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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Prices of medicines have increasingly come under payer and societal scrutiny in many countries around the world. As the price-setting process is quite untransparent, the concept of cost-based pricing has been brought forward as an alternative method to inform reimbursement decision-making. A Real-Option rate of Return (ROroR) approach, was recently proposed as a method for a multi-stakeholder driven collaborative investment model. This study showed that there are public-private medicine development opportunities that could lead to lower research and development (R&D) costs for products with a challenging business model. The aim of the current study is to assess the practical use of the ROroR approach and highlight its sensitivity regarding input parameters.
Methods
The ROroR approach incorporates medicine-specific parameters: R&D costs, the number of patients treated per year, the time horizon for recouping the investments set by the stakeholders, the production costs and a predefined profit margin. Three hypothetical case-studies were selected for the ROroR analysis comprising of an orphan, oncology, and a more regular medicine. Parameter input data was derived from the available literature. Cost-based prices were calculated based on applying the ROroR equation under a constant profit margin. Ultimately, the corresponding prices of the case-studies were analyzed for their sensitivity using ten changes of the original value.
Results
The ROroR approach was most sensitive to the length of the time horizon and the number of patients treated per year. The largest sensitivity was found for the oncological drug, with an asymmetric price change ranging from -25 percent to +271 percent if varying the time horizon or number of patients. The profit margin, and total R&D costs have the least effect on the price: +/-4 percent and +/-45 percent, respectively.
Conclusions
This study shows that cost-based pricing is highly beneficial in uncovering pricing-underlying business or economic mechanisms and suggesting a transparent price. Further research is needed on implementing public-private development models and cost-based price determination using the core parameters.
While there are increasing calls for transformative change and transformative governance, what this means in the context of addressing biodiversity loss remains debated. The aim of this edited volume Transforming Biodiversity Governance is to open up this debate and identify ways forward in the context of the implementation of the Post-2020 Global Biodiversity Framework (GBF) of the Convention on Biological Diversity (CBD). To become transformative, biodiversity governance needs to be transformed: yet how and by whom? These questions are urgent, given the fact that around one million species are threatened with extinction (Díaz et al., 2019), despite over half a century of global efforts to avoid this tragedy.
We offer a dynamic Bayesian forecasting model for multiparty elections. It combines data from published pre-election public opinion polls with information from fundamentals-based forecasting models. The model takes care of the multiparty nature of the setting and allows making statements about the probability of other quantities of interest, such as the probability of a plurality of votes for a party or the majority for certain coalitions in parliament. We present results from two ex ante forecasts of elections that took place in 2017 and are able to show that the model outperforms fundamentals-based forecasting models in terms of accuracy and the calibration of uncertainty. Provided that historical and current polling data are available, the model can be applied to any multiparty setting.
Delirium is very frequent in older patients presenting to the emergency department (ED), but is often undetected. The purpose of this study was to evaluate the performance of the French version of the 4 A’s Test (4AT-F) for the detection of delirium and cognitive impairment in older patients.
Methods
The study was conducted in four Canadian ED. Participants (n= 320) were independent or semi-independent patients (able to perform ≥5 activities of daily living) aged 65 and older and had an 8-hour exposure to the ED environment. The Telephone Interview for Cognitive Status (TICS-m), the Confusion Assessment Method (CAM) as well as the 4AT-F were administered to patients at the initial interview. The CAM and 4AT-F were then administered twice a day during the patients’ ED or hospital stay. The 4AT-F’s sensitivity and specificity were compared to those of the CAM (for delirium), and to that of the TICS (for cognitive impairment).
Results
Our results suggest that the 4AT-F has a sensitivity of 84% (95% CI: [76, 93]) and a specificity of 74% (95% CI: [70, 78]) for delirium, as well as a sensitivity of 49% (95% CI: [34, 64]) and a specificity of 87% (95% CI: [82, 92]) for cognitive impairment.
Conclusion
The 4AT-F is a fast and reliable screening tool for delirium and cognitive impairment in ED. Due to its quick administration time, it allows a systematic screening of patients at risk of delirium, without significantly increasing the workload of the ED staff.
In the fast pace of the Emergency Department (ED), clinicians are in need of tailored screening tools to detect seniors who are at risk of adverse outcomes. We aimed to explore the usefulness of the Bergman-Paris Question (BPQ) to expose potential undetected geriatric syndromes in community-living seniors presenting to the ED.
Methods
This is a planned sub-study of the INDEED multicentre prospective cohort study, including independent or semi-independent seniors (≥65 years old) admitted to hospital after an ED stay ≥8 hours and who were not delirious. Patients were assessed using validated screening tests for 3 geriatric syndromes: cognitive and functional impairment, and frailty. The BPQ was asked upon availability of a relative at enrolment. BPQ’s sensitivity and specificity analyses were used to ascertain outcomes.
Results
A response to the BPQ was available for 171 patients (47% of the main study’s cohort). Of this number, 75.4% were positive (suggesting impairment), and 24.6% were negative. To detect one of the three geriatric syndromes, the BPQ had a sensitivity of 85.4% (95% CI [76.3, 92.0]) and a specificity of 35.4% (95% CI [25.1, 46.7]). Similar results were obtained for each separate outcome. Odds ratio demonstrated a higher risk of presence of geriatric syndromes.
Conclusion
The Bergman-Paris Question could be an ED screening tool for possible geriatric syndrome. A positive BPQ should prompt the need of further investigations and a negative BPQ possibly warrants no further action. More research is needed to validate the usefulness of the BPQ for day-to-day geriatric screening by ED professionals or geriatricians.
The consequences of minor trauma involving a head injury (MT-HI) in independent older adults are largely unknown. This study assessed the impact of a head injury on the functional outcomes six months post-injury in older adults who sustained a minor trauma.
Methods
This multicenter prospective cohort study in eight sites included patients who were aged 65 years or older, previously independent, presenting to the emergency department (ED) for a minor trauma, and discharged within 48 hours. To assess the functional decline, we used a validated test: the Older Americans’ Resources and Services Scale. The cognitive function of study patients was also evaluated. Finally, we explored the influence of a concomitant injury on the functional decline in the MT-HI group.
Results
All 926 eligible patients were included in the analyses: 344 MT-HI patients and 582 minor trauma without head injury. After six months, the functional decline was similar in both groups: 10.8% and 11.9%, respectively (RR=0.79 [95% CI: 0.55–1.14]). The proportion of patients with mild cognitive disabilities was also similar: 21.7% and 22.8%, respectively (RR=0.91 [95% CI: 0.71–1.18]). Furthermore, for the group of patients with a MT-HI, the functional outcome was not statistically different with or without the presence of a co-injury (RR=1.35 [95% CI: 0.71–2.59]).
Conclusion
This study did not demonstrate that the occurrence of a MT-HI is associated with a worse functional or cognitive prognosis than other minor injuries without a head injury in an elderly population, six months after injury.
Notre objectif primaire est de mesurer l’incidence d’HPI selon quatre définitions différentes retrouvées dans la littérature. Notre principal objectif secondaire est d’évaluer l’impact de la présence d’instabilité hémodynamique avant l’intubation sur l’incidence d’HPI. Le deuxième objectif secondaire consiste à déterminer l’incidence de l’HPI en fonction de l’intervalle de temps durant lequel la première hypotension survient.
Méthode
Une cohorte prospective a été constituée par les patients intubés en salle de réanimation à l’hôpital de l’Enfant-Jésus entre le 28/06/2011 et le 12/07/2012. L’HPI était globalement définie comme ≥1 mesure de tension artérielle systolique <90 mmHg suivant l’intubation. Les différentes définitions étudiées faisaient varier le temps de mesure de la tension artérielle (TA) après l’intubation, soit 1) jusqu’à 5 minutes, 2) jusqu’à 15 minutes, 3) jusqu’à 30 minutes et 4) en tout temps lors du séjour en salle de réanimation.
Résultat
Au cours de la période à l’étude, 155 patients ont été intubés sur place dont 81 patients qui répondaient aux critères d’inclusion. L’incidence de l’HPI pour chaque définition est respectivement de 9.9%, 18.5%, 24.7% et 28.4%. La comparaison entre chacune de ces incidences révèle une différence statistiquement significative (p<0.05), à l’exception des deux dernières. L’incidence cumulative d’HPI à tout moment suivant l’intubation chez les patients présentant une hypotension pré-intubation est de 62.5% (IC 95% 28.5-87.5) en opposition aux patients hémodynamiquement stables en pré-intubation qui présentaient une incidence d’HPI de 24.7% (IC 95% 16.1-35.8).
Conclusion
L’hypotension post-intubation est un effet indésirable fréquent chez les patients au département d’urgence et son incidence varie de façon significative en fonction de la définition temporelle utilisée au sein d’une même cohorte de patients.
The objective of this study was to explore correlates of cognitive functioning of older adults visiting the emergency department (ED) after a minor injury.
Methods:
These results are derived from a large prospective study in three Canadian EDs. Participants were aged ≥ 65 years and independent in basic activities of daily living, visiting the ED for minor injuries and discharged home within 48 hours (those with known dementia, confusion, and delirium were excluded). They completed the Montreal Cognitive Assessment (MoCA). Potential correlates included sociodemographic and injury variables, and measures of psychological and physical health, social support, mobility, falls, and functional status.
Results:
Multivariate analyses revealed that male sex, age ≥ 85 years, higher depression scores, slower walking speed, and self-reported memory problems were significantly associated with lower baseline MoCA scores.
Conclusions:
These characteristics could help ED professionals identify patients who might need additional cognitive evaluations or follow-ups after their passage through the ED. Obtaining information on these characteristics is potentially feasible in the ED context and could help professionals alter favorably elderly's trajectory of care. Since a significant proportion of elderly patients consulting at an ED have cognitive impairment, the ED is an opportunity to prevent functional and cognitive decline.
Recently, the development of a versatile thermochemical nanolithography (TCNL) technique has been reported. It allows simultaneous control of the local chemistry and topography of thin polymer films. This technique can pattern sub 15 nm chemical and topographical features at the rate of 1.4 mm per second by inducing thermally-activated chemical reactions by means of a heated atomic force microscope (AFM) tip. TCNL is achievable in different environments and can easily be adapted to a variety of substrates and chemical functionalities. Here, we demonstrate that a thin polymer film can be chemically modified twice using TCNL to tune its wettability. We are able to write hydrophilic nanopatterns over a hydrophobic polymer surface upon a first step heating and then revert back to hydrophobic surface by a second step heating. This write-read-overwrite capability is particularly useful in data storage application and complex nanofluidic device design.
We revisit Salmon's ‘Dirac bracket projection’ approach to constructing generalized
semi-geostrophic equations. One of the obstacles to the method's applicability is
that it leads to a sign-indefinite energy functional in the computational domain.
In some instances this can cause severe failure of the model. We demonstrate in
the simple context of shallow-water semi-geostrophy that the Hamiltonian remains
positive definite when the asymptotic expansion at the heart of this method is carried
to the next order. The resulting new model can be interpreted in the framework of
regularization by Lagrangian averaging, which is currently receiving much attention.
This paper analyzes the joint time-series properties of the level and volatility of expected excess stock returns. An unobservable dynamic factor is constructed as a nonlinear proxy for the market risk premia with its first moment and conditional volatility driven by a latent Markov variable. The model allows for the possibility that the risk–return relationship may not be constant across the Markov states or over time. We find an overall negative contemporaneous relationship between the conditional expectation and variance of the monthly value-weighted excess return. However, the sign of the correlation is not stable, but instead varies according to the stage of the business cycle. In particular, around the beginning of recessions, volatility rises substantially, reflecting great uncertainty associated with these periods, while expected return falls, anticipating a decline in earnings. Thus, around economic peaks there is a negative relationship between conditional expectation and variance. However, toward the end of a recession expected return is at its highest value as an anticipation of the economic recovery, and volatility is still very high in anticipation of the end of the contraction. That is, the risk–return relation is positive around business-cycle troughs. This time-varying behavior also holds for noncontemporaneous correlations of these two conditional moments.