Medical conditions and depressive, anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder

OBJECTIVE: The objective of this study was to examine medical illness and anxiety, depressive, and somatic symptoms in older medical patients with generalized anxiety disorder (GAD). METHOD: A case-control study was designed and conducted in the University of California, San Diego (UCSD) Geriatrics Clinics. A total of fifty-four older medical patients with GAD and 54 matched controls participated. MEASUREMENTS: The measurements used for this study include: Brief Symptom Inventory-18, Mini International Neuropsychiatric Interview, and the Anxiety Disorders Interview Schedule. RESULTS: Older medical patients with GAD reported higher levels of somatic symptoms, anxiety, and depression than other older adults, as well as higher rates of diabetes and gastrointestinal conditions. In a multivariate model that included somatic symptoms, medical conditions, and depressive and anxiety symptoms, anxiety symptoms were the only significant predictors of GAD. CONCLUSION: These results suggest first, that older medical patients with GAD do not primarily express distress as somatic symptoms; second, that anxiety symptoms in geriatric patients should not be discounted as a byproduct of medical illness or depression; and third, that older adults with diabetes and gastrointestinal conditions may benefit from screening for anxiety.

Individual differences in the sensory perception of fats

Excessive consumption of dietary fat is acknowledged to be a widespread problem linked to a range of medical conditions. Despite this, little is known about the specific sensory appeal held by fats and no previous published research exists concerning human perception of non-textural taste qualities in fats. This research aimed to address whether a taste component can be found in sensory perception of pure fats. It also examined whether individual differences existed in human taste responses to fat, using both aggregated data analysis methods and multidimensional scaling. Results indicated that individuals were able to detect both the primary taste qualities of sweet, salty, sour and bitter in pure processed oils and reliably ascribe their own individually-generated taste labels, suggested that a taste component may be present in human responses to fat. Individual variation appeared to exist, both in the perception of given taste qualities and in perceived intensity and preferences. A number of factors were examined in relation to such individual differences in taste perception, including age, gender, genetic sensitivity to 6-n-propylthiouracil, body mass, dietary preferences and intake, dieting behaviours and restraint. Results revealed that, to varying extents, gender, age, sensitivity to 6-n-propylthiouracil, dietary preferences, habitual dietary intake and restraint all appeared to be related to individual variation in taste responses to fat. However, in general, these differences appeared to exist in the form of differing preferences and levels of intensity with which taste qualities detected in fat were perceived, as opposed to the perception of specific taste qualities being associated with given traits or states. Equally, each of these factors appeared to exert only a limited influence upon variation in sensory responses and thus the potential for using taste responses to fats as a marker for issues such as over-consumption, obesity or eating disorder is at present limited.

The clinical assessment of systemic hypertension in optometric practice

This thesis sets out to examine in detail the condition of systemic hypertension (high Blood Pressure) in relation to optometric practice in the United Kingdom. Systemic hypertension, which is asymptomatic in the early stages, is diagnosed from the Blood Pressure (BP) measurement recorded by a sphygmomanometer and/or from the complications that have developed in target organs. Optometric practice based surveys revealed that diagnosed systemic hypertension was the most prevalent cardiovascular medical condition (20.5%). Measurement of BP of patients in this sample revealed that if an optometrist included sphygmomanometry into the sight examination then at least one patient each day would be referred for suspect systemic hypertension. Optometric opinion felt that the measurement of BP in optometric practice would advance the profession, being appreciated by both patients and General Practitioners (GPs), but was felt to be an unnecessary routine procedure. The present sight examination for the systemic hypertensive is similar to that of the normotensive patient, but may involve an altered fundus examination and a visual field test. The GPs were in favour of optometric BP measurement and a future role in the share care management of the systemic hypertensive. The application of a new pictorial grading scale for the grading of vascular changes associated with pre-malignant systemic hypertension was found to be both accurate and reliable. Clinical trial of the grading scale in optometric practice found positive correlations between BP and increasing severity of the retinal vascular features. The subtle pre-malignant vascular changes require reliable accurate detection and analysis to assist in the management of the systemic hypertensive patient. Vessel width was shown to decrease with increasing age. Image analysis of the A/V ratio, arteriolar tortuosity and focal calibre changes revealed a positive correlation to the patient's BP (p<0.001). The retinal vasculature is relatively stable longitudinally with only minor changes in response to early disease states. Age and elevated BP increased a patient's risk of developing systemic medical conditions over a two-year period. The application of the pictorial grading scale to optometric practice and training the optometrist in the use of sphygmomanometry would improve the management of the systemic hypertensive patient in optometric practice. Future advances in image analysis hold substantial benefits for the detection and monitoring of subtle vascular changes associated with systemic hypertension.

The importance of detecting and managing comorbidities in people with dementia?

Dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which gradually interferes with social and occupational performance. It is a common worldwide condition with a significant impact on society. There are currently 36 million people worldwide with Alzheimer's disease (AD) and other dementias [1]. This is expected to more than double by 2030 (65 million) and reach ∼115 million in 2050, unless a major breakthrough is made. The worldwide societal costs were estimated at USD 604 billion in 2010 and rising [2]. To date research on the specific physical healthcare needs of people with dementia has been neglected. Yet, physical comorbidities are reported as common in people with dementia [3] and have been shown to lead to increased disability and reduced quality of life for the affected person and their carer [4]. Dementia is most frequently associated with older people who often present with other medical conditions, known as co-morbidities. Such co-morbidities include diabetes, chronic obstructive pulmonary disorder, musculoskeletal disorders and chronic cardiac failure and are common, 61% of people with …

Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented).

Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis:results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio-economic development of the country or the specific health care system.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Pharmacology and the safe prescribing of drugs

Understanding the pharmacological principles and safe use of drugs is just as important in surgical practice as in any other medical specialty. With an ageing population with often multiple comorbidities and medications, as well as an expanding list of new pharmacological treatments, it is important that surgeons understand the implications of therapeutic drugs on their daily practice. The increasing emphasis on high quality and safe patient care demands that doctors are aware of preventable adverse drug reactions (ADRs) and interactions, try to minimize the potential for medication errors, and consider the benefits and harms of medicines in their patients. This chapter examines these aspects from the view of surgical practice and expands on the implications of some of the most common medical conditions and drug classes in the perioperative period. The therapeutic care of surgical patients is obvious in many circumstances – for example, antibacterial prophylaxis, thromboprophylaxis, and postoperative analgesia. However, the careful examination of other drug therapies is often critical not only to the sustained treatment of the associated medical conditions but to the perioperative outcomes of patients undergoing surgery. The benefit–harm balance of many therapies may be fundamentally altered by the stress of an operation in one direction or the other; this is not a decision that should wait until the anaesthetist arrives for a preoperative assessment or one that should be left to junior medical or nursing staff on the ward.

Patient/carers' recollection of medicines related information from an out-patient clinic appointment

AIM: To identify what medicines related information children/young people or their parents/carers are able to recall following an out-patient clinic appointment. METHOD: A convenience sample of patients' prescribed at least one new long-term (>6 weeks) medicine were recruited from a single UK paediatric hospital out-patient pharmacy. A face-to-face semi-structured questionnaire was administered to participants when they presented with their prescription. The questionnaire included the following themes: names of the medicines, therapeutic indication, dose regimen, duration of treatment and adverse effects.The results were analysed using Microsoft Excel 2013. RESULTS: One hundred participants consented and were included in the study. One hundred and forty-five medicines were prescribed in total. Participants were able to recall the names of 96 (66%) medicines and were aware of the therapeutic indication for 142 (97.9%) medicines. The dose regimen was accurately described for 120 (82.8%) medicines with the duration of treatment known for 132 (91%). Participants mentioned that they had been advised about side effects for 44 (30.3%) medicines. Specific counselling points recommended by the BNFc1, were either omitted or not recalled by participants for the following systemic treatments: cetirizine (1), chlorphenamine (1), desmopressin (2), hydroxyzine (2), itraconazole (1), piroxicam (2), methotrexate (1), stiripentol (1) and topiramate (1). CONCLUSION: Following an out-patient consultation, where a new medicine is prescribed, children and their parents/carers are usually able to recall the indication, dose regimen and duration of treatment. Few were able to recall, or were told about, possible adverse effects. This may include some important drug specific effects that require vigilance during treatment.Patients, along with families and carers, should be involved in the decision to prescribe a medicine.2 This includes a discussion about the benefits of the medicine on the patient's condition and possible adverse effects.2 Treatment side effects have been shown to be a factor in treatment non-adherence in paediatric long-term medical conditions.3 Practitioners should explain to patients, and their family members or carers where appropriate, how to identify and report medicines-related patient safety incidents.4 However, this study suggests that medical staff may not be comfortable discussing the adverse effects of medicines with patients or their parents/carers.Further research in to the shared decision making process in the paediatric out-patient clinic when a new long-term medicine is prescribed is required to further support medicines adherence and the patient safety agenda.

Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers

The use of human mesenchymal stem cells (hMSCs) in regenerative medicine is a potential major advance for the treatment of many medical conditions, especially with the use of allogeneic therapies where the cells from a single donor can be used to treat ailments in many patients. Such cells must be grown attached to surfaces and for large scale production, it is shown that stirred bioreactors containing ~200 μm particles (microcarriers) can provide such a surface. It is also shown that the just suspended condition, agitator speed NJS, provides a satisfactory condition for cell growth by minimizing the specific energy dissipation rate, εT, in the bioreactor whilst still meeting the oxygen demand of the cells. For the cells to be used for therapeutic purposes, they must be detached from the microcarriers before being cryopreserved. A strategy based on a short period (~7 min) of very high εT, based on theories of secondary nucleation, is effective at removing >99% cells. Once removed, the cells are smaller than the Kolmogorov scale of turbulence and hence not damaged. This approach is shown to be successful for culture and detachment in 4 types of stirred bioreactors from 15 mL to 5 L.

Synthesis and characterisation of hydrogel polymers for medical applications

A fundamental if poorly understood problem that hydrogels display is the tendency of these contact lens materials to dehydrate, causing certain complications of the corneal epithelium. However, recent studies have indicated that the evaporation rate of water from different hydrogel lenses is the same and the severity of conditions such as corneal staining is controlled by the states of water in the material. A study was therefore undertaken which concluded that increased corneal desiccating staining occurred as the proportion of water existing in the bound state decreased. The possibility of using dehydrated hydrogels as packaging materials with desiccating properties has also been investigated. As hydrogels have a high affinity for water they have adequate ability to function as a moisture scavenger in an enclosed atmosphere. It was concluded that this ability is maximised by a high total water content and an increase in the proportion of this water existing in the bound state for the material when it is fully hydrated. N-vinyl pyrrolidone has a low reactivity in vinyl polymerisation reactions which results in polymers with local domains of the same chemical type which can lead to deposition. As contact lenses comprising of this monomer are susceptible to deposition, a monomer with a higher reactivity in vinyl polymerisations is acryloylmorpholine and its incorporation in favour of NVP is encouraged. Unfortunately a large proportion of high EWC hydrogels are mechanically weak and attempts to increase this property by increasing hydrophobicity or cross-linking results in a decrease in EWC. Monomers with the potential to carry a positive charge were incorporated into a high EWC, AMO-HEMA copolymer and the physical properties were investigated. Although EWC increased, mechanical properties decreased only slightly. Therefore simultaneous incorporation of a positively charged monomer and a negatively charged monomer was investigated. The resulting copolymers showed increased water content and increased initial modulus. A technique for measuring the coefficient of friction of contact lenses during lubrication has been developed.

The use of driven equilibrium conditions in the measurement of NMR relaxation times

The further development of the use of NMR relaxation times in chemical, biological and medical research has perhaps been curtailed by the length of time these measurements often take. The DESPOT (Driven Equilibrium Single Pulse Observation of T1) method has been developed, which reduces the time required to make a T1 measurement by a factor of up to 100. The technique has been studied extensively herein and the thesis contains recommendations for its successful experimental application. Modified DESPOT type equations for use when T2 relaxation is incomplete or where off-resonance effects are thought to be significant are also presented. A recently reported application of the DESPOT technique to MR imaging gave good initial results but suffered from the fact that the images were derived from spin systems that were not driven to equilibrium. An approach which allows equilibrium to be obtained with only one non-acquisition sequence is presented herein and should prove invaluable in variable contrast imaging. A DESPOT type approach has also been successfully applied to the measurement of T1. T_1's can be measured, using this approach significantly faster than by the use of the classical method. The new method also provides a value for T1 simultaneously and therefore the technique should prove valuable in intermediate energy barrier chemical exchange studies. The method also gives rise to the possibility of obtaining simultaneous T1 and T1 MR images. The DESPOT technique depends on rapid multipulsing at nutation angles, normally less than 90^o. Work in this area has highlighted the possible time saving for spectral acquisition over the classical technique (90^o-5T_1)_n. A new method based on these principles has been developed which permits the rapid multipulsing of samples to give T_1 and M_0 ratio information. The time needed, however, is only slightly longer than would be required to determine the M_0 ratio alone using the classical technique. In ^1H decoupled ^13C spectroscopy the method also gives nOe ratio information for the individual absorptions in the spectrum.

Anticholinergic medication use and cognitive impairment in the older population:the Medical Research Council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=-0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.

The effect of the environment on the mechanical properties of medical grade silicones

Silicone spacers have been in use as replacement joints in the human hand for over 30 years. Since they were first used there has been a number of designs all of which have had problems with fracture. This may be due to a defect in the material caused during implantation, or by bony intrusions within the arthritic hand after implantation. The aim of this research was to investigate the effect of the environment on the mechanical properties of medical grade silicones used for human implantation. The materials were subjected to static tensile testing after various forms of ageing. The environmental conditions included temperatures of 37 and 80°C and the environments of Ringer's solution, distilled water, and air. The environmental conditions employed resulted in reduced mechanical strength with ageing time of the silicones. This research supports the view that failure of silicone implants in the hand could be partly attributed to the effects of environmental ageing of the material.