The association between pre-hospital antibiotic therapy and subsequent in-hospital mortality in adults presenting with community-acquired pneumonia: an observational study

Background The majority of patients with community acquired-pneumonia (CAP) are treated in primary care and the mortality in this group is very low. However, a small but significant proportion of patients who begin treatment in the community subsequently require admission due to symptomatic deterioration. This study compared patients who received community antibiotics prior to admission to those who had not, and looked for associations with clinical outcomes. Methods This study analysed the Advancing Quality (AQ) Pneumonia database of patients admitted with CAP to 9 acute hospitals in the northwest of England over a 12-month period. Results There were 6348 subjects (mean age 72 [SD 16] years; gender ratio 1:1) admitted with CAP, of whom 17% had been pre-treated with antibiotics. The in-hospital mortality was 18.6% for the pre-treatment group compared to 13.2% in the “antibiotic naïve” group (p < 0.001). On multivariate analysis, age, male gender and antibiotic pre-treatment were predictors of in-hospital mortality along with a history of cerebrovascular accident, congestive cardiac failure, dementia, renal disease and cancer. After adjustment for CURB-65 score, age, co-morbidities and pre-treatment with antibiotics remained as independent risk factors for in-hospital mortality (OR 1.43, 95% CI 1.19–1.71). Conclusion CAP patients admitted to hospital were more likely to die during admission if they had received antibiotics for the same illness pre-admission. Future studies should endeavor to determine the mechanisms underlying this association, such as microbiological factors and the role of comorbidities. Patients hospitalized with CAP despite prior antibiotic treatment in the community require close monitoring

Explicit Logic Circuits Discriminate Neural States

The magnitude and apparent complexity of the brain's connectivity have left explicit networks largely unexplored. As a result, the relationship between the organization of synaptic connections and how the brain processes information is poorly understood. A recently proposed retinal network that produces neural correlates of color vision is refined and extended here to a family of general logic circuits. For any combination of high and low activity in any set of neurons, one of the logic circuits can receive input from the neurons and activate a single output neuron whenever the input neurons have the given activity state. The strength of the output neuron's response is a measure of the difference between the smallest of the high inputs and the largest of the low inputs. The networks generate correlates of known psychophysical phenomena. These results follow directly from the most cost-effective architectures for specific logic circuits and the minimal cellular capabilities of excitation and inhibition. The networks function dynamically, making their operation consistent with the speed of most brain functions. The networks show that well-known psychophysical phenomena do not require extraordinarily complex brain structures, and that a single network architecture can produce apparently disparate phenomena in different sensory systems

Use of telemonitoring in patient self-management of chronic disease: a qualitative meta-synthesis.

Background Telemonitoring for the remote patient self-management of chronic conditions can be a cost-effective method for delivering care in chronic disease; nonetheless, its implementation in clinical practice remains low. The aim of this meta-synthesis is to explore barriers and facilitators associated with the use of remote patient monitoring of chronic disease, drawing on qualitative research, and assessing participant interactions with this technology. Method A meta-synthesis of qualitative studies was performed. MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database date of inception to 5 February 2021. The Critical Appraisal Skills Programme (CASP) was used to critically appraise each study. Thematic synthesis was performed to identify user (patients, carers and healthcare professionals) perspectives and experiences of patient remote monitoring of chronic disease (Type 2 diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease). Results Searches returned 10,401 studies and following independent screening by two reviewers, nine studies were included in this meta-synthesis. Data were synthesised and categorised into four key themes: (1) Improved care; (2) Communication; (3) Technology feasibility & acceptability; and (4) Intervention concerns. Most patients using patient remote devices felt motivated in managing their own lifestyles and felt reassured by the close monitoring and increased communication. Barriers identified involved generational differences and difficulties with the technology used. Conclusion Most studies showed a positive attitude to telemonitoring, with patients preferring the convenience of telemonitoring in comparison to attending regular clinics. Further research is required to assess the most effective technology for chronic disease management, how to maintain long-term patient adherence, and identify effective approaches to address generational variation in telemonitoring up-take

Interactive remote patient monitoring devices for managing chronic health conditions: systematic review and meta-analysis

Background: Telemedicine is an expanding and feasible approach to improve medical care for patients with long-term conditions. However, there is a poor understanding of patients’ acceptability of this intervention and their rate of uptake. Objective: To systematically review the current evidence on telemonitoring in the management of patients with long-term conditions, and to evaluate the patients’ uptake and acceptability of this technology. Methods: MEDLINE, SCOPUS, and CENTRAL were searched from date of inception to 5 February 2021, with no language restrictions. Studies were eligible for inclusion if they reported any of the following outcomes: (i) intervention uptake and adherence; (ii) study retention; (iii) patient acceptability, satisfaction and experience using intervention: (iv) changes in physiological values; (v) all-cause and cardiovascular related hospitalization; (vi) all-cause and disease specific mortality; (vii) patient-reported outcome measures; (viii) quality of life. Two reviewers independently assessed articles for eligibility. Results: Ninety-six studies studies were included and fifty-eight were pooled for meta-analyses. Meta-analyses showed reduction in mortality (RR= 0.71, 95% CI 0.56 to 0.89, P=0.003, I2=0%); and improvements in BP (MD -3.85 mmHg, 95% CI -7.03 to -0.68, P<.02, I2= 100%) and HbA1c (MD -0.33, 95% CI -0.57 to -0.09, P=.008, I2= 99%); but no significant improvements in quality of life (MD 1.45, 95% CI -0.10 to 3, P=.07, I2=80%); and increased risk of hospitalization (RR 1.02, 95% CI 0.85 to 1.23, P=.81, I2=79%) with telemonitoring compared to usual care. Twelve studies reported adherence outcomes and nine on satisfaction/acceptance, however heterogeneity in the assessment methods meant meta-analysis could not be performed. Conclusion: Telemonitoring is a valid alternative to usual care, reducing mortality and improving self-management of the disease, with patients reporting good satisfaction and adherence. Further studies are required to address some potential concerns regarding higher hospitalisation rates and a lack of a positive impact on patients’ quality of life. This systematic review was registered on PROSPERO (CRD42021236291)

Medicinal importance of grapefruit juice and its interaction with various drugs

Grapefruit juice is consumed widely in today's health conscious world as a protector against cardiovascular diseases and cancers. It has however, been found to be an inhibitor of the intestinal cytochrome P – 450 3A4 system, which is responsible for the first pass metabolism of many drugs. The P – glycoprotein pump, found in the brush border of the intestinal wall which transports many of these cytochrome P – 450 3A4 substrates, has also been implicated to be inhibited by grapefruit juice. By inhibiting these enzyme systems, grapefruit juice alters the pharmacokinetics of a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on the calcium channel antagonist and the statin group of drugs. In the case of many drugs, the increased serum concentration has been found to be associated with increased frequency of dose dependent adverse effects. In this review, we have discussed the phytochemistry of grapefruit juice, the various drugs involved in the drug – grapefruit juice eraction with their mechanisms of action and have presented the clinical implications of these interactions

Adult Body Weight Is Programmed by a Redox-Regulated and Energy-Dependent Process during the Pronuclear Stage in Mouse

In mammals fertilization triggers a series of Ca2+ oscillations that not only are essential for events of egg activation but also stimulate oxidative phosphorylation. Little is known, however, about the relationship between quantitative changes in egg metabolism and specific long-term effects in offspring. This study assessed whether post-natal growth is modulated by early transient changes in NAD(P)H and FAD2+ in zygotes. We report that experimentally manipulating the redox potential of fertilized eggs during the pronuclear (PN) stage affects post-natal body weight. Exogenous pyruvate induces NAD(P)H oxidation and stimulates mitochondrial activity with resulting offspring that are persistently and significantly smaller than controls. Exogenous lactate stimulates NAD+ reduction and impairs mitochondrial activity, and produces offspring that are smaller than controls at weaning but catch up after weaning. Cytosolic alkalization increases NAD(P)+ reduction and offspring of normal birth-weight become significantly and persistently larger than controls. These results constitute the first report that post-natal growth rate is ultimately linked to modulation of NAD(P)H and FAD2+ concentration as early as the PN stage