Epidemic forecasts as a tool for public health: interpretation and (re)calibration

Objective: Recent studies have used Bayesian methods to predict timing of influenza epidemics many weeks in advance, but there is no documented evaluation of how such forecasts might support the day‐to‐day operations of public health staff. Methods: During the 2015 influenza season in Melbourne, Australia, weekly forecasts were presented at Health Department surveillance unit meetings, where they were evaluated and updated in light of expert opinion to improve their accuracy and usefulness. Results: Predictive capacity of the model was substantially limited by delays in reporting and processing arising from an unprecedented number of notifications, disproportionate to seasonal intensity. Adjustment of the predictive algorithm to account for these delays and increased reporting propensity improved both current situational awareness and forecasting accuracy. Conclusions: Collaborative engagement with public health practitioners in model development improved understanding of the context and limitations of emerging surveillance data. Incorporation of these insights in a quantitative model resulted in more robust estimates of disease activity for public health use. Implications for public health: In addition to predicting future disease trends, forecasting methods can quantify the impact of delays in data availability and variable reporting practice on the accuracy of current epidemic assessment. Such evidence supports investment in systems capacity.     

Spouse Confidence in Self-Efficacy for Arthritis Management Predicts Improved Patient Health

Background

In addition to patient self-efficacy, spouse confidence in patient efficacy may also independently predict patient health outcomes. However, the potential influence of spouse confidence has received little research attention.

Purpose

The current study examined the influence of patient and spouse efficacy beliefs for arthritis management on patient health.

Methods

Patient health (i.e., arthritis severity, perceived health, depressive symptoms, lower extremity function), patient self-efficacy, and spouse confidence in patients’ efficacy were assessed in a sample of knee osteoarthritis patients (N?=?152) and their spouses at three time points across an 18-month period. Data were analyzed using structural equation models.

Results

Consistent with predictions, spouse confidence in patient efficacy for arthritis management predicted improvements in patient depressive symptoms, perceived health, and lower extremity function over 6 months and in arthritis severity over 1 year.

Conclusions

Our findings add to a growing literature that highlights the important role of spouse perceptions in patients’ long-term health.     

Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking

Rationale

GABA_A receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine.

Objective

We investigated the reinforcing properties of cocaine in GABA_A α2-subunit knockout (KO) mice using an intravenous self-administration procedure.

Methods

α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg).

Results

No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not.

Conclusions

Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking.     

Exaggerated Waiting Impulsivity Associated with Human Binge Drinking,and High Alcohol Consumption in Mice

There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18–25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.Impulsivity has been consistently implicated as both a determinant and a consequence of alcohol abuse. Binge patterns of alcohol consumption, in particular, have been associated with impaired attentional function and executive function (Scaife and Duka, 2009; Townshend and Duka, 2005), and increased impulsive behavior in both humans and rodent models (Bell et al, 2013; Duka et al, 2003; Stephens and Duka, 2008). However, it is unclear whether high levels of impulsivity are a cause or consequence of alcohol intake.Given the prevalence of binge drinking in adolescence (Healey et al, 2014), the first aim of our study was to examine the relationship of binge drinking to measures of waiting impulsivity and attentional abilities in human adolescents (18–25 years old) and in rodents, which consume alcohol. Taking the rodent 5CSRTT (Robbins, 2002) as a model, we developed a novel, iPad-based task (Sussex 5CSRTT; Sx-5CSRTT), to assess both attentional performance and anticipatory behavior in humans. BD were also characterized in four additional measures of impulsivity, based on different operational definitions of the construct. The Stop Signal Task, used to assess ability to inhibit a prepotent response (Logan, 1994), served as an additional measure of ‘motoric impulsivity''. The Delay Discounting Questionnaire measured preference for immediate over-delayed rewards (Petry, 2001) and, combined with the Two-Choice Impulsivity paradigm (Dougherty et al, 2005), provided an index of ‘choice'' impulsivity or decision making; the fourth behavioral measure used was the Time Estimation Task. Although each of these five measures has been used in the clinical context as an index of impulsive behavior, the sensitivity of each task to characterize impulsive phenotype in young social BD, and their relationship to one another has not been explored. We anticipated binge drinking might be differentially associated with different aspects of impulsive behavior, but generally that high binge drinking scores would be associated with high levels of trait and behavioral motor impulsivity and aversion to delay.The role of premorbid impulsivity as a predictor of elevated alcohol intake cannot be easily disentangled in human studies, as impulsivity measures are almost inevitably assessed after a period of alcohol use. Animal models are more powerful tools in this respect as they allow the exclusion of alcohol experience as a potential contributor to impulsivity. Therefore, having established that 5CSRTT waiting impulsivity was associated with human binge drinking, we asked whether waiting impulsivity in alcohol-naïve mice predicted alcohol drinking in two widely used B6 and D2 inbred strains, that also differ in alcohol consumption (Crabbe et al, 1994). We have previously reported (Walker et al, 2011) that prior exposure to high alcohol concentrations over several weeks in adulthood has only transitory effects in increasing impulsivity in B6 mice. We predicted greater impulsivity in the high-ethanol-preferring mice indicating a potential causal relationship between waiting impulsivity and high alcohol consumption.Using homologous measures of impulsivity in mouse and humans, we provide evidence that waiting impulsivity is associated with binge drinking in young adult humans, and predicts alcohol consumption in mice.     

[4Fe-4S]-cluster-depleted Azotobacter vinelandii ferredoxin I: a new 3Fe iron-sulfur protein.

Fe(CN)6(-3) oxidation of the aerobically isolated 7Fe Azotobacter vinelandii ferredoxin I, (7Fe)FdI, is a degradative reaction. Destruction of the [4Fe-4S] cluster occurs first, followed by destruction of the [3Fe-3S] cluster. At a Fe(CN)6(-3)/(7Fe)FdI concentration ratio of 20, the product is a mixture of apoprotein and protein containing only a [3Fe-3S] cluster, (3Fe)FdI. This protein mixture, after partial purification, has been characterized by absorption, CD, magnetic CD, and EPR and Fe x-ray absorption spectroscopies. EPR and magnetic CD spectra provide strong evidence that the [3Fe-3S] cluster in (3Fe)FdI is essentially identical in structure to that in (7Fe)FdI. Analysis of the extended x-ray absorption fine structure (EXAFS) of (3Fe)FdI finds Fe scattering at an average Fe...Fe distance of approximately equal to 2.7 A. The structure of the oxidized [3Fe-3S] cluster in solutions of oxidized (3Fe)FdI, and, by extension, of oxidized (7Fe)FdI, is thus different from that obtained by x-ray crystallography on oxidized (7Fe)FdI. Possible interpretations of this result are discussed.     

Rationing Limited Healthcare Resources in the COVID-19 Era and Beyond: Ethical Considerations Regarding Older Adults

Coronavirus disease 2019 (COVID-19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age-Related Considerations in the COVID-19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.