Etta J. Vinik

Effect of octreotide LAR dose and weight on octreotide blood levels in patients with neuroendocrine tumors

Objectives: Octreotide long acting repeatable (LAR) is widely used for the control of symptoms of functional neuroendocrine tumors. At doses of 30 mg/mo, up to 40% of patients require subcutaneous octreotide “rescue” and up to 40% of patients are given more than 30 mg of LAR/mo. Octreotide acetate binds to the sst2 receptor with an affinity (Kd) of approximately 1 × 10−9 mol/L (≅1000 pg/mL), but higher (≅10,000 pg/mL) concentrations of octreotide are required to completely saturate this receptor. Octreotide blood level measurement may be useful to guide LAR therapy in symptomatic patients or in patients who have tumor growth on traditional LAR doses. We hypothesize that LAR doses of 60 mg/mo will produce blood levels of 10,000 pg/mL or greater. At identical monthly LAR doses, patients with higher weights will require more medication to achieve similar plasma octreotide levels than individuals with lower body weights. Methods: Trough plasma, serum, urine, and saliva octreotide levels were obtained from 52 patients with carcinoid syndrome receiving 20 (n = 8), 30 (n = 19), or 60 mg LAR/mo (n = 10). Octreotide levels were determined by radioimmunoassay. Results: The mean ± SD plasma octreotide levels for patients receiving 20, 30, or 60 mg LAR/mo were 2518 ± 1020, 5241 ± 3004, and 10,925 ± 5330 pg/mL, respectively. Patient weight (kilograms) was inversely related to plasma octreotide levels. There was a significant correlation between plasma octreotide levels and octreotide levels measured in urine, saliva, and serum. Conclusions: Frequent measurement of octreotide levels may be useful to guide octreotide therapy in patients with poorly controlled symptoms or those patients experiencing tumor growth.

Quality of Life and Objective Measures of Diabetic Neuropathy in a Prospective Placebo-Controlled Trial of Ruboxistaurin and Topiramate

Background: The Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) is a validated comprehensive questionnaire designed to capture the entire spectrum of DN related to large fiber, small fiber, and autonomic neuropathy not captured in existing instruments. We aimed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers. Methods: Sixty patients with DN were allocated to treatment on ruboxistaurin (RBX) (n = 18), topiramate (TPX) (n = 18), or placebo (n = 18). QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period. Results: Total QOL scores improved significantly in the active treatment groups (RBX −9.56 ± 4.13; TPX −12.22 ± 2.76) but not in placebo (−5.56 ± 3.49). There were differences in nerve function improvement between treatments. Neurological symptom scores (NSS) improved with TPX from 5.5 (2.3) to 4.3 (0.65) (p = .007), sensory scores improved with TPX from 15.5 (1.79) to 8.3 (1.19) (p < .001), motor scores did not change, and sensory and motor impairment scores improved with TPX from 18.8 (2.15) to 12.1 (1.71) (p = .003). Total neuropathy scores (TNS) improved with TPX from 24.35 (2.61) to 16.35 (2.02) (p = .001). Neuropathy total symptom score−6 (NTSS−6) changes were significant for both treatments: RBX 4.38 (0.75) to 1.49 (0.38) (p < .001) and TPX 7.57 (1.3) to 4.26 (0.95) (p = .036). Changes in QOL-DN large fiber subscores correlated (Spearmans rank) significantly with changes in NTSS-6 (r = 0.55; p < .0001), NSS (r = 0.31; p < .04), neuropathy impairment score (NIS) (r = 0.35; p < .02), and TNS (r = 0.48; p < .0006). Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores (r = 0.40; p < .005) and intraepidermal nerve fiber density (IENFD) (r = −0.29; p < .05). Conclusion: Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures. The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains. Correlations were found between objective measures of neuropathy and total QOL, but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures.

Development of the Norfolk quality of life tool for assessing patients with neuroendocrine tumors.

Objective: To develop a disease-specific questionnaire for identifying domains having the greatest impact on the quality of life (QOL) of patients with neuroendocrine tumors (NETS). Methods: Patient responses to clinical interviews provided an 80-item initial pool for the development of the QOL-NET. The Delphi panel reviewed the items for content validity; the patient focus group reviewed the items for content/readability. Domains were derived from analysis of224 questionnaire responses. After principal components analysis, a scree plot suggested 7 domains. Exploratory factor analysis with forced 7-factor varimax rotation determined an ideal structure. Reliability/reproducibility was determined by test/retest 4 to 6 weeks apart. Logistic regression determined each domain score. Results: All 7 domains exhibited strong internal consistency (Cronbach &agr; = 0.86-0.97). Physical functioning contributed 40% of the total QOL score, followed by flushing, gastrointestinal symptoms, respiratory, cardiovascular, depression, and attitude domains. Most items loaded 0.40 or higher. No significant differences in test and retest scores. The mean values for the total QOL and 4 of 7 factor scores were significantly higher (P < 0.05) for NETS than controls: sensitivity was 71.4% and specificity was 69.6% to discriminate the NETS from the controls. Conclusions: We developed a 7-domain tool to determine QOL in NETS. Strong internal consistency exists within each domain of the QOL-NET. The QOL-NET is reliable and reproducible but weakly identifies NETS. Physical functioning is a greatest contributor to QOL impairment in NETS.Abbreviations: NETs - neuroendocrine tumors, NETS - patients with neuroendocrine tumors, QOL - quality of life, CgA - chromogranin A, 5-HIAA - 5-hydroxyindoleacetic acid

Falls Risk in Older Adults with Type 2 Diabetes

Falls are a major health issue for older adults, especially for those who develop type 2 diabetes who must contend with age-related declines in balance, muscle strength, and walking ability. They must also contend with health-related issues specific to the disease process. Given the general association between these variables and falls, being able to identify which measures negatively impact on balance in older diabetic persons is a critical step. Moreover, designing specific interventions to target these physiologic functions underlying balance and gait control will produce the greatest benefit for reducing falls in older persons with diabetes.

Norfolk QOL‐DN: validation of a patient reported outcome measure in transthyretin familial amyloid polyneuropathy

The Norfolk Quality of Life‐Diabetic Neuropathy (QOL‐DN) questionnaire is an instrument to assess QOL in diabetic polyneuropathy. The objective of this observational, cross‐sectional study in 61 patients with V30M transthyretin familial amyloid polyneuropathy (TTR‐FAP) and 16 healthy volunteers was to validate the Norfolk QOL‐DN for assessment of QOL in TTR‐FAP. Comparisons were conducted to identify the best items to discriminate disease stages and assess which individual Norfolk domains (symptoms, large fiber, small fiber, autonomic, and activities of daily living) would be most affected by disease stage. Analysis of individual items revealed a significant pattern of discrimination among disease stages (p < 0.001). Total QOL scores increased (indicating worsening) with duration of symptoms, with a steeper increase observed earlier in the course of disease. Significant correlations were observed between each Norfolk domain and other measures of neurological function. Limitations include cross‐sectional study design, low patient numbers in this rare disease, and the ordinal‐based character of the metric used; future areas to explore include item response theory approaches such as Rasch analysis. These results suggest the Norfolk QOL‐DN is a reliable indicator of the impact of disease severity on QOL in patients with TTR‐FAP.

German-Translated Norfolk Quality of Life (QOL-DN) Identifies the Same Factors as the English Version of the Tool and Discriminates Different Levels of Neuropathy Severity

Background: The development and validation of Norfolk QOL-DN, a fiber-specific, quality-of-life tool for diabetic neuropathy, was published previously (Part 1). This study (Part 2) defines the psychometric properties of the German-translated Norfolk QOL-DN in a large multicenter (96 sites) population with neuropathy ranging from minimal to severe, comparing them with those in the origina51 English/American version in a 30-center European/North American population with mild neuropathy; determines the power of the German-translated version in a five-staged diabetic peripheral neuropathy (DPN) German population to discriminate different levels of neuropathy severity; and establishes factors having the greatest impact on QOL. Methods: One hundred eighty-six German patients were assessed: asymptomatic of DPN (n = 40), symptomatic (n = 46), DN with foot-ulcer history (n = 32), DN with amputations (n = 22), and DN amputation history (n = 46). German-translated Norfolk QOL-DN was administered to 177 patients with staged DN complications. German-translated Norfolk QOL-DN data were compared with QOL-DN data from the European/American study of 379 mild neuropathy patients. Exploratory factor analysis assessed factor structure consistency in the translated instrument. Ordinal regression analysis (polytomous universal model) was used to evaluate the association between factor scores and complication stages. Results: The German translation identified the same five factors in more advanced neuropathy as in the English mild neuropathy population. Total QOL scores differed among each of the five neuropathy severity groups [analysis of variance p < 0.001, Tukey-Kramer post hoc, α = 0.05]. Two factors emerged as predictors of impaired QOL and disease severity: physical function/large fiber (Wald X2 = 6.188, p = 0.013) and activities of daily living (ADL)(Wald X2 = 9.098, p = 0.003). Conclusions: Norfolk QOL-DN discriminates levels of neuropathy within and between populations. Physical functioning and ADL are the most important determinants of QOL. Early occurrence of orthostasis suggests a redefinition of autonomic neuropathy to be more symptom inclusive.

Measuring the Relationship of Quality of Life and Health Status, Including Tumor Burden, Symptoms, and Biochemical Measures in Patients with Neuroendocrine Tumors

The measurement of health-related quality of life (HRQOL) has become essential for evaluating the impact of neuroendocrine tumors (NETs) on symptoms and social, emotional, psychological, and physical functioning of patients who harbor these tumors. This article describes instruments that have been developed to capture the spectrum of symptoms and the impact of the disease on their overall well-being. The authors discuss the importance of adequate sensitivity, specificity, and reproducibility and the value of psychometric factor analysis to explore the domains that embrace the manifestations of these tumors as well as aspects of the instruments that reflect tumor burden, biochemical, and hormonal status.

Pancreatic islet cell regeneration and growth

Most popular website for free eBooks. Platform for free books is a high quality resource for free PDF books.As of today we have many PDF for you to download for free. You have the option to browse by most popular titles, recent reviews, authors, titles, genres, languages and more.Books are available in several formats, and you can also check out ratings and reviews from other users.The apec2003.org is home to thousands of free audiobooks, including classics and out-of-print books.Look here for bestsellers, favorite classics and more.

Clinical measures in transthyretin familial amyloid polyneuropathy

This observational, cross‐sectional, single‐center study aimed to identify instruments capable of measuring disease progression in transthyretin familial amyloid polyneuropathy (TTR‐FAP).

Epidemiology of Diabetic Foot Ulcers and Amputations in Romania: Results of a Cross-Sectional Quality of Life Questionnaire Based Survey

This is a post hoc analysis of quality of life in diabetic neuropathy patients in a cross-sectional survey performed in 2012 in Romania, using the Norfolk QOL-DN in which 21,756 patients with self-reported diabetes were enrolled. This current analysis aims to expand research on the diabetic foot and to provide an update on the number of foot ulcers found in Romania. Of the 21,174 patients included in this analysis, 14.85% reported a history of foot ulcers and 3.60% reported an amputation. The percentage of neuropathy patients with foot ulcers increased with age; the lowest percentage was observed in the 20–29-year age group (6.62%) and the highest in the 80–89-year age group (17.68%). The highest number of amputations was reported in the 70–79-year age group (largest group). Compared to patients without foot ulcers, those with foot ulcers had significantly higher scores for total DN and all its subdomains translating to worse QOL (p < 0.001). This analysis showed a high rate of foot ulcers and amputations in Romanian diabetic patients. It underscores the need for implementation of effective screening and educational programs.