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This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.
Perceived purpose in life (PIL) has been linked to a broad range of adverse physical, mental, and cognitive outcomes. However, limited research has examined factors associated with PIL that can be targeted in prevention and treatment efforts in aging populations at heightened risk of adverse outcomes. Using data from predominantly older US veterans, we sought to identify important correlates of PIL.
Methods:
Cross-sectional data were analyzed from the 2019–2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 US military veterans (Mage = 62.2). Elastic net and relative importance analyses were conducted to evaluate sociodemographic, military, health, and psychosocial variables that were strongly associated with PIL.
Results:
Of the 39 variables entered into an elastic net analysis, 10 were identified as significant correlates of PIL. In order of magnitude, these were resilience (18.7% relative variance explained [RVE]), optimism (12.1%), depressive symptoms (11.3%), community integration (10.7%), gratitude (10.2%), loneliness (9.8%), received social support (8.6%), conscientiousness (8.5%), openness to experience (5.4%), and intrinsic religiosity (4.7%).
Conclusions:
Several modifiable psychosocial factors emerged as significant correlates of PIL in US military veterans. Interventions designed to target these factors may help increase PIL and mitigate risk for adverse health outcomes in this population.
Mental health and psychosocial support (MHPSS) staff in humanitarian settings have limited access to clinical supervision and are at high risk of experiencing burnout. We previously piloted an online, peer-supervision program for MHPSS professionals working with displaced Rohingya (Bangladesh) and Syrian (Turkey and Northwest Syria) communities. Pilot evaluations demonstrated that online, peer-supervision is feasible, low-cost, and acceptable to MHPSS practitioners in humanitarian settings.
Objectives
This project will determine the impact of online supervision on i) the wellbeing and burnout levels of local MHPSS practitioners, and ii) practitioner technical skills to improve beneficiary perceived service satisfaction, acceptability, and appropriateness.
Methods
MHPSS practitioners in two contexts (Bangladesh and Turkey/Northwest Syria) will participate in 90-minute group-based online supervision, fortnightly for six months. Sessions will be run on zoom and will be co-facilitated by MHPSS practitioners and in-country research assistants. A quasi-experimental multiple-baseline design will enable a quantitative comparison of practitioner and beneficiary outcomes between control periods (12-months) and the intervention. Outcomes to be assessed include the Kessler-6, Harvard Trauma Questionnaire and Copenhagen Burnout Inventory and Client Satisfaction Questionnaire-8.
Results
A total of 80 MHPSS practitioners will complete 24 monthly online assessments from May 2022. Concurrently, 1920 people receiving MHPSS services will be randomly selected for post-session interviews (24 per practitioner).
Conclusions
This study will determine the impact of an online, peer-supervision program for MHPSS practitioners in humanitarian settings. Results from the baseline assessments, pilot evaluation, and theory of change model will be presented.
Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation.
Objectives:
To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD).
Methods:
Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG.
Results:
There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling.
Conclusions:
This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)
When comparing the efficay of antipsychotics in clinical studies it would be of high practical relevance to know which doses of the respective drugs would result in equivalent blocking of dopamine-D2-receptors. This study aimed to find clinically applicable dose equivalents for haloperidol, risperidone and olanzapine.
Method
As the occurrence of EPS correlates closely with a blockade of about 80% or more of dopamin-D2-receptors the proportion of patients developing EPS in relation to various doses of either Haloperidol (n=5252), risperidone (n=5017) or olanzapine (n =5029) was calculated. This retrospective, observational study included 20.252 inpatients from 20 hospitals with a diagnosis of schizophrenia and related disorders (ICD10 F20-25). The prescription of anticholinergic medication was utilized as surrogate parameter for the occurrence of EPS. OR, RR and NNH under different doses of AP were calculated and data entered into a probit model to predict the risk of EPS over a continuous dose range. For filtering the data ToscanaJ (FBA) was used.
Results
1.) Same doses of risperidone and haloperidol induced the same proportion of EPS, reflected in a constant dose ratio of both drugs of ∼ 1:1 over the whole dose range.
2.) Over the whole dose range there was no linear relation between olanzapine on one hand and haloperidol and risperidone on the other hand.
3.) The results were corroborated by the probit analysis.
Conclusions
Previous clinical trials comparing olanzapine, risperidone and haloperidol found higher risks of EPS for Haloperidol. We propose a new model to calculate dose equivalents.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
We investigate the processes of active galactic nuclei (AGN) feeding and feedback in the narrow line regions (NLRs) and host galaxies of nearby AGN through spatially resolved spectroscopy with the Gemini Near-Infrared Integral Field Spectrograph (NIFS) and the Hubble Space Telescope’s Space Telescope Imaging Spectrograph (STIS). We examine the connection between nuclear and galactic inflows and outflows by adding long-slit spectra of the host galaxies from Apache Point Observatory. We demonstrate that nearby AGN can be fueled by a variety of mechanisms. We find that the NLR kinematics can often be explained by in situ ionization and radiative acceleration of ambient gas, often in the form of dusty molecular spirals that may be the fueling flow to the AGN.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
The physical processes driving the chemical evolution of galaxies in the last ~ 11Gyr cannot be understood without directly probing the dust-obscured phase of star-forming galaxies and active galactic nuclei. This phase, hidden to optical tracers, represents the bulk of the star formation and black hole accretion activity in galaxies at 1 < z < 3. Spectroscopic observations with a cryogenic infrared observatory like SPICA, will be sensitive enough to peer through the dust-obscured regions of galaxies and access the rest-frame mid- to far-infrared range in galaxies at high-z. This wavelength range contains a unique suite of spectral lines and dust features that serve as proxies for the abundances of heavy elements and the dust composition, providing tracers with a feeble response to both extinction and temperature. In this work, we investigate how SPICA observations could be exploited to understand key aspects in the chemical evolution of galaxies: the assembly of nearby galaxies based on the spatial distribution of heavy element abundances, the global content of metals in galaxies reaching the knee of the luminosity function up to z ~ 3, and the dust composition of galaxies at high-z. Possible synergies with facilities available in the late 2020s are also discussed.
A far-infrared observatory such as the SPace Infrared telescope for Cosmology and Astrophysics, with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last ~10 Gyr of the Universe (z = 1.5–2), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionised gas. We quantify the detectability of galaxy-scale massive molecular and ionised outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.
Digital elevation models of the bed and surface of Unteraargletscher, Switzerland, are used to reconstruct the theoretical pattern of basal water drainage for the years 1927, 1947, 1961 and 1997, during which period the glacier was thinning and receding. The theoretical drainage pattern for 1997 compares well, in a broad sense, with the locations of active moulins and the hydraulic connection status of boreholes drilled to the glacier bed. Changes in the basal water-flow pattern over the period 1927–97 that are revealed by the theoretical reconstructions of the subglacial drainage system structure are likely to have resulted from changes in glacier geometry. Concurrent with the retreat and thinning of the glacier, the height of medial moraines increased, probably due to the insulating effect of the debris cover reducing the melt of the underlying ice. This increase of moraine heights has led to the formation of hydraulic barriers at the glacier bed such that water flow has become channelized beneath the ice along drainage axes that parallel the course of the medial moraines on the glacier surface.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
A new generation of solar instruments provides improved spectral, spatial, and temporal resolution, thus facilitating a better understanding of dynamic processes on the Sun. High-resolution observations often reveal multiple-component spectral line profiles, e.g., in the near-infrared He i 10830 Å triplet, which provides information about the chromospheric velocity and magnetic fine structure. We observed an emerging flux region, including two small pores and an arch filament system, on 2015 April 17 with the ‘very fast spectroscopic mode’ of the GREGOR Infrared Spectrograph (GRIS) situated at the 1.5-meter GREGOR solar telescope at Observatorio del Teide, Tenerife, Spain. We discuss this method of obtaining fast (one per minute) spectral scans of the solar surface and its potential to follow dynamic processes on the Sun. We demonstrate the performance of the ‘very fast spectroscopic mode’ by tracking chromospheric high-velocity features in the arch filament system.
Objectives: The role and impact of health technology assessment (HTA) in health policy has been widely discussed. Researchers have started to analyze how decisions on coverage of new technologies are made. Although the involvement of HTA may be an indicator of a well established decision process, this hypothesis requires validation. Also, it is not known whether HTA involvement is associated with other characteristics of decision making like participation or transparency. The primary objective of this study was to develop and test statements on the association between the publication of an HTA and coverage decision making for newborn screening tests in European Union countries.
Methods: Five statements were defined on the relative role of HTA during the steps of decision processes: trigger, participation, publication, assessment, and appraisal. For this purpose, data on twenty-two decision processes in the area of newborn screening across Europe were analyzed, defined as a coverage decision for a given disorder in a specific country. Decision processes were compared by whether the decision was accompanied by the publication of an HTA report. To test differences, nonparametric statistical tests were used.
Results: The decision steps of trigger, participation and publication differed between the HTA and the non-HTA groups. No clear association between HTA and assessment methods in coverage decision making was identified.
Conclusions: It appeared that there is an association between HTA and coverage decision processes that are more explicit, inclusive, and transparent. It is unclear whether HTA is associated with formal evidence reviews and economic evaluations.