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A significant proportion of inpatient antimicrobial prescriptions are inappropriate. Post-prescription review with feedback has been shown to be an effective means of reducing inappropriate antimicrobial use. However, implementation is resource intensive. Our aim was to evaluate the performance of traditional statistical models and machine-learning models designed to predict which patients receiving broad-spectrum antibiotics require a stewardship intervention.
We performed a single-center retrospective cohort study of inpatients who received an antimicrobial tracked by the antimicrobial stewardship program. Data were extracted from the electronic medical record and were used to develop logistic regression and boosted-tree models to predict whether antibiotic therapy required stewardship intervention on any given day as compared to the criterion standard of note left by the antimicrobial stewardship team in the patient’s chart. We measured the performance of these models using area under the receiver operating characteristic curves (AUROC), and we evaluated it using a hold-out validation cohort.
Both the logistic regression and boosted-tree models demonstrated fair discriminatory power with AUROCs of 0.73 (95% confidence interval [CI], 0.69–0.77) and 0.75 (95% CI, 0.72–0.79), respectively (P = .07). Both models demonstrated good calibration. The number of patients that would need to be reviewed to identify 1 patient who required stewardship intervention was high for both models (41.7–45.5 for models tuned to a sensitivity of 85%).
Complex models can be developed to predict which patients require a stewardship intervention. However, further work is required to develop models with adequate discriminatory power to be applicable to real-world antimicrobial stewardship practice.
Recently, Echinacea purpurea and its extracts have gained much interest due to their improvement on meat quality, but little information is available on the application of the purified Echinacea purpurea polysaccharide (4-O-methyl-glucuronoarabinoxylan, 4OMG). Thus, this trial aimed at assessing the effects of dietary supplementation of 4OMG on growth performance, thigh meat quality and small intestine development of broilers. A total of 240 1-day-old female broiler chicks were randomly distributed to four groups with three replicates of 20 within each group. Each group received either 0, 15, 20 or 25 g 4OMG/kg DM of diet. During the entire experiment, broilers had ad libitum access to water and feed, and the feed intake was recorded daily. All broilers were weighed before and end of the experiment. For each group, three pens with a total of 20 broilers were randomly selected to slaughter after 30 days. Increasing dietary supplementation of 4OMG linearly increased final live weight and daily body weight gain (P = 0.013) of broilers, Gain-to-Feed ratio (P < 0.001), muscle pH (P = 0.024) and redness (P = 0.001), but decreased drip loss (P = 0.033), shear force value (P = 0.004) and hardness (P = 0.022) of the thigh meat. Broilers fed diet with higher 4OMG had greater weight index, villus height and ratio of villus height to crypt depth in both duodenum and jejunum. These results indicated that increasing dietary supplementation of 4OMG was beneficial for growth performance, meat quality and development of the small intestine of broilers.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients.
We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients.
Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006.
Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology.
Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.
The association between gray matter and cognitive dysfunction in young major depression remains unclear.
To investigate the brain gray matter and the correlation with cognitive function in first-episode, treatment-naive patients with major depressive disorder (MDD).
To explore brain structural pathological mechanisms of cognitive impairment in MDD.
46 MDD aged 18-45 year and 46 controls were assessed by Wisconsin Card Sorting Test (WCST) and Trail making test (TMT). Then, 30 patients and 30 controls were obtained by MRI scan.
The total number of errors, number of preservative errors, random errors of WSCT in MDD were significantly more than that in controls, and the completion time in the TMT-A and TMT-B was longer than that in controls. MDD showed significant less gray matter volumns than controls in frontal lobe (right precentral gyrus, bilateral superior frontal gyrus and right middle frontal gyrus), parietal lobe (left postcentral gyrus, left paracentral lobule, and bilateral precuneus), temporal lobe (right superior temporal gyrus), and occipital lobe (left superior occipital gyrus). There was a significant negative correlation between left postcentral gyrus and left superior occipital gyrus gray matter density and the TMT-B completion time (r=-0.462, P=0.017; r=-0.448, P=0.022).
The first-episode MDD patient exhibiteded cognitive impairment and showed significant lower gray matter density than controls in frontal lobe, parietal lobe, temporal lobe, occipital lobe. Decreased gray matter density in left postcentral gyrus and left superior occipital gyrus may be involved in the executive dysfunction.
In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.
Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.
11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.
The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.
The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.
To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.
Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.
Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.
Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment.
IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment.
The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults.
The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.
Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment.
Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls.
For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079).
EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.
We conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.
In this manuscript we use realistic data to conduct a network meta-analysis using a Bayesian approach to analysis. The purpose of this manuscript is to explain, in lay terms, how to interpret the output of such an analysis. Many readers are familiar with the forest plot as an approach to presenting the results of a pairwise meta-analysis. However when presented with the results of network meta-analysis, which often does not include the forest plot, the output and results can be difficult to understand. Further, one of the advantages of Bayesian network meta-analyses is in the novel outputs such as treatment rankings and the probability distributions are more commonly presented for network meta-analysis. Our goal here is to provide a tutorial for how to read the outcome of network meta-analysis rather than how to conduct or assess the risk of bias in a network meta-analysis.
Vaccination against putative causal organisms is a frequently used and preferred approach to controlling bovine respiratory disease complex (BRD) because it reduces the need for antibiotic use. Because approximately 90% of feedlots use and 90% of beef cattle receive vaccines in the USA, information about their comparative efficacy would be useful for selecting a vaccine. We conducted a systematic review and network meta-analysis of studies assessing the comparative efficacy of vaccines to control BRD when administered to beef cattle at or near their arrival at the feedlot. We searched MEDLINE, MEDLINE In-Process, MEDLINE Daily Epub Ahead of Print, AGRICOLA, Cambridge Agricultural and Biological Index, Science Citation Index, and Conference Proceedings Citation Index – Science and hand-searched the conference proceedings of the American Association of Bovine Practitioners and World Buiatrics Congress. We found 53 studies that reported BRD morbidity within 45 days of feedlot arrival. The largest connected network of studies, which involved 17 vaccine protocols from 14 studies, was included in the meta-analysis. Consistent with previous reviews, we found little compelling evidence that vaccines used at or near arrival at the feedlot reduce the incidence of BRD diagnosis.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy for clinical mastitis in lactating dairy cattle. Controlled trials in lactating dairy cattle with natural disease exposure were eligible if they compared an antimicrobial treatment to a non-treated control, placebo, or a different antimicrobial, for the treatment of clinical mastitis, and assessed clinical or bacteriologic cure. Potential for bias was assessed using a modified Cochrane Risk of Bias 2.0 tool. From 14775 initially identified records, 54 trials were assessed as eligible. Networks were established for bacteriologic cure by bacterial species group, and clinical cure. Disparate networks among bacteriologic cures precluded meta-analysis. Network meta-analysis was conducted for trials assessing clinical cure, but lack of precision of point estimates resulted in wide credibility intervals for all treatments, with no definitive conclusions regarding relative efficacy. Consideration of network geometry can inform future research to increase the utility of current and previous work. Replication of intervention arms and consideration of connection to existing networks would improve the future ability to determine relative efficacy. Challenges in the evaluation of bias in primary research stemmed from a lack of reporting. Consideration of reporting guidelines would also improve the utility of future research.
Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center.
We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses.
Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93–4.99] QALYs at an additional cost of $22,200 (95% CI: −28,902–78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: −4777–253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year.
EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.
The gut is composed of a single layer of intestinal epithelial cells and plays important roles in the digestion and absorption of nutrients, immune and barrier functions and amino acid metabolism. Weaning stress impairs piglet intestinal epithelium structural and functional integrities, which results in reduced feed intake, growth rates and increased morbidity and mortality. Several measures are needed to maintain swine gut development and growth performance after weaning stress. A large body of evidence indicates that, in weaning piglets, glutamine, a functional amino acid, may improve growth performance and intestinal morphology, reduce oxidative damage, stimulate enterocyte proliferation, modulate cell survival and death and enhance intestinal paracellular permeability. This review focuses on the effects of glutamine on intestinal health in piglets. The aim is to provide evidentiary support for using glutamine as a feed additive to alleviate weaning stress.
Molecular dynamics simulations of different defective kaolinites under tension were performed to reveal the effects of defect location, type, density and temperature on their mechanical properties. Four types of defective kaolinite with Si vacancies were constructed. Based on the atomic-scale deformation and failure processes of defective kaolinite and its stress–strain curves, the Young's moduli and tensile strengths in three crystal directions were obtained and compared with the existing theoretical values from the literature. The defect location at each layer does not affect the mechanical properties of kaolinite and the cracks initiated at the defective sites. The atom density of each model was calculated in order to investigate the defect-type effect on the mechanical properties of kaolinite. The simulation results also showed that kaolinite exhibits brittle failure behaviour and the mechanical properties degrade significantly with increasing defect density and temperature. The influence of temperature on the mechanical properties of defective kaolinite is discussed in detail.