Angela C. Martino

Assessing Fidelity to an Intervention in a Randomized Controlled Trial to Improve Medication Adherence

Background:Behavioral intervention effectiveness in randomized controlled trials requires fidelity to the protocol. Fidelity assessment tools tailored to the intervention may strengthen intervention research. Objective:The aim of this study was to describe the assessment of fidelity to the structured intervention protocol in an examination of a nurse-delivered telephone intervention designed to improve medication adherence. Methods:Fidelity assessment included random selection and review of approximately 10% of the audiorecorded intervention sessions, stratified by interventionist and intervention session. Audiotapes were reviewed along with field notes for percentage of agreement, addressing whether key components were covered during the sessions. Visual analog scales were used to provide summary scores (0 = low to 5 = high) of interaction characteristics of the interventionists and participants with respect to engagement, demeanor, listening skills, attentiveness, and openness. Results:Four nurse interventionists delivered 871 structured intervention sessions to 113 participants. Three trained graduate student researchers assessed 131 intervention sessions. The mean percentage of agreement was 92.0% (±10.5%), meeting the criteria of 90% congruence with the intervention protocol. The mean interventionist interaction summary score was 4.5 ± 0.4, and the mean participant interaction summary score was 4.5 ± 0.4. Discussion:Overall, the interventionists successfully delivered the structured intervention content, with some variability in both the percentage of agreement and quality of interaction scores. Ongoing assessment aids in ensuring fidelity to study protocol and having reliable study results.

Pro‐inflammatory chemokine C‐C motif ligand 16 (CCL‐16) dysregulation in irritable bowel syndrome (IBS): a pilot study

Background  Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10–15% of people worldwide and has economic consequences in the United States of over

Sleep quality, BDNF genotype and gene expression in individuals with chronic abdominal pain

30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2 : 1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes.

Validation of the MOS-HIV as a Measure of Health-Related Quality of Life in Persons Living with HIV and Liver Disease

BackgroundSleep quality and genetics may contribute to the etiology of gastrointestinal (GI) symptoms. Individuals with impaired sleep often have a number of associated symptoms including chronic abdominal pain (CAP). The current study examined the interactions of brain-derived neurotrophic factor (BDNF) genotype with sleep quality in persons with CAP and healthy controls. In addition, associations among sleep quality, BDNF genotype, and gene expression were explored in the participants.MethodsData were collected on 59 participants (46% male, 61% White, 26.9 ± 6.6 years; CAP (n=19) and healthy controls (n=40)). Participants with CAP reported poorer sleep quality compared to healthy controls. BDNF genotype, categorized as Val/Val homozygotes versus the Met carriers.ResultsMicroarray analysis found twenty-four differentially expressed genes by a two-fold magnitude in participants with poor sleep quality compared to good sleep quality, and seven differentially expressed genes comparing CAP to healthy control. Three specific genes in the pain group overlap with sleep quality, including insulin-like growth factor 1 (IGF1), spermatogenesis associated serine-rich 2-like (SPATS2L), and immunoglobulin heavy constant gamma 1 or mu (IGHG1/// IGHM). BDNF was shown to have an interaction effect with GI and sleep symptoms.ConclusionsParticipants with CAP reported poor sleep quality compared to healthy controls. The role of the BDNF Met allele on differential gene expression was not distinct as main factor, but impacted interactions with sleep quality and CAP. Down-regulation of IGF1, SPATS2L, and IGHG1 expression may be related to the etiology of poor sleep quality and CAP.Trial registrationClinicaltrial.gov # NCT00824941

Letter: gender‐associated cell‐free microRNA profiles in non‐alcoholic fatty liver disease

Abstract Background. Management of human immunodeficiency virus (HIV) infection with potent antiretroviral medication has transformed HIV into a chronic condition and has shifted much of the burden of disease to co-morbid conditions such as liver disease (LD). LD alone has been shown to have a significant effect on ones health-related quality of life (HRQOL). Clinical evidence suggests that the growing number of persons living with HIV+LD may have a poorer HRQOL than persons with HIV without LD. To date, the widely accepted instrument to assess HRQOL, Medical Outcomes Study-HIV Health Survey (MOS-HIV), has not been evaluated for reliability and validity in a population of HIV-infected persons with LD. Methods. HRQOL was prospectively assessed using the MOS-HIV in a sample of 532 HIV-infected adults on antiretroviral therapy (n=305 HIV and n=227 HIV+LD). In addition, participants completed standardized questionnaires of sociodemographics and co-morbid conditions. Results. The psychometric properties of the MOS-HIV were supported by testing reliability and construct, convergent, discriminative, and predictive validity. The MOS-HIV discriminated between those persons living with HIV with and without LD on the basis of the physical function subscale scores (p=0.018). Conclusion. This study found the MOS-HIV valid and reliable instrument in persons with HIV+LD.

Symptom Status Predicts Patient Outcomes in Persons with HIV and Comorbid Liver Disease

Sirs; The study by Schwimmer et al. suggested the existence of a gender phenomenon in non-alcoholic fatty liver disease (NAFLD).1 First, the majority of children diagnosed with NAFLD were male. Second, NAFLD boys had significantly higher levels of serum alanine aminotransferases (ALT) than NAFLD girls. This ALT trend, however, was also seen in non-NAFLD children who were obese and overweight. Therefore, ALT alone was likely inadequate, if at all involved, in explaining the biology underlying the gender-skewed prevalence of NAFLD in their study and others.2 We have identified miRNA profiles in fasting serum from NAFLD patients (n = 5) recruited to the National Institutes of Health (NIH) Clinical Research Center between January 2009 and December 2012, compared with age and race matched controls with no NAFLD (n=5) using nCounter® (Nanostring). Male NAFLD patients also had significantly (P < 0.05) upregulated expressions of the hsa-miR-432-5p, hsa-miR-578, and hsa-miR-155-5p compared to female NAFLD patients (See Figure 1). The hsa-miR-432-5p and hsa-miR-301b levels were significantly (P < 0.05) higher in NAFLD male patients compared to male controls. In contrast, female NAFLD patients did not have significantly different miRNA levels compared to female controls. Thus, our pilot study showed empirical evidence for a male NAFLD-associated miRNA profile. Figure 1 MicroRNA Expressions in Male NAFLD versus Female NAFLD Patients. The male NAFLD-associated miRNA species found above are linked to inflammatory cytokines.3 Our findings also add to the literature suggesting the intriguing involvement of oestrogen and endocrine/metabolic signaling in NAFLD pathogenesis. In mice, oestrogen withdrawal leads to alterations in the peroxisome proliferator-activated receptor (PPAR) genes, which are the predicted targets of hsa-miR-142, which in turn is a target of hsa-miR-155. 4,5,6 We suggest that these male NAFLD miRNA profiles provide a starting point not only for the development of biomarkers for male NAFLD screening, but also for understanding the molecular basis of a gender-unique NAFLD pathogenesis.

Stress and Gene Expression of Individuals With Chronic Abdominal Pain

Persons living with human immunodeficiency virus (HIV) are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL) than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Clearys model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease) using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts), symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV) mental function), functional status (missed appointments and MOS-HIV physical function), general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition), and overall quality of life (QOL) (Satisfaction with Life Scale and MOS-HIV overall QOL). The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease.

The Gastrointestinal Pain Pointer: A Valid and Innovative Method to Assess Gastrointestinal Symptoms.

Background: Research examining the role of stress in gastrointestinal (GI) symptoms such as chronic abdominal pain (CAP) is controversial. The purpose of this study was to examine the expression of genes involved in metabolic stress and toxicity in men and women with high and low levels of perceived stress with and without CAP. Methods: Data and samples were collected and the expression of genes involved in metabolic stress and toxicity was analyzed in 26 individuals who had consented to participate in a natural history protocol. Subjects completed the 10-item Perceived Stress scale (PSS). Fasting participants’ peripheral whole blood was collected for proteomic and genomic studies. Polymerase chain reaction (PCR) array was used to analyze the expression of 84 key genes involved in human stress and toxicity plus 5 housekeeping genes. Plasma interleukin-1 alpha (IL-1α) protein was quantified via enzyme-linked immunosorbent assay (ELISA). Results: Interleukin-1 alpha gene (IL1A) was upregulated in females with high stress versus females with low stress by 2.58-fold (95% CI [0.88, 4.28]). IL1A was upregulated in participants with high stress and CAP versus those with low stress and CAP by 3.47-fold (95% CI [1.14, 5.80]). Conclusions: An upregulation of the gene coding the pro-inflammatory cytokine IL-1α suggests that the mechanism behind stress-related changes in GI symptoms is pro-inflammatory in nature. The results of this study contribute to the knowledge of the mechanism behind stress-related CAP symptoms and gender differences associated with these disorders.

Weight Phenotype Diagnostic Test Method: Body Mass Index or Body Fat Percent for Gene Expression

Abdominal pain is a chronic condition experienced by approximately 20% of individuals in the United States. The purpose of the study was to assess the validity of the Gastrointestinal Pain Pointer as a measure of abdominal pain intensity. A prospective longitudinal time-series study design was utilized. The sample included 93 outpatients (58.1% female). Participants met Rome III criteria for irritable bowel syndrome (n = 32) or were healthy controls (n = 61). The Gastrointestinal Pain Pointer, a new electronic pain assessment tool, was used to assess self-reported abdominal pain intensity among participants before and after ingestion of an intestinal permeability test solution across 11 time points over a 5-hour time period. The results were compared with the Short-Form McGill Pain Questionnaire. The Gastrointestinal Pain Pointer was found to be valid in the assessment of abdominal pain intensity. The tool is a novel and valid measure of abdominal pain intensity that enhances the ability for clinicians to better quantify, in real time, patient-related pain outcomes for both clinical care and research.

T1056 Validation of the Gastrointestinal Pain Pointer (GIPP) as a Measure of Symptom Severity in Persons With Abdominal Pain

Obesity continues increasing at epidemic levels worldwide, as does the number of genetic studies that focus on obesity. Body mass index (BMI) is often used to characterize weight phenotypes and obesity status due to its simplicity. Refined measurements of body composition may be needed to understand variations in gene expression. This study explores gene expression when individuals are characterized as overweight based on BMI versus body fat percent. Individuals were recruited to a natural history protocol at the National Institutes of Health. Twelve Caucasian participants with the highest and lowest BMI were included. Whole-body air displacement plethysmography was performed to calculate body fat percent, and BMI was calculated. Fasting whole blood was collected and RNA extracted. Quantitative real time PCR array was used to determine expression of 96 obesity related genes. The PCR array from participants with high BMI compared to low BMI showed dysregulation of four genes: peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), pro-opiomelanocortin (POMC), growth hormone secretagogue receptor (GHSR), and leptin (LEP), whereas participants with high body fat compared to low body fat showed dysregulation of one gene: PPARGC1A. This research showed differential gene expression and clinical indices depending on method of weight classification.