Platelet-foreign surface interactions: the release reaction from singly adherent platelets and adherent platelet aggregates.
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BACKGROUND: The economic impact of therapeutic non-adherence in chronic diseases has rarely been examined using qualitative standards for economic evaluation. This study illustrates the impact of non-adherence on the cost utility of renal transplantation versus haemodialysis from the societal perspective and examines the scope for adherence-enhancing interventions. METHODS: Long-term costs and outcomes in adherent and non-adherent renal transplant patients were simulated in a Markov model. The cost (euros, year 2000 values) and outcome data that were imputed in the model were derived from a prospective study in renal transplantation candidates performed in 2002. Probabilities of adverse events, graft rejection, graft loss and death in adherent and non-adherent renal transplant patients were derived from literature. RESULTS: Compared with dialysis, renal transplantation offers a better outcome in both adherent and non-adherent patients. Lifetime costs after transplantation in the adherent patient group are higher than lifetime dialysis costs and lifetime costs in the non-adherent patient group, mainly because adherent patients live longer after transplantation. Long-term outcomes after transplantation are better for adherent than for non-adherent patients. The mean cost per QALY gained in adherent patients relative to non-adherent patients was euro 35 021 per QALY (95% CI 26 959, 46 620). CONCLUSION: Compared with established healthcare interventions, such as haemodialysis, renal transplantation can be considered a cost-effective therapy for patients with end-stage renal disease, even if patients are non-adherent after transplantation. The low incremental cost per QALY calculated in this model for adherent renal transplant patients, suggests there may be scope for adherence-enhancing interventions (provided that such interventions with a sufficiently high effectiveness exist or can be developed). As the findings are based on simulated long-term costs and outcomes, they should not be considered as precise estimates of the impact of non-adherence. This study is rather meant as an illustration of how non-adherence may impact on the results of cost-effectiveness analyses.
Increases in cell-surface intercellular adhesion molecule-1 (ICAM-1; CD54) and major histocompatibility complex antigen class I (MHC-I) and class II (MHC-II) expression during flavivirus infection of murine macrophages was strongly dependent on adherence status. CD54 and MHC expression was significantly increased during infection with the flavivirus West Nile (WNV) on adherent, but not on non-adherent, macrophages. In contrast, increased CD54 and MHC-I expression was induced by interferon-gamma (IFN-gamma) in both cultures but was significantly greater on adherent cells than non-adherent cells. Adherent status was also important in human embryonic fibroblasts (HEF), adherent cells of non-immune origin. Similar to macrophages, WNV induced increased CD54 or MHC-I expression on adherent but not non-adherent HEF. Again, induction of these antigens by IFN-gamma occurred in both cultures but was significantly greater on adherent cells than non-adherent cells. Macrophages or HEF that aggregated when cultured at high density under non-adherent conditions, responded to WNV and IFN-gamma in a manner similar to adherent cells. Unresponsive non-adherent cells infected with WNV or treated with IFN-gamma under non-adherent conditions for 24 or 48 hr recovered if transferred to adherent culture conditions for 24 or 48 hr. Moreover, these cells expressed significantly higher cell-surface CD54 and MHC-I concentrations, compared to similarly treated HEF cultured under adherent conditions during the entire culture period. WNV infection also induced significant nitric oxide production in macrophages, and adherence status was similarly important in this response, with adherent cells producing higher amounts of nitrite/nitrate than non-adherent cells. These results suggest that adherent status may be critical for effective antiviral immune responses involving macrophages.
Few studies have examined the prevalence, demographic variables and adverse consequences associated with non-adherence to immunosuppressive therapy in the adolescent liver transplant population. Our hypothesis is that a significant proportion of adolescent liver transplant recipients exhibit non-adherence to medical regimens and that certain demographic and medical condition-related characteristics can be identified as potential predictors of non-adherent behavior. Furthermore, non-adherence leads to a greater incidence of morbidity and mortality in this population as compared with the adherent subset of adolescent patients. We reviewed the charts of 97 patients from 1987 to 2002 who by December of 2002 had survived at least 1 yr post-transplant and were followed by the Pediatric Liver Transplant Service at any point during their adolescent period (ages of 12-21). Non-adherence was defined as documentation of a report of non-adherence by a patient, parent or healthcare provider that was recorded in the patient's legal medical record. Descriptive statistics were used to determine the prevalence, demographic variables and adverse outcomes associated with non-adherence to immunosuppressive therapy. Categorical variables were analyzed using the chi-square test or the Fisher exact probability test. The unpaired Student's t-test was used to analyze the continuous variable of age at transplant. Using the inclusion criteria, a total of 97 patients represented the study sample of whom 37 subjects (38.1%) were defined as non-adherent and 60 (61.8%) were adherent. Non-adherent subjects were more likely to be female, older (>18 yr) and from a single-parent household. There was no significant difference in immunosuppressive regimen between non-adherent and adherent patients. Non-adherence was significantly (p<0.025) associated with lower socioeconomic status (SES), older age at transplant (p<0.005, 95% CI: -5.5 to -.99, Student's t-test) and episodes of late acute rejection (p<.001). Non-adherence was also significantly associated with re-transplantation and death secondary to chronic rejection by the Fisher exact test (p<0.006 and p<0.05, respectively). Non-adherence to immunosuppressive therapy is a prevalent problem that is correlated with certain demographic and medical condition-related risk factors and more frequent adverse consequences in the adolescent liver transplant population. The greater incidence of late acute rejection, death and re-transplantation owing to chronic rejection in non-adherent patients suggests that non-adherence is significantly associated with an increased risk of morbidity and mortality. Further investigation to identify patients at greatest risk for non-adherence is necessary to design the most effective intervention to increase patient survival and well being.
Poor adherence with prescribed therapy often results in decreased efficacy, annoying for patient both and physician. Negative health improvement adds extensive costs to the healthcare system. Thus, physicians need to carefully examine medication adherence before investigating possible pharmacologic reasons for drug failure or initiating alternative treatments and special diagnostic tests. Documenting medication adherence can also help with the development of new drugs and establishing optimized treatment regimens. Reliable distinction between non-adherence and nonresponse is a new issue for medicine, the pharmaceutical industry and its regulators. Investigation of adherence patterns has been established on evidence-based clinical and biostatistical research agendas. Originally, the term 'compliance' was used to describe how a patient adheres to a recommended therapy plan. Subsequently, 'compliance' has been changed to the more appropriate term 'adherence'. Several approaches to studying the relationship between medication adherence and medical outcome exist. This article provides an overview on medical adherence and methods of measuring adherence, especially electronic monitoring. Traditional methods of adherence assessment (patient interview, diaries, questionnaires, pill counts, prescription refill surveys) often do not deliver reliable data. Thus, researchers have tried to approach adherence by measuring serum drug concentrations or other biologic or chemical markers to gain more objective data. However, the state of the art for analyzing adherence is the use of electronic monitoring devices, electronic event monitors. Such devices not only provide more reliable data but also more detailed data about actual patient adherence, such as dose frequency, dose time, dose interval and dose timing--details that traditional methods do not show. Electronic monitoring shows that poor adherence, especially dosage omission or changing intervals, is more prevalent than previously recognized. The detailed adherence patterns provided by electronic monitoring show the need for a new kind of drugs. These drugs should provide good therapeutic coverage despite dosage omission and are therefore called 'forgiving pharmaceuticals'. Adherence and medical outcome have been extensively studied in patients with psychiatric disorders, hypertension and other cardiovascular disorders and most recently in patients receiving HIV/AIDS therapy. But non-adherence can be found in any medical field. Regarding the lack of equivalent studies on adherence and therapeutic efficacy in treating skin diseases, this topic should be looked at more closely in dermatology. Recalcitrant atopic dermatitis, psoriasis, tinea pedis and acne would be ideal study areas.
We examined the role of the neutrophil membrane antigen complex designated CDw18 (LFA-1/Mac-1/p150, 95) in human peripheral blood neutrophil adherence to cultured human umbilical vein endothelial cells (HEC) pretreated with lipopolysaccharide (LPS), interleukin 1 (IL 1), or recombinant tumor necrosis factor-alpha (rTNF-alpha). Pretreatment of HEC with LPS produced a dose-and time-dependent increase in subsequent neutrophil adherence (7 +/- 1% adherence to untreated HEC vs 38 +/- 3% adherence to HEC pretreated for 4 hr with LPS 150 ng/ml; mean +/- SE of 22 experiments: p less than 0.001). This effect was observed in primary and passaged HEC, but not in bovine aortic endothelial cells or human dermal fibroblasts. The LPS-induced activity appeared to be associated with the HEC surface, since it was not removed by washing and was not detected in the supernatant medium. Inhibition of RNA or protein synthesis during pretreatment of HEC with LPS prevented induction of the adherence-promoting activity. Pretreatment of HEC with IL 1 and rTNF-alpha produced a similar protein synthesis-dependent increase in neutrophil adherence to HEC. Coincubation of neutrophils with murine monoclonal antibody (MoAb) 60.3, an antibody directed to the CDw18 complex, produced a 70 +/- 4% inhibition of neutrophil adherence to LPS-pretreated HEC, 59 +/- 5% inhibition of adherence to IL 1-pretreated HEC, and 65 +/- 11% inhibition of adherence to rTNF-alpha-pretreated HEC (means +/- SE of 18, seven, and five experiments, respectively). Notably, MoAb 60.3 did not completely inhibit neutrophil adherence to pretreated HEC, although it completely inhibited adherence to untreated HEC when neutrophils were activated directly with phorbol ester. Similarly, the adherence of neutrophils from a patient with an inherited deficiency of the CDw18 complex to LPS-, IL 1-, and rTNF-alpha-pretreated HEC was markedly reduced compared with normal neutrophils (5 to 11% adherence with CDw18-deficient neutrophils vs 43 to 54% adherence with normal neutrophils), but adherence to pretreated HEC was still significantly greater than adherence to HEC that were not pretreated (2% adherence). We conclude that LPS, IL 1, and rTNF-alpha induce synthesis of an endothelial cell-surface factor(s) that promotes neutrophil adherence primarily by a mechanism involving the CDw18 complex. It thus appears that the CDw18 complex is important for augmented neutrophil adherence to endothelium in vitro whether the is stimulated directly by inflammatory mediators or indirectly by endothelial-dependent mechanisms.
Although several methods are available for examination of microbial adherence to epithelial cells, these do not distinguish between adherence of viable and non-viable micro-organisms. This study reports the use of acridine orange-stained blastospores of Candida albicans in conjunction with direct epifluorescence microscopy to determine viable (orange-fluorescing) and non-viable (green-fluorescing) blastospore adherence to buccal epithelial cells. The method was also employed to examine the effects of chlorhexidine treatment at subminimum inhibitory concentrations on the adherence of viable and non-viable blastospores. There was good correlation in the assessment of blastospore viability between the direct epifluorescence microscopy technique and the standard serial dilution and plating method for viable counting, confirming the reliability of direct epifluorescence microscopy. Chlorhexidine treatment before acridine orange staining did not alter this assessment of viability. Blastospore adherence to buccal epithelial cells resulted in a similarly skewed distribution whether examined using a crystal violet stain in conjunction with light microscopy or using direct epifluorescence microscopy, therefore validating the direct epifluorescence microscopy technique for the enumeration of blastospore adherence. Chlorhexidine treatment (0.0005% v/v, 30 min) of either blastospores or buccal epithelial cells altered the distribution of adherent blastospores per epithelial cell by increasing the number of epithelial cells having no adherent blastospores. No differences in adherence were, however, observed between blastospore or epithelial cells after treatment with this agent. Examination of the adherence of viable and non-viable blastospores to buccal epithelial cells using direct epifluorescence microscopy revealed a greater adherence capacity of non-viable than viable blastospores for buccal epithelial cells. Treatment of blastospores with chlorhexidine altered the frequency distributions of viable and non-viable blastospores with lower numbers of blastospores adherent per epithelial cell. The larger reduction in adherent viable blastospores in comparison with their non-viable counterparts is, however, an important observation which might have clinical relevance. Microbial cells adhere to epithelial cells resulting in a skewed distribution; study of this distribution gives useful information about the adherence process. Viable and non-viable components of a microbial population have different adherence capabilities and treatment of such populations with an antimicrobial agent exerting anti-adherent activity at sub-minimum inhibitory concentrations reduces the amount of adherence of these viable/non-viable components to different extents.
Two assays were developed to quantitate the adherence of an Escherichia coli strain (RDEC-1) known to colonize the mucosal surface of the small intestine of rabbits to brush borders isolated from rabbit intestinal epithelial cells. In the first assay, the mean adherence per rabbit brush border was determined by counting the number of organisms adhering to each of 40 brush borders under phase microscopy. The mean adherence of RDEC-1 (11.5 +/- 0.7 per rabbit brush border) was significantly greater than adherence of two nonpathogenic strains: HS (2.7 +/- 0.4 per rabbit brush border) and 640 (0.8 +/- 0.1 per rabbit brush border). A similar distinction between the adherence of RDEC-1 and the control (nonadherent) organisms could be made more rapidly by determining the percentage of the total number of brush borders which had 10 or more adherent organisms; this second assay was used to define the optimum conditions for adherence. Maximum adherence was seen within 15 min. Adherence was temperature dependent, with adherence after 1 min at 37 degrees C being fourfold greater than that at 4 degrees C. The pH optimum for adherence was between 6.5 and 7.0, and adherence was abolished below pH 5.0. With the first, more sensitive assay, the effect of electrolytes and a number of hexoses and hexosamines on adherence was analyzed. RDEC-1 adherence was inhibited at high ionic strengths; however, adherence was not influenced at moderately high concentrations (20 mg/ml) by either d-mannose or l-fucose, in contrast to the case for other reported enteric pathogens. These two quantitative in vitro assays for adherence produce consistent results and have been used to partially characterize the adherence of RDEC-1 to rabbit brush borders.
BACKGROUND: Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. METHODS: CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. FINDINGS: We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups. INTERPRETATION: Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.
The purposes of the study were to measure adherence with antiretroviral therapy to dose, schedule, and dietary instructions in a sample of patients with HIV infection in Stockholm, Sweden, over a 2-year period and identify baseline predictors of the three types of adherence. The study cohort consists of 144 patients who completed at least six out of seven follow-up self-reported adherence questionnaires. Baseline self-administrated questionnaire examined socio-demographics, medication-related, psychological, cognitive, and social context factors and self-reported adherence. Biomedical data were obtained through patients' medical records. Summary dose, schedule, and dietary instructions adherence scores provided outcome measures reflecting 100% adherence across all time points or not 100% adherence during at least one measurement period. A total of 61% maintained consistent full-dose adherence throughout baseline and all follow-up visits and equivalent proportion of 100% schedule adherence was 39%. Among patients with dietary instructions, 37% retained consistent adherence at all visits. Only schedule adherence was predicted by baseline data; perceived pressures from those close to the patient to take HIV medications (OR 0.51, p<.05), life stress (OR 0.13, p 0.009), ART health concerns (OR 0.19, p 0.003), and ART prolongs one's life (OR 0.39, p 0.04) predicted reduced schedule adherence over time. Perceived medication pressures from medical staff (OR 1.76, p<.05), post-traumatic stress disorder symptoms (OR 1.07 p<.01), and adherence self-efficacy (OR 3.50, p<.05) predicted positive schedule adherence over time. These results clearly illustrate difficulties in sustaining ART adherent behaviour, in particular schedule and dietary restrictions, over time and thus emphasizes the importance of multiple periodic assessments of all three types of adherence. Interventions aimed at improving schedule adherence should in particular focus on psychological and cognitive factors.
The purposes of the study were to measure adherence with antiretroviral therapy to dose, schedule, and dietary instructions in a sample of patients with HIV infection in Stockholm, Sweden, over a 2-year period and identify baseline predictors of the three types of adherence. The study cohort consists of 144 patients who completed at least six out of seven follow-up self-reported adherence questionnaires. Baseline self-administrated questionnaire examined socio-demographics, medication-related, psychological, cognitive, and social context factors and self-reported adherence. Biomedical data were obtained through patients' medical records. Summary dose, schedule, and dietary instructions adherence scores provided outcome measures reflecting 100% adherence across all time points or not 100% adherence during at least one measurement period. A total of 61% maintained consistent full-dose adherence throughout baseline and all follow-up visits and equivalent proportion of 100% schedule adherence was 39%. Among patients with dietary instructions, 37% retained consistent adherence at all visits. Only schedule adherence was predicted by baseline data; perceived pressures from medical staff to take HIV medications (OR 0.51, p < .05), life stress (OR 0.13, p < .01), ART health concerns (OR 0.19, p < .01), and ART prolongs one's life (OR 0.39, p < .05) predicted reduced schedule adherence over time. Perceived medication pressures from those close to the patient (OR 1.76, p < .05), post-traumatic stress disorder symptoms (OR 1.07 p<.01), and adherence self-efficacy (OR 3.50, p < .05) predicted positive schedule adherence over time. These results clearly illustrate difficulties in sustaining ART adherent behaviour, in particular schedule and dietary restrictions, over time and thus emphasizes the importance of multiple periodic assessments of all three types of adherence. Interventions aimed at improving schedule adherence should in particular focus on psychological and cognitive factors.
Group B streptococci (GBS) are the leading cause of neonatal pneumonia and meningitis. Adherence of GBS to host tissues may play an important role in the pathogenesis of infection. The host molecules which mediate GBS adherence to host tissues are unknown. Many bacterial pathogens adhere to fibronectin, an important component of the extracellular matrix (ECM). Some pathogens adhere to both immobilized and soluble fibronectin, while others adhere to immobilized fibronectin, but not to soluble fibronectin. Previous data indicated that GBS do not adhere to soluble fibronectin. We studied the ability of GBS to adhere to immobilized fibronectin. Forty-five per cent of the input inoculum of COH1, a virulent GBS isolate, adhered to fibronectin immobilized on polystyrene. COH1 did not adhere to the other ECM proteins tested (laminin, type I collagen, vitronectin, and tenascin). Nine out of nine GBS strains from human sources tested adhered specifically to fibronectin at levels varying from 4-60%. We considered the possibility that GBS were adherent to a contaminant in the fibronectin preparation. Properties of fibronectin, including the presence of an immunologic epitope of fibronectin and binding to collagen, were verified to be properties of the molecule to which GBS adhere. COH1 adhered to fibronectin captured by a monoclonal antibody to fibronectin (FN-15), confirming that the molecule to which GBS adhere bears immunologic determinants of fibronectin. Adherence of COH1 to fibronectin was inhibited by collagen, confirming that the molecule to which GBS adhere binds to collagen. These data strongly suggest that GBS adhere to fibronectin, and not to a contaminant.(ABSTRACT TRUNCATED AT 250 WORDS)
Prothrombinase complex assembly, in real time, on platelets adherent to immobilized von Willebrand Factor (vWf) was examined by total internal reflection fluorescence spectroscopy (TIRFS). Electron microscopy showed that the platelets adhered to vWf in a largely unactivated state and could be activated by thrombin. Antibody binding to glycoprotein (GP) Ib and functional GPIIb-IIIa receptor molecules on adherent platelet membranes monitored by TIRFS also indicated that platelets adhered in a largely unactivated state. Maximal expression of the receptor form of GPIIb-IIIa detected by antibody binding was seen only after thrombin stimulation of the adherent platelets. Antibody binding to GPIb was detected on adherent platelets. A reduction in antibody binding was observed after thrombin stimulation of the platelets, indicating a change in GPIb as a consequence of thrombin stimulation of the platelets. The binding of the protein components of the prothrombinase complex to adherent and thrombin-stimulated adherent platelets was then studied individually. Factor Va bound to adherent and thrombin-stimulated adherent platelets was then studied individually. Factor Va bound to adherent and thrombin-stimulated adherent platelets with an estimated Kd of 58 nmol/L. Minimal factor Xa binding was observed on adherent platelets before thrombin stimulation. Factor Xa binding was, however, readily observed on thrombin-stimulated adherent platelets. This factor Xa binding was not saturable, and no Kd value could be estimated. Direct measurement of prothrombinase complex assembly was demonstrated by using an energy transfer phenomenon between fluorescein-labeled factor Va and rhodamine-labeled factor Xa. Prothrombinase complex assembly was observed on both adherent and thrombin-stimulated adherent platelets. The estimated Kd for the factor Va/factor Xa interaction was 4 nmol/L. TIRFS demonstrated that adherent platelets have the ability to support prothrombinase complex assembly, as shown by a direct energy transfer reaction between fluorescently labeled factors Va and Xa.
We studied adherence to human cells by a strain of Escherichia coli. Adherence to erythrocytes was assessed directly by phase-contrast microscopy and indirectly by hemagglutination; adherence to peripheral blood leukocytes, using radiolabeled bacteria and subsequent determination of leukocyte-associated radioactivity; and adherence to renal glomeruli, by microscopy of fluoresceinated bacteria and of Gram-stained nonfluoresceinated bacteria. In serum-free systems, E. coli of this strain adhered to human erythrocytes, which have surface receptors for the third component of complement (C3), but not to erythrocytes from species lacking this receptor. 1 mM trypan blue, a reagent that inhibits complement receptor function, inhibited adherence to human erythrocytes, as well as adherence to leukocytes and glomeruli. Preincubation of erythrocytes and leukocytes with complement-coated zymosan particles partially blocked subsequent bacterial adherence. Incubation of human erythrocytes with aging human serum, with trypsin-cleaved C3, or with C3 cleaved by the classical pathway convertase (EAC142)-all of which treatments deposited C3 on the erythrocyte surface, presumably at C3 receptors-inhibited subsequent E. coli adherence. Finally, incubation of E. coli with rabbit antiserum to human C3 blocked adherence to erythrocytes.Bacterial hemagglutination and erythrocyte adherence were not inhibited by mannose in concentrations up to 2.5%. And this strain of E. coli did not adhere to or agglutinate guinea pig erythrocytes, the usual test particle used for demonstration of common pili. Finally, electron microscopy of adherent bacteria showed only rare surface pili. In contrast, adherence to and agglutination of guinea pig erythrocytes by a stock piliated E. coli was inhibited by mannose but not by trypan blue. We conclude that organisms of this strain of E. coli adhere to human erythrocytes, leukocytes, and glomeruli at complement receptors. Complement is not required for this interaction. Adherence apparently involves a C3-like structure on the bacterial surface, but bacterial surface pili play no role. The physiological or pathological role of this adherence is not apparent, but study of this phenomenon may elucidate functions of complement receptors on various cells.
OBJECTIVE: To measure patient adherence to antiretroviral therapy over a two-year period and to identify factors impacting adherence. METHODS: In a regional HIV treatment center, 100 consecutive patients starting any new antiretroviral agent were enrolled in this study, which consisted of a one-year retrospective data review and a one-year prospective component. The tools used for evaluating adherence were the monthly prescription refill data and a patient questionnaire. Data analyzed included overall adherence, adherence to individual antiretrovirals, and change in adherence over time, as well as factors reported as influencing adherence. RESULTS: Greater than 80% adherence in taking prescribed doses was seen in 75% of patients during the retrospective phase of the study; adherence increased to 84% in the prospective phase. Throughout the prospective phase of the study, monthly median adherence rates were 98-100%. Suboptimal adherence secondary to pill fatigue or number of daily pills did not occur. Reported nonadherence to dietary restrictions varied among drugs. The primary cause given for poor adherence was difficulty remembering followed by inconvenient dosing schedule and difficulty scheduling administration times around meals. At least one adherence tool was used by 61% of patients. A diagnosis of AIDS was associated with lower adherence in our patient population (p = 0.039); substance abuse and psychiatric history had no influence. CONCLUSIONS: Adherence to antiretroviral treatment regimens did not diminish over the two years studied. Several patients with poor adherence were identified, emphasizing the importance of addressing this issue both prior to and throughout treatment. A personalized approach by healthcare providers can optimize patient adherence to antiretroviral therapy by providing careful drug selection in addition to routine follow-up and the provision of information, feedback, and reminder systems.
OBJECTIVE: Approximately 40% of patients with schizophrenia are poorly adherent to their antipsychotics at any given time. However, little is known about patients' adherence over time, although this has important services implications. We examined antipsychotic adherence over 4 years at the aggregate and the individual level among a large cohort of patients. METHOD: We identified 34,128 Veterans Affairs patients who received a schizophrenia diagnosis and an antipsychotic fill in fiscal year (FY) 1999, completed schizophrenia visits in each of the next 4 years (FY2000, FY2001, FY2002, FY2003), and had valid medication possession ratios (MPRs) in each of these years. We examined whether patients had consistently good adherence (MPRs >or= 0.8 in all 4 years), consistently poor adherence (MPRs < 0.8 in all years), or inconsistent adherence. We examined predictors of consistently poor or inconsistent adherence. RESULTS: The cross-sectional prevalence of poor adherence among the patient population remained stable over time; 36%-37% were poorly adherent in each year. However, 61% of patients had adherence difficulties at some point over the 4-year period. Approximately 18% had consistently poor adherence, 43% were inconsistently adherent, and 39% had consistently good adherence. Patients who were younger and nonwhite, with a substance use diagnosis, a psychiatric hospitalization, or predominant treatment with first-generation antipsychotics, were more likely to have consistently poor adherence. CONCLUSIONS: Antipsychotic adherence is not a stable trait; most patients have difficulties with adherence over time. Health organizations and clinicians must emphasize adherence-enhancing interventions that can be provided on a longer term basis to the majority of patients.