Misunderstandings, misperceptions, and missed opportunities: Perspectives on adherence barriers from people with CF, caregivers, and CF team members.

OBJECTIVE: To identify differences in perspectives of people with cystic fibrosis (PwCF) and caregivers versus healthcare providers on adherence barriers. Mismatched perspectives may lead to miscommunication and missed opportunities to reduce barriers and improve CF outcomes. METHODS: PwCF, caregivers, and CF providers completed audio-taped, semi-structured interviews about adherence barriers. Interviews were transcribed and coded for themes. Themes were reviewed to identify when PwCF-caregiver perspectives differed from providers'. RESULTS: Participants included 14 adolescents with CF (mean age = 15.89 years, 64 % female, 71 % Caucasian), 14 adults with CF (mean age = 30.03 years, 64 % female, 57 % Caucasian), 29 caregivers (76 % female; 72 % Caucasian), and 42 providers. Four barriers were identified that could generate miscommunication between PwCF-caregivers and providers: Tired = Fatigued/Sleepy versus Tired = Burnout, Vacation and Travel, Knowledge and Skills About CF Regimen, and Daily Habits or Routines. PwCF and caregivers used similar words as providers, but conceptualized barriers differently. PwCF and caregivers discussed barriers pragmatically, however, providers viewed certain barriers more abstractly or unidimensionally, or did not discuss them. CONCLUSIONS: PwCF-caregivers and providers may not align in how they discuss barriers, which may contribute to miscommunication about adherence challenges. PRACTICE IMPLICATIONS: Patient-centered communication strategies may enhance providers' understandings of PwCF-caregiver perspectives on barriers and facilitate adherence interventions.

Clustered randomized controlled trial of a clinic-based problem-solving intervention to improve adherence in adolescents with cystic fibrosis.

BACKGROUND: In Cystic Fibrosis (CF), adherence to pulmonary medications is about 50% and decreases during adolescence. Effective interventions have not been integrated into CF care. This effectiveness study tested a brief, clinic-based behavioral intervention to improve adherence. METHODS: iCARE (I Change Adherence and Raise Expectations) was a pragmatic, clustered, 2-arm randomized controlled trial at 18 CF Centers. 607 adolescents with CF, ages 11-20 years, participated. Centers were randomized to IMPACT (n = 9; 300 adolescents), a brief problem-solving + education intervention, or standard care (SC; n = 9; 307 adolescents). IMPACT was delivered during a regularly scheduled clinic visit by a member of the clinical care team. The primary outcome was composite pulmonary medication possession ratio (cMPR); secondary endpoints were lung function, Body Mass Index percentile, courses of IV antibiotics, and health-related quality of life at 12 months. RESULTS: Effectiveness of the intervention was tested using mixed models, generalized estimating equations comparing IMPACT to SC. Fifty-eight percent of problem-solving sessions targeted barriers to airway clearance, exercise or nutrition, while 18% addressed pulmonary medications. Average intervention fidelity score was 67% (SD = 14%; Range = 25-100%). No significant intervention effects were found for cMPR or any of the secondary outcomes compared to SC. CONCLUSIONS: The IMPACT intervention did not improve medication adherence or health outcomes over 12 months. Challenges to implementing the intervention as intended during busy clinic visits were identified. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01232478; URL: www.clinicaltrials.gov.

Identifying Factors that Facilitate Treatment Adherence in Cystic Fibrosis: Qualitative Analyses of Interviews with Parents and Adolescents.

Cystic fibrosis (CF) is a progressive, genetic disease affecting multiple organ systems. Treatments are complex and take 2-4 h per day. Adherence is 50% or less for pulmonary medications, airway clearance, and enzymes. Prior research has identified demographic and psychological variables associated with better adherence; however, no study has extensively identified facilitators of treatment adherence (e.g., adaptive behaviors and cognitions) in a sample of parents and adolescents. Forty-three participants were recruited from four CF centers as part of a larger measurement study. Participants included 29 parents (72% mothers; 72% Caucasian) and 14 adolescents (ages 11-20, 64% female, 71% Caucasian). Participants completed semi-structured interviews to elicit barriers to adherence. However, facilitators of adherence naturally emerged, therefore indicating need for further exploration. Interviews were audiotaped, transcribed and content-analyzed in NVivo to identify those behaviors and beliefs that facilitated adherence, using a phenomenological analysis. Frequencies of these themes were tabulated. Nine themes emerged, with individual codes subsumed under each. Themes included social support, community support, organizational strategies, "intrinsic characteristics," combining treatments with pleasurable activity, flexibility, easier or faster treatment, prioritizing treatments, and negative effects of non-adherence. Results demonstrated the importance of identifying strategies that positively affect adherence. Interventions that are strength-focused, build on prior success, and utilize positive models generated by those who have successfully integrated CF treatments into their lives are more likely to be efficacious.

Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies.

BACKGROUND: Proteinuria leading to nephrotic syndrome is a rare adverse event arising from treatment with bevacizumab. There is limited evidence to guide the frequency and appropriate test for monitoring for proteinuria. The purpose of this study was to determine the prevalence and severity of proteinuria during bevacizumab administration to patients with gynecologic malignancies, and to evaluate risk factors associated with this toxicity; a secondary objective was to evaluate the cost of routine proteinuria monitoring to assess for opportunities of cost containment that could change clinical practice. METHODS: A retrospective chart review was performed at an academic gynecologic oncology clinic. Women over 18 years of age with a diagnosed gynecologic malignancy were evaluated for the development of proteinuria while receiving bevacizumab treatment as measured by a urine protein-to-creatinine ratio. Patient and disease-specific risk factors were evaluated using logistic regression to determine correlations of risk factors to development of proteinuria. Cost assessment was performed using institution-specific data for urine laboratory tests. RESULTS: Eighty-nine patients were identified, and the overall prevalence of proteinuria of any grade was 35%. The mean number of bevacizumab cycles was 13 (2-64 cycles). The majority of patients experienced grade 1 proteinuria (70%, 62 patients). Grade 3 proteinuria was observed in two patients (2%). There was a trend toward increased bevacizumab cycles associated with increased grade proteinuria (p = 0.053), however there were no factors significantly associated with the development of proteinuria as measured by urine protein-to-creatinine ratio. CONCLUSION: Monitoring of urine protein-to-creatinine ratios with each cycle may be unnecessary due to the low prevalence of grade 3 proteinuria observed. Additionally, urine protein-to-creatinine ratios may not provide adequate assessment of proteinuria toxicity associated with bevacizumab therapy. Potential cost savings opportunities for the institution can be realized with a cost-reductive monitoring algorithm that will utilize less costly laboratory techniques for patients at high risk of developing proteinuria.

Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74.

The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74 from human herpesvirus 8 are both constitutively active. We show that both receptors constitutively activate the transcription factors nuclear factor of activated T cells (NFAT) and cAMP response element binding protein (CREB) and that both pathways are modulated by their respective endogenous receptor ligands. By addition of specific pathway modulators against the G protein subunit Galphai, phospholipase C, protein kinase C, calcineurin, p38 MAP kinase, and MEK1, we find that the constitutive and ligand-dependent inductions are mediated by multiple yet similar pathways in both receptors. The NFAT and CREB transcription factors and their upstream activators are known inducers of host and virally encoded genes. We propose that the activity of these virally encoded chemokine receptors coordinates host and potentially viral gene expression similarly. As ORF74 is a known inducer of neoplasia, these findings may have important implications for cytomegalovirus-associated pathogenicity.

The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins.

Open reading frame 74 (ORF74) of many gamma(2)-herpesviruses encodes a CXC chemokine receptor. The molecular pharmacological profile of ORF74 from herpesvirus saimiri, ECRF3, is characterized here and compared with that of the well known ORF74 from human herpesvirus 8 (HHV8). The ECRF3 receptor bound the so-called ELR (Glu-Leu-Arg) CXC chemokines (125)I-CXCL1/GRO alpha, (125)I-CXCL6/GCP-2, and (125)I-CXCL8/interleukin-8 with high affinity; but in contrast to ORF74 from HHV8, it did not bind the non-ELR CXC chemokine (125)I-CXCL10/IP10. Interestingly, the B(max) value for CXCL6/GCP-2 was 3-fold higher than the capacity for maximal binding of CXCL1/GRO alpha to ECRF3 and 85-fold higher than that of CXCL8/interleukin-8, despite similar affinities. Like ORF74 from HHV8, ECRF3 activated a broad range of pathways (G(q), G(i), and G(12/13) as well as the cAMP response element-binding protein, NF-kappa B, NFAT, and serum response element transcription factors) in a ligand-regulated manner, with CXCL6/GCP-2 being the most potent and efficacious agonist. ECRF3 signaled constitutively through G(i) and G(12/13), but surprisingly not through G(q). At the level of transcription factor activation, the serum response element was activated constitutively by ECRF3, whereas cAMP response element-binding protein, NFAT, and NF-kappa B were only ligand-regulated. The maximal signaling capacities were similar for the two receptors; however, the ligand-regulated signaling was responsible for the major part of the total ECRF3 signaling and only for a minor part of the total HHV8 ORF74 signaling. The activation pattern of ECRF3 with constitutive activation of some (but not all) of the employed pathways has not been seen before in endogenous or virus-encoded chemokine receptors. The results suggest that the unique ligand selectivity of ECRF3 among ORF74 receptors could reflect differences in the cellular tropism of the gamma(2)-herpesviruses.