Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis.

ObjectivesThiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 and thiamin transporter-2), and mitochondrial thiamin pyrophosphate transporter.DesignRandomized controlled study.SettingResearch laboratory at a Veterans Affairs Medical Center.SubjectsTwenty-four Sprague-Dawley rats were randomized into controls, mild, moderate, and severe sepsis with equal number of animals in each group.InterventionsSepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25%, 50%, and 75% of cecal length, defined as severe, moderate, and mild sepsis, respectively. Control animals underwent laparotomy only.Measurements and main resultsAfter 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [H]thiamin. Expressions of thiamin transporter-1, thiamin transporter-2, and mitochondrial thiamin pyrophosphate transporter proteins and messenger RNA were measured. Proinflammatory cytokines (interleukin-1β and interleukin-6) and adenosine triphosphate were also measured. Sepsis inhibited [H]thiamin uptake, and the inhibition was a function of sepsis severity. Both cell membrane thiamin transporters and mitochondrial thiamin pyrophosphate transporter expression levels were suppressed; also levels of adenosine triphosphate in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham-operated controls.ConclusionsFor the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion

Feldenkrais Method Balance Classes Improve Balance in Older Adults: A Controlled Trial

The objective of this study was to investigate the effects of Feldenkrais Method balance classes on balance and mobility in older adults. This was a prospective non-randomized controlled study with pre/post measures. The setting for this study was the general community. A convenience sample of 26 community-dwelling older adults (median age 75 years) attending Feldenkrais Method balance classes formed the Intervention group. Thirty-seven volunteers were recruited for the Control group (median age 76.5 years). A series of Feldenkrais Method balance classes (the 33312Getting Grounded Gracefully33313 series), two classes per week for 10 weeks, were conducted. Main outcome measures were Activities-Specific Balance Confidence (ABC) questionnaire, Four Square Step Test (FSST), self-selected gait speed (using GAITRite instrumented gait mat). At re-testing, the Intervention group showed significant improvement on all of the measures (ABC, P = .016, FSST, P = .001, gait speed, P < .001). The Control group improved significantly on one measure (FSST, P < .001). Compared to the Control group, the Intervention group made a significant improvement in their ABC score (P = .005), gait speed (P = .017) and FSST time (P = .022). These findings suggest that Feldenkrais Method balance classes may improve mobility and balance in older adults

“I give it everything for an hour then i sleep for four.” The experience of post-stroke fatigue during outpatient rehabilitation including the perspectives of carers : A qualitative study

Background: Fatigue is a debilitating post-stroke symptom negatively impacting rehabilitation. Lack of acknowledgment from carers can be additionally distressing. The purpose of this study was to describe the experience of post-stroke fatigue during outpatient rehabilitation, including the perspectives of carers. Methods: This qualitative study was guided by descriptive phenomenology within a constructivist paradigm. Semi-structured interviews were conducted with stroke survivors experiencing fatigue (Fatigue Assessment Scale >23) and attending outpatient rehabilitation. Carers were also interviewed where identified, providing insight into their own and stroke survivor experiences. Data were analyzed according to Colaizzi's analytic method. Results: Fourteen stroke survivors (50% culturally and linguistically diverse), and nine carers participated. Six themes were identified: 1. The unpredictable and unprepared uncovering of fatigue; 2. Experience and adjustment are personal 3. Being responsible for self-managing fatigue; 4. The complex juggle of outpatient stroke rehabilitation with fatigue; 5. Learning about fatigue is a self-directed problem-solving experience; 6. Family and carers can support or constrain managing fatigue. Conclusion: Despite engaging in outpatient rehabilitation, stroke survivors largely learnt to manage fatigue independent of healthcare professionals. Carers often facilitated learning, monitoring rehabilitation, daily routines and fatigue exacerbation. Conversely, family could be dismissive of fatigue and possess unrealistic expectations. Post-stroke fatigue must be considered by clinicians when delivering outpatient rehabilitation to stroke survivors. Clinicians should consistently screen for fatigue, provide flexible session scheduling, and educate about individual indicators and strategies for management. Clinicians should also explicitly engage carers who play a critical role in the management of fatigue

The health profile of people living with Parkinson\u27s Disease managed in a comprehensive care setting

Background: Globally there are few reports of the impairments, disabilities and medications used in people living with idiopathic Parkinson&rsquo;s disease. Caregiver characteristics and caregiver burden have seldom been reported. We examined the health status in a large cohort of people living with Parkinson&rsquo;s disease and their caregivers managed in a comprehensive health care setting. Methods/Design: A prospective, cross sectional analysis of impairments, disabilities and Parkinson&rsquo;s disease medication use was conducted in a sample of 100 people with Parkinson&rsquo;s disease rated I-IV on the modified Hoehn &amp; Yahr scale. Participants were recruited from the Victorian Comprehensive Parkinson Program in Melbourne, Australia. Their caregivers were invited to provide their views on the burden of care, services provided and support received. Results: The severity of impairments and disabilities was strongly associated with disease duration (mean of 5.5 years). Those with long standing disease or more severe disease also used more Parkinson&rsquo;s disease medications and participated in fewer social roles than people who were newly diagnosed or mildly affected. The severity of impairments was strongly correlated with limitations in performing activities of daily living. Limitations in performing daily activities were also found to be a significant contributing factor for health-related quality of life (PDQ-39 SI &beta;=0.55, p=0.000; EQ-5D SI &beta;=0.43, p=0.001). People with Parkinson&rsquo;s disease lived at home with relatives. The average caregiver was a spouse or child providing approximately 3.5 hours of care per day, with the capacity to provide 9.4 hours per day and had provided care for four years. Additional support was high (63%) for 2.5 hours per day. Conclusion: The comprehensive care setting of this cohort describes a relatively benign condition despite a wide range of disease duration and severity. This report provides a baseline with which to compare other delivery models

Unpacking the enabling factors for hand, cord and birth-surface hygiene in Zanzibar maternity units.

Recent national surveys in The United Republic of Tanzania have revealed poor standards of hygiene at birth in facilities. As more women opt for institutional delivery, improving basic hygiene becomes an essential part of preventative strategies for reducing puerperal and newborn sepsis. Our collaborative research in Zanzibar provides an in-depth picture of the state of hygiene on maternity wards to inform action. Hygiene was assessed in 2014 across all 37 facilities with a maternity unit in Zanzibar. We used a mixed methods approach, including structured and semi-structured interviews, and environmental microbiology. Data were analysed according to the WHO 'cleans' framework, focusing on the fundamental practices for prevention of newborn and maternal sepsis. For each 'clean' we explored the following enabling factors: knowledge, infrastructure (including equipment), staffing levels and policies. Composite indices were constructed for the enabling factors of the 'cleans' from the quantitative data: clean hands, cord cutting, and birth surface. Results from the qualitative tools were used to complement this information.Only 49% of facilities had the 'infrastructural' requirements to enable 'clean hands', with the availability of constant running water particularly lacking. Less than half (46%) of facilities met the 'knowledge' requirements for ensuring a 'clean delivery surface'; six out of seven facilities had birthing surfaces that tested positive for multiple potential pathogens. Almost two thirds of facilities met the 'infrastructure (equipment) requirement' for 'clean cord'; however, disposable cord clamps being frequently out of stock, often resulted in the use of non-sterile thread made of fabric. This mixed methods approach, and the analytical framework based on the WHO 'cleans' and the enabling factors, yielded practical information of direct relevance to action at local and ministerial levels. The same approach could be applied to collect and analyse data on infection prevention from maternity units in other contexts

Implementation of the StandingTall programme to prevent falls in older people:a process evaluation protocol

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156

Quantity does not always mean quality: the importance of qualitative social science in conservation research

Qualitative methods are important in gaining a deep understanding of complex problems and poorly researched areas. They can be particularly useful to help explain underlying conservation problems, as in Rust et al. (2016). However, the significance in choosing and justifying appropriate methodological frameworks in conservation studies should be given more attention to ensure data are collected and analysed appropriately. We thank Potgieter et al. (2017) for their critical analysis of Rust et al. (2016), but they appear unaware of when, why and how such methods should be used. We clarify the methods described in Rust et al. (2016) and explain sampling strategies in qualitative studies. To improve familiarity with qualitative methods among natural scientists we recommend expanded training in social sciences and collaborating with social scientists. Given the scale of human impacts on the environment, this type of nuanced analytical skill is critical for moving conservation forward

The FLASSH study: protocol for a randomised controlled trial evaluating falls prevention after stroke and two sub-studies

This randomised controlled trial aims to evaluate the effectiveness of a multi-factorial falls prevention program for stroke survivors who are at high risk of falling when they return home after rehabilitation. Intervention will consist of a home exercise program as well as individualised falls prevention and injury minimisation strategies based on identified risk factors for falls. Additionally, two sub-studies will be implemented in order to explore other key areas related to falls in this population. The first of these is a longitudinal study evaluating the relationship between fear of falling, falls and function over twelve months, and the second evaluates residual impairment in gait stability and obstacle crossing twelve months after discharge from rehabilitation

Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure

AIMS: The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. METHODS AND RESULTS: We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46% of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11%, isolated abnormal transaminases in 26%, and a combination of abnormal AP and transaminases in 9%. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9%, P = 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4% and 31.6 vs. 22.4%, respectively; both P < 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. CONCLUSION: Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patient