiation received following occupational or accidental exposure. Biodosimetry relies on the assumption that translocations are not cell-lethal and persist with little or no loss over time. While translocations do exhibit substantially greater persistence than other aberration types (e.g., dicentrics), there is evidence that translocation frequencies also decline over time, at least following acute doses above 1 Gy. To the extent that translocation frequencies decline, the predicted absorbed doses will be underestimated. Yet unknown is whether translocations induced by ionizing radiation at doses below 1 Gy also show significant declines. Here we report on the persistence of translocations induced by 137Cs gamma-rays at acute doses ranging from 0.2 to 4 Gy using peripheral blood lymphocytes from two unrelated healthy male donors. Chromosome aberrations were evaluated by simultaneously painting chromosomes 1, 2, and 4 in red and 3, 5, and 6 in green in cells harvested 2-7 days following exposure and were scored using the PAINT system. Translocations were also enumerated using several other methods and these results are reported separately by us in this issue. For comparison, the persistence of dicentrics, rings, acentric fragments, and color junctions was also evaluated and showed rapid losses with time. The results from both donors provide evidence that translocation frequencies decline with time in a statistically significant manner at doses as low as 0.2-0.3 Gy. The frequency of translocations for all dose groups declined from day 2 to 7 by averages of 39% and 26% for donors 1 and 2, respectively. These data emphasize the importance of considering translocation loss in biological dosimetry long times after exposure.

Adult↗
PubMed2004

Effectiveness of brachytherapy and fractionated stereotactic radiotherapy boost for persistent nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) with local persistence after primary radiotherapy carries a high risk of treatment failure. We compared the effectiveness of brachytherapy and a fractionated stereotactic radiotherapy (SRT) boost in improving tumor control. METHODS: We retrospectively reviewed the records of 755 patients with NPC treated from 1994 to 2001. Fifty-two patients (7%) had persistent local disease, but seven of them were unsuitable for radiotherapy boost. Overall, 24 patients received brachytherapy boost at a median dose of 20 Gy, and 21 patients received an SRT boost at a median dose of 15 Gy. RESULTS: Despite the radiotherapy boost, the overall 3-year local failure-free control rate was still significantly lower for patients with persistent disease than for the rest (71% vs 86%, p < .01). Only the SRT subgroup achieved a local failure-free control rate close to that of the complete responders (82% vs 86%, p = .71). CONCLUSIONS: SRT boost is more effective in reverting the poor prognostic influence of local persistent disease.

Adolescent↗
PubMedDate not supplied

The persistence of hepatitis A IgM antibody after acute clinical hepatitis A.

Hepatitis A IgM antibody (IgM anti-HAV), detected by commercially available solid-phase radioimmunoassay, is an accepted marker of acute viral hepatitis A infection. However, persistence of this serological marker far beyond the acute illness and immediate convalescent period has been reported. To determine the persistence of IgM anti-HAV following clinically manifest acute hepatitis A infection, 59 patients with this diagnosis were followed prospectively until this marker disappeared or persisted for greater than 60 days. Timed from the onset of jaundice, IgM anti-HAV persisted for less than 30 to greater than 420 days; most patients became seronegative by 120 days. These findings suggest that some patients may become seronegative early in the disease course while others (13.5%) remain positive for prolonged periods greater than 200 days. Awareness of this marked variability is important in the interpretation of IgM anti-HAV as a serologic marker of recent hepatitis A infection.

Adult↗
PubMed2004

Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels.

The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 mug pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy of blocking virus production (epsilon) and infected cell loss during treatment (mdelta) compared with patients with elevated ALT levels. Differences were significant for epsilon (P = .02) and delta (P = .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters epsilon, delta, and mdelta was observed in patients with elevated gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.

Adult↗
PubMed2005

Acute phase HBV-specific T cell responses associated with HBV persistence after HBV/HCV coinfection.

To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses associated with self-limited and persistent HBV infections, we compared a patient with acute HBV/HCV coinfection, who was able to control HCV but developed chronic hepatitis B, with patients who resolved acute HBV infection spontaneously. Acute-phase CD4 responses were efficient in self-limited infections but undetectable in the coinfected patient with HBV persistence. CD8 responses were multispecific irrespective of the outcome of infection, but the CD8 repertoire associated with HBV persistence lacked the most dominant specificities detectable in self-limited infections. In conclusion, insufficient CD4 help and defective CD8 repertoire may play a role at the early stages of infection in influencing HBV persistence.

Acute-Phase Reaction↗
PubMed2002

Complete nucleotide sequence of a Coxsackievirus B-4 strain capable of establishing persistent infection in human pancreatic islet cells: effects on insulin release, proinsulin synthesis, and cell morphology.

The aim of the present investigation was to study the effect of infection of human pancreatic islet cells with a strain (VD2921) of Coxsackie B virus serotype 4 capable of establishing persistent infection in these cells, as well as to sequence the strain, to study the determinants of virulence and persistence. Groups of islets were infected and assessments of proinsulin, insulin content, and virus replication were made. Insulin release in response to high glucose was measured. Infected and control islets displayed a strong insulin response to high glucose 3-4 days as well as 7-8 days post-infection (dpi). At 11-17 dpi, the infected islets did not respond at all to high glucose, and the response of the control islets was at this late time point somewhat reduced. The insulin and proinsulin content of the infected islets did not differ significantly from that of the control islets. TCID(50) titrations showed that the VD2921 strain replicated in the islet cells during the whole study. Electron microscopic examination of infected islets did not reveal any virus-induced changes of cell morphology compared with the controls, although higher magnifications of the infected beta-cells showed virus-like particles in the cytoplasm. These results show that certain strains of Coxsackievirus B-4 in vitro can establish a persistent infection that might mimic, the more gradual loss of beta-cell function seen during the clinical course of autoimmune diabetes. The ability of this Coxsackievirus B-4 strain to establish a persistent infection might be due to substitution of 11 amino acids located at the surface of the structural protein VP1, adjacent to the predicted receptor binding canyon of the virus.

Amino Acid Sequence↗
PubMed1995

Persistent B19 parvovirus infections in haemophilic HIV-1 infected patients.

B19 infection can be acquired by transmission with blood factors in patients with congenital bleeding disorders, requiring clotting factor concentrates. In immunodeficient patients, the failure of immunity to clear B19 virus may produce persistent infections. The presence of B19 DNA in blood samples from seven haemophilic patients with concomitant HIV-1 infection was studied over a period of three-to-four years. Dot blot hybridization assays with DNA and RNA probes were used to detect medium high viremias, and polymerase chain reaction (PCR) to detect very low viremic titres. Three patients were negative for B19 DNA in all the blood samples, while four patients were persistently positive for B19 DNA. Viral persistence, which in one patient was detected throughout the study period (40 months), occurred at low titre in all four positive patients with some recurrent increases in viral titre. In the four patients persistently positive for B19 DNA, acute or chronic clinical symptoms and signs that could be associated with B19 were not noted when virus was present at low titre (B19 DNA detectable only by PCR). When patients had a higher viral titre (B19 DNA detectable by dot blot hybridization) acute manifestations (aplastic crisis, Fifth disease, fevers, pneumonitis) were found.

Adolescent↗