Characteristics of Restart a Heart 2019 event locations in the UK.

INTRODUCTION: Restart a Heart (RSAH) is an annual CPR mass training initiative delivered predominantly by ambulance services in the UK. The aim of this study was to identify to what extent voluntary participation in the 2019 initiative delivered training to the population with the highest need. METHODS: A cross-sectional observational study of location characteristics for RSAH training events conducted by UK ambulance services. Descriptive statistics were used to analyse event and area characteristics. National cardiac arrest registry data were used to establish proportions of training coverage in "hot spot" areas with above national median incidence of cardiac arrest and below median bystander CPR rates. The significance of observed differences were tested using chi-square for proportions and t-test for means. RESULTS: Twelve of 14 UK ambulance services participated, training 236,318 people. Most of the events (82%) were held in schools, and schoolchildren comprised most participants (81%). RSAH events were held in areas that were less densely populated (p < 0.001), were more common in affluent areas (p < 0.001), and had a significantly lower proportion of black residents (p < 0.05) and higher proportion of white residents (p < 0.05). Events were held in 28% of known "hot spot" areas in England. CONCLUSION: With mandatory CPR training for school children in England, Scotland and Wales there is an opportunity to re-focus RSAH resources to deliver training for all age groups in OHCA "hot spots", communities with higher proportions of black residents, and areas of deprivation. In Northern Ireland, we recommend targeting schools in areas with similar characteristics.

Knockout of apolipoprotein A-I decreases parenchymal and vascular ß-amyloid pathology in the Tg2576 mouse model of Alzheimer's disease.

AIMS: Apolipoprotein A-I (apoA-I), the principal apolipoprotein associated with high-density lipoproteins in the periphery, is also found at high concentrations in the cerebrospinal fluid. Previous studies have reported either no impact or vascular-specific effects of apoA-I knockout (KO) on ß-amyloid (Aß) pathology. However, the putative mechanism(s) by which apoA-I may influence Aß deposition is unknown. METHODS: We evaluated the effect of apoA-I deletion on Aß pathology, Aß production and clearance from the brain in the Tg2576 mouse model of Alzheimer's disease (AD). RESULTS: Contrary to previous reports, deletion of the APOA1 gene significantly reduced concentrations of insoluble Aß40 and Aß42 and reduced plaque load in both the parenchyma and blood vessels of apoA-I KO × Tg2576 mice compared to Tg2576 animals. This was not due to decreased Aß production or alterations in Aß species. Levels of soluble clusterin/apoJ were significantly higher in neurons of apoA-I KO mice compared to both wildtype (WT) and apoA-I KO × Tg2576 mice. In addition, clearance of Aß along intramural periarterial drainage pathways was significantly higher in apoA-I KO mice compared to WT animals. CONCLUSION: These data suggest that deletion of apoA-I is associated with increased clearance of Aß and reduced parenchymal and vascular Aß pathology in the Tg2576 model. These results suggest that peripheral dyslipidaemia can modulate the expression of apolipoproteins in the brain and may influence Aß clearance and aggregation in AD.

Afferent and efferent immunological pathways of the brain. Anatomy, function and failure.

Immunological privilege appears to be a product of unique lymphatic drainage systems for the brain and receptor-mediated entry of inflammatory cells through the blood-brain barrier. Most organs of the body have well-defined lymphatic vessels that carry extracellular fluid, antigen presenting cells, lymphocytes, neoplastic cells and even bacteria to regional lymph nodes. The brain has no such conventional lymphatics, but has perivascular pathways that drain interstitial fluid (ISF) from brain parenchyma and cerebrospinal fluid (CSF) from the subarachnoid space to cervical lymph nodes. ISF and solutes drain along narrow, ∼100 nm-thick basement membranes within the walls of cerebral capillaries and arteries to cervical lymph nodes; this pathway does not allow traffic of lymphocytes or antigen presenting cells from brain to lymph nodes. Although CSF drains into blood through arachnoid villi, CSF also drains from the subarachnoid space through channels in the cribriform plate of the ethmoid bone into nasal lymphatics and thence to cervical lymph nodes. This pathway does allow the traffic of lymphocytes and antigen presenting cells from CSF to cervical lymph nodes. Efferent pathways by which lymphocytes enter the brain are regulated by selected integrins on lymphocytes and selective receptors on vascular endothelial cells. Here we review: (1) the structure and function of afferent lymphatic drainage of ISF and CSF, (2) mechanisms involved in the efferent pathways by which lymphocytes enter the brain and (3) the failure of lymphatic drainage of the brain parenchyma with age and the role of such failure in the pathogenesis of Alzheimer's disease.

Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy.

Failure of elimination of proteins from the brain is a major feature in many neurodegenerative diseases. Insoluble proteins accumulate in brain parenchyma and in walls of cerebral capillaries and arteries. Cerebral amyloid angiopathy (CAA) is a descriptive term for amyloid in vessel walls. Here, we adopt the term protein elimination failure angiopathy (PEFA) to focus on mechanisms involved in the pathogenesis of a spectrum of disorders that exhibit both unique and common features of protein accumulation in blood vessel walls. We review (a) normal pathways and mechanisms by which proteins and other soluble metabolites are eliminated from the brain along 100- to 150-nm-thick basement membranes in walls of cerebral capillaries and arteries that serve as routes for lymphatic drainage of the brain; (b) a spectrum of proteins involved in PEFA; and (c) changes that occur in artery walls and contribute to failure of protein elimination. We use accumulation of amyloid beta (Aß), prion protein and granular osmiophilic material (GOM) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as examples of different factors involved in the aetiology and pathogenesis of PEFA. Finally, we discuss how knowledge of factors involved in PEFA may help to focus on new therapies for neurodegenerative diseases. When Aß (following immunotherapy) and prion protein are released from brain parenchyma they deposit in walls of cerebral capillaries and arteries; GOM in CADASIL accumulates primarily in artery walls. Therefore, the focus of therapy for protein clearance in neurodegenerative disease should perhaps be on facilitating perivascular elimination of proteins and reducing PEFA.

Early extubation for adult cardiac surgical patients.

BACKGROUND: Over 30 studies reported that early extubation (within eight hours) appears to be safe without an increased incidence of morbidity. A benefit of the practice may be cost savings associated with shorter Intensive Care Unit and hospital length of stays. OBJECTIVES: To assess the effects of early extubation and the impact of the extubating clinician's profession on morbidity, mortality, intensive care unit and hospital length of stay, with a subgroup analysis for extubation within four hours or four to eight hours. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)(issue 1, 2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1980 to June 2003), CINAHL (January 1982 to December 2002), SIGLE(January 1980 to December 2002). We searched reference lists of articles and contacted researchers in the field. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials of adult cardiac surgical patients (coronary artery bypass grafts, aortic valve replacement, mitral valve replacement, aortic aneurysm repair). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. A meta-analysis for most outcomes was conducted. MAIN RESULTS: Six trials were included in the review. There was no evidence of a difference between early and conventionally extubated patients shown in the relative risk and 95% confidence interval for the following outcomes: mortality in intensive care was 0.8 (0.42 to 1.52); thirty day mortality was 1.2 (0.63 to 2.27); myocardial ischaemia was 0.96 (0.71 to 1.30); reintubation within 24 hours of surgery was 5.93 (0.72 to 49.14). Time spent in intensive care and in hospital were significantly shorter for patients extubated early (7.02 hours (- 7.42 to - 6.61) and 1.08 days ( - 1.35 to - 0.82) respectively). REVIEWER'S CONCLUSIONS: There is no evidence of a difference in mortality and morbidity rates between the study groups. Early extubation reduces intensive care unit and hospital length of stay. Studies were underpowered and designed to show differences between study groups rather than equivalence between the groups. Suggested future areas of investigation: establishing the safety and efficacy of immediate extubation compared with early extubation; establishing the most effective means of pain control and reducing anxiety for patients; systematic reviews of the evidence for different parts of the patients journey through a cardiac surgery episode; and the impact of the profession of the clinician making the decision to extubate.

Hospitalizations for bacterial septicemia after renal transplantation in the united states.

BACKGROUND: It is common belief in the transplant community that rates of septicemia in transplant recipients have declined, but this has not been studied in a national population. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from July 1, 1994 to June 30, 1997 were analyzed in a retrospective registry study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of septicemia (ICD9 Code 038.x). RESULTS: Renal transplant recipients had an adjusted incidence ratio of hospitalizations for septicemia of 41.52 (95% CI 35.45-48.96) compared to the general population. Hospitalizations for septicemia were most commonly associated with urinary tract infection as a secondary diagnosis (30.6%). In multivariate analysis, diabetes and urologic disease, female gender, delayed graft function, rejection, and pre-transplant dialysis, but not induction antibody therapy, were associated with hospitalizations for septicemia. Recipients hospitalized for septicemia had a mean patient survival of 9.03 years (95% CI 7.42-10.63) compared to 15.73 years (95% CI 14.77-16.69) for all other recipients. CONCLUSIONS: Even in the modern era, renal transplant recipients remain at high risk for hospitalizations for septicemia, which are associated with substantially decreased patient survival. Newly identified risks in this population were female recipients and pre-transplant dialysis.

Hospitalizations for fungal infections after renal transplantation in the United States.

Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post-transplant, but only 22% by two months. In logistic regression analysis, end-stage renal disease due to diabetes, duration of pre-transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22-3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre-transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.

Antibiotic resistance: a clinician's perspective.

Since the introduction of antimicrobial agents, resistance has increased steadily across all classes of antibiotics. Organisms vary in susceptibility. Therefore, an antibiogram or susceptibility profile is needed for each infecting organism to determine the most appropriate antibiotic. When the infecting organism has not yet been identified, an informed decision can be made only by obtaining an accurate profile of antibiotic resistance in the hospital, the community, and, in some instances, the world. The appropriate use of antibiotics is correlated with a more favorable clinical outcome and also delays the emergence of resistance. Ensuring such prescribing behavior requires a multidisciplinary approach. Familiarity with the trends and prevalence of antibiotic resistance also facilitates the early identification of individuals harboring resistant organisms. Early isolation can then be initiated, thereby minimizing the risk of nosocomial cross-infection. This article offers a clinician's pragmatic view of antimicrobial resistance.

Factitious halothane detection during trigger-free anesthesia in a malignant hyperthermia susceptible patient.

PURPOSE: To discuss the problems encountered when halothane was detected in a presumed 'clean' patient circuit during the 'trigger-free' anesthetic management of a known Malignant Hyperthermia Susceptible (MHS) patient for routine orthopedic surgery. CLINICAL FEATURES: A 29-yr-old MHS woman had a wrist arthroscopy/exploration/fusion under general anesthesia. During the course of the 'trigger-free' anesthetic the respiratory gas analyser detected end-tidal halothane in the patient circuit. The patient was disconnected from the circuit as attempts to identify the source of the readings were undertaken. After ruling out the presence of halothane by various clinical manoeuvre the patient was reconnected to the circuit without sequelae. CONCLUSION: By exclusion the problem was presumed to be a factitious reading resulting from the respiratory gas analyser incorrectly identifying patient-expired methane as halothane.

Human immunodeficiency virus RNA levels in US adults: a comparison based upon race and ethnicity.

Volunteers in a natural history study of human immunodeficiency virus type 1 (HIV-1) at two military medical centers were studied to determine whether plasma HIV-1 RNA levels differ among racial and ethnic groups of US adults infected with HIV-1. Cross-sectional analyses of plasma HIV-1 RNA and CD4 cell counts were done using demographic and clinical data collected during study visits. Age, gender, CD4 cell count, seroconversion status, and use of antiretroviral therapy were studied in 545 military members (46% white, 49% black, and 6% Hispanic). No association was found between HIV-1 RNA levels and race or ethnicity among infected adults for whom access to care and socioeconomic status were not confounding factors.

Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).