Abstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect). Results Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, l -tryptophan, l -alanine, 2,2,2-trichloroethanol, lactic acid and d -glucose. Conclusions In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. d -Glucose, lactic acid, succinic acid, l -alanine, l -tryptophan and trichloroethanol were pathways that may merit further investigation. Trial Registration : EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ).
Care that confers no benefit or benefit that is disproportionately low compared with its cost is of low value and potentially wastes limited resources. It has been claimed that low-value care consumes at least 20% of health care resources in the United States - the comparable figure in Australia is unknown but there is emerging evidence of overuse of diagnostic tests and therapeutic procedures. Very few clinical interventions are of no value in every clinical circumstance, and efforts to label interventions as being so will meet with professional resistance. In the context of complex and highly individualised clinical decisions, nuanced clinical judgements of experienced and well informed clinicians are likely to outperform any service-level measurement and incentive program aimed at recognising and reducing low-value care. Public policy interventions should focus on supporting clinician-led efforts to seek professional consensus on what constitutes low-value care and the best means for reducing it.
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Abstract Background Systemic sclerosis (SSc) is a connective tissue disease that is characterized by vascular dysfunction and extensive fibrosis. The current literature suggests a 15-35% prevalence of cardiac manifestations in patients with SSc, the majority of which remains subclinical. Patients with SSc often demonstrate angiographically normal epicardial coronary arteries despite underlying dysregulation in the coronary microvasculature. Coronary flow reserve (CFR) is a noninvasive marker of coronary microvascular circulation. Purpose This meta-analysis aimed to compare CFR between patients with SSc and healthy controls. Methods A comprehensive literature search of the major bibliographic databases, including PubMed/MEDLINE, Embase, and the Cochrane Library was conducted. The aim was to identify studies comparing CFR between patients with SSc and healthy controls. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model. Statistical significance was set at p < 0.05. Heterogeneity was assessed using the Higgins I2 metric. Results Four studies were included in this meta-analysis, with a total of 210 participants (129 patients with SSc; 81 healthy controls). In the SSc and control groups, 88.3% and 70.3% of the patients, respectively, were female. The mean ages of the SSc and control group were 52.2 ± 13.2 and 47.77 ± 9.8, respectively. The pooled analysis demonstrated a statistically significant reduction in CFR associated with SSc [SMD: -1.44; 95% CI: -1.76, -1.13; p<0.00001] compared to healthy controls. No heterogeneity was observed in the effect estimates [I2 = 0%]. Conclusion SSc is associated with a higher risk of coronary microvascular dysfunction, as indicated by the reduced CFR. The results of this meta-analysis demonstrate the importance of a comprehensive cardiac evaluation in patients with SSc. Early aggressive targeted interventions for impaired CFR in SSc patients may lead to improved clinical outcomes. Further prospective studies are required to elucidate the prognostic impact of a blunted CFR. Figure 1
• Objective: To review the adverse drug events (ADEs) risk of polypharmacy; the process of deprescribing and evidence of efficacy in reducing inappropriate polypharmacy; the enablers and barriers to deprescribing; and patient and system of care level strategies that can be employed to enhance deprescribing. • Methods: Literature review. • Results: Inappropriate polypharmacy, especially in older people, imposes a significant burden of ADEs, ill health, disability, hospitalization and even death. The single most important predictor of inappropriate prescribing and risk of ADEs in older patients is the number of prescribed medicines. Deprescribing is the process of systematically reviewing, identifying, and discontinuing potentially inappropriate medicines (PIMs), aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies, and deprescribing protocols have been developed and validated for clinical use. Barriers and enablers to deprescribing by individual prescribers center on 4 themes: (1) raising awareness of the prevalence and characteristics of PIMs; (2) overcoming clinical inertia whereby discontinuing medicines is seen as being a low value proposition compared to maintaining the status quo; (3) increasing skills and competence (self-efficacy) in deprescribing; and (4) countering external and logistical factors that impede the process. • Conclusion: In optimizing the scale and effects of deprescribing in clinical practice, strategies that promote depresribing will need to be applied at both the level of individual patient-prescriber encounters and systems of care.
Objectives. To determine the spectrum of disease among non-urgent referrals to a tertiary hospital hepatology outpatient clinic, assess the adequacy of referral information in terms of risk stratification and determine whether a specifically designed referral template altered urgency for specialist assessment. Methods. A snapshot of the waiting list of a hepatology clinic at a tertiary hospital was taken from the scheduling database. Information was retrieved from referrals and attached investigations. Updated information was requested from subjects and their current general practitioner. Results. Hepatitis C virus accounted for 68.7% of the 1223 reviewed referrals. Clinical information provided by referring clinicians was often incomplete. Provision of updated information identified the presence of comorbidities (obesity, ‘heavy’ alcohol consumption, mental health issues) and altered the need or urgency for specialist assessment in 22% of cases. Conclusions. Hepatitis C virus accounts for the majority of non-urgent referrals waiting to access hepatology outpatient consultations. Using a standardised assessment form as part of the referral process provides more information on comorbidities and risk factors and facilitates more accurate triaging of clinical urgency. Wider adoption of this strategy may increase appropriate access to hepatology services and reduce the future burden of cirrhosis and hepatocellular cancer. What is known about the topic? Little published data are available that describe the content and standard of hepatology referrals, or the urgency with which these patients need to be reviewed. Inadequate clinical information impairs the ability to accurately triage referrals and may lead to delays in access. What does the paper add? Almost 70% of reviewed referrals were for management of patients with hepatitis C virus infection, confirming this condition remains a major priority area in liver disease. Clinical information provided by referring clinicians was often incomplete, impairing the ability to accurately triage referrals. Only a minority of referrals provided information about relevant comorbidities (alcohol intake, injecting drug use, mental health issues and obesity) that negatively impact on the progression of liver disease or the response to antiviral treatment. What are the implications for practitioners? Hepatitis C virus remains a major health priority area in liver disease, increasing the future burden of cirrhosis and hepatocellular cancer. Many referred patients have comorbidities that increase their risk of progressive liver disease and related complications. Strategies to increase recognition and management of liver disease and its comorbidities in the community are required. The use of a standardised assessment form in referrals to hepatology outpatient services may assist with triaging of patients and improve access to appropriate care.
The population is aging, with frailty emerging as a significant risk factor for poor outcomes for older people who become acutely ill. We describe the development and implementation of the Frail Older Persons’ Collaborative Program, which aims to optimise the care of frail older adults across healthcare systems in Queensland. Priority areas were identified at a co-design workshop involving key stakeholders, including consumers, multidisciplinary clinicians, senior Queensland Health staff and representatives from community providers and residential aged care facilities. Locally developed, evidence-based interventions were selected by workshop participants for each priority area: a Residential Aged Care Facility acute care Support Service (RaSS); improved early identification and management of frail older persons presenting to hospital emergency departments (GEDI); optimisation of inpatient care (Eat Walk Engage); and enhancement of advance care planning. These interventions have been implemented across metropolitan and regional areas, and their impact is currently being evaluated through process measures and system-level outcomes. In this narrative paper, we conceptualise the healthcare organisation as a complex adaptive system to explain some of the difficulties in achieving change within a diverse and dynamic healthcare environment. The Frail Older Persons’ Collaborative Program demonstrates that translating research into practice and effecting change can occur rapidly and at scale if clinician commitment, high-level leadership, and adequate resources are forthcoming.
To investigate what role family physicians currently play in the management of patients with nutrition-related issues and whether implementation of current nutrition counseling guidelines is feasible in primary care practices.Mailed survey.Family practice offices in British Columbia.A total of 451 Canadian-trained family physicians practising in British Columbia.Respondents' demographic characteristics; respondents' attitudes about and perceived barriers to nutrition counseling, as well as their current practices and training in this area.Among the 757 physicians surveyed, the response rate was 59.6%. Overall, respondents had positive attitudes about the role of nutrition in patient health, and most physicians (58.1%) believed that more than 60% of their patients would benefit from nutrition counseling. However, there was a considerable gap between the proportion of patients who respondents thought would benefit from nutrition counseling and the proportion of patients who received such counseling either in the family physicians' offices or through referral to dietitians. Rural physicians referred patients to dietitian services more frequently than urban physicians did (41.7% vs 21.7% made more than 20 referrals to dietitians each year). Nearly all physicians identified lack of time and compensation as the strongest barriers to providing nutrition guidance. Training was not considered to be as strong a barrier to counseling, even though 82.3% of family physicians reported their formal nutrition training in medical school to be inadequate, and only 30% of family physicians reported currently using any nutrition-related resources.For family physicians, successful implementation of the 2006 Canadian Clinical Practice Guidelines on the Management and Prevention of Obesity requires access to adequate training, compensation, and evidence-based interventions related to nutrition. This study highlights current nutrition counseling practices in family medicine and identifies several obstacles to integrating the current guidelines in primary care settings.
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