A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Economic evaluation of clinical quality registries: a systematic review

Objectives: The objective of this systematic review was to examine the existing evidence base for the cost-effectiveness or cost-benefit of clinical quality registries (CQRs). Design: Systematic review and narrative synthesis. Data sources: Nine electronic bibliographic databases, including MEDLINE, EMBASE and CENTRAL, in the period from January 2000 to August 2019. Eligibility criteria: Any peer-reviewed published study or grey literature in English which had reported on an economic evaluation of one or more CQRs. Data extraction and synthesis: Data were screened, extracted and appraised by two independent reviewers. A narrative synthesis was performed around key attributes of each CQR and on key patient outcomes or changes to healthcare processes or utilisation. A narrative synthesis of the cost-effectiveness associated with CQRs was also conducted. The primary outcome was cost-effectiveness, in terms of the estimated incremental cost-effectiveness ratio (ICER), cost savings or return-on-investment (ROI) attributed to CQR implementation. Results: Three studies and one government report met the inclusion criteria for the review. A study of the National Surgical Quality Improvement Programme (NSQIP) in the USA found that the cost-effectiveness of this registry improved over time, based on an ICER of US$8312 per postoperative event avoided. A separate study in Canada estimated the ROI to be US$3.43 per US$1.00 invested in the NSQIP. An evaluation of a post-splenectomy CQR in Australia estimated that registry cost-effectiveness improved from US$234 329 to US$18 358 per life year gained when considering the benefits accrued over the lifetime of the population. The government report evaluating five Australian CQRs estimated an overall return of 1.6–5.5 times the cost of investment. Conclusions: Available data indicate that CQRs can be cost-effective and can lead to significant returns on investment. It is clear that further studies that evaluate the economic and clinical impacts of CQRs are necessary

Out-of-hospital cardiac arrest outcomes in emergency departments

Background: The emergency department (ED) plays an important role in out-hospital-cardiac arrest (OHCA) management. However, ED outcomes are not widely reported. This study aimed to (1) describe OHCA ED outcomes and reasons for ED deaths, and (2) whether these differed between hospitals. Methods: Data were obtained from the Victorian Ambulance Cardiac Arrest Registry and 12 hospitals for adult, non-traumatic OHCA cases transported to ED between 2014 and 2016. Multivariable logistic regression was used to examine the association of level of cardiac arrest centre on ED survival in a subset of cases (non-paramedic witnessed OHCA who were unconscious on ED arrival with ROSC). Results: Of 1547 eligible OHCA cases, 81% (N = 1254) survived ED, varying between 57% to 88% between EDs. Among non-survivors, the majority had either: cessation of resuscitation after presenting with CPR in progress (27%); withdrawal of life-sustaining treatment for non-neurological (n = 65, 22%) or neurological (16%) reasons; or a unsuccessful resuscitation following a rearrested in ED (20%). These causes of ED deaths varied between the different levels of cardiac arrest centres, and in our subset of interest (n = 952) ED survival was associated with transportation to centres with high annual OHCA volumes and with 24-hour cardiac intervention capabilities (AOR = 3.43, 95% CI 1.89–6.21). Conclusion: Our study found wide variation in survival between EDs, which was associated with hospital characteristics. Such data suggests the need for a detailed review of ED deaths, particularly in non-cardiac arrest centres, and potentially the need for monitoring ED survival as a measure of quality

A randomized controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen in myocarDial infarction study (AVOID Study)

Background: The role of routine supplemental oxygen for patients with uncomplicated acute myocardial infarction (AMI) has recently been questioned. There is conflicting data on the possible effects of hyperoxia on ischemic myocardium. The few clinical trials examining the role of oxygen in AMI were performed prior to the modern approach of emergent reperfusion and advanced medical management. Methods: Air Verses Oxygen In myocarDial infarction study (AVOID Study) is a prospective, multi-centre, randomized, controlled trial conducted by Ambulance Victoria and participating metropolitan Melbourne hospitals with primary percutaneous coronary intervention capabilities. The purpose of the study is to determine whether withholding routine supplemental oxygen therapy in patients with acute ST-elevation myocardial infarction but without hypoxia prior to reperfusion decreases myocardial infarct size. AVOID will enroll 490 patients, >18 years of age with acute ST-elevation myocardial infarction of less than 12 hours duration. Conclusions: There is an urgent need for clinical trials examining the role of oxygen in AMI. AVOID will seek to clarify this important issue. Results from this study may have widespread implications on the treatment of AMI and the use of oxygen in both the pre-hospital and hospital settings

The barriers associated with emergency medical service use for acute coronary syndrome: the awareness and influence of an Australian public mass media campaign.

BACKGROUND: Emergency medical services (EMS) transport to hospital is recommended in acute coronary syndrome (ACS) guidelines, but only half of patients with ACS currently use EMS. The recent Australian Warning Signs campaign conducted by the Heart Foundation addressed some of the known barriers against using EMS. Our aim was to examine the influence of awareness of the campaign on these barriers in patients with ACS. METHODS: Interviews were conducted with patients admitted to an Australian tertiary hospital between July 2013 and April 2014 with a diagnosis of ACS. Patient selection criteria included: aged 35-75 years, competent to provide consent, English speaking, not in residential care and medically stable. Multivariable logistic regression was used to examine factors associated with EMS use. RESULTS: Only 54% of the 199 patients with ACS interviewed used EMS for transport to hospital. Overall 64% of patients recalled seeing the campaign advertising, but this was not associated with increased EMS use (52.0%vs56.9%, p=0.49) or in the barriers against using EMS. A large proportion of patients (43%) using other transport thought it would be faster. Factors associated with EMS use for ACS were: age >65 years, ST-elevation myocardial infarction, a sudden onset of pain and experiencing vomiting. CONCLUSION: In medically stable patients with ACS, awareness of the Australian Warning Signs campaign was not associated with increased use of EMS or a change in the barriers for EMS use. Future education strategies could emphasise the clinical role that EMS provide in ACS

Differences in predictors of incident heart failure according to atherosclerotic cardiovascular disease status

Abstract Aims Heart failure (HF) is a common cause of morbidity and mortality, related to a broad range of sociodemographic, lifestyle, cardiometabolic, and comorbidity risk factors, which may differ according to the presence of atherosclerotic cardiovascular disease (ASCVD). We assessed the association between incident HF with baseline status across these domains, overall and separated according to ASCVD status. Methods and results We included 5758 participants from the Baker Biobank cohort without HF at baseline enrolled between January 2000 and December 2011. The primary endpoint was incident HF, defined as hospital admission or HF‐related death, determined through linkage with state‐wide administrative databases (median follow‐up 12.2 years). Regression models were fitted adjusted for sociodemographic variables, alcohol intake, smoking status, measures of adiposity, cardiometabolic profile measures, and individual comorbidities. During 65 987 person‐years (median age 59 years, 38% women), incident HF occurred among 784 participants (13.6%) overall. Rates of incident HF were higher among patients with ASCVD (624/1929, 32.4%) compared with those without ASCVD (160/3829, 4.2%). Incident HF was associated with age, socio‐economic status, alcohol intake, smoking status, body mass index (BMI), waist circumference, waist–hip ratio, systolic blood pressure (SBP), and low‐ and high‐density lipoprotein cholesterol (LDL‐C and HDL‐C), with non‐linear relationships observed for age, alcohol intake, BMI, waist circumference, waist–hip ratio, SBP, LDL‐C, and HDL‐C. Risk factors for incident HF were largely consistent regardless of ASCVD status, although diabetes status had a greater association with incident HF among patients without ASCVD. Conclusions Incident HF is associated with a broad range of baseline sociodemographic, lifestyle, cardiometabolic, and comorbidity factors, which are mostly consistent regardless of ASCVD status. These data could be useful in efforts towards developing risk prediction models that can be used in patients with ASCVD