Is Self-Determined Motivation a Useful Agent to Overcome Perceived Exercise Barriers in Patients With Type 2 Diabetes Mellitus?

Background: Devising a program to increase physical activity (PA)/exercise behavior in patients with type 2 diabetes mellitus (T2DM) can meet with limited effectiveness in real-world settings because of the variety of barriers to PA/exercise that individuals need to overcome. An alternative approach is to explore whether targeting motivation as a facilitator may be effective to increase PA/exercise. This study aimed to understand attitudes toward perceived barriers to PA/exercise by examining individual levels of motivation, grounded on self-determination theory, in patients with T2DM. Methods: This study used an integrated approach combining qualitative and quantitative analysis. Sixteen patients with T2DM were grouped (n = 8 for each group) into either a higher self-motivation (HSM) or lower self-motivation (LSM) group via the Relative Autonomy Index. Thematic and deductive analysis were used to identify attitudes based on ten preconceived barrier themes: apathy, dislike, no priority, lack of support, health problems, lack of knowledge, unfavorable environment, tiredness, lack of time, and financial constraints. Quantitative analysis was to assess statistical differences in the volume of PA/exercise across the two groups, and a mixed-methods analysis was employed to highlight unique cases. Results: Patients in the HSM group expressed positive attitudes toward barriers to PA/exercise, while patients in the LSM group expressed a greater degree of hindrance. Although regular PA/exercise is necessary for T2DM management, patients with LSM considered PA/exercise a lesser priority displaying negative attitudes such as apathy and dislike. Conversely, patients with HSM placed greater emphasis on the benefits of PA/exercise regardless of apathy and dislike. Lack of time and health problems were commonly reported in both groups. The volume of PA/exercise corresponded to motivation levels, but there were some unique cases which arose from active commuting habits and severe health problems. Conclusion: These findings provide insights on how attitudes to perceived barriers to PA/exercise differ by levels of motivation. One insight was that examining motivation should be an essential consideration when designing practical strategies to overcome PA/exercise barriers in patients with T2DM. Lack of time and health problems exist regardless of motivation levels. Future research requires a tailored approach to managing barriers to PA/exercise in patients with T2DM

Smartphone apps for calculating insulin dose: a systematic assessment

Background: Medical apps are widely available, increasingly used by patients and clinicians, and are being actively promoted for use in routine care. However, there is little systematic evidence exploring possible risks associated with apps intended for patient use. Because self-medication errors are a recognized source of avoidable harm, apps that affect medication use, such as dose calculators, deserve particular scrutiny. We explored the accuracy and clinical suitability of apps for calculating medication doses, focusing on insulin calculators for patients with diabetes as a representative use for a prevalent long-term condition. Methods: We performed a systematic assessment of all English-language rapid/short-acting insulin dose calculators available for iOS and Android. Results: Searches identified 46 calculators that performed simple mathematical operations using planned carbohydrate intake and measured blood glucose. While 59% (n = 27/46) of apps included a clinical disclaimer, only 30% (n = 14/46) documented the calculation formula. 91% (n = 42/46) lacked numeric input validation, 59% (n = 27/46) allowed calculation when one or more values were missing, 48% (n = 22/46) used ambiguous terminology, 9% (n = 4/46) did not use adequate numeric precision and 4% (n = 2/46) did not store parameters faithfully. 67% (n = 31/46) of apps carried a risk of inappropriate output dose recommendation that either violated basic clinical assumptions (48%, n = 22/46) or did not match a stated formula (14%, n = 3/21) or correctly update in response to changing user inputs (37%, n = 17/46). Only one app, for iOS, was issue-free according to our criteria. No significant differences were observed in issue prevalence by payment model or platform. Conclusions: The majority of insulin dose calculator apps provide no protection against, and may actively contribute to, incorrect or inappropriate dose recommendations that put current users at risk of both catastrophic overdose and more subtle harms resulting from suboptimal glucose control. Healthcare professionals should exercise substantial caution in recommending unregulated dose calculators to patients and address app safety as part of self-management education. The prevalence of errors attributable to incorrect interpretation of medical principles underlines the importance of clinical input during app design. Systemic issues affecting the safety and suitability of higher-risk apps may require coordinated surveillance and action at national and international levels involving regulators, health agencies and app stores.Published versio

Alterations in SAMD9, AHSG, FRG2C, and FGFR4 Genes in a Case of Late-Onset Massive Tumoral Calcinosis

Background/Objective: Tumoral calcinosis (TC) is a rare, arcane, and debilitating disorder of phosphate metabolism manifesting as hard masses in soft tissues. Primary hyperphosphatemic TC has been shown to be caused by pathogenic variants in the genes encoding FGF23, GALNT3, and KLOTHO. We report a case of massive TC mechanistically associated with phosphatonin resistance associated with heterozygous alterations in the sterile alfa motif domain–containing protein-9 gene (SAMD9), alfa 2-Heremans-Schmid glycoprotein gene (AHSG), FSHD region gene 2-family member-C gene (FRG2C), and fibroblast growth factor receptor-4 gene (FGFR4). Case Report: A middle-aged Malay woman with systemic sclerosis presented with painful hard lumps of her axillae, lower limbs, and external genitalia. She was eucalcemic with mild hyperphosphatemia associated with reduced urinary phosphate excretion. Magnetic resonance imaging revealed calcified soft tissue masses. Paradoxically, the serum intact FGF23 level increased to 89.6 pg/mL, corroborated by Western blots, which also showed overexpression of sFRP4 and MEPE, consistent with phosphatonin resistance. Discussion: Whole genome sequencing identified 2 heterozygous alterations (p.A454T and p.T479M) in SAMD9, 2 heterozygous alterations (p.M248T and p.S256T) in AHSG, a frameshift alteration (p.Arg156fs) in FRG2C, and a heterozygous alteration (p.G388R) in FGFR4, all of which are associated with calcinosis. Nonsynonymous alterations of FRP4 and MEPE were also detected. Conclusion: This highlights that the simultaneous occurrence of alterations in several genes critical in phosphate homeostasis may trigger massive TC despite their heterozygosity. These findings should prompt functional studies in cell and animal models to reveal mechanistic insights in the pathogenesis of such crippling mineralization disorders

Paraneoplastic secretion of multiple phosphatonins from a deep fibrous histiocytoma causing oncogenic osteomalacia

Context: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. Case Description: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. Conclusion: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia

Determinants of Health-Related Quality of Life (HRQoL) in the Multiethnic Singapore Population - A National Cohort Study

Background: HRQoL is an important outcome to guide and promote healthcare. Clinical and socioeconomic factors may influence HRQoL according to ethnicity. Methodology: A multiethnic cross-sectional national cohort (N = 7198) of the Singapore general population consisting of Chinese (N = 4873), Malay (N = 1167) and Indian (N = 1158) adults were evaluated using measures of HRQoL (SF-36 version 2), family functioning, health behaviours and clinical/laboratory assessments. Multiple regression analyses were performed to identify determinants of physical and mental HRQoL in the overall population and their potential differential effects by ethnicity. No a priori hypotheses were formulated so all interaction effects were explored. Principal Findings: HRQoL levels differed between ethnic groups. Chinese respondents had higher physical HRQoL (PCS) than Indian and Malay participants (p<0.001) whereas mental HRQoL (MCS) was higher in Malay relative to Chinese participants (p<0.001). Regressions models explained 17.1% and 14.6% of variance in PCS and MCS respectively with comorbid burden, income and employment being associated with lower HRQoL. Age and family were associated only with MCS. The effects of gender, stroke and musculoskeletal conditions on PCS varied by ethnicity, suggesting non-uniform patterns of association for Chinese, Malay and Indian individuals. Conclusions: Differences in HRQoL levels and determinants of HRQoL among ethnic groups underscore the need to better or differentially target population segments to promote well-being. More work is needed to explore HRQoL and wellness in relation to ethnicity

The role of infrared thermography (IRT) and magnetic resonance imaging (MRI) in brown fat evaluation and their application to study the effect of thyroid status on brown fat activity and white fat partitioning

My proposed research falls under the field of Metabolic Physiology. Metabolism, being the sum total of all anabolic and catabolic activities of cells and organs determine the net energy balance of all vertebrates. The complex metabolic networks that fuel life itself are functionally a downstream effector layer governed by regulatory feedback loops including those constituting a part of the endocrine system. Among the wide range of hormones controlling intermediary metabolism such as insulin, glucagon, cortisol and catecholamines, the homeostatic equilibrium established by thyroid hormones appear to be a key driver of metabolic rate which influences the boundary between health and disease. Recent work revealed that the potent thermogenic effect of thyroid hormones is mediated by brown adipose tissue (BAT). Dissecting the physiological mechanisms and metabolic pathways of this process is a very active field of investigation that is interdisciplinary in nature and requires a variety of approaches. Research in this field of metabolic physiology has allowed me to explore and interrogate the effect of thyroid status on brown fat thermogenesis, metabolic rate, fat distribution, body composition and weight control. The clinical significance of deciphering the relationship between thyroid status, brown fat activation and the browning of white fat lies in unravelling the possibility for optimisation of health and quality of life of numerous thyroid patients and offering insights in augmenting energy expenditure as a strategy to counter the present epidemic of obesity and diabetes confronting the world. An overarching goal is that of developing and validating infrared thermography (IRT) that incorporates a novel image processing algorithm for heat power efflux quantification and also establishing fat fraction MRI for precise brown fat volumetric measurement to address my hypotheses and facilitate studies of brown fat. The quest to better understand the inter-relationships above essentially form much of my research work and endeavor that is detailed in the pages of this PhD thesis.Doctor of Philosoph

General Error Analysis in the Relationship between Free Thyroxine and Thyrotropin and Its Clinical Relevance

Background. This treatise investigates error sources in measurements applicable to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic set point computation. The hypothalamus-pituitary transfer characteristic (HP curve) describes the relationship between plasma free thyroxine [FT4] and thyrotropin [TSH]. Objective. We define the origin, types, causes, and effects of errors that are commonly encountered in TFT measurements and examine how we can interpret these to construct a reliable HP function for set point establishment. Design and Methods. The error sources in the clinical measurement procedures are identified and analyzed in relation to the constructed HP model. Results. The main sources of measurement and interpretation uncertainties are (1) diurnal variations in [TSH], (2) TFT measurement variations influenced by timing of thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4] (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4] range, (5) memory effects (rate-independent hysteresis effect). Conclusions. When the main uncertainties in thyroid function tests (TFT) are identified and analyzed, we can find the most acceptable model space with which we can construct the best HP function and the related set point area

Interconversion of Plasma Free Thyroxine Values from Assay Platforms with Different Reference Intervals Using Linear Transformation Methods

Clinicians often encounter thyroid function tests (TFT) comprising serum/plasma free thyroxine (FT4) and thyroid stimulating hormone (TSH) measured using different assay platforms during the course of follow-up evaluations which complicates reliable comparison and interpretation of TFT changes. Although interconversion between concentration units is straightforward, the validity of interconversion of FT4/TSH values from one assay platform to another with different reference intervals remains questionable. This study aims to establish an accurate and reliable methodology of interconverting FT4 by any laboratory to an equivalent FT4 value scaled to a reference range of interest via linear transformation methods. As a proof-of-concept, FT4 was simultaneously assayed by direct analog immunoassay, tandem mass spectrometry and equilibrium dialysis. Both linear and piecewise linear transformations proved relatively accurate for FT4 inter-scale conversion. Linear transformation performs better when FT4 are converted from a more accurate to a less accurate assay platform. The converse is true, whereby piecewise linear transformation is superior to linear transformation when converting values from a less accurate method to a more robust assay platform. Such transformations can potentially apply to other biochemical analytes scale conversions, including TSH. This aids interpretation of TFT trends while monitoring the treatment of patients with thyroid disorders