The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this ...paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies.
The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included.
Studies were identified for metoclopramide (n=6), domperidone (n=6), cisapride (n=14), erythromycin (n=3), botulinum toxin (n=2), and levosulpiride (n=3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors.
In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.
•Structural LTP produces opposite effects at synapses on immature versus adult dendrites.•Local subcellular compartments mediate synaptogenesis at P15 and synapse enlargement in adults.•A unified ...theory of resource-dependent silent spinogenesis and synapse enlargement is presented.
Nature teaches us that form precedes function, yet structure and function are intertwined. Such is the case with synapse structure, function, and plasticity underlying learning, especially in the hippocampus, a crucial brain region for memory formation. As the hippocampus matures, enduring changes in synapse structure produced by long-term potentiation (LTP) shift from synaptogenesis to synapse enlargement that is homeostatically balanced by stalled spine outgrowth and local spine clustering. Production of LTP leads to silent spine outgrowth at P15, and silent synapse enlargement in adult hippocampus at 2hours, but not at 5 or 30min following induction. Here we consider structural LTP in the context of developmental stage and variation in the availability of local resources of endosomes, smooth endoplasmic reticulum and polyribosomes. The emerging evidence supports a need for more nuanced analysis of synaptic plasticity in the context of subcellular resource availability and developmental stage.
Choice of variables, climate models and emissions scenarios all influence the results of species distribution models under future climatic conditions. However, an overview of applied studies suggests ...that the uncertainty associated with these factors is not always appropriately incorporated or even considered. We examine the effects of choice of variables, climate models and emissions scenarios can have on future species distribution models using two endangered species: one a short-lived invertebrate species (Ptunarra Brown Butterfly), and the other a long-lived paleo-endemic tree species (King Billy Pine). We show the range in projected distributions that result from different variable selection, climate models and emissions scenarios. The extent to which results are affected by these choices depends on the characteristics of the species modelled, but they all have the potential to substantially alter conclusions about the impacts of climate change. We discuss implications for conservation planning and management, and provide recommendations to conservation practitioners on variable selection and accommodating uncertainty when using future climate projections in species distribution models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article ...presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI.
A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: "acute bronchitis," "respiratory tract infection," "pharyngitis," "rhinosinusitis," and "the common cold."
Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected.
Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis.
Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening).
Clinicians should not prescribe antibiotics for patients with the common cold.
The morphology and molecular composition of synapses provide the structural basis for synaptic function. This article reviews the electron microscopy of excitatory synapses on dendritic spines, using ...data from rodent hippocampus, cerebral cortex, and cerebellar cortex. Excitatory synapses have a prominent postsynaptic density, in contrast with inhibitory synapses, which have less dense presynaptic or postsynaptic specializations and are usually found on the cell body or proximal dendritic shaft. Immunogold labeling shows that the presynaptic active zone provides a scaffold for key molecules involved in the release of neurotransmitter, whereas the postsynaptic density contains ligand-gated ionic channels, other receptors, and a complex network of signaling molecules. Delineating the structure and molecular organization of these axospinous synapses represents a crucial step toward understanding the mechanisms that underlie synaptic transmission and the dynamic modulation of neurotransmission associated with short- and long-term synaptic plasticity.
Abstract Background Major Depressive Disorder (MDD) is a leading cause of the disease burden for women of childbearing age, but the burden of MDD attributable to perinatal depression is not yet ...known. There has been little effort to date to systematically review available literature and produce global estimates of prevalence and incidence of perinatal depression. Enhanced understanding will help to guide resource allocation for screening and treatment. Methods A systematic literature review using the databases PsycINFO and PubMed returned 140 usable prevalence estimates from 96 studies. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies and to guide a subsequent random-effects meta-analysis. Results The meta-regression explained 31.1% of the variance in prevalence reported between studies. Adjusting for the effects of all other variables in the model, prevalence derived using symptom scales was significantly higher than prevalence derived using diagnostic instruments (odds ratio OR 1.6, 95% confidence interval CI 1.3–2.0). Additionally, prevalence was significantly higher in women from low and middle income countries compared to women from high income countries (OR 1.8, 95% CI 1.4–2.2). The overall pooled prevalence was 11.9% of women during the perinatal period (95% CI 11.4–12.5). There were insufficient data to calculate pooled incidence. Limitations Studies in low income countries were especially scarce in this review, demonstrating a need for more epidemiological research in those regions. Conclusions Perinatal depression appears to impose a higher burden on women in low- and middle-income countries. This review contributes significantly to the epidemiological literature on the disorder.
Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater ...inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few studies have examined spontaneous remission from major depression. This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a ...year, and whether remission rates vary by disorder severity.
Wait-list controlled trials and observational cohort studies published up to 2010 with data describing remission from untreated depression at ≤ 2-year follow-up were identified. Remission was defined as rescinded diagnoses or below threshold scores on standardized symptom measures. Nineteen studies were included in a regression model predicting the probability of 12-month remission from untreated depression, using logit transformed remission proportion as the dependent variable. Covariates included age, gender, study type and diagnostic measure.
Wait-listed compared to primary-care samples, studies with longer follow-up duration and older adult compared to adult samples were associated with lower probability of remission. Child and adolescent samples were associated with higher probability of remission. Based on adult samples recruited from primary-care settings, the model estimated that 23% of prevalent cases of untreated depression will remit within 3 months, 32% within 6 months and 53% within 12 months.
It is undesirable to expect 100% treatment coverage for depression, given many will remit before access to services is feasible. Data were drawn from consenting wait-list and primary-care samples, which potentially over-represented mild-to-moderate cases of depression. Considering reported rates of spontaneous remission, a short untreated period seems defensible for this subpopulation, where judged appropriate by the clinician. Conclusions may not apply to individuals with more severe depression.
Background
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the resulting COVID‐19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to ...identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point‐of‐care antigen and molecular tests to detect current SARS‐CoV‐2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory‐based diagnostic methods, with the aim of reducing household and community transmission.
Objectives
To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests to determine if a person presenting in the community or in primary or secondary care has current SARS‐CoV‐2 infection.
Search methods
On 25 May 2020 we undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions.
Selection criteria
We included studies of people with suspected current SARS‐CoV‐2 infection, known to have, or not to have SARS‐CoV‐2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established clinical diagnostic criteria).
Data collection and analysis
Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS‐2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular‐based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer.
Main results
We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS‐CoV‐2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in‐house antigen test. Five of the studies included were only available as preprints.
We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over‐sampling of samples with confirmed COVID‐19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT‐PCR to confirm the absence of COVID‐19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations.
Antigen tests
Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test.
Rapid molecular assays
Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID‐19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%).
Individual tests
We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of −2.8% (95% CI −6.4 to 0.8))
Authors' conclusions
This review identifies early‐stage evaluations of point‐of‐care tests for detecting SARS‐CoV‐2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID‐19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT‐PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice.
Prospective and comparative evaluations of rapid tests for COVID‐19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point‐of‐care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.
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