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Impact of antiretroviral regimen switches on adherence.

PURPOSE: An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen. METHOD: Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken. RESULTS: During 1,056 person-months of follow-up, 129 medication regimen changes occurred among 84 patients (66% of participants). Among the 89 analyzable switches (representing 66 patients), the most common reasons for switch included pill to liquid ritonavir (n = 26), gastrointestinal intolerance (n = 11), virologic failure (n = 8), and peripheral neuropathy (n = 7). Overall, mean adherence prior to regimen switch exceeded mean adherence after regimen switch (0.75 vs. 0.70; p =.035). Among subgroups of switches, adherence decreased significantly after switching from pill to liquid ritonavir (0.83 vs. 0.68; p <.001). When this group was excluded, there was no change in adherence after switches (0.72 vs. 0.71; p =.74). CONCLUSION: Antiretroviral regimen changes are not associated with adherence improvement and may be associated with declining adherence when a new regimen is unpalatable. Antiretroviral regimen changes should trigger reassessment of adherence and, when appropriate, adherence intervention.

Adult↗

Self-reported adherence, management behavior, and barriers to care after an emergency department visit by inner city children with asthma.

OBJECTIVE: The inability to adhere to a prescribed therapeutic program for the treatment of a chronic disease may be responsible in part for continued disease activity. This problem may be more of an issue in the treatment of asthma, a common, potentially lethal chronic condition in which the lack of symptoms may be interpreted as remission. Adherence was one of the key areas of interest for the National Cooperative Inner-City Asthma Study. The focus of this study was to identify those issues reported by families that could adversely affect their adherence to an asthma care program. The identification of barriers to adherence could then form the basis of a successful intervention program. This study describes barriers to adherence, asthma management behavior, and self-reported adherence. METHODS: Patients presenting during an acute attack of asthma at an emergency department (ED) were recruited for this study. The medical record of the ED encounter was abstracted and compared with information that was obtained during a baseline interview 3 to 5 weeks later. During the baseline interview, parents were asked about health care behaviors related to adherence. RESULTS: There were 344 children 4 to 9 years of age living in inner city census tracts in the study. Four areas of adherence (medicine use, appointment-keeping, emergency actions, and asthma attack prevention) were investigated. The parental report of medications prescribed at the ED and the information on the abstracted ED report agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for cromolyn. Among respondents, 85.4% of parents reported that they are able to follow the ED recommendations almost all of the time; side effects of medicines were a concern for 81.1% of caretakers who were adherent and for 89.5% of caretakers who were nonadherent. Doubts regarding the usefulness of medications occurred in 34.4% of those considered adherent and 54.2% who admitted nonadherence. Medications were forgotten some of the time by 45.2% of the children, and 52.8% tried to get out of taking medicine. Appointments for follow-up care were kept by 69% of those given an appointment in the ED, by an estimated 60.0% of those who were told specifically to call for an appointment, and by an estimated 25.2% of those who were neither given an appointment nor told specifically to make one. Only one third of parents report that they were able to keep the child away from known asthma triggers nearly all of the time. Approximately half avoided allergens; however, only 37.5% reported avoidance of cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a medicine and taking the child to a physician were reported as the first or second action during an acute attack of asthma by 72.1% of respondents. CONCLUSIONS: Adherence to an asthma-management program involves a number of areas: medication, appointment-keeping, prevention, and applying an emergency plan of action. Barriers to adherence may exist in one or all four of these areas, leading to ineffective control of asthma. Recommendations are made for improving the patient-physician partnership to improve adherence.

Asthma↗

Patterns of early adherence to the antidepressant citalopram among older primary care patients: the prospect study.

OBJECTIVE: Our purpose was to determine the personal characteristics associated with different patterns of adherence to the antidepressant citalopram in a primary care trial of depression management. METHOD: The study sample consisted of 228 adults aged 60 years and older recruited from primary care settings and who participated in a depression intervention. The intervention consisted of services of trained care managers, who offered recommendations to physicians following a clinical algorithm and helped patients with treatment adherence. Adherence to the antidepressant citalopram was measured using pill counts. We employed the latent class model to classify patients according to the pattern of adherence to citalopram over time. We examined the association of sociodemographic characteristics, depression status, cognitive status, and medical comorbidity with the resulting classes of adherence. RESULTS: The latent class model generated three classes of adherence: known to be adherent, unknown adherence, and known to be nonadherent. Participants who were white were more likely to be in the known to be adherent class than in the known to be nonadherent class (odds ratio (OR) = 10.38, 95% confidence interval (CI) [3.47, 31.12]). Married participants were less likely to be in the unknown adherence class than the known to be nonadherent class (OR = 0.28, 95% CI [0.09, 0.85]). No associations between age, gender, education level, depression status, cognitive status, or medical comorbidity and classes of adherence were found. CONCLUSIONS: We found stronger relationships between ethnicity and marital status with patterns of adherence to citalopram than we did other personal characteristics. Identification of a subgroup of patients at particularly high risk of nonadherence is important for the development of adherence interventions.

Aged↗

[Relationships between insight and medication adherence in subjects with psychosis].

BACKGROUND: Poor medication adherence in subjects with psychosis has a high prevalence and a negative impact on clinical outcome. Several studies have reported that a poor level of insight was a strong predictor of poor medi-cation adherence. However, few studies have investigated whether insight was associated with medication adherence, independently from other clinical and treatment characteristics. OBJECTIVE: To explore the link between insight and medi-cation adherence in subjects with psychosis, and to assess the impact of potential confounding factors on this association. METHOD: Subjects included in the study were patients aged 60 or less, consecutively admitted in a psychiatric ward, and presenting with at least one psychotic symptom (delusion or hallucination). Medication adherence was assessed using: 1) history of total discontinuation of treatment against medical advice over the 2 weeks before admission; 2) the 7-point rating scale developed by Kemp et al.; 3) the self-report questionnaire Drug Attitude Inventory (DAI). The Scale to assess Unawareness of Mental Disorder (SUMD) was used to measure level of insight. Assessment of symptoms was performed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale (CDS). DSM IV diagnoses were assessed using the Diagnostic Interview for Psychosis (DIP). The associations between level of insight (SUMD scores) and the three measures of medication adherence were explored using the non-parametric Mann-Whitney and Spearman's tests. Logistic regression models giving Odds Ratios (ORs) and 95% confidence intervals (95% CI) were used to examine the impact of potential confounding variables on the associations between level of insight and medication adherence. RESULTS: 42 patients presenting with schizophrenia broadly defined (n=25) or psychotic mood disorder (n=17) were assessed. Significant associations were found between higher SUMD scores (ie poorer insight) and discontinuation of treatment before admission (z=- 2.6, p=0.009), poor medication adherence rated using the Kemp et al.'s scale (r=- 0.64; p=0.0001), and negative perception of treatment assessed using the DAI (r=- 0.405; p=0.009). The Kemp'scale score and the DAI score were categorised into poor vs. good according to the median for logistic regression analyses. Subjects were 1.7 times more likely (OR=1.7, 95% CI 1.1-2.5, p=0.01) to have discontinued their treatment, 1.9 times more likely (OR=1.9, 95% CI 1.3-2.8), p=0.0003) to have poor medication adherence rated with the Kemp's scale, and 1.8 times (OR=1.8, 95% CI 1.2-2.6, p=0.005) more likely to have a negative perception of the treatment for one point increase at the SUMD score (ie lower level of insight). The associations between SUMD score and the three measures of medication adherence were not modified after adjustment for demographic characteristics (age, gender, educational level, occupational status, marital status) and categorical diagnosis (schizophrenia broadly defined vs. psychotic mood disorder), severity of symptoms (SANS, SAPS, CDS scores), characteristics of the psychotropic treatment, diagnosis of substance or alcohol use disorder, age at onset, and number of previous admissions. CONCLUSION: The study demonstrates that medication adherence is associated with the level of insight, independently from other patient's demographic and clinical characteristics. The association between low level of insight and poor medication adherence should be confirmed using prospective studies carried out in ambulatory patients. These findings suggest that psycho-educational programs aimed at improving insight should be developed in order to improve medication adherence.

Adult↗

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

Animals↗

Identification of Philadelphia-negative granulocyte-macrophage colony-forming units generated by stroma-adherent cells from chronic myelogenous leukemia patients.

Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem cell characterized by the coexistence of Philadelphia-negative (Ph-) with Ph+ progenitors. CML progenitor cells have been shown to be defective in adherence to marrow stroma. The present study investigated at the cytogenetic level marrow-derived CML clonogenic cells generated from the stroma-adherent cell fraction. On direct cytogenetic analysis, the overall mean (+/- SEM) percentage of Ph- metaphases was 3% +/- 1%. Mononuclear marrow cells from CML patients (n = 18) were incubated with mafosfamide (100 micrograms/mL) or control medium, seeded onto marrow stromal layers and allowed to adhere (2 hours, 37 degrees C). After a short-term (3-day) liquid culture, the cells were harvested, incorporated in methyl-cellulose, and individual colonies were analyzed by single colony karyotyping. The mean (+/- SEM) percentage of Ph- colonies generated from the stroma-adherent fraction was 35% +/- 6%. As compared with marrow colony-forming unit granulocyte-macrophage plated before any manipulation, the mean (+/- SEM) percentage of Ph- clones was significantly increased by stroma adherence (35% +/- 6% v 15% +/- 4%, P < or = .005) and mafosfamide (100 micrograms/mL) incubation of marrow cells before stroma adherence (58% +/- 9% v 35% +/- 6%, P < or = .005). An additive effect was observed by combining mafosfamide treatment and stroma adherence. Single-colony transfer experiments showed that 50% +/- 4% stroma-adherent and 70% +/- 4% stroma-adherent mafosfamide-treated progenitors gave rise to secondary colonies. To further characterize the stroma-adherent fraction, experiments were performed in which CD34+ marrow cells were used. The mean (+/- SEM) output of progenitors generated by 10,000 CD34+, stroma-adherent cells was 888 +/- 188 and 570 +/- 258 for untreated and mafosfamide-treated cells, respectively. Individual colonies were analyzed by single-colony karyotyping and fluorescent in situ hybridization using a biotinylated cosmid DNA probe that hybridize to abl oncogene. The CD34+, stroma-adherent fraction contained 38% +/- 14% (untreated) and 56% +/- 18% (mafosfamide-treated) (P < or = .025) Ph- progenitors. In conclusion, the present data show the possibility to select Ph- clones that (1) have a maintained capability of stroma adherence, (2) are mafosfamide resistant, (3) are derived from the CD34+ fraction, and (4) have high-replating potential.

Adult↗

Phenotype and progeny of primitive adherent human hematopoietic progenitors.

Hematopoietic progenitor cells can be classified as plastic- and stroma-adherent (P+S+), stroma-adherent (P-S+) and non-adherent (P-S-). Both P+S+ and P-S+ populations are detected in delta (delta) culture systems where they produce non-adherent (P-S-) granulocyte-macrophage colony-forming cells (CFU-GM) and erythroid burst-forming units (BFU-E). Here we demonstrate that the plastic-adherent progenitor cells (P delta cells) comprise 5-10 percent of the CD34+, population in adult human marrow. Moreover, they do not express CD3 or CD22 and 88 percent of them are CD38-, 88 percent are CD33- and 74 percent are HLA-DR-. Production of CFU-GM by purified plastic-adherent CD34+, adherent cells was 60 percent of the number produced by recombined CD34+, and CD34- fractions. We have shown also that the plastic-adherent P+S+ cells are the precursors of the stroma-adherent P-S+ cells (S delta cells), day 21 cobblestone-area forming cells (CAFC) and cells capable of sustained hematopoiesis in a modified long-term bone marrow culture system. These observations support the primitive nature of P delta cells and establish a phenotypic sequence of plastic and stroma adherence through stroma adherence to non-adherence in hematopoietic cell development. To further investigate the relationship between P delta cells, S delta cells and long-term culture-initiating cells (LTCIC), we cultured whole mononuclear cell tractions and plastic-adherent cell-depleted mononuclear cell fractions in long-term culture and in the S delta assay. The results indicated the P delta cells were inhibited in the presence of stromal cells.

ADP-ribosyl Cyclase↗

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy &#xd7; intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy &#xd7; randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans↗

Do follow-up recommendations for abnormal Papanicolaou smears influence patient adherence?

OBJECTIVE: To compare adherence to follow-up recommendations for colposcopy or repeated Papanicolaou (Pap) smears for women with previously abnormal Pap smear results. DESIGN: Retrospective cohort study. SETTING: Three northern California family planning clinics. PATIENTS: All women with abnormal Pap smear results referred for initial colposcopy and a random sample of those referred for repeated Pap smear. Medical records were located and reviewed for 90 of 107 women referred for colposcopy and 153 of 225 women referred for repeated Pap smears. INTERVENTION: Routine clinic protocols for follow-up--telephone call, letter, or certified letter--were applied without regard to the type of abnormality seen on a Pap smear or recommended examination. MAIN OUTCOME MEASURES: Documented adherence to follow-up within 8 months of an abnormal result. Attempts to contact the patients for follow-up, adherence to follow-up recommendations, and patient characteristics were abstracted from medical records. The probability of adherence to follow-up vs the number of follow-up attempts was modeled with survival analysis. Cox proportional hazards models were used to examine multivariate relationships related to adherence. RESULTS: The rate of overall adherence to follow-up recommendations was 56.0% (136/243). Adherence to a second colposcopy was not significantly different from that to a repeated Pap smear (odds ratio, 1.40; 95% confidence interval, 0.80-2.46). The use of as many as 3 patient reminders substantially improved adherence to follow-up. Women without insurance and women attending 1 of the 3 clinics were less likely to adhere to any follow-up recommendation (hazard ratio for no insurance, 0.43 [95% confidence interval, 0.20-0.93], and for clinic, 0.35 [95% confidence interval, 0.15-0.73]). CONCLUSIONS: Adherence to follow-up was low in this family planning clinic population, no matter what type of follow-up was advised. Adherence was improved by the use of up to 3 reminders. Allocating resources to effective methods for improving adherence to follow-up of abnormal results may be more important than which follow-up procedure is recommended.

Adolescent↗

Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus.

OBJECTIVES: To longitudinally follow a cohort of adolescents with human immunodeficiency virus (HIV) and to investigate long-term antiretroviral therapy adherence and factors associated with adherence. DESIGN, SETTING, AND PATIENTS: Adolescents infected with HIV (N = 231; mean age, 18.4 years; 72.7% female; 74.9% African American) from 13 cities throughout the United States were assessed at 3-month intervals. MAIN OUTCOME MEASURES: Self-reported adherence measures were validated by comparison with HIV-1 RNA viral load, and behavioral factors that may be associated with antiretroviral therapy adherence were assessed. RESULTS: At the initial visit, approximately 69% of the adolescents reported being adherent to antiretroviral therapy. Adolescents in the later HIV disease stage were less likely to be adherent compared with those in the earlier disease stage. Less alcohol use and being in school were associated with adherence by adolescents on weekends and over the preceding month. Longitudinal adherence was investigated among 65 subjects initially adherent with available information for at least 4 consecutive visits. The median time to nonadherence was 12 months, and failure to maintain adherence was significantly associated with younger age and depression. Among adolescents who attained an undetectable viral load, only about 50% maintained an undetectable viral load for the year. CONCLUSIONS: These findings indicate an urgent need for better interventions to assist adolescents with HIV in adhering to their medication regimens. Adolescents with advanced disease are likely to need more intervention. New treatments recently found effective for adolescent depression may assist in improving adherence for a majority of adolescents with HIV.

Adolescent↗

Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis.

CONTEXT: Adherence to antiretroviral therapy is a powerful predictor of survival for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns about incomplete adherence among patients living in poverty have been an important consideration in expanding the access to antiretroviral therapy in sub-Saharan Africa. OBJECTIVE: To evaluate estimates of antiretroviral therapy adherence in sub-Saharan Africa and North America. DATA SOURCES: Eleven electronic databases were searched along with major conference abstract databases (inclusion dates: inception of database up until April 18, 2006) for all English-language articles and abstracts; and researchers and treatment advocacy groups were contacted. Study Selection and Data Abstraction To best reflect the general population, studies of mixed populations in both North America and Africa were selected. Studies evaluating specific populations such as men only, homeless individuals, or drug users, were excluded. The data were abstracted in duplicate on study adherence outcomes, thresholds used to determine adherence, and characteristics of the populations. A random-effects meta-analysis was performed in which heterogeneity was examined using multivariable random-effects logistic regression. A sensitivity analysis was performed using Bayesian methods. DATA SYNTHESIS: Thirty-one studies from North America (28 full-text articles and 3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa were included. African studies represented 12 sub-Saharan countries. Of the North American studies, 71% used patient self-report to assess adherence; this was true of 66% of the African assessments. Studies reported similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A pooled analysis of the North American studies (17,573 patients total) indicated a pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the populations achieving adequate levels of adherence. Our pooled analysis of African studies (12,116 patients total) indicated a pooled estimate of 77% (95% confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds, and study quality were significant predictors of heterogeneity. Bayesian analysis was used as an alternative statistical method for combining adherence rates and provided similar findings. CONCLUSION: Our findings indicate that favorable levels of adherence, much of which was assessed via patient self-report, can be achieved in sub-Saharan African settings and that adherence remains a concern in North America.

Africa South of the Sahara↗

Interventions to enhance medication adherence.

BACKGROUND: People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects. OBJECTIVES: To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions. SEARCH STRATEGY: Computerized searches were updated to September 2004 without language restriction in MEDLINE, EMBASE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsycINFO and SOCIOFILE. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of original and review articles on the topic. SELECTION CRITERIA: Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. DATA COLLECTION AND ANALYSIS: Study design features, interventions and controls, and results were extracted by one reviewer and confirmed by at least one other reviewer. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. MAIN RESULTS: For short-term treatments, four of nine interventions reported in eight RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient compliance, but did not enhance the clinical outcome. For long-term treatments, 26 of 58 interventions reported in 49 RCTs were associated with improvements in adherence, but only 18 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Six studies showed that telling patients about adverse effects of treatment did not affect their adherence. AUTHORS' CONCLUSIONS: Improving short-term adherence is relatively successful with a variety of simple interventions. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Drug Therapy↗

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS.

BACKGROUND: Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. OBJECTIVES: To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. SEARCH STRATEGY: A systematic search of electronic databases was performed from January 1996 to May 2005. SELECTION CRITERIA: Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. DATA COLLECTION AND ANALYSIS: Study selection, quality assessments and data abstraction were performed independently by two reviewers. MAIN RESULTS: Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. AUTHORS' CONCLUSIONS: We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

Acquired Immunodeficiency Syndrome↗

Interventions to improve adherence to lipid lowering medication.

BACKGROUND: Lipid lowering drugs are still widely underused, despite compelling evidence about their effectiveness in the treatment and prevention of cardiovascular disease. Poor patient adherence to medication regimen is a major factor in the lack of success in treating hyperlipidaemia. In this review we focus on interventions, which encourage patients at risk of heart disease or stroke to take lipid lowering medication regularly. OBJECTIVES: To assess the effect of interventions aiming at improved adherence to lipid lowering drugs, focusing on measures of adherence and clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycInfo and CINAHL. Date of most recent search was in February 2003. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of adherence-enhancing interventions to lipid lowering medication in adults for both primary and secondary prevention of cardiovascular disease in an ambulatory setting. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently and assessed studies according to criteria outlined by the Cochrane Reviewers' Handbook. MAIN RESULTS: The eight studies found contained data on 5943 patients. Interventions could be stratified into four categories : 1. simplification of drug regimen, 2. patient information/education, 3. intensified patient care such as reminding and 4. complex behavioural interventions such as group sessions. Change in adherence ranged from -3% to 25% (decrease in adherence by 3% to increase in adherence by 25%). Three studies reported significantly improved adherence through simplification of drug regimen (category 1), improved patient information/education (category 2) and reminding (category 3). The fact that the successful interventions were evenly spread across the categories, does not suggest any advantage of one particular type of intervention. The methodological and analytical quality was generally low and results have to be considered with caution. Combining data was not appropriate due to the substantial heterogeneity between included randomised controlled trials (RCTs). REVIEWERS' CONCLUSIONS: At this stage, no specific intervention aimed at improving adherence to lipid lowering drugs can be recommended. The lack of a gold standard method of measuring adherence is one major barrier in adherence research. More reliable data might be achieved by newer methods of measurement, more consistency in adherence assessment and longer duration of follow-up. Increased patient-centredness with emphasis on the patient's perspective and shared-decision-making might lead to more conclusive answers when searching for tools to encourage patients to take lipid lowering medication.

Cardiovascular Diseases↗

Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions.

Adherence of sickle erythrocytes to endothelium in venules is thought to initiate or propagate vaso-occlusive episodes. Because of blood shear forces with normal microvascular flow, adherence in post-capillary venules requires binding via high-affinity receptor-mediated pathways. Microvascular flow in sickle patients is episodic, even in asymptomatic patients, so adherence may also occur at low shear not requiring high-affinity binding. Sickle cell binding to endothelium was quantified under flow or static incubation with unusually large vWF, thrombospondin, alpha(4)beta(1)/VCAM-1 or alpha(4)beta(1)/fibronectin (FN). Adherence under flow at 0.5 dyne/cm(2) shear stress leads to the greatest number of adherent sickle cells. Adherence under flow at 1.0 dyne/cm(2) leads to the strongest adherence. Static incubation conditions promote weak adherence of low numbers of sickle cells to endothelium. Following attachment at 1.0 dyne/cm(2), adherence strength was 2.5 +/- 0.1 or 2.6 +/- 0.2 dynes/cm(2) for alpha(4)beta(1)/VCAM-1 or alpha(4)beta(1)/FN pathways, a level 50% greater than adherence strength mediated by thrombospondin or ULvWF (1.7 +/- 0.08 or 1.6 +/- 0.07 dynes/cm(2), respectively). Sickle cell adhesion promoted by simultaneous activation of alpha(4)beta(1)/VCAM-1 and alpha(4)beta(1)/FN pathways is the strongest at 6.2 +/- 0.2 dynes/cm(2) and adherent red cells resist detachment shear stresses up to 10 dynes/cm(2). These data demonstrate that sickle cell adhesion to endothelium is regulated both by receptor/ligand affinity and flow conditions. Thus, both microvascular flow conditions and receptor-ligand interactions may regulate sickle cell adherence in vivo.

Anemia, Sickle Cell↗

Thrombin-induced adherence of neutrophils to cultured endothelial monolayers: increased endothelial adhesiveness.

We examined the effects of alpha-thrombin on the adherence of neutrophils to endothelial cell monolayers. Endothelial cells derived from the ovine pulmonary artery and ovine neutrophils were used. Thrombin (10(-8) M) resulted in a time-dependent increase in neutrophil adherence to the endothelium. The response was concentration-dependent with a maximal response at 10(-8) M. Thrombin did not induce neutrophil adherence either to plastic or to endothelial cell-derived matrix. The adherence response was inhibited in the presence of alpha-thrombin that had been inactivated with anti-thrombin III (1U:1U) or with hirudin (1 U/ml). However, the addition of either anti-thrombin III or hirudin simultaneously with alpha-thrombin to the cultured endothelial monolayers did not prevent neutrophil adherence. The monoclonal antibody MoAb 60.3, which precipitates a complex of four neutrophil surface glycoproteins (CDw18) was used to further characterize the reaction. MoAb 60.3 decreased the thrombin-induced adherence of neutrophils to the endothelial monolayer. Addition of 10(-8) M thrombin to the endothelial monolayer for 60 min, followed by washing the endothelium with fresh medium, caused resting neutrophils to adhere to the endothelial monolayers. MoAb 60.3 decreased neutrophil adherence to the washed endothelium. The factor(s) responsible for adherence was partially transferable. Medium obtained from incubating endothelial monolayers with thrombin (10(-8) M) for 60 min, adding hirudin to the medium to inactivate thrombin, and transferring it to untreated endothelial monolayers, elicited neutrophil adherence. The response was less than that obtained with thrombin alone (22.9 +/- 2.3% vs. 12.9 +/- 3.3%). The results indicate that the catalytic site of the thrombin molecule is responsible for the adherent activity. Thrombin elicits a rapid activation of endothelial cells with a response that involves the expression of endothelial adhesion sites and sites that interact with the neutrophil CDw18 adhesive glycoprotein complex. In addition, soluble transferable factor(s) which are generated by the endothelium also contribute to thrombin-induced neutrophil adherence.

Animals↗

Sickle erythrocytes adhere to fibronectin-thrombospondin-integrin complexes exposed by thrombin-induced endothelial cell contraction.

Vascular damage appears to be associated with sickle erythrocyte (SS RBC) adherence to the endothelium. Thrombin, which has been found in abnormal levels in many sickle patients, causes endothelial cell (EC) retraction and increased SS RBC adherence, and SS RBC adhere in the gaps opened between the EC. Our objective was to elucidate the mechanism of adherence to activated EC monolayers and to determine whether the matrix proteins thrombospondin (TSP) and fibronectin (FN) are mediators of this adherence. Thrombin activation elicited the same 2.5-fold increase in adherence whether 10 or 35% of the matrix was exposed, and the majority of the RBC adhered at the edges of the EC regardless of the extent of matrix exposed. Using static adherence assays we investigated whether TSP, FN, or the integrins alpha(v)beta(3) and alpha(5)beta(1) mediated adherence. Blocking antibodies to any of these four had no effect on adherence to untreated monolayers. However, all the increased adherence elicited by thrombin was abrogated by each one, whereas control antibodies had no effect. Immunofluorescent microscopy demonstrated that both integrins were present on the luminal surface of confluent EC. Neither TSP nor FN was exposed in confluent cultures but they both became available as receptors after EC retraction. These data suggest that SS RBC adhere to a complex of matrix TSP and FN maintained in an adhesive conformation by interactions with both integrins.

Anemia, Sickle Cell↗

An investigation of factors associated with fluid adherence among hemodialysis patients: a self-efficacy theory based approach.

This research tested the hypothesis that fluid adherence (i.e. mean weekend interdialysis fluid weight gain) among adult chronic hemodialysis patients would have significant associations with fluid adherence efficacy expectation, fluid adherence outcome expectation, and fluid adherence motivation. The association of these variables with patients' medical characteristics was also examined. Results provide partial support for the hypothesis. Fluid adherence efficacy expectation was found to be a significant predictor of mean weekend interdialysis fluid weight gain (fluid adherence). Patients with higher fluid adherence efficacy expectations had lower mean weekend interdialysis fluid weight gains. However, fluid adherence outcome expectation and fluid adherence motivation were not found to be significant predictors of fluid adherence. Results also revealed that certain of the investigated medical characteristics were significantly associated with mean weekend interdialysis fluid weight gain and fluid adherence efficacy expectation. Implications for studying and modifying fluid adherence among hemodialysis patients are discussed.

Adaptation, Psychological↗