Assessing the Impact of Growth Hormone Deficiency (GHD) in Adults: Interpreting Change of the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD).

BACKGROUND: This study's purpose was to assess the minimal important difference (MID) for the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD), a patient-reported outcome measure assessing growth hormone deficiency (GHD) impacts. The measure was demonstrated to have adequate psychometric measurement properties, and be reliable and valid. For scores to be interpretable, the TRIM-AGHD must be responsive to treatment benefit and the MID in scores quantified. METHODS: A prospective, non-interventional, observational, clinic-based survey study of naïve-to-treatment adult GHD patients (N = 98) was conducted. Key assessments were at baseline and follow-up (between 4 and approximately 8 weeks), with weekly telephone monitoring post-baseline (last n = 34 patients). Responsiveness was evaluated using the effect size of change scores from baseline to follow-up. MID estimates were derived from distribution-based (half standard deviation [0.5 SD], standard error of measurement [SEm]) and anchor-based methods (patient global rating of change [PGRC]) using change scores from baseline to initial report of minimal improvement in GHD severity. Findings from each method were converged to establish an acceptable MID. RESULTS: Patients were mean age 49.7 years, 65.6% female, and 76.0% Caucasian. The TRIM-AGHD was highly responsive to treatment with the total score effect size being 1.38. For the total score, the 0.5 SD was 8.09 and the SEm was 2.66. The difference found using the PGRC was 20.43. The converged MID value for the total score was 10 points. CONCLUSIONS: The TRIM-AGHD is a highly responsive measure assessing AGHD treatment impacts. A 10-point change score is considered a clinically meaningful improvement.

Impact of adult growth hormone deficiency on daily functioning and well-being.

BACKGROUND: Adult Growth Hormone Deficiency (AGHD) is a debilitating condition resulting from tumors, pituitary surgery, radiation of the head, head injury, or hypothalamic-pituitary disease. This qualitative study was conducted to better understand the multi-faceted impacts and treatment effects of GHD on adult patients' daily lives.Seven focus groups and four telephone interviews were conducted in three countries. Eligible AGHD patients were age 22 or older who had started and stopped growth hormone treatment at least once as an adult. Transcripts were analyzed thematically. RESULTS: Thirty-nine patients were interviewed; majority etiology was pituitary disease or tumor (62%). Thirty-four patients (87%) were currently on growth hormone replacement therapy; therapy initiation mean age was 43 years. Analysis identified five domains of disease impact: 1) Psychological Health--changed body or self-image and negative emotional impacts; 2) Physical Health--problems with sleep/fatigue, sex drive, weight gain, hair, skin, muscle/bone loss; 3) Cognition--concentration or memory trouble; 4) Energy Loss and its negative impacts (productivity, exercise, chores, socialization, or motivation); and 5) Treatment Effect--treatment enhances quality of life, enabling patients to increase effort (exercise, chores, or work improvements). Energy and sleep are improved. Saturation of themes was reached after the sixth focus group. A conceptual model of GHD disease impacts was developed. CONCLUSIONS: Untreated AGHD has significant negative impacts for patients, which treatment often improves. It is important for clinicians and researchers to understand these multiple impacts so that they can address them in individualized treatment plans and incorporate them when assessing treatment outcomes.

Assessing the impact of growth hormone deficiency and treatment in adults: development of a new disease-specific measure.

CONTEXT: Approximately 50 000 adults in the United States are diagnosed with GH deficiency, which has negative impacts on cognitive functioning, psychological well-being, and quality of life. OBJECTIVE: This paper presents development and validation of a patient-reported outcome measure (PRO), the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD). The TRIM-AGHD was developed to measure the impact of GH deficiency and its treatment. DESIGN AND SETTINGS: The development and validation of the TRIM-AGHD was conducted according to the Food and Drug Administration guidance on the development of PROs. Concept elicitation, conducted in three countries included interviews with patients, clinical experts, and literature review. Qualitative data were analyzed based on grounded theory principles, and draft items were cognitively debriefed. The measure underwent psychometric validation in a US clinic-based population. An a priori statistical analysis plan included assessment of the measurement model, reliability, and validity. Item functioning was reviewed using item response theory analyses. PATIENTS OR OTHER PARTICIPANTS: Forty-eight patients and six clinical experts participated in concept elicitation and 169 patients completed the validation study. MAIN OUTCOME MEASURE: TRIM-AGHD was measured. RESULTS: Factor analysis resulted in four domains: energy level, physical health, emotional health, and cognitive ability. The item response theory confirmed adequate item fit and placement within their domain. Internal consistency ranged from 0.82 to 0.95 and test-retest ranged from 0.80 to 0.92. All prespecified hypotheses for convergent validity and all but two for discriminant validity were met. CONCLUSIONS: The final 26-item TRIM-AGHD can be considered a reliable and valid PRO of the impact of disease and treatment for adult GH deficiency.

Post-prandial glucose and diabetic complications: systematic review of observational studies.

Post-prandial hyperglycemia is considered a relevant therapeutic target in type 2 diabetic patients, and it could represent per se an independent risk factor for diabetic complications. Aim of the present systematic review is to collect and summarize evidence from observational studies on the relationship between post-prandial glucose (PPG) and cardiovascular or microvascular disease in patients with diabetes. An extensive search of Medline (any date up to December 31, 2010) was performed for all longitudinal epidemiological studies with a cohort design. The following endpoints were taken into consideration: death from any cause; cardiovascular death and micro- and macrovascular complications. The number of epidemiological studies assessing the relationship between PPG and microvascular or cardiovascular disease in subjects with diabetes is surprisingly scarce. In fact, of the 391 retrieved studies, only 8 fulfilled the inclusion criteria. Most of those investigations enrolled small samples, which in many instances were not representative of the general population. Furthermore, the assessment of PPG varied widely across studies. These considerations prevent any formal meta-analysis. Despite this, the few available studies show that higher PPG is associated with increased all-cause and cardiovascular death, incidence of major cardiovascular events (including myocardial infarction and stroke), and progression of diabetic retinopathy.