To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes.
Systematic review and meta-analysis.
Electronic ...databases EMBASE and MEDLINE and the reference sections of previous reviews.
Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions.
Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = -.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02).
This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.
MicroRNAs (miRNAs) act within Argonaute proteins to guide repression of messenger RNA targets. Although various approaches have provided insight into target recognition, the sparsity of miRNA-target ...affinity measurements has limited understanding and prediction of targeting efficacy. Here, we adapted RNA bind-n-seq to enable measurement of relative binding affinities between Argonaute-miRNA complexes and all sequences ≤12 nucleotides in length. This approach revealed noncanonical target sites specific to each miRNA, miRNA-specific differences in canonical target-site affinities, and a 100-fold impact of dinucleotides flanking each site. These data enabled construction of a biochemical model of miRNA-mediated repression, which was extended to all miRNA sequences using a convolutional neural network. This model substantially improved prediction of cellular repression, thereby providing a biochemical basis for quantitatively integrating miRNAs into gene-regulatory networks.
Ascorbic acid (vitamin C) is an unusual antioxidant in that it donates a single reducing equivalent, and the radical it forms, monodehydroascorbate, reacts preferentially with radicals instead of ...with non-radical compounds. This happens because removal of an electron from monodehydroascorbate would create a tricarbonyl structure that is energetically unfavored. Instead of forming this structure, ascorbic acid oxidizes only to monodehydroascorbate, and monodehydroascorbate reacts with other radicals, oxidizing by mechanisms that may circumvent formation of this unfavored structure. Ironically, this tricarbonyl compound, which we suggest be called pseudodehydroascorbate, is commonly and mistakenly cited as the real product of ascorbic acid oxidation. In fact, it has been known for over 40 years that dehydroascorbate has a bicyclic hemiketal structure, and kinetic considerations suggest that it may be produced and reduced without forming pseudodehydroascorbate as an intermediate. This and other significant questions about the chemical basis of the antioxidant properties of ascorbic acid are obscured by this misconception about its oxidation product, dehydroascorbate.
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•Ascorbic acid (vitamin C) donates a single H atom to form monodehydroascorbate.•Monodehydroascorbate (A•-) prefers to react with radicals•The fully oxidized form of ascorbic acid, dehydroascorbate, is a bicyclic hemiketal.•The tricarbonyl structure commonly called dehydroascorbate rarely occurs in nature.•A•- reacts with radicals to form the hemiketal directly and avoid the tricarbonyl
Recent pediatric studies suggest a survival benefit exists for higher-volume extracorporeal membrane oxygenation (ECMO) centers.
To determine if higher annual ECMO patient volume is associated with ...lower case-mix-adjusted hospital mortality rate.
We retrospectively analyzed an international registry of ECMO support from 1989 to 2013. Patients were separated into three age groups: neonatal (0-28 d), pediatric (29 d to <18 yr), and adult (≥18 yr). The measure of hospital ECMO volume was age group-specific and adjusted for patient-level case-mix and hospital-level variance using multivariable hierarchical logistic regression modeling. The primary outcome was death before hospital discharge. A subgroup analysis was conducted for 2008-2013.
From 1989 to 2013, a total of 290 centers provided ECMO support to 56,222 patients (30,909 neonates, 14,725 children, and 10,588 adults). Annual ECMO mortality rates varied widely across ECMO centers: the interquartile range was 18-50% for neonates, 25-66% for pediatrics, and 33-92% for adults. For 1989-2013, higher age group-specific ECMO volume was associated with lower odds of ECMO mortality for neonates and adults but not for pediatric cases. In 2008-2013, the volume-outcome association remained statistically significant only among adults. Patients receiving ECMO at hospitals with more than 30 adult annual ECMO cases had significantly lower odds of mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.46-0.80) compared with adults receiving ECMO at hospitals with less than six annual cases.
In this international, case-mix-adjusted analysis, higher annual hospital ECMO volume was associated with lower mortality in 1989-2013 for neonates and adults; the association among adults persisted in 2008-2013.
The cortical surface is organized into a large number of cortical areas; however, these areas have not been comprehensively mapped in the human. Abrupt transitions in resting-state functional ...connectivity (RSFC) patterns can noninvasively identify locations of putative borders between cortical areas (RSFC-boundary mapping; Cohen et al. 2008). Here we describe a technique for using RSFC-boundary maps to define parcels that represent putative cortical areas. These parcels had highly homogenous RSFC patterns, indicating that they contained one unique RSFC signal; furthermore, the parcels were much more homogenous than a null model matched for parcel size when tested in two separate datasets. Several alternative parcellation schemes were tested this way, and no other parcellation was as homogenous as or had as large a difference compared with its null model. The boundary map-derived parcellation contained parcels that overlapped with architectonic mapping of areas 17, 2, 3, and 4. These parcels had a network structure similar to the known network structure of the brain, and their connectivity patterns were reliable across individual subjects. These observations suggest that RSFC-boundary map-derived parcels provide information about the location and extent of human cortical areas. A parcellation generated using this method is available at http://www.nil.wustl.edu/labs/petersen/Resources.html.
Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo ...(non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS).
Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47 ± 18 with IBS diagnosed by Rome III criteria and with a score ≥ 150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).
Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2 ± 1.0 vs. 4.0 ± 1.1, p<.001) and at 21-day endpoint (5.0 ± 1.5 vs. 3.9 ± 1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08).
Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.
ClinicalTrials.gov NCT01010191.
Failures of self-regulation are common, leading to many of the most vexing problems facing contemporary society, from overeating and obesity to impulsive sexual behavior and STDs. One reason that ...people may be prone to engaging in unwanted behaviors is heightened sensitivity to cues related to those behaviors; people may overeat because of hyperresponsiveness to food cues, addicts may relapse following exposure to their drug of choice, and some people might engage in impulsive sexual activity because they are easily aroused by erotic stimuli. An open question is the extent to which individual differences in neural cue reactivity relate to actual behavioral outcomes. Here we show that individual differences in human reward-related brain activity in the nucleus accumbens to food and sexual images predict subsequent weight gain and sexual activity 6 months later. These findings suggest that heightened reward responsivity in the brain to food and sexual cues is associated with indulgence in overeating and sexual activity, respectively, and provide evidence for a common neural mechanism associated with appetitive behaviors.
ABSTRACT
We combine orbital information from N-body simulations with an analytic model for star formation quenching and SDSS observations to infer the differential effect of the group/cluster ...environment on star formation in satellite galaxies. We also consider a model for gas stripping, using the same input supplemented with H i fluxes from the ALFALFA survey. The models are motivated by and tested on the Hydrangea cosmological hydrodynamical simulation suite. We recover the characteristic times when satellite galaxies are stripped and quenched. Stripping in massive ($M_{\rm vir}\sim 10^{14.5}\, {\rm M}_\odot$) clusters typically occurs at or just before the first pericentric passage. Lower mass ($\sim 10^{13.5}\, {\rm M}_\odot$) groups strip their satellites on a significantly longer (by $\sim 3\, {\rm Gyr}$) time-scale. Quenching occurs later: Balmer emission lines typically fade $\sim 3.5\, {\rm Gyr}$ ($5.5\, {\rm Gyr}$) after first pericentre in clusters (groups), followed a few hundred Myr later by reddenning in (g − r) colour. These ‘delay time-scales’ are remarkably constant across the entire satellite stellar mass range probed (∼109.5–$10^{11}\, {\rm M}_\odot$), a feature closely tied to our treatment of ‘group pre-processing’. The lowest mass groups in our sample ($\sim 10^{12.5}\, {\rm M}_\odot$) strip and quench their satellites extremely inefficiently: typical time-scales may approach the age of the Universe. Our measurements are qualitatively consistent with the ‘delayed-then-rapid’ quenching scenario advocated for by several other studies, but we find significantly longer delay times. Our combination of a homogeneous analysis and input catalogues yields new insight into the sequence of events leading to quenching across wide intervals in host and satellite mass.
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