James Frith

Newcastle University | NCL · Institute of Cellular Medicine

Objectives Fatigue is one of the most important symptoms needing improvement in Primary Sjögren's syndrome (PSS). Previous data from our group suggest that noninvasive stimulation of the vagus nerve (nVNS) may improve symptoms of fatigue. This experimental medicine study uses the gammaCore device (electroCore) and a sham device to investigate the r...

Orthostatic hypotension (OH) is a very common and debilitating condition, characterised by a significant drop in blood pressure (BP) on standing upright. Multiple neuro-cardiovascular mechanisms should stabilise BP when moving to an upright position but in OH, BP decline results from dysfunction of neuro-cardiovascular mechanisms. With the advent o...

Background A postural blood pressure assessment is required to diagnose Orthostatic Hypotension. With increasing remote consultations, alternative methods of performing postural blood pressure assessment are required. Objective Determine whether postural blood pressure measurement at home, without a clinician, is reliable, feasible and safe. Desi...

Introduction The Newcastle upon Tyne Hospitals NHS Foundation Trust’s Older People’s Medicine (OPM) department includes six inpatient wards. It was hypothesized that an increasing prevalence of inpatient frailty would be associated with increased length of stay. Method Data were collected on OPM wards, on a single day of February 2020 and July 202...

Objectives: Autonomic symptoms are a common feature of the synucleinopathies, and may be a distinguishing feature of prodromal Lewy body disease. We aimed to assess whether the cognitive prodrome of dementia with Lewy bodies, mild cognitive impairment (MCI) with Lewy bodies (MCI-LB), would have more severe reported autonomic symptoms than cognitiv...

Objectives: Orthostatic hypotension is a common feature of normal ageing, and age-related neurodegenerative diseases, in particular the synucleinopathies including dementia with Lewy bodies. Orthostatic hypotension and other abnormal cardiovascular responses may be early markers of Lewy body disease. We aimed to assess whether abnormal blood press...

Purpose Non-pharmacologic therapies are a safe and effective treatment for orthostatic hypotension (OH) in older adults. However, adherence to non-drug therapies is challenging and may require specific behaviour change approaches to promote uptake and adherence. The study aim is to identify specific behavioural change techniques to promote uptake a...

Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caff...

Topics for DTB review articles are selected by DTB’s editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.

Background: orthostatic hypotension (OH) is highly prevalent in older populations and is associated with reduced quality of life and increased mortality. Although non-pharmacologic therapies are recommended first-line, evidence for their use is lacking. Objective: determine the efficacy of combination non-pharmacologic therapy for OH in older pe...

Introduction First-line treatment for OH is typically with non-pharmacologic therapy. However, the current evidence base is poor, particularly in older people. Aim Determine the safety, efficacy and acceptability of single and combination therapies for OH in older people. Methods A three-stage, mixed-methods study consisting of a phase 2 efficacy...

In the UK each year there are over 250,000 emergency hospital admissions due to falls, costing £4.4 billion for falls-related fractures alone. To help reduce pressure on the NHS, the UK Fire Service are now providing home safety checks which include a review of falls hazards, provision of falls and loneliness advice and in some cases, immediate pro...

Objectives Initial orthostatic hypotension (IOH) is defined as a reduction in systolic or diastolic blood pressure (1) of 40 mmHg or 20 mmHg or greater within 15 seconds of standing. However, little is known about the characteristics of individuals with IOH and its relevance in the older population. The present study aimed to determine factors asso...

Background It is considered well-established that orthostatic hypotension (OH) is associated with falls, population-based studies have found that a large proportion of community-dwelling older adults fulfill the criteria for OH without experiencing falls. It is therefore postulated that older individuals with OH may only experience fall if cerebral...

Purpose Consensus definitions currently define initial orthostatic hypotension (IOH) as ≥ 40 mmHg systolic (SBP) or ≥ 20 mmHg in diastolic blood pressure (DBP) reductions within 15 s of standing, while classical orthostatic hypotension (COH) is defined as a sustained reduction ≥ 20 mmHg SBP or ≥ 10 mmHg SBP within 3 min of standing. The clinical re...

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterised by low platelet counts and increased bleeding risk. In 2009, two cross‐sectional studies determined that fatigue and cognitive impairment (CI) were common in ITP. Here, we report the results from a longitudinal study of 34 people with ITP. Fatigue severity remained unchan...

Academic geriatric medicine activity lags behind the scale of clinical activity in the specialty. A meeting of UK academic geriatricians was convened in March 2018 to consider causes and solutions to this problem. The meeting highlighted a lack of research-active clinicians, a perception that research is not central to the practice of geriatric med...

Background Orthostatic hypotension (OH) is highly prevalent in older populations. It is associated with a reduced quality of life and an increased risk of dementia, stroke and death. Non-pharmalogical therapies are the recommended first-line therapy and are preferred to drug treatments by older people. However, uptake and adherence is low and evide...

Is Impaired Cerebral Autoregulation Associated with Falls in Older Persons with Orthostatic Hypotension? Saedon NI1,2, Goh CH 1,2, Frith J3,4, Ahmad WAW5, Tan KS6, Kamaruzzaman SB1,2, Tan MP1,2 1. Ageing and Age-Associated Disorders Research Group. 2. Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya....

Introduction: multiple conditions in later life (multi-morbidity) is a major challenge for health and care systems worldwide, is of particular relevance for older people, but has not (until recently) received high priority as a topic for research. We have identified the top 10 research priorities from the perspective of older people, their carers,...

Background: Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies. Methods: MEDLIN...

Objective: To determine the efficacy and safety of nonpharmacologic interventions for orthostatic hypotension (OH) secondary to aging. Methods: A total of 150 orthostatic challenges were performed in 25 older people (age 60-92 years) to determine cardiovascular responses to bolus water drinking, compression stockings, abdominal compression, and...

Background: Chronic fatigue syndrome (CFS) in many cases is characterised by abnormal autonomic function and lower blood pressure (BP). In animals the liver is a capacitance vessel for BP homeostasis. We developed a novel liver magnetic resonance (MR) imaging technique to compare liver volume in CFS to controls, and to explore its role in cardiovas...

Objective: To describe how the effects of gravity may adversely affect the neuro-cardiovascular physiology of individuals with severe Chronic Fatigue Syndrome (CFS). Design: A narrative review of the literature relating to microgravity, orthostatic intolerance and severe CFS. Emphasis is placed on the clinical significance and implications for the...

Orthostatic hypotension (OH) is defined as a systolic (SBP) drop >20mmHg or diastolic BP (DBP) >10mmHg within 3 minutes of standing. Little is known about the characteristics of individuals with OH or its relevance in the older population.

Background: orthostatic hypotension (OH) is a common disabling condition associated with increased morbidity and mortality. Much of the evidence available is derived from younger populations with chronic neurological disease leading to uncertainty for the diagnosis and management of older people. Objective: to provide an overview of recent and e...

Introduction. Obesity among young people has increased dramatically worldwide, and the prevalence continues to increase. Studies performed in both adults and children have confirmed that abnormalities of cardiac function and autonomic nervous system are present in those with obesity and might explain at least in part the increased mortality seen in...

Objective: The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. Methods: MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were sear...

Objectives To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements. Methods Cardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47)...

To validate a new patient-reported outcome measure for routine clinical use. A total of 50 older individuals with orthostatic hypotension who attended a falls and syncope clinic completed three questionnaires, the recently developed Orthostatic Hypotension Questionnaire, the existing Orthostatic Grading Scale and the quality of life measure EQ-5D-5...

Orthostatic hypotension (OH) affects 6% of community-dwelling older people. This increases to 60% when non-invasive, continuous blood pressure (BP) monitoring is used, due to identification of transient drops in BP which recover rapidly. To determine the clinical relevance of these transient orthostatic BP drops. 5-year clinical observational study...

Orthostatic hypotension (OH) is very common, particularly in older populations. Diagnostic criteria exist but appear to be arbitrary rather than evidence based. This review will visit the evidence for diagnostic strategies for OH. Medline (OvidSP), EMBASE (OvidSP), ISI Web of Science, the Health Technology Assessments Database and the Cochrane Libr...

Background: Several small studies have investigated cognitive impairment in primary SS (PSS) using self-reported measures. We sought to quantify cognitive impairment symptoms in a large cohort of 150 PSS patients compared with controls and to explore the relationship between cognitive impairment with fatigue, pain and mood symptoms. Methods: PSS p...

With a rapidly expanding older population and increased survival of older people with chronic disease, we can expect to see increasing numbers of people with orthostatic hypotension (OH). Unfortunately the evidence base for people with OH, with particular relevance to older people, has not kept up and has resulted in a real lack of progress and lit...

Primary biliary cirrhosis (PBC) is a chronic liver disease characterised by cholestasis. Recent MRI studies have confirmed the presence of cardiac abnormalities in non-cirrhotic PBC patients. However cardiorespiratory consequences of these abnormalities have not been explored. Thoracic fluid content (TFC) is a non-invasive bio-electrical impedance...

Summary Falls and fall-related injury are common and become more prevalent with increasing age. Risk factors for falling are numerous, synergistic and complex, and require multidisciplinary assessment. The evidence base for intervention strategies continues to improve, but is often limited by the methodological difficulties that are inherent in fal...

Background and aims: Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are common and increasing in prevalence. We examined prevalence and predictors of functional impairment in biopsy-proven ALD and NAFLD. Change in function over 3 years was explored. Methods: Validated functional, cognitive, autonomic, and fatigue sym...

Symptoms such as fatigue are common in NAFLD and lead to the impaired quality of life and reduced functional ability that are recognized in this disease. Daytime sleepiness and autonomic dysfunction are frequently found in fatigued patients with NAFLD and are potentially treatable. Understanding the full experience of patients with NAFLD will impro...

Improved survival with chronic liver disease (CLD) and increased incidence in the older has led to a rapidly expanding population which faces similar "geriatric syndromes" as the general population. With risk factors such as autonomic dysfunction, cognitive impairment, and muscle abnormalities in CLD it is expected that falls and injury will be com...

Several studies have demonstrated that primary Sjögren's syndrome (SS) is associated with reduced productivity; however, the impact of primary SS on daily function is not fully understood. This study aims to assess the physical function of primary SS patients and determine the relationship between the functional impairment experienced by primary SS...

Autonomic dysfunction is common in chronic fatigue syndrome (CFS). This study set out to derive an autonomic biomarker using a comprehensive assessment of heart rate and blood pressure variability. Heart rate and non-invasive continuous blood pressure measurements (task force monitor) at rest and on standing were performed in CFS (Fukuda n = 68) an...

Objectives To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS. Methods Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of...

Older people are an increasing proportion of the population and, although there are no gastrointestinal diseases specific to older people, many symptoms and diseases such as gastrointestinal cancers, peptic ulcer disease, and diverticulosis become more common in older age groups. There are several possible contributory factors predisposing the olde...

People with adult immune thrombocytopenia (ITP) are commonly thought to have an isolated blood disorder, but many also describe memory and concentration problems. Cognitive impairment commonly associates with autonomic dysfunction. Here, we quantified cognitive symptoms in a large cohort of patients with ITP compared with controls and explored the...

To assess patient-reported functional ability and its relationship with symptoms in primary biliary cirrhosis (PBC). Functional status was assessed in a representative cohort of 75 patients with PBC using the Patient-Reported Outcome Measure Information System Health-Assessment Questionnaire (PROMIS-HAQ) functional assessment tool and was related t...

We compared functional ability and symptom severity in liver transplant recipients and matched chronic liver disease (CLD) and community controls. A total of 103/140 consecutive liver transplant recipients from a single centre (73%) and matched controls completed the patient-reported functional outcome measure: Patient-Reported Outcomes Measurement...

Long-term outcome in primary biliary cirrhosis (PBC) remains unclear. Whilst response to ursodeoxycholic acid (UDCA) is associated with good outcome, this effect is not universal. Early data from our group have suggested that one factor associated with a poorer outcome in PBC is fatigue. The aim of this study was to explore the inter-relationship b...

Postural orthostatic tachycardia syndrome (POTS) is associated with tachycardia on orthostasis. Patients frequently report palpitations, presyncope, and fatigue. Conventional therapy is effective in less than 60%. Case reports suggest ivabradine (a selective sinus node blocker, with no effect on blood pressure) may alleviate POTS-related symptoms....

to examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability. longitudinal cohort study of patients with CFS (Fukuda criteria). specialist CFS clinical service. phase 1: 100 patients who participated in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients c...

Cognitive impairment is recognised in the early stages of primary biliary cirrhosis (PBC). To determine the mechanisms that underlie the cognitive dysfunction that can occur in early-stage PBC, with a particular focus on the role of autonomic dysfunction and altered cerebral autoregulation. Early-stage PBC patients, and age- and sex-matched control...

Chronic liver disease (CLD) is on the increase worldwide. Occupational therapists are well placed to address many of the symptoms associated with CLD; however, there is a dearth of literature to support this or to define the current working practice of occupational therapists in this clinical area. This study used questionnaires and mixed methodolo...

Osteoporosis and autonomic dysfunction are prevalent in the autoimmune liver disease primary biliary cirrhosis (PBC). Postural hypotension is one consequence of autonomic dysfunction and is a recognized risk factor for falls, which, alongside osteoporosis could lead to significant injury and fractures. To determine the prevalence and sequelae of fa...

The management of non-alcoholic liver disease (NAFLD) concerns lifestyle modification and exercise; however, adherence is poor. Factors such as lack of confidence to exercise, poor understanding of the benefits of exercise, and a fear of falling all influence engagement in physical activity. To increase exercise in NAFLD it is important to understa...

Clinicians are seeing increasing number of patients with chronic liver disease (CLD). The prevalence of diseases such as nonalcoholic fatty liver disease is increasing dramatically, our population is ageing and people with CLD are surviving into old age. Signs and symptoms of CLD in the older patient are often subtle and non-specific and a high ind...

Non-alcoholic fatty liver disease (NAFLD) is principally a disease of middle and old age. Previous studies reported it to be benign in old age, however more recent studies suggest an increased mortality in the >60-year-olds. To define the prevalence of risk factors and the laboratory and histological differences between different age groups with NA...

The prevalence of chronic liver disease is increasing in older people. The presentation of these diseases is often asymptomatic or nonspecific, so they easily go undiagnosed. Investigating the older person who has abnormal liver function is important in primary care, and the same vigilance should he applied to an older person as to a young person,...

Autonomic dysfunction (AD) is common in chronic liver disease (CLD) of all aetiologies and even more so in those awaiting transplantation. As yet, the pathophysiology is not completely understood but the clinical effects are dramatic for the patient, who has a heavy symptomatic burden. There are several considerations, specific to liver disease, wh...

The proportion of older people with chronic liver disease is increasing, and it is therefore important that both geriatricians and hepatologists become more aware of the issues this group will face. The presentation of liver disease in older people may be non-specific, but older people often have signs of liver disease as they present later and hav...

The prevalence of chronic liver disease is increasing in the elderly population. With a mostly asymptomatic or non-specific presentation, these diseases may easily go undiagnosed. Abnormal liver function tests of unknown cause are a common reason for referral to secondary care. Investigating the older person with abnormal liver function is importan...