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Elective alcohol detoxification - a resource and efficacy evaluation.
No full textAn evaluation was performed to assess efficacy and resource utilisation of an elective inpatient alcohol detoxification service at a large inner-city teaching hospital. Abstinence rates at 3, 6 and 12 months post-detoxification were 68.1, 44.7 and 36.2%, respectively. Relapse was associated with referrals from acute hospital services, previous detoxifications, longer time between referral and admission for detoxification, presence of alcohol in the blood on the day of admission and requirement for benzodiazepines during withdrawal. The service operates within the national 18-week referral target and runs at a cost substantially lower than that of residential alcohol detoxification facilities but with similar sobriety rates. We demonstrate that elective detoxification with specialist follow-up provides an effective service both in terms of patient outcomes and resource use. Further investment in these services at both local and national level should be considered
Mild primary hyperparathyroidism-to treat or not to treat?
No full textINTRODUCTION
The presentation of primary hyperparathyroidism (PHPT) has shifted from a disease characterized by renal and skeletal complications to a mild or asymptomatic condition. Modern imaging allows localization of a surgical target in the majority of cases.
SOURCES OF DATA
Data were collected from literature searches of online databases including PUBMED, MEDLINE and Cochrane. A narrative review was performed.
AREAS OF AGREEMENT
Parathyroidectomy is the only therapy with curative potential with good outcomes and low risk of complications in experienced hands. Current guidelines advocate that surgery is offered in all symptomatic cases and in those who meet criteria depending on age, serum calcium concentration, skeletal and renal parameters. A structured monitoring approach should be offered to those who do not undergo surgery.
AREAS OF CONTROVERSY
Thresholds for intervention to improve skeletal and renal outcomes are debatable. In addition, controversy persists over the benefit of surgery for non-skeletal/renal outcomes.
GROWING POINTS
The role of medical management of PHPT using agents such as bisphosphonates, denosumab and cinacalcet are discussed.
AREAS TIMELY FOR DEVELOPING RESEARCH
In summary, further data on the natural history and effects of treatment of mild and asymptomatic PHPT are required to determine thresholds for surgery. In particular, further investigations of non-skeletal and non-renal parameters, such as neurocognitive quality of life and cardiovascular disease are required. Data on normocalcaemic PHPT are lacking. Large-scale randomized controlled trials would be welcome in these areas, however in view of the cost implications a more pragmatic approach may be to develop collaborative multi-centre registries
Caseload management and outcome of patients with aortic stenosis in primary/secondary versus tertiary care settings-design of the IMPULSE enhanced registry.
No full textBackground
Severe aortic stenosis (AS) is one of the most common and most serious valve diseases. Without timely intervention with surgical aortic valve replacement or transcatheter aortic valve replacement, patients have an estimated survival of 2-3 years. Guidelines for the treatment of AS have been developed, but studies suggest that as many as 42% of patients with AS are not treated according to these recommendations.The aims of this registry are to delineate the caseload of patients with AS, outline the management of these patients and determine appropriateness of treatments in participating centres with and without onsite access to surgery and percutaneous treatments.
Methods/design
The IMPULSE enhanced registry is an international, multicentre, prospective, observational cohort registry conducted at four central full access centres (tertiary care hospitals) and at least two satellite centres per hub (primary/secondary care hospitals). An estimated 800 patients will be enrolled in the registry and patient follow-up will last for 12 months.
Discussion
In addition to the primary aims determining the caseload management and outcome of patients with AS in primary, secondary and tertiary care settings, the registry will also determine a time course for the transition from asymptomatic to symptomatic status and the diagnostic steps, treatment decisions and the identification of decision-makers in tertiary versus primary/secondary care hospitals. The last patient will be enrolled in the registry in 2018 and results of the registry are anticipated in 2019.
Registration number
NCT03112629
Allergic Diseases and Long Term Risk of Autoimmune Disorders: .
No full textBACKGROUND
The association between allergic diseases (ADs) and autoimmune disorders (AIDs) is not well established.
OBJECTIVE
To determine incidence rates of AIDs in allergic rhinitis/conjunctivitis (ARC), atopic eczema (AE) and asthma, and investigate for co-occurring patterns.
METHODS
: Retrospective cohort study (1990-2018) employing "The Health Improvement Network" (UK primary care database).: ARC, AE and asthma - all ages.: For each exposed patient, up to 2 randomly selected age- and gender-matched controls with no documented AD.Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.
RESULTS
782 320, 1 393 570 and 1 049 868 patients with ARC, AE and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), vitiligo, rheumatoid arthritis (RA), psoriasis, pernicious anaemia, inflammatory bowel disease (IBD), coeliac disease (CD) and autoimmune thyroid disease were uniformly higher in the 3 ADs compared to controls. Specifically, aIRRs of SLE (1.45) and SS (1.88) were higher in ARC; SLE (1.44), SS (1.61) and myasthenia (1.56) higher in asthma; SLE (1.86), SS (1.48), vitiligo (1.54) and psoriasis (2.41) higher in AE.There was no significant effect of the 3 ADs on multiple sclerosis and ARC and AE on myasthenia.ARM: ADs clustered with multiple AIDs. Three age- and gender-related clusters were identified, with relatively complex pattern in females ≥55 years.
CONCLUSION
The long-term risk of AIDs are significantly higher in patients with ADs. ADs and AIDs show age- and gender-related clustering patterns
Whole genome sequencing of toxigenic Clostridium difficile in asymptomatic carriers: insights into possible role in transmission.
No full textBACKGROUND
Estimates of the prevalence of asymptomatically carried Clostridium difficile in elderly patients in long-term care range from 0% to 51%. Asymptomatic carriage is possibly a risk factor for the development of infection, and there is ongoing debate surrounding the role of asymptomatic carriage in transmission.
AIM
To investigate the prevalence of asymptomatic carriage amongst patients residing in intermediate care (bedded) facilities (ICBFs), and to investigate whether asymptomatically carried C. difficile strains contribute to nosocomial C. difficile infection (CDI).
METHODS
Stools were collected from eligible asymptomatic patients in ICBFs, and a subset was also processed from symptomatic patients accessing primary or secondary care outside of ICBFs. All samples were cultured for C. difficile, and resulting colonies were processed through whole genome sequencing.
FINDINGS
In total, 151 asymptomatic patients were sampled, 22 of which were positive for C. difficile through stool culture, representing a carriage rate of 14.6%. Sequencing of these isolates, alongside 14 C. difficile polymerase chain reaction and culture-positive isolates from symptomatic individuals, revealed that all asymptomatic patients were carrying toxigenic C. difficile, and these strains were genetically similar to those from symptomatic patients.
CONCLUSION
This small study of asymptomatic carriage revealed a rectal asymptomatic carriage rate of 14.6% in patients nursed in ICBFs, and a high level of genetic similarity of these strains to those recovered from symptomatic patients. As such, asymptomatic carriers may be important for the transmission of symptomatic CDI, although it is acknowledged that this study was small, and many other factors govern whether C. difficile is carried asymptomatically or causes symptoms
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.
No full textNicotinamide adenine dinucleotide (NAD) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR
Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial.
No full textPURPOSE
Myocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects.
METHODS
Two cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values.
RESULTS
Levosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43-2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers.
CONCLUSION
Adding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction
Review article: impact of exercise on physical frailty in patients with chronic liver disease.
No full textBACKGROUND
Physical frailty is common in chronic liver disease and the setting of liver transplantation. It is associated with poor quality of life, increased hospitalisation and mortality. Despite this, the impact of exercise in these patients remains poorly understood.
AIM
To summarise the impact of physical exercise on physical frailty in patients with chronic liver disease until after liver transplantation.
METHODS
A MEDLINE and PubMed search was undertaken using the terms; "physical activity", "functional capacity", "exercise", "prehabilitation", "frailty", "liver cirrhosis", "liver failure", "liver transplantation" "chronic liver disease" and "end-stage liver disease" from January 1990 to June 2019.
RESULTS
Eleven studies (five randomised controlled, five observational, one case study) demonstrated that exercise improves VO peak, anaerobic threshold, 6-minute walk distance, muscle mass/function and quality of life in patients with compensated and decompensated cirrhosis. Improvements were most significant with a combination of aerobic and resistance exercises at moderate-high intensity. The studies were small (n = 1-50) and mainly focused on supervised, hospital-based exercises, excluding patients with significant liver failure (MELD > 12). Seven studies (four randomised controlled and three observational) demonstrated that predominantly supervised (only one home-based) aerobic exercise after liver transplantation improves aerobic capacity, muscle mass/strength and quality of life. There was marked heterogeneity in timing, intensity and type of exercises.
CONCLUSION
Exercise improves key components of physical frailty (functional/aerobic capacity, sarcopenia) and quality of life in chronic liver disease and after liver transplantation. Understanding the type, compliance, intensity and duration of exercise and its impact on hard clinical outcomes should be the focus of future large controlled clinical trials
