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Health system preparedness for COVID-19 includes projecting the number and timing of cases requiring various types of treatment. Several tools were developed to assist in this planning process. This review highlights models that project both caseload and hospital capacity requirements over time.
We systematically reviewed the medical and engineering literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We completed searches using PubMed, EMBASE, ISI Web of Science, Google Scholar and the Google search engine.
The search strategy identified 690 articles. For detailed review, we selected six models that met our pre-defined criteria. Half of the models did not include age-stratified parameters, and only one included the option to represent a second wave. Hospital patient flow was simplified in all models; however, some considered more complex patient pathways. One model included fatality ratios with Length of Stay (LOS) adjustments for survivors versus those who die, and accommodated different LOS for critical care patients with or without a ventilator.
The results of our study provide information to physicians, hospital administrators, emergency response personnel and governmental agencies on available models for preparing scenario-based plans for responding to the COVID-19 or similar type of outbreak.
Ambulatory healthcare-associated infections (HAIs) occur frequently in children and are associated with morbidity. Less is known about ambulatory HAI costs. This study estimated additional costs associated with pediatric ambulatory central-line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTI), and surgical site infections (SSIs) following ambulatory surgery.
Retrospective case-control study.
Four academic medical centers.
Children aged 0–22 years seen between 2010 and 2015 and at risk for HAI as identified by electronic queries.
Chart review adjudicated HAIs. Charges were obtained for patients with HAIs and matched controls 30 days before HAI, on the day of, and 30 days after HAI. Charges were converted to costs and 2015 USD. Mixed-effects linear regression was used to estimate the difference-in-differences of HAI case versus control costs in 2 models: unrecorded charge values considered missing and a sensitivity analysis with unrecorded charge considered $0.
Our search identified 177 patients with ambulatory CLABSIs, 53 with ambulatory CAUTIs, and 26 with SSIs following ambulatory surgery who were matched with 382, 110, and 75 controls, respectively. Additional cost associated with an ambulatory CLABSI was $5,684 (95% confidence interval [CI], $1,005–$10,362) and $6,502 (95% CI, $2,261–$10,744) in the 2 models; cost associated with a CAUTI was $6,660 (95% CI, $1,055, $12,145) and $2,661 (95% CI, −$431 to $5,753); cost associated with an SSI following ambulatory surgery at 1 institution only was $6,370 (95% CI, $4,022–$8,719).
Ambulatory HAI in pediatric patients are associated with significant additional costs. Further work is needed to reduce ambulatory HAIs.
Efforts to address the major health, environmental, and social threats that can be found across the globe rely on changes in human behavior. Yet identifying effective and efficient ways to change behavior remains a vexing challenge. To meet this need, investigators need to design and evaluate behavioral intervention strategies in a manner that affords the creation of evidence-based guidelines that specify not only whether interventions work but also how and under what conditions. In this chapter, the design and testing of interventions are situated within the experimental medicine approach. This approach leverages the strength of the experimental method to test how behavior change intervention strategies work and to identify the conditions under which they operate effectively. Moreover, it organizes how investigators specify the questions that underlie the study of behavior change interventions and requires them to articulate precisely what intervention strategy they are using, how they think the strategy operates, and the outcomes it generates. Through the systematic use of this approach, evidence will emerge that addresses practitioners’ prevailing concerns directly – what intervention strategy is the most effective and efficient way to address the problem at hand. This chapter provides an overview of how to implement the experimental medicine approach, describes its key features, and addresses the importance of precision and, finally, considers this approach within a broader set of initiatives that have emerged to support a programmatic approach to the design, evaluation, and implementation of behavior change interventions.
Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.
We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.
Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.
Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.
Chickens adapt to P and Ca restriction during the very first days of life by improving P utilisation efficiency. The present study was built to identify the mechanisms underlying this adaptive capacity, and to identify the optimal window of application of the restriction (depletion). A total of 1600 Cobb 500TM male broilers were used. During each phase (from age 0 to 4 d, 5 to 8 d, 9 to 18 d and 19 to 33 d), the animals received either a control diet (H) or a restricted diet (L) with reduced levels of non-phytate P (nPP) and Ca (between −14 and −25 % for both) with four dietary sequences: HHHH, HLHL, LHHL and LLHL. None of the feeding strategies affected growth. Tibia ash content at day 4 and 8 was impaired when the L diet was fed from 0 to 4 and 5 to 8 d, respectively (P = 0⋅038 and P = 0⋅005). Whatever the early restriction period or length between 0 and 8 d of age, the mineralisation delay was compensated by day 18. This was accompanied by an increased mRNA expression of the Ca transporter, CALB1, and an increased apparent ileal digestibility of Ca at day 8 (P < 0⋅001). This adaptation was limited to the starter phase in restricted birds. No effect was seen on P transporters mRNA or protein expression. In conclusion, birds adapted to mineral restriction by increasing Ca and nPP utilisation efficiencies. Depletion−repletion strategies are promising in improving the sustainability of broiler production but need to be validated in phytase-supplemented diets.
Bulachite specimens from Cap Garonne, France, comprise two intimately mixed hydrated aluminium arsenate minerals with the same Al:As ratio of 2:1 and with different water contents. The crystal structures of both minerals have been solved using data from low-dose electron diffraction tomography combined with synchrotron powder X-ray diffraction. One of the minerals has the same powder X-ray diffraction pattern (PXRD) as for published bulachite. It has orthorhombic symmetry, space group Pnma with unit-cell parameters a = 15.3994(3), b = 17.6598(3), c = 7.8083(1) Å and Z = 4, with the formula [Al6(AsO4)3(OH)9(H2O)4]⋅2H2O. The second mineral is a higher hydrate with composition [Al6(AsO4)3(OH)9(H2O)4]⋅8H2O. It has the same Pnma space group and unit-cell parameters a = 19.855(4), b = 17.6933(11) and c = 7.7799(5) Å i.e. almost the same b and c parameters but a much larger a parameter. The structures are based on polyhedral layers, parallel to (100), of composition [Al6(AsO4)3(OH)9(H2O)4] and with H-bonded H2O between the layers. The layers contain  spiral chains of edge-shared octahedra, decorated with corner connected AsO4 tetrahedra that are the same as in the mineral liskeardite. The spiral chains are joined together by octahedral edge-sharing to form layers parallel to (100). Synchrotron PXRD patterns collected at different temperatures during heating of the specimen show that the higher-hydrate mineral starts transforming to bulachite when heated to 50°C, and the transformation is complete between 75 and 100°C.
In a previous study, we showed that access to willow fodder decreased somatic cell counts (SCC) in the milk of local Mamber goats grazing in brushland at the end of lactation. To test whether the consumption of willow affects the cells of the immune system, Alpine crossbred dairy goats grazing in the same environment were either offered free access to freshly cut willow fodder (W, n = 24) or not (C, n = 24) for 2 weeks. The willow fodder contained 7.5 g/kg DM of salicin. The other major secondary compounds were catechin, myricitrin, hyperin and chlorogenic acid (2.2, 2.6, 1.0 and 0.75 g/kg DM, respectively). Udder health status was determined before the experiment, and each of the two groups included five (W) or six (C) goats defined as infected, as established by microbial cfu in milk, and 19 (W) or 18 (C) non-infected goats. Goats ingested, on average, 600 g of DM from willow (25% of food intake), resulting in minor changes in dietary quality compared to the controls, as established by faecal near-IR spectrometry. Throughout the 2 weeks of experiment, differences between groups in dietary CP contents were minor and affected neither by infection nor by access to willow; the dietary percentage of neutral detergent fibre (NDF) decreased in C and increased in W; dietary acid detergent fibre (ADF) increased; and the dietary tannin contents decreased for both treatments. However, milking performance and milk quality attributes in both W and C goats were similar. Initial SCC and milk neutrophil (cluster of differentiation (CD)18+ and porcine granulocyte (PG)68) cell counts were higher in infected than in non-infected goats; counts decreased significantly in W but not in C uninfected goats. The percentage of CD8+ T-cells increased in all C goats, while in the W group, a significant increase was found only for infected goats. The consumption of willow mitigated an increase in CD8+ in blood and triggered an increase in CD8+ in milk, suggesting an immune-regulatory effect independent of udder status. To our knowledge, this is the first report of a direct nutraceutical effect of fodder ingestion on the immune status of goats.
Catheter-associated urinary tract infections (CAUTIs) occur frequently in pediatric inpatients, and they are associated with increased morbidity and cost. Few studies have investigated ambulatory CAUTIs, despite at-risk children utilizing home urinary catheterization. This retrospective cohort and case-control study determined incidence, risk factors, and outcomes of pediatric patients with ambulatory CAUTI.
Broad electronic queries identified potential patients with ambulatory urinary catheters, and direct chart review confirmed catheters and adjudicated whether ambulatory CAUTI occurred. CAUTI definitions included clean intermittent catheterization (CIC). Our matched case-control analysis assessed risk factors.
Five urban, academic medical centers, part of the New York City Clinical Data Research Network.
Potential patients were age <22 years who were seen between October 2010 and September 2015.
In total, 3,598 eligible patients were identified; 359 of these used ambulatory catheterization (representing186,616 ambulatory catheter days). Of these, 63 patients (18%) experienced 95 ambulatory CAUTIs. The overall ambulatory CAUTI incidence was 0.51 infections per 1,000 catheter days (1.35 for indwelling catheters and 0.47 for CIC; incidence rate ratio, 2.88). Patients with nonprivate medical insurance (odds ratio, 2.5; 95% confidence interval, 1.1–6.3) were significantly more likely to have ambulatory CAUTIs in bivariate models but not multivariable models. Also, 45% of ambulatory CAUTI resulted in hospitalization (median duration, 3 days); 5% resulted in intensive care admission; 47% underwent imaging; and 88% were treated with antibiotics.
Pediatric ambulatory CAUTIs occur in 18% of patients with catheters; they are associated with morbidity and healthcare utilization. Ambulatory indwelling catheter CAUTI incidence exceeded national inpatient incidence. Future quality improvement research to reduce these harmful infections is warranted.
Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved.
To determine the influence of dissociative symptoms on psychotherapy outcome in PTSD.
We conducted a systematic search in Cochrane, Embase, PILOTS, PsycINFO, PubMed and Web of Science for relevant clinical trials. A random-effects meta-analysis examined the impact of dissociation on psychotherapy outcome in PTSD (pre-registered at Prospero CRD42018086575).
Twenty-one trials (of which nine were randomised controlled trials) with 1714 patients were included. Pre-treatment dissociation was not related to treatment effectiveness in patients with PTSD (Pearson's correlation coefficient 0.04, 95% CI −0.04 to 0.13). Between-study heterogeneity was high but was not explained by moderators such as trauma focus of the psychotherapy or risk of bias score. There was no indication for publication bias.
We found no evidence that dissociation moderates the effectiveness of psychotherapy for PTSD. The quality of some of the included studies was relatively low, emphasising the need for high-quality clinical trials in patients with PTSD. The results suggest that pre-treatment dissociation does not determine psychotherapy outcome in PTSD.
This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program – Neuroreader™.
Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models.
Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses.
This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.
Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare. In Germany, until now no such intervention has been implemented, let alone subjected to a clinical trial.
“Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM) is a multicentre RCT conducted in five psychiatric hospitals in Germany (Günzburg, Düsseldorf, Regensburg, Greifswald, and Ravensburg). Subjects asked to provide informed consent to participate have to be of adult age with a primary diagnosis of schizophrenia or affective disorder, and a defined high utilisation of psychiatric care during two years prior to the current admission. Subjects are asked to provide detailed outcome data at four measurement points during a period of 18 months. Recruitment (which started in April 06) is still ongoing. Thus, baseline data of about 350 participants will be presented.
Recruitment has been quite successful and the study has been generally well accepted by participating patients and their clinicians in in- and outpatient treatment settings. Subjects showed substantial initial impairment on outcome measures (e.g. needs, psychopathology, quality of life, and level of functioning) and high utilisation of mental health care. Further results on conduct and feasibility of the trial will be presented.
The first phase of this mulicentre trial was promising. The potential of this study to strengthen the integration of mental health care provision in Germany will be discussed.
Aim of this contribution is to describe the intervention used in the study “Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM). This intervention applies principles of needs-led care and focusses on the inpatient-outpatient transition. The NODPAM intervention manual includes a range of predefined standardised options based on number and type of needs.
For the intervention group, a trained intervention worker provides a coherent package of needs-oriented discharge planning and monitoring focussing on the care process. He or she emphasises continuity of the care process vis-à-vis both patient and clinician (and carers if possible) via providing two manualised intervention sessions): (a) A discharge planning session takes place just before discharge with the patient and responsible clinician at the inpatient service; (b) A monitoring session takes place three months after discharge with the patient and outpatient clinician (office-based or public outpatient mental health service-based). A written treatment plan is signed by and forwarded to all participants after each session.
Acceptance of the intervention by patients and clinicians has been high so far. Further results on duration, participant characteristics, and participants' appraisal of the NODPAM intervention will be presented.
These first results indicate that the NODPAM intervention is feasible in inpatient mental health services in Germany. Discussion will focus on its applicability in other service systems.
The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.
In alcoholism, one relevant mechanism contributing to relapse is the exposure to stimuli that are associated with alcohol intake. Such conditioned cues can elicit conditioned responses like alcohol craving and consumption. In the last decade, considerable progress has been made in identifying basic neuronal mechanisms that underlie cue-induced alcohol craving.
We explored whether functional brain activation during exposure to alcohol-associated stimuli is related to the prospective relapse risk in detoxified alcohol-dependent patients.
46 alcohol-dependent and 46 healthy volunteers participated in a fMRI study using a cue reactivity paradigm, in which visual alcohol-related and control stimuli were presented. Patients were followed for 3 months. Afterwards data was analysed regarding the subsequent relapse, resulting in 16 abstainers and 30 relapsers.
Alcohol-related versus neutral stimuli activated a frontocortical-limbic network including inferior, medial and middle frontal gyrus as well as putamen in the group of patients relative to healthy controls. Moreover, abstainers showed a stronger activation in orbitofrontal cortex as well as midbrain during the presentation of alcohol-related cues whereas relapsers revealed a stronger activation of cingulate gyrus.
This study suggests that cue-induced activation of orbitofrontal cortex and dopaminergic innervated midbrain is negatively associated with the prospective relapse risk in alcohol-dependent patients. This could indicate a more pronounced and conscious processing of alcohol cues which might serve as a warning signal and a behavioural controlling function. In contrast, prospective relapsers showed a stronger activation of cingulate gyrus, a region involved in the attribution of motivational value.
Microglia express the TSPO (TranSlocalor PrOtein) receptor formerly known as the PBR (peripheral benzodiazepine receptor). The densitiy of the TSPO is dependent on the inflammatory state of microglia. The radiopharmaceutical [11C]PK11195 binds in excess to the TSPO in activated microglia. We showed that the hippocampus of psychotic patients experienced significantly more [11C]PK11195 binding than the hippocampus of healthy controls. To elucidate the effect of antipsychotic medication on brain inflammation the herpes encephalitis rat model was chosen, because of pathophysiological similarity: Herpes simplex virus preferentially infects hippocampus. In adult rats 10E5 pfu of HSV-1 (clinical strain) was administered intranasally. After 3–5 days sickness behavior developed. At the 6th day and at the 13th day after inoculation a [11C]PK11195 PET scan was performed. Drugs were delivered by osmotic minipumps (haloperidol, clozapine, saline). Only clozapine treatment delayed sickness behavior. Clozapine treatment reduced the inflammation in the mesecephalon and immediate surrounding regions after 6 days and reduced dissemination of inflammation to brain cortex at 13 days after inoculation.
In a herpes infection model clozapine exerts potent antiinflammatory effects on microglia. The hippocampus might be the link between infectious pathology and inflammation in schizophrenia patients.
The development and maintenance of an alcohol addiction is a complex interaction between genetic and environmental factors. Genetic effects seem to contribute substantially to the risk of developing an addiction, but also to its course and patients’ responses to different treatments. Recent studies identified associations between polymorphisms in the genes of glutamate and μ-opioid receptors and addiction risk. Those receptors are of special interest, because they are targets of therapeutic agents, such as acamprosate and topiramate.
Objectives and aims
Several studies were conducted, in order to further determine the effects of genetic polymorphisms in glutamate and opioid receptor genes on addictive behavior, neural response to alcohol cues and relapse risk.
Genetic effects were investigated in samples of alcohol-dependent patients using functional imaging techniques, neuropsychological tests and follow-up investigation after standard clinical treatment. Data on clinical parameters, neuronal response to alcohol cues, functional neuronal connectivity and relapse risk were collected and analyzed.
Results demonstrate effects of genetic polymorphisms in glutamate and opioid receptors on neuronal response to alcohol cues in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings will be discussed in the light of existing evidence on the contribution of genetic effects to treatment outcome and patient stratification.
The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The 'Austrian' tradition is well-known for its definitive contributions to economics in the twentieth century. However, Austrian economics also offers an exciting research agenda outside the traditional boundaries of economics, especially in the management disciplines. This Element examines how Austrian ideas play a key role in expanding the understanding of fields like entrepreneurship, strategy, and organization. It focuses especially on the vital role that entrepreneurs play in guiding economic progress by shaping firms and their strategic behavior. In doing so, it explains a wide range of contributions that Austrian economics makes to the understanding of key problems in management, while also highlighting many directions for future work in this inspiring tradition.
The intrinsic oxygen fugacity of a planet profoundly influences a variety of its geochemical and geophysical aspects. Most rocky bodies in our solar system formed with oxygen fugacities approximately five orders of magnitude higher than that corresponding to a hydrogen-rich gas of solar composition. Here we derive oxygen fugacities of extrasolar rocky bodies from the elemental abundances in 15 white dwarf (WD) stars polluted by accretion of rocks. We find that the intrinsic oxygen fugacities of rocks accreted by the WDs are similar to those of terrestrial planets and asteroids in our solar system. This result suggests that at least some rocky exoplanets are geophysically and geochemically similar to Earth.