Self monitoring of blood glucose in type 2 diabetes:Longitudinal qualitative study of patients' perspectives

Objective: To explore views of patients with type 2 diabetes about self monitoring of blood glucose over time. Design: Longitudinal, qualitative study. Setting: Primary and secondary care settings across Lothian, Scotland. Participants: 18 patients with type 2 diabetes. Main outcome measures: Results from repeat in-depth interviews with patients over four years after clinical diagnosis. Results: Analysis revealed three main themes - the role of health professionals, interpreting readings and managing high values, and the ongoing role of blood glucose self monitoring. Self monitoring decreased over time, and health professionals' behaviour seemed crucial in this: participants interpreted doctors' focus on levels of haemoglobin A1c, and lack of perceived interest in meter readings, as indicating that self monitoring was not worth continuing. Some participants saw readings as a proxy measure of good and bad behaviour - with women especially, chastising themselves when readings were high. Some participants continued to find readings difficult to interpret, with uncertainty about how to respond to high readings. Reassurance and habit were key reasons for continuing. There was little indication that participants were using self monitoring to effect and maintain behaviour change. Conclusions: Clinical uncertainty about the efficacy and role of blood glucose self monitoring in patients with type 2 diabetes is mirrored in patients' own accounts. Patients tended not to act on their self monitoring results, in part because of a lack of education about the appropriate response to readings. Health professionals should be explicit about whether and when such patients should self monitor and how they should interpret and act upon the results, especially high readings.

Alzheimer's disease and vision: a proposed new diagnostic test

A potential non-invasive neurobiological test for Alzheimer's disease has been recently proposed and published. This test is likely to be of considerable interest to optometrists as it involves measurements of pupil dilation. This article decsribes some of the controversial issues surrounding the clinical diagnosis of Alzheimer's disease and discusses the advantages, limitations, and implications of the new test.

Large diameter optic nerve axon fibres in Alzheimer's disease

A variety of visual symptoms have been associated with Alzheimer's disease (AD). These include delays in flash visual evoked potentials which indicate a disruption of the integrity of the visual pathway. Examination of the visual cortex has revealed the presence of both senile plaques and neurofibrillary tangles. The purpose of this study was to determine whether there were differences in the number and/or size of optic nerve axons between AD patients and non-demented age-matched controls. Five optic nerves from AD patients and five from age-matched controls were embedded in epon resin and 1 micron sections prepared on a Reichert ultramicrotome. The sections were then stained in toluidine blue and examined at x400 magnification. The numbers of axons were counted in photographs of three fields taken at random from each section. To evaluate the axon diameters, 70 axons were chosen at random from each patient and measured using a calibrated eyepiece graticule. The total axon counts revealed no significant differences between the AD optic nerves and the age-matched controls. However, the frequency distribution of axon diameters was significantly different in the two groups. In particular, there were fewer larger diameter axons in patients with AD as previously reported. Degeneration of the large diameter axons suggests involvement of the magnocellular as opposed to the parvocellular pathways. Hence, there could be differences in visual performance of AD patients compared with normals which could be important in clinical diagnosis.

Patients' perceptions and experiences of taking oral glucose-lowering agents: a longitudinal qualitative study

Aims The aims of this study were to examine Type 2 diabetic patients' expectations, perceptions and experiences of oral glucose-lowering agents (OGLAs), including their reasons for taking/not taking these drugs as prescribed and to provide recommendations for developing interventions to improve OGLA adherence. Methods Longitudinal, qualitative study using repeat in-depth interviews with patients (n = 20) over 4 years following clinical diagnosis. Respondents were recruited from primary and secondary care settings across Lothian, Scotland, UK. Results Despite experiences of side-effects, dislikes and concerns about taking multiple drugs and a belief that OGLAs could themselves cause one's diabetes to progress, most respondents appeared motivated to take these drugs as prescribed. This motivation seemed to arise from respondents' experiences of taking OGLAs and observing them to 'work'. Some respondents described feeling better after taking OGLAs, others, typically those who were asymptomatic, used blood glucose self-monitoring and/or glycated haemoglobin results to observe and evidence the effects of their OGLAs. Most respondents demonstrated a 'passive' expectation that health professionals should be responsible for decisions about medications. Hence, non-adherence typically resulted from forgetfulness rather than ambivalence about either medication or consultation style. Respondent concern about OGLA's largely centred upon lack of knowledge about the medication and what to do when doses were missed. Conclusion The findings call for multifaceted strategies to promote adherence. These could include education to address misconceptions and advise patients how to respond to missed doses; reminders to help patients remember to take their drugs; and structured feedback on the impact of OGLAs on glycaemic control.

Type 2 diabetes and dog walking:patients' longitudinal perspectives about implementing and sustaining physical activity

Background - Physical activity is particularly important for people with type 2 diabetes, as evidence suggests that any reduction in sedentary time is good for metabolic health. Aim - To explore type 2 diabetes patients' talk about implementing and sustaining physical activity. Design of study - Longitudinal, qualitative study using repeat in-depth interviews with 20 patients over 4 years following clinical diagnosis. Setting - Patients were recruited from 16 general practices and three hospitals across Lothian, Scotland. Results - Discussion, and salience, of physical activity was marginal in patient accounts of their diabetes management. Patients claimed to have only received vague and non-specific guidance about physical activity from health professionals, and emphasised a perceived lack of interest and encouragement. Aside from walking, physical activities which were adopted tended to attenuate over time. Patients' accounts revealed how walking a dog assisted this kind of activity maintenance over time. Three main themes are highlighted in the analysis: 1) incidental walking; 2) incremental physical activity gains; and 3) augmenting physical activity maintenance. The problems arising from walking without a dog (for example, lack of motivation) are also examined. Conclusion - Asking patients about pet preferences might seem tangential to medical interactions. However, encouraging dog walking or identifying another interest that promotes a regular commitment to undertake physical activity may yield long-term health benefits.

Fabrication of high quality optical coherence tomography (OCT) calibration artefacts using femtosecond inscription

Optical coherence tomography (OCT) is a non-invasive three-dimensional imaging system that is capable of producing high resolution in-vivo images. OCT is approved for use in clinical trials in Japan, USA and Europe. For OCT to be used effectively in a clinical diagnosis, a method of standardisation is required to assess the performance across different systems. This standardisation can be implemented using highly accurate and reproducible artefacts for calibration at both installation and throughout the lifetime of a system. Femtosecond lasers can write highly reproducible and highly localised micro-structured calibration artefacts within a transparent media. We report on the fabrication of high quality OCT calibration artefacts in fused silica using a femtosecond laser. The calibration artefacts were written in fused silica due to its high purity and ability to withstand high energy femtosecond pulses. An Amplitude Systemes s-Pulse Yb:YAG femtosecond laser with an operating wavelength of 1026 nm was used to inscribe three dimensional patterns within the highly optically transmissive substrate. Four unique artefacts have been designed to measure a wide variety of parameters, including the points spread function (PSF), modulation transfer function (MTF), sensitivity, distortion and resolution - key parameters which define the performance of the OCT. The calibration artefacts have been characterised using an optical microscope and tested on a swept source OCT. The results demonstrate that the femtosecond laser inscribed artefacts have the potential of quantitatively and qualitatively validating the performance of any OCT system.

Visual hallucinations in the Parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes,viz., Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD) can be difficult. Visual hallucinations, however, are a chronic complication of some parkinsonian disorders and their presence may be a useful aid to diagnosis. The visual hallucinations in parkinsonism are often recurrent, well-formed, and detailed and occur in a significant proportion of cases of DLB and PD but are less common in PSP, MSA, and CBD. Hallucinations in PD often occur later in the disease and are complex, with flickering lights, and illusionary misconceptions often preceding the most common manifestation, viz., stereotypical colourful images. Hallucinations in DLB, however, are often present earlier in the disease and are similar to those in the 'misidentification syndromes', 'visual agnosias', and in 'delerium' but differ from those produced by hallucinogenic drugs such as LSD. Most typically in DLB, the hallucinations involve people or animals invading the patient's home but may also include inanimate objects and the appearance of writing on walls or ceilings. Visual hallucinations may involve a number of brain mechanisms including a change in the balance of neurotransmitter activity between the cholinergic and monoaminergic systems and may be a specific consequence of Lewy body (LB) pathology in brain stem nuclei. Ocular and retinal pathology may also contribute to hallucinations by reducing occipital stimulation. Hence, in patients with unclassifiable or with indeterminate parkinsonian symptoms, the presence of visual hallucinations should be regarded as a 'red flag' symptom indicating underlying Lewy body pathology and therefore, supporting a diagnosis of PD or DLB rather than PSP, MSA, or CBD. The presence of early visual hallucinations would support a diagnosis of DLB rather than PD. © 2013 Nova Science Publishers, Inc. All rights reserved.

Dissociable brain structural changes associated with predisposition, resilience, and disease expression in bipolar disorder

Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states. Copyright © 2009 Society for Neuroscience.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. © 2010 Cambridge University Press.

Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities

Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. © 2013 Elsevier Inc.

Corticobasal degeneration and dementia

Corticobasal degeneration is a rare, progressive neurodegenerative disorder which significantly impairs movement. The most common initial symptom is asymmetric limb clumsiness with or without accompanying rigidity or tremor. Subsequently, the disease progresses to affect gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Clinical diagnosis of the disorder is difficult as the symptoms resemble those of related neurodegenerative disorders. Histopathologically, there is widespread neuronal and glial pathology including tau-immunoreactive neuronal cytoplasmic inclusions, neuropil threads, oligodendroglial inclusions, astrocytic plaques, together with abnormally enlarged ‘ballooned’ neurons. Corticobasal degeneration has affinities both with the parkinsonian syndromes including Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy and with the fronto-temporal dementias. Treatment of corticobasal degeneration involves managing and reducing the effect of symptoms.

Does the Swedish Interactive Threshold Algorithm (SITA) accurately map visual field loss attributed to vigabatrin?

Background: Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. Methods: The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years∈±∈14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. Results: SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots, defect area and defect severity. Conclusions: Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients.

Increased risk of diabetes mellitus among persons with psychotic symptoms:results from the WHO World Health Survey

OBJECTIVE: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population. METHOD: Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004. RESULTS: An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999). CONCLUSIONS: Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.

Machine learning for large-scale wearable sensor data in Parkinson disease:concepts, promises, pitfalls, and futures

For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, “wearable,” sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that “learn” from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P=0.001 and P=0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P=0.0001, P=0.0001 and P=0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.