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Higher costs and therapeutic factors associated with adherence to NCQA HEDIS antidepressant medication management measures: analysis of administrative claims.

OBJECTIVE: To determine if the type of antidepressant drug is related to adherence to National Committee for Quality Assurance (NCQA) Antidepressant Medication Management (AMM) quality measures and to assess the 6-month health care costs among newly diagnosed depressed patients. METHODS: The MarketScan Commercial Claims and Encounter database for medical and pharmacy claims from January 2001 to September 2004 was used to assess adherence to the 3 AMM quality-of-care measures. AMM measures include (a) acute phase, the percentage of eligible members who remained on antidepressant medication continuously for 3 months after the initial diagnosis as determined by at least 84 days supply of antidepressant drugs during the first 114 days following receipt of the index antidepressant; (b) continuation phase, the percentage of eligible members who remained on antidepressant medication continuously for the 6 months after the initial diagnosis as determined by at least 180 days supply of antidepressants during the first 214 days following receipt of the index antidepressant; and (c) practitioner contacts, the percentage of members who received at least 3 follow-up office visits or telephone contacts with health care providers, including at least 1 contact with a practitioner licensed to prescribe (may not necessarily be the prescriber of the antidepressant). A fourth measure, overall adherence, was added, if all 3 AMM measures were met. Multivariate regression models determined demographic, clinical (such as receipt of mental health specialty care, the Charlson Comorbidity Index score, and co-occurring bipolar or schizophrenia), and therapy-related factors associated with outcomes of adherence and costs (paid amounts for insurance-reimbursable health care services for inpatient admissions, emergency department services, outpatient services, and outpatient prescription drugs). Health care expenditures (both total and mental-health-specific costs) were measured for each patient for 6 months following the date of service for the index antidepressant. RESULTS: A total of 60,386 adult patients (10.7%) of 562,898 patients with a depression diagnosis met NCQA inclusion criteria in the AMM Technical Specifications (e.g., aged 18 years or older, newly diagnosed with depression and initiating antidepressant therapy, 365 days of continuous enrollment; patients were excluded if there were missing data on dose or quantity of index drug in pharmacy claims or initiated therapy on 2 or more antidepressants as the index medication, exclusion criteria not in the AMM Technical Specifications). Only 19% of patients achieved overall adherence. Rates for the 3 AMM measures were 39% for practitioner contacts, 65% for acute phase, and 44% for continuation phase. Receipt of mental health specialty care was the only factor that was positively associated with greater adherence on all 4 measures (overall measure: odds ratio [OR]=3.895, 95% confidence interval [CI], 3.72-4.07; acute OR=1.38, 95% CI, 1.33-1.43; continuation OR=1.46, 95% CI, 1.41-1.51; contacts OR=5.83, 95% CI, 5.62-6.06). Most patients were initiated on selective serotonin reuptake inhibitors (SSRIs, 69.5%), followed by venlafaxine (21.4%), tricyclic antidepressants (TCAs, 21.4%), bupropion (11.0%), and other antidepressants (e.g., mirtazapine, nefazadone, trazadone; 7.2%). Before adjustment for confounding factors, patients initiated on venlafaxine, TCAs, or other antidepressants had higher rates of adherence on the overall performance measure versus initiators on SSRIs, but the absolute differences were relatively small: 21.4% for venlafaxine and TCAs and 23.1% for other antidepressants versus 18.5% for SSRIs (P <0.001). Patients initiated on venlafaxine, TCAs, or other antidepressants were also more likely to receive care from a mental health specialist, 16.8%, 15.0%, and 54.8%, respectively, compared with SSRIs (13.0%, all P <0.001). Regression analysis showed that only venlafaxine had a higher OR (1.13; 95% CI, 1.05-1.22) compared with SSRIs for adherence on the overall measure. Initiating dose level was in the target range for 70.0% of all patients (24.9% were below target dose and 5.2% above target dose), and adherent patients on all 3 AMM measures were less likely than nonadherent patients (70.4% vs. 68.4%, P <0.001) to be initiated in the target dose range. After multivariate adjustment, the initiating dose (target vs. high) was a significant factor in explaining adherence to the overall measure (OR=1.26; 95% CI, 1.16- 1.37). Adherent patients had 6-month median unadjusted total health care expenses that were nearly 2 times higher compared with nonadherent patients ($5,169 vs. $2,734) and mental health expenditures that were nearly 3 times higher ($1,922 vs. $677). After adjustment, adherent patients compared with nonadherent patients incurred an additional $644 in mental health expenditures and $806 in overall health care expenditures in the 6 months following initiation of antidepressant therapy. CONCLUSIONS: Only 19% of depressed patients initiated on antidepressants met all 3 criteria set forth in the NCQA Health Plan Employer Data and Information Set (HEDIS) AMM quality-of-care performance measures. Receipt of mental health specialty care was the single factor most strongly associated with quality treatment by these measures. Type and dosage level of initial antidepressant was associated with adherence to the NCQA HEDIS AMM measures, but the absolute difference in rates of adherence were relatively small among types of antidepressants. Costs were higher for guideline-adherent individuals in the 6 months following treatment initiation. These analyses were limited to administrative claims that lack indicators of depression disease severity.

Adult↗

Association between adherence to statin therapy and lipid control in Hong Kong Chinese patients at high risk of coronary heart disease.

AIMS: To examine the pattern of adherence to statin therapy and to determine the association of adherence to statin therapy and the control of serum low-density lipoprotein (LDL)-cholesterol in a cohort of Hong Kong Chinese patients at high risk of coronary heart disease (CHD). METHODS: This was a prospective observational cohort study conducted at the outpatient clinics of a public teaching hospital in Hong Kong. Patients at high risk of CHD who had been initiated on statin monotherapy for < 12 months were recruited. The statin prescription was dispensed in a bottle with the Medication Event Monitoring System (MEMS). Adherence was assessed in two dimensions: dose-count was defined as the percentage of doses taken, and dose-time was defined as the percentage of doses taken within the suggested time interval. Lipid profiles were obtained at baseline and during two follow-up visits at month 3 and month 6. RESULTS: Eighty-three patients completed the study. The median adherence to dose-count and to dose-time were 95% (25-75th percentile = 87-99%) and 78% (25-75th percentile = 17-92%), respectively. Both dose-count and dose-time adherence declined slightly over the first 6 months of therapy. Living with family [relative risk (RR) = 0.79, 95% confidence interval (CI) 0.63, 0.91] and duration of therapy (RR = 0.99, 95% CI 0.98, 1.00) were negative predictors while number of family members (among those living with family) (RR = 1.05, 95% CI 1.00, 1.08) was a positive predictor for adherence to dose-count. Monthly household income (RR = 1.01, 95% CI 1.00, 1.02) and angina (RR = 1.29, 95% CI 1.05, 1.58) were positive predictors while living with family (RR = 0.74, 95% CI 0.55, 0.90) was a negative predictor for dose-time adherence. Percent reduction in serum LDL-cholesterol was correlated to dose-count (P < 0.001) and dose-time (P = 0.047) adherence. Statistically significant correlations were observed between adherence to dose-count and LDL reduction (R(2) = 0.130; P = 0.001), and between dose-time adherence and LDL reduction (R(2) = 0.048; P = 0.047). CONCLUSION: High adherence to statin therapy was found in a cohort of Chinese patients at high risk of CHD and the adherence declined slightly over time. A weak association between adherence to statin dose-count and LDL reduction and a marginal association between dose-time adherence and LDL reduction were observed.

Adult↗

Priming of human monocyte superoxide production and arachidonic acid metabolism by adherence to collagen- and basement membrane-coated surfaces.

Monocytes (m phi s) come into intimate contact with basement membranes and extracellular matrix proteins as they extravasate from the blood to the interstitium or to sites of tissue injury. We examined the in vitro effects of m phi adherence to an endothelial cell-derived basement membrane or to purified extracellular matrix proteins on phorbol myristate acetate (PMA)-stimulated superoxide production and prostanoid secretion. Elutriation-purified human peripheral blood m phi s were adhered to tissue culture wells that were precoated with the following purified proteins: bovine serum albumin (BSA), collagen type I (COL I), collagen type IV (COL IV), fibronectin (FN), or laminin (LM). To model the provisional matrix at sites of tissue injury, m phi s were also adhered to wells coated with either denatured collagen type I or gelatin (GEL) or coated with basement membrane (BM) derived from endothelial cell monolayers. The m phi s were adhered to the protein-coated surfaces for 1 h at 37 degrees C in serum-free medium and washed to remove nonadherent cells, and the number of adherent m phi s was measured. Monolayers of m phi s were also incubated for an additional 18 h, at which time both adherence and cell spreading were measured. PMA-stimulated superoxide production by adherent m phi s was determined after 1 and 18 h of adherence to the protein-coated surfaces. PMA-stimulated release of two prostanoids, prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) was measured after 18 h of m phi adherence to the surfaces. Following 18 h of adherence, PMA-stimulated superoxide anion secretion and secretion of PGE2 and TxB2 were augmented of primed by m phi s adherent to COL I, GEL, or BM. In contrast, no such priming effects were observed by m phi s adherent to COL IV, FN, or LM. The results suggest that adherence to basement membranes, collagen type I-containing surfaces in the interstitium, or denatured collagen at sites of tissue injury primes m phi respiratory burst and arachidonate metabolism to inflammatory agonists. Induction of priming events by substrate-specific adherence may be an important factor regulating host defense functions of m phi s in the extracellular matrix.

Antigens, CD↗

Medication beliefs as mediators of the health literacy-antiretroviral adherence relationship in HIV-infected individuals.

Identifying modifiable barriers to antiretroviral adherence remains an important aim. We hypothesized that mistaken beliefs regarding taking HIV medications mediated the relation between low literacy and poor adherence. We studied 87 HIV-infected individuals on standard antiretroviral regimens for >or= 3 months. Adherence was assessed using pharmacy refill records. Medication beliefs, including an individual's norm for acceptable adherence, were measured using questions developed by expert panel. Literacy was associated with >or=95% adherence (64% for >or=9th grade level vs. 40% for <9th grade level). Participants with <95% adherence had a lower threshold of acceptable adherence than those with >or=95% adherence [80% adherence (interquartile range 70-90%) vs. 90% adherence (interquartile range 80-90%)]. However, the effect was independent of literacy. No other beliefs assessed were associated with adherence. Although the beliefs assessed do not mediate the relation between literacy and adherence, we identified low adherence norms as a potentially modifiable belief associated with adherence.

Adult↗

Adherence and arrhythmic mortality in the cardiac arrhythmia suppression trial (CAST).

Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CAST), a placebo-controlled double-blind clinical trial of post-myocardial infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect counterbalanced the effect of the active medication.

Anti-Arrhythmia Agents↗

Adherence to antiretroviral therapy: an empirical test of the information-motivation-behavioral skills model.

Consistent and nearly perfect adherence is considered an essential requirement for HIV-positive patients on antiretroviral therapy (ART) to fully realize its life-extending benefits. The current study evaluated a comprehensive model of ART adherence--the information-motivation-behavioral skills (IMB) model. This model views adherence behavior as a function of the interrelations between adherence-related information, motivation, and behavioral skills. It hypothesizes that adherence-related information and motivation work through adherence-related behavioral skills to affect the initiation and maintenance of optimal ART adherence. In a series of structural equation models, the IMB model's critical constructs and assumptions were evaluated with a sample of 100 HIV-positive patients in clinical care. Across all analyses, the authors found support for the assumptions of the IMB model of ART adherence. Consistent with the model, adherence-related information and motivation related significantly to adherence-related behavioral skills, and behavioral skills related significantly to self-reported optimal adherence. Further, as predicted, the effects of information and motivation on self-reported adherence were mediated by adherence-related behavioral skills. Current study results are explored, and implications for adherence promotion interventions based on the model are discussed.

Adult↗

Successful adherence after multiple HIV treatment failures.

BACKGROUND: Non-adherence to human immunodeficiency virus (HIV) medications often results in irreparable drug resistance and poor outcomes. Hence, care providers generally think that treatment of HIV disease should be delayed until a person is 'ready' to adhere. However, little research has focused on understanding the process that results in readiness for successful adherence. AIM: The aim of this phenomenological study was to describe and understand the experience and decision-making processes of people who became adherent to their HIV medication regimens after previously failing treatment because of non-adherence. METHOD: A Husserlian phenomenological approach was taken, and in-depth interviews were analysed using Giorgi's method of phenomenological description and analysis. FINDINGS: Thirteen HIV-positive men and women who had previously failed two or more treatment regimens because of non-adherence were purposefully selected from two infectious diseases clinics in the Midwest region of the United States. They had achieved and sustained adherence to their HIV medications for 1 year or longer without formal intervention. All participants experienced a 'trigger' event preceding the process that led to the ability to incorporate lifestyle and health behaviour changes necessary for successful adherence. Factors associated with the process leading to adherence were: changing attitudes towards HIV medication, finding the right health care provider, creating the right support system, getting control of life and having goals. CONCLUSIONS: This study demonstrated that HIV-positive individuals who had been non-adherent and had been viewed as 'difficult to treat' nonetheless successfully adhered to treatment once they became 'ready'. Findings from this study implicate that readiness may be a necessary component for successful adherence, particularly in HIV-positive individuals who have previously failed treatment. Understanding the relationship between the phenomenon of readiness and subsequent HIV treatment adherence has implications for clinical decision-making and for development of interventions that enhance adherence and prevent HIV drug resistance.

Adult↗

Modifiable barriers to adherence to inhaled steroids among adults with asthma: it's not just black and white.

BACKGROUND: Sociobehavioral factors influence adherence to inhaled corticosteroid (ICS) in adults with asthma and warrant exploration as explanations of apparent racial disparities in adherence. OBJECTIVE: The purposes of this study were to identify barriers to adherence, potentially modifiable by healthcare providers, in a group of African Americans and non-African Americans and to test modifiable barriers as explanations of racial-ethnic differences in adherence. METHODS: We conducted a cohort study of 85 adults (mean age, 47 +/- 15 years; 61 [72%] female; 55 [65%] African American) with moderate or severe persistent asthma to determine modifiable sociobehavioral predictors of adherence. These were knowledge of the function of ICS, patient-perceived adequacy of communication with the provider, social support, attitude (perception of risks/benefits of ICS), depression, and self-efficacy. Adherence was calculated from electronic monitoring data as the mean of the number of doses recorded per 12 hours divided by the number prescribed, truncated at 100%. Past adherence, baseline severity of symptoms, and sociodemographics were treated as fixed confounders in ordinal logistic modeling. RESULTS: Adherence was 60% +/- 30%. In bivariate analyses, favorable attitude to ICS (P =.01) was associated with better adherence. Of immutable predictors, African American race-ethnicity (P =.001), lower educational achievement (P =.01), lower household income (P =.002), and more baseline symptoms (P =.003) were associated with poorer adherence. In multivariable analysis, controlling for immutable predictors, favorable attitude was associated with adherence. Favorable attitude was associated with greater adherence in African Americans and non-African Americans. Controlling for immutable factors, the race-adherence relationship was not mediated by the mutable factors, but economic factors (income and insurance) were mediators. CONCLUSION: Attitude is strongly related to adherence but does not mediate the effect of race-ethnicity.

Administration, Inhalation↗

Patient-perceived barriers to antiretroviral adherence: associations with race.

New antiretroviral (ARV) regimens require strict adherence if optimal suppression of HIV is to be maintained. This study is a theory-based examination of racial differences in patient-perceived barriers and reported ARV adherence. Participants (N=149) completed the Patient Medication Adherence Questionnaire (PMAQ), measuring adherence and perceived barriers to adherence. Adherence was defined as a self-report of 100% adherence in the past four weeks. Odds ratios were calculated to determine the relation of reported barriers to adherence for race and gender groups, and for the sample overall. For every ten-point increase in barrier score, there was an 86% increased risk of being non-adherent (OR=1.86; 95% CI: 1.19, 2.91). Adherence was not different between racial and gender groups, nor was total barrier score. However, individual barriers were differentially endorsed across groups. Rather than relying on demographic predictors, which may be only an indirect marker of adherence, evaluations of adherence should examine the psychological and social barriers to positive adherence outcomes in individual patients. Our findings support the use of theory-based behavioural interventions that address perceived barriers to adherence and other health promotion activities.

Adult↗

A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women.

OBJECTIVES: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women. DESIGN: Prospective observational study. METHODS: One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month. RESULTS: Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of > or = 88%, 28% of those with 45-87% adherence, 43% of those with 13-44% adherence, and 71% of those with < or = 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count. CONCLUSIONS: Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.

Adult↗

Patient adherence and medical treatment outcomes: a meta-analysis.

BACKGROUND: Adherence is a factor in the outcome of medical treatment, but the strength and moderators of the adherence-outcome association have not been systematically assessed. OBJECTIVES: A quantitative review using meta-analysis of three decades of empirical research correlating adherence with objective measures of treatment outcomes. METHOD: Sixty-three studies assessing patient adherence and outcomes of medical treatment were found involving medical regimens recommended by a nonpsychiatrist physician, and measuring patient adherence and health outcomes. Studies were analyzed according to disease (acute/chronic, severity), population (adult/child), type of regimen (preventive/treatment, use of medication), and type and sensitivity of adherence and outcomes measurements. RESULTS: Overall, the outcome difference between high and low adherence is 26%. According to a stringent random effects model, adherence is most strongly related to outcomes in studies of nonmedication regimens, where measures of adherence are continuous, and where the disease is chronic (particularly hypertension, hypercholesterolemia, intestinal disease, and sleep apnea). A less stringent fixed effects model shows a trend for higher adherence-outcome correlations in studies of less serious conditions, of pediatric patients, and in those studies using self-reports of adherence, multiple measures of adherence, and less specific measures of outcomes. Intercorrelations among moderator variables in multiple regression show that the best predictor of the adherence-outcome relationship is methodological-the sensitivity/quality of the adherence assessment.

Data Interpretation, Statistical↗

Prevalence and risk factors of non-adherence with immunosuppressive medication in kidney transplant patients.

Non-adherence with immunosuppressive regimen is a major risk factor for poor outcome after kidney transplantation. Identifying patients at risk for non-adherence requires understanding the risk factors for non-adherence. This prospective study included a convenience sample of 249 adult kidney transplant patients >1 year post-transplant. Non-adherence was monitored electronically using MEMS(R). Selected socio-economic, therapy-, patient-, condition- and healthcare team-related risk factors for non-adherence were assessed. Period prevalences were expressed as the percent of prescribed doses taken (taking adherence), the percent of correctly dosed days (dosing adherence), the percentage of inter-dose intervals not exceeding 25% of the prescribed interval (timing adherence), and the number of drug holidays per 100 days (no intake for > 48 h if once daily or for > 24 h if twice daily intake). Testing occurred by simple mixed logistic regression analysis. Factors significant after correction for multiple testing were entered into a multiple logistic regression model. Mean taking, dosing, timing adherence, and drug holidays were 98%, 96%, 93%, and 1.1 days, respectively. Non-adherence was associated with lower self-efficacy, higher self-reported non-adherence, no pillbox usage, and male gender. Adherence declined between Monday and Sunday. This study provides a framework for identifying patients at risk for non-adherence and for developing adherence-enhancing interventions.

Adult↗

Characteristics of adherence of enteroaggregative Escherichia coli to human and animal mucosa.

An Escherichia coli strain (serotype O127a:H2) that had been isolated from a child with diarrhea in Thailand and that was negative for the virulence factors of the four categories of diarrheagenic E. coli (enterotoxigenic, enteropathogenic, enteroinvasive, and enterohemorrhagic) and that showed an aggregative pattern of adherence to HeLa cells was investigated for adherence to native or Formalin-fixed human and animal mucosa. The hemagglutinating activity and adherence ability of the bacteria were resistant to D-mannose and were strictly regulated by environmental conditions. Genetic data supported the close relation between the hemagglutinating activity and adherence ability. In accordance with the adherence pattern on tissue-cultured cells, the bacteria adhered to human and animal mucosa, as evidenced by a direct gold-labeling analysis. In human intestines, Formalin-fixed mucous coatings, epithelial cells of colonic mucosa, epithelial cells of ileal single lymphoid follicles and Peyer's patches, and the absorptive cells of jejunal or ileal villi provided adherence targets. Adherence to M cells in the Peyer's patch-associated epithelium was also confirmed. The adherence levels to native jejunal or ileal human villi were low, as was the case with the corresponding Formalin-fixed villi. In human urinary tract, the superficial epithelial cells of both native and Formalin-fixed ureter provided striking adherence targets. In animal (porcine and rabbit) small intestines, the bacteria adhered to the native villi to a lesser extent than to the Formalin-fixed villi. The adherence levels were compared with those of enterotoxigenic E. coli with colonization factor antigen (CFA)/I pili or CFA/II pili. The data suggested unique mucosa adherence characteristics of the enteroaggregative E. coli strain. The possibility of the adherence ability as a virulence factor was discussed.

Adult↗

A meta-analysis of the association between adherence to drug therapy and mortality.

OBJECTIVE: To evaluate the relation between adherence to drug therapy, including placebo, and mortality. DESIGN: Meta-analysis of observational studies. DATA SOURCES: Electronic databases, contact with investigators, and textbooks and reviews on adherence. Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality. RESULTS: Data were available from 21 studies (46,847 participants), including eight studies with placebo arms (19,633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11). CONCLUSION: Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the "healthy adherer" effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.

Drug Therapy↗

Effects of antibiotics on adherence of Pseudomonas aeruginosa and Pseudomonas fluorescens to human fibronectin.

The effect of subminimal inhibitory concentration (1/2 MIC) of antimicrobial agents on the adherence of fluorescent Pseudomonas to human fibronectin (FN) was investigated by examining two Pseudomonas fluorescens and four Pseudomonas aeruginosa strains. The Escherichia coli (MC1061 and JM109) strains, used as negative controls, adhered poorly to FN immobilized on microtiter wells (adherence indices of 0.04 +/- 0.02 and 0.03 +/- 0.01 10(5) CFU/well, respectively). Two P. aeruginosa strains (NK125502 and ER82483) were highly adherent to FN (adherence indices of 3.22 +/- 0.75 10(5) and 3.08 +/- 1.42 10(5) CFU/well, respectively), the two others (ER98513 and ER92581) adhered less efficiently (adherence indices of 0.91 +/- 0.05 10(5) and 0.45 +/- 0.23 10(5) CFU/well, respectively). The two P. fluorescens strains (MF0 and ER74508) were highly adherent to fibronectin (adherence indices of 7.06 +/- 1.00 10(5) and 2.08 +/- 0.67 10(5) CFU/well, respectively). Cefsulodin was the only antimicrobial agent tested that decreased the FN adherence of the majority of the strains: decrease in adherence highly significant (p < 0.01) for the P. fluorescens MF0 strain, significant (p < 0.05) for the P. aeruginosa NK125502, ER98513 and the P. fluorescens ER74508 strains, and not significant for the P. aeruginosa ER92581 strain. The effects of chloramphenicol and polymyxin B on the adherence of Pseudomonas were strain dependent. Gentamicin had no statistically significant effect on bacterial adherence. We conclude that, in addition to its antibacterial activity, cefsulodin could be effective in preventing the adherence of fluorescent Pseudomonas to FN, an important property in the presence of injured epithelium and coated biomaterials.

Anti-Bacterial Agents↗

Bacterial adherence in the pathogenesis of endocarditis. Interaction of bacterial dextran, platelets, and fibrin.

The role of dextran in the pathogenesis of bacterial endocarditis was investigated by studying the adherence of dextran producing oral streptococci to the constituents of nonbacterial thrombotic endocarditis (NBTE) in vitro and in vivo. The adherence of Streptococcus sanguis to fibrin and platelets was determined in an in vitro assay system simulating nonbacterial thrombotic endocarditis. Adherence was increased when the organisms were grown in sucrose-supplemented media (adherence ratio X 10(4), 177 +/- 6 in 5% sucrose vs. 140 +/- 7 in 0.5% sucrose, P less than 0.001), and decreased by incubating the organisms in dextranase (adherence ratio X 10(4), 117 +/- 16, P less than 0.001), an effect which was nullified by heat inactivating this enzyme (adherence ratio X 10(4), 192 +/- 7, P less than 0.001). The amount of dextran produced in broth by three different oral streptococci correlated directly with the adherence observed to fibrin and a fibrin-platelet matrix in vitro (P less than 0.001). These organisms adhered more readily to a fibrin-platelet matrix than to fibrin alone (adherence ratio X 10(4), 455 +/- 30 vs. 177 +/- 6, respectively, P less than 0.001). The role of dextran formation was also examined in vivo in rabbits with preexisting NBTE. After injection of 10(7) S. sanguis, 12 of 17 animals developed endocarditis. In contrast, when the organisms were pretreated with dextranase (an enzyme that removes dextran from the bacterial cell surface), the same inoculum resulted in endocarditis in only 5 of 19 animals (P less than 0.05). In addition, a fresh strain of S. sanguis that produced high levels of dextran (1,220 +/- 50 microgram/ml) and adhered avidly to fibrin (adherence ratio X 10(4), 220 +/- 11) produced endocarditis in 12 of 18 rabbits after injection of 10(7) organisms. Another isolate of the same strain that had been passed repeatedly in the laboratory produced less dextran (400 +/- 30 microgram/ml), adhered poorly to fibrin (adherence ratio X 10(4), 140 +/- 7), and produced endocarditis in only 3 of 14 rabbits under identical conditions (P less than 0.05). This study demonstrates that dextran production is important in the adherence of oral streptococci to the constituents of NBTE and may play a role in the pathogenesis of bacterial endocarditis by oral streptococci.

Animals↗

Mechanisms of eosinophil adherence to cultured vascular endothelial cells. Eosinophils bind to the cytokine-induced ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor.

We have examined the mechanisms involved in the adherence of normal peripheral blood eosinophils to cultured human umbilical vein endothelial cells (HEC) under three conditions: (a) adherence in the absence of treatment of HEC or eosinophils with activating agents (basal adherence); (b) adherence induced by stimulation of eosinophils with phorbol ester (eosinophil-dependent adherence); and (c) adherence induced by pretreatment of HEC with LPS, tumor necrosis factor (TNF), or IL-1 (endothelial-dependent adherence). A mechanism was identified that was equally active in basal, eosinophil-dependent, and endothelial-dependent adherence. This mechanism was optimally active in the presence of both Ca++ and Mg++, and reduced in the presence of Ca++ only or Mg++ only. Furthermore, like the other mechanisms of eosinophil adherence, it was active at 37 degrees C but not at 4 degrees C. A second mechanism of adherence was involved in eosinophil- and in endothelial-dependent adherence. This mechanism was dependent on the CD11/CD18 adhesion complex of eosinophils (i.e., inhibited by anti-CD18 MAb) and it was active in the presence of Ca++ and Mg++ or Mg++ only, but not Ca++ only. The third mechanism of adherence was specific for endothelial-dependent adherence. It involved the endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) and the eosinophil receptor very late activation antigen-4 (VLA-4, CD49d/CD29, i.e., inhibited by anti-VCAM-1 MAb or anti-VLA-4 MAb). This mechanism was active in the presence of Ca++ and Mg++ but not of Ca++ only or Mg++ only, and was not up- or downregulated when eosinophils were stimulated with phorbol ester. In contrast, the endothelial leukocyte adhesion molecule-1 (ELAM-1), that binds neutrophils and monocytes, was not involved in eosinophil adherence to LPS-, TNF-, or IL-1-stimulated HEC (i.e., not inhibited by anti-ELAM-1 MAb). We conclude that eosinophils, like monocytes and lymphocytes, bind to the cytokine-induced endothelial ligand VCAM-1 via the integrin receptor VLA-4.

Antibodies, Monoclonal↗

Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures.

BACKGROUND: A variety of measures have been developed to calculate refill adherence from administrative data such as pharmacy claims databases. These measures have focused on improving the accuracy of adherence measures or clarifying the evaluation time frame. As a result, there are many measures used to assess adherence that may or may not be comparable or accurate. OBJECTIVE: To compare available refill adherence measures. METHODS: A systematic literature review was conducted to identify current or recently used measures of calculating adherence from administrative data. A MEDLINE search (January 1990-March 2006) was undertaken using the search terms adherence or compliance in the title combined with administrative, pharmacy, or records in any field, including subheadings medical, nursing, and hospital records. Non-English articles were excluded. Seven hundred fifteen articles were available for review. Review articles and letters were excluded from measure selection, but were included in the search terms and used to identify additional research articles. Adherence measures were excluded if they were incompletely described, produced non-numeric values, or were duplicates. Eleven refill adherence measures were identified and compared using data from the LOSE Weight (Long-term Outcomes of Sibutramine Effectiveness on Weight) study. Measures compared include Continuous Measure of Medication Acquisition (CMA); Continuous Multiple Interval Measure of Oversupply (CMOS); Medication Possession Ratio (MPR); Medication Refill Adherence (MRA); Continuous Measure of Medication Gaps (CMG); Continuous, Single Interval Measure of Medication Aquisition (CSA); Proportion of Days Covered (PDC); Refill Compliance Rate (RCR); Medication Possession Ratio, modified (MPRm); Dates Between Fills Adherence Rate (DBR); and Compliance Rate (CR). RESULTS: The results suggest that the CMA, CMOS, MPR, and MRA are identical in terms of measuring adherence to prescription refills throughout the study period, each with a value of 63.5%; CMG and PDC are slightly lower (63.0%) and are equivalent to MRA when oversupply is truncated. CR, MPRm, RCR, and CSA result in higher adherence values of 84.4%, 86.6%, 104.8%, and 109.7%, respectively. CONCLUSIONS: Five measures produce equivalent results for measuring prescription refill adherence over the evaluation period. Of these, MRA has the fewest calculations, is easily truncated if one desires to exclude surplus medication issues, and requires the least amount of data. MRA is therefore recommended as the preferred measure of adherence using administrative data.

Appetite Depressants↗