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The composition and metabolic activity of the bacteria that inhabit the large intestine can have a major impact on health. Despite considerable inter-individual variation across bacterial species, the dominant phyla are generally highly conserved. There are several exogenous and gut environmental factors that play a role in modulating the composition and activities of colonic bacteria including diet with intakes of different macronutrients, including protein, accounting for approximately 20% of the microbial variation. Certain bacterial species tend to be considered as generalists and can metabolise a broad range of substrates, including both carbohydrate- and protein-derived substrates, whilst other species are specialists with a rather limited metabolic capacity. Metabolism of peptides and amino acids by gut bacteria can result in the formation of a wide range of metabolites several of which are considered deleterious to health including nitrosamines, heterocyclic amines and hydrogen sulphide as some of these products are genotoxic and have been linked to colonic disease. Beneficial metabolites however include SCFA and certain species can use amino acids to form butyrate which is the major energy source for colonocytes. The impact on health may however depend on the source of these products. In this review, we consider the impact of diet, particularly protein diets, on modulating the composition of the gut microbiota and likely health consequences and the potential impact of climate change and food security.
Background: Pediatric influenza vaccination rates remain <50% in the United States. Children with chronic medical conditions are at higher risk of morbidity and mortality from influenza, yet most experience missed opportunities for immunization in outpatient settings. In an adult cohort study, 74% of patients who had not received the influenza vaccine before or during hospitalization remained unvaccinated through the rest of the season. Thus, inpatient settings represent another important opportunity for vaccinating an especially susceptible population. In addition, 4 published studies have shown promise in improving inpatient pediatric influenza vaccination. However, these studies had limited effect sizes and included interventions requiring ongoing maintenance with dedicated staff. In this study, we hypothesized that a clinical decision support (CDS) intervention designed with user-centered design principles would increase inpatient influenza vaccine administration rates in the 2019–2020 influenza season. Methods: We performed a workflow analysis of different care settings to determine optimal timing of influenza vaccine decision support. Through formative usability testing with frontline clinicians, we developed electronic health record (EHR) prototypes of an order set module containing a default influenza vaccine order. This module was dynamically incorporated into order sets for patients meeting the following criteria: ≥6 months old, no prior influenza vaccine in the current season in our medical system or the state immunization registry, and no prior anaphylaxis to the vaccine. We implemented the CDS into select order sets based on operational leader support. We compared the proportion of eligible hospitalized patients in which the influenza vaccine was administered between our intervention period and the 2018–2019 season (historical controls). To account for secular trends, we also compared the vaccination rates for hospitalized patients exposed to our CDS to those that were not exposed to the CDS during the intervention period (concurrent controls). Results: During the intervention period (September 5, 2019–November 1, 2019), influenza vaccine was administered to 762 of 3,242 (24%) of eligible patients, compared to 360 of 2,875 (13%) among historical controls (P < .0001). Among the 42% of patients exposed to the CDS, vaccination rates were 33% compared to 9% for concurrent controls (p < .0001). Our intervention was limited by end-user uptake, with some physicians or nurses discontinuing the default vaccine order. In addition, early in the intervention, some vaccines were ordered but not administered, leading to vaccine waste. Conclusions: CDS targeting eligible hospitalized patients for influenza vaccination incorporated early into the workflow of nurses and ordering clinicians can substantially improve influenza vaccination rates among this susceptible and hard-to-reach population.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly common in the United States and have the potential to spread widely across healthcare networks. Only a fraction of patients with CRE carriage (ie, infection or colonization) are identified by clinical cultures. Interventions to reduce CRE transmission can be explored with agent-based models (ABMs) comprised of unique agents (eg, patients) represented by a synthetic population or model-generated representation of the population. We used electronic health record data to determine CRE carriage risk, and we discuss how these results can inform CRE transmission parameters for hospitalized agents in a regional healthcare network ABM. Methods: We reviewed the laboratory data of patients admitted during July 1, 2016−June 30, 2017, to any of 7 short-term acute-care hospitals of a regional healthcare network in North Carolina (N = 118,022 admissions) to find clinically detected cases of CRE carriage. A case was defined as the first occurrence of Enterobacter spp, Escherichia coli, or Klebsiella spp resistant to any carbapenem isolated from a clinical specimen in an admitted patient. We used Poisson regression to estimate clinically detected CRE carriage risk according to variables common to data from both the electronic health records and the ABM synthetic population, including patient demographics, systemic antibiotic administration, intensive care unit stay, comorbidities, length of stay, and admitting hospital size. Results: We identified 58 (0.05%) cases of CRE carriage among all admissions. Among these cases, 30 (52%) were ≥65 years of age and 37 (64%) were female. During their admission, 47 cases (81%) were administered systemic antibiotics and 18 cases (31%) had an intensive care unit stay. Patients administered systemic antibiotics and those with an intensive care unit stay had CRE carriage risk 6.5 times (95% CI, 3.4–12.5) and 4.9 times (95% CI, 2.8–8.5) higher, respectively, than patients without these exposures (Fig. 1). Patients ≥50 years of age and those with a higher Elixhauser comorbidity index score and with longer length of stay also had increased CRE carriage risk. Conclusions: Among admissions in our dataset, CRE carriage risk was associated with systemic antibiotic exposure, intensive care unit stay, higher Elixhauser comorbidity index score, and longer length of stay. We will use these risk estimates in the ABM to inform agents’ CRE carriage status upon hospital admission and the CRE transmission parameters for short-term acute-care hospitals. We will explore CRE transmission interventions in the parameterized regional healthcare network ABM and assess the impact of CRE carriage underestimation.
Funding: This work was supported by Centers for Disease Control and Prevention (CDC) Cooperative Agreement number U01CK000527. The conclusions, findings, and opinions expressed do not necessarily reflect the official position of CDC.
It is unknown whether patient disengagement from early intervention services for psychosis is as prevalent in low- and middle-income countries (LMICs) like India, as it is in high-income countries (HICs). Addressing this gap, we studied two first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized lower service disengagement among patients and higher engagement among families in Chennai, and that family engagement would mediate cross-site differences in patient disengagement.
Sites were compared on their 2-year patient disengagement and family engagement rates conducting time-to-event analyses and independent samples t tests on monthly contact data. Along with site and family involvement, Cox proportional hazards regression included known predictors of patient disengagement (e.g. gender).
The study included data about 333 patients (165 in Montreal, 168 in Chennai) and their family members (156 in Montreal, 168 in Chennai). More Montreal patients (19%) disengaged before 24 months than Chennai patients (1%), χ2(1, N = 333) = 28.87, p < 0.001. Chennai families had more contact with clinicians throughout treatment (Cohen's d = −1.28). Family contact significantly predicted patient disengagement in Montreal (HR = 0.87, 95% CI 0.81–0.93). Unlike in Chennai, family contact declined over time in Montreal, with clinicians perceiving such contact as not necessary (Cohen's d = 1.73).
This is the first investigation of early psychosis service engagement across a HIC and an LMIC. Patient and family engagement was strikingly higher in Chennai. Maintaining family contact may benefit patient engagement, irrespective of context. Findings also suggest that differential service utilization may underpin cross-cultural variations in psychosis outcomes.
During a psychotic episode, patients frequently suffer from severe maladaptive beliefs known as delusions. Despite the abundant literature investigating the simple presence or absence of these beliefs, there exists little detailed knowledge regarding their actual content and severity at the onset of illness.
This study reports on delusions during the initiation of indicated treatment for first-episode psychosis (FEP).
Data were systematically collected from a sample of 636 patients entering a catchment-based early intervention service for FEP. The average severity and frequency of each delusional theme at baseline was reported with the Scale for the Assessment of Positive Symptoms. Delusional severity (globally and per theme) was examined across a number of sociodemographic and clinical variables.
Delusions were present in the vast majority of individuals experiencing onset of FEP (94%), with persecutory (77.7%) being the most common theme. Persecutory delusions remained consistent in severity across diagnoses, but were more severe with older age at onset of FEP. No meaningful differences in delusional severity were observed across gender, affective versus non-affective psychosis, or presence/absence of substance use disorder. Globally, delusion severity was associated with anxiety, but not depression. Delusions commonly referred to as passivity experiences were related to hallucinatory experiences.
This community sample offers a rare clinical lens into the severity and content of delusions in FEP. Although delusional severity was consistent across certain sociodemographic and clinical variables, this was not always the case. Future research should now consider the course of delusion themes over time.
Reproductive externalities are important for fertility behavior in Kenya. We identify from anthropology structural forms of social interaction operating across individuals belonging to different ethnic and religious groups on the number of children ever born. We use the 1998 Demographic and Health Survey, combined with primary meteorological data on Kenya, and GMM methods, to show that social interaction effects by ethnicity are important over and above an individual's characteristics such as their religion to explain variations in fertility. Our findings have implications for policy debates in Kenya and in other developing countries about ethnic, religious, and other differences in fertility behavior.
Fibre-optic nasoendoscopy and fibre-optic laryngoscopy are high-risk procedures in the coronavirus disease 2019 era, as they are potential aerosol-generating procedures. Barrier protection remains key to preventing transmission.
A device was developed that patients can wear to reduce potential aerosol contamination of the surroundings.
This device is simple, reproducible, easy to use, economical and well-tolerated. Full personal protection equipment should additionally be worn by the operator.
Purported superior outcomes for treatment of psychosis in low- and middle-income (LMICs) compared with high-income (HICs) countries have not been examined in the context of early intervention services (EIS).
To compare 2-year clinical outcomes in first-episode psychosis (FEP) treated in EIS in Chennai (LMIC) and Montreal (HIC) using a similar EIS treatment protocol and to identify factors associated with any outcome differences.
Patients with FEP treated in EIS in Chennai (n = 168) and Montreal (n = 165) were compared on change in level of symptoms and rate and duration of positive and negative symptom remission over a 2-year period. Repeated-measures analysis of variance, and logistic and linear regression analyses were conducted.
Four patients died in Chennai compared with none in Montreal. Family support was higher for Chennai patients (F = 14.05, d.f. = 1, P < 0.001, ƞp2 = 0.061) and increased over time at both sites (F = 7.0, d.f. = 1.915, P < 0.001, ƞp2 = 0.03). Negative symptom outcomes were significantly better in Chennai for level of symptoms (time × site interaction F = 7.36, d.f. = 1.49, P = 0.002, ƞp2 = 0.03), duration of remission (mean 16.1 v. 9.78 months, t = −7.35, d.f. = 331, P < 0.001, Cohen's d = 0.80) and the proportion of patients in remission (81.5% v. 60.3%, χ2 = 16.12, d.f. = 1, P < 0.001). The site differences in outcome remained robust after adjusting for inter-site differences in other characteristics. Early remission and family support facilitated better outcome on negative symptoms. No significant differences were observed in positive symptom outcomes.
Patients with FEP treated in EIS in LMIC contexts are likely to show better outcome on negative symptoms compared with those in HIC contexts. Early remission and family support may benefit patients across both contexts.
Pharyngocutaneous fistulae are dreaded complications following total laryngectomy. This paper presents our experience using 3–5 ml gastrografin to detect pharyngeal leaks following total laryngectomy, and compares post-operative videofluoroscopy with clinical follow-up findings in the detection of pharyngocutaneous fistulae.
A retrospective case–control study was conducted of total laryngectomy patients. The control group (n = 85) was assessed clinically for development of pharyngocutaneous fistulae, while the study group (n = 52) underwent small-volume (3–5 ml) post-operative gastrografin videofluoroscopy.
In the control group, 24 of 85 patients (28 per cent) developed pharyngocutaneous fistulae, with 6 requiring surgical correction. In the study group, 24 of 52 patients (46 per cent) had videofluoroscopy-detected pharyngeal leaks; 4 patients (8 per cent) developed pharyngocutaneous fistulae, but all cases resolved following non-surgical management. Patients who underwent videofluoroscopy had a significantly lower risk of developing pharyngocutaneous fistulae; sensitivity and specificity in the detection of pharyngocutaneous fistulae were 58 per cent and 100 per cent respectively.
Small-volume gastrografin videofluoroscopy reliably identified small pharyngeal leaks. Routine use in total laryngectomy combined with withholding feeds in cases of early leaks may prevent the development of pharyngocutaneous fistulae.
Alzheimer’s disease (AD), a neurodegenerative disorder, is the leading cause of dementia in the world whose aetiology is still unclear. AD was always related to ageing though there have been instances where people at an early age also succumb to this disease. With medical advancements, the mortality rate has significantly reduced which also makes people more prone to AD. AD is rare, yet the prominent disease has been widely studied with several hypotheses trying to understand the workings of its onset. The most recent and popular hypothesis in AD is the involvement of mitochondrial dysfunction and calcium homeostasis in the development of the disease though their exact roles are not known. With the sudden advent of the mitochondrial calcium uniporter (MCU), many previously known pathological hallmarks of AD may be better understood. Several studies have shown the effect of excess calcium in mitochondria and the influence of MCU complex in mitochondrial function. In this article, we discuss the possible involvement of MCU in AD by linking the uniporter to mitochondrial dysfunction, calcium homeostasis, reactive oxygen species, neurotransmitters and the hallmarks of AD – amyloid plaque formation and tau tangle formation.
While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings.
A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India.
Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed.
A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.
Panchromatic SED fitting allows us to better resolve degeneracies between quantities like the star formation rate and dust. This in turn allows us to more robustly extract information about the different stellar populations that comprise a galaxy’s Star Formation History (SFH). Using the Dense Basis SED fitting method (Iyer & Gawiser 2017), we reconstruct the SFHs with uncertainties for a large sample of galaxies using an atlas of SEDs corresponding to a physically motivated basis of SFHs. Using Gaussian Process Regression, we encode the parameters describing these SFHs in a functionally independent form. This give us more robust estimates for quantities like Stellar Masses and Star Formation Rates, that directly depend on the SFH. These SFHs can additionally be used to answer questions like the time at which a galaxy’s star formation peaked, and how many major episodes of star formation occurred in a galaxy’s past, allowing us to go beyond the traditionally estimated ‘Galaxy Age’, which is often poorly constrained. They also allow us to probe the high-redshift low-stellar mass regime of the SFR-M* correlation by constructing trajectories in SFR-M* space for each galaxy.
Comparing the feasibility of ovine and synthetic temporal bones for simulating endoscopic ear surgery against the ‘gold standard’ of human cadaveric tissue.
A total of 10 candidates (5 trainees and 5 experts) performed endoscopic tympanoplasty on 3 models: Pettigrew temporal bones, ovine temporal bones and cadaveric temporal bones. Candidates completed a questionnaire assessing the face validity, global content validity and task-specific content validity of each model.
Regarding ovine temporal bone validity, the median values were 4 (interquartile range = 4–4) for face validity, 4 (interquartile range = 4–4) for global content validity and 4 (interquartile range = 4–4) for task-specific content validity. For the Pettigrew temporal bone, the median values were 3.5 (interquartile range = 2.25–4) for face validity, 3 (interquartile range = 2.75–3) for global content validity and 3 (interquartile range = 2.5–3) for task-specific content validity. The ovine temporal bone was considered significantly superior to the Pettigrew temporal bone for the majority of validity categories assessed.
Tympanoplasty is feasible in both the ovine temporal bone and the Pettigrew temporal bone. However, the ovine model was a significantly more realistic simulation tool.
Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.
Eigenmodes of averaged small-amplitude perturbations to a turbulent channel flow – which is one of the most fundamental canonical flows – are identified for the first time via an extensive set of high-fidelity graphics processing unit accelerated direct numerical simulations. While the system governing averaged small-amplitude perturbations to turbulent channel flow remains unknown, the fact such eigenmodes can be identified constitutes direct evidence that it is linear. Moreover, while the eigenvalue associated with the slowest-decaying anti-symmetric eigenmode mode is found to be real, the eigenvalue associated with the slowest-decaying symmetric eigenmode mode is found to be complex. This indicates that the unknown linear system governing the evolution of averaged small-amplitude perturbations cannot be self-adjoint, even for the case of a uni-directional flow. In addition to elucidating aspects of the flow physics, the findings provide guidance for development of new unsteady Reynolds-averaged Navier–Stokes turbulence models, and constitute a new and accessible benchmark problem for assessing the performance of existing models, which are used widely throughout industry.