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Two years on from the implementation of the Assisted Decision-Making (Capacity) Act (ADMCA) 2015, significant legal uncertainty persists in Ireland’s acute hospitals for the care of people who lack capacity to consent to treatment. Consultation-liaison psychiatrists must navigate a legal landscape where clear lacunae have emerged in the regulation of frequently encountered clinical scenarios. We identify three of these – eating disorders requiring refeeding, refusal of life-saving treatment, and unsafe discharges – where neither the ADMCA nor the Mental Health Act 2001 provide legal authority to intervene. In such cases, the Inherent Jurisdiction of the High Court has become the default mechanism for authorising treatment or deprivation of liberty, raising serious concerns about proportionality, clinical delays and uncertainty, cost, and consistency. We also consider a fourth category of patients who require immediate life-saving treatment, and the legal status of Advance Healthcare Directives in this context. Many of the patients who fall into these categories will have an established or suspected mental illness requiring the clinical input of a consultation-liaison psychiatry team.
We contrast Ireland’s evolving capacity legislation with developments in England and Wales. Reflecting on these comparisons, we consider the proposed Protection of Liberty Safeguards may provide some clarification but also contain potential risks of becoming unwieldy and bureaucratic and still fail to provide a workable statutory basis for authorising medical treatment in acute hospital settings. A proportionate, patient-centred, and clinically usable legal framework remains urgently needed.
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Recent theories have implicated inflammatory biology in the development of psychopathology and maladaptive behaviors in adolescence, including suicidal thoughts and behaviors (STB). Examining specific biological markers related to inflammation is thus warranted to better understand risk for STB in adolescents, for whom suicide is a leading cause of death.
Method:
Participants were 211 adolescent females (ages 9–14 years; Mage = 11.8 years, SD = 1.8 years) at increased risk for STB. This study examined the prospective association between basal levels of inflammatory gene expression (average of 15 proinflammatory mRNA transcripts) and subsequent risk for suicidal ideation and suicidal behavior over a 12-month follow-up period.
Results:
Controlling for past levels of STB, greater proinflammatory gene expression was associated with prospective risk for STB in these youth. Similar effects were observed for CD14 mRNA level, a marker of monocyte abundance within the blood sample. Sensitivity analyses controlling for other relevant covariates, including history of trauma, depressive symptoms, and STB prior to data collection, yielded similar patterns of results.
Conclusions:
Upregulated inflammatory signaling in the immune system is prospectively associated with STB among at-risk adolescent females, even after controlling for history of trauma, depressive symptoms, and STB prior to data collection. Additional research is needed to identify the sources of inflammatory up-regulation in adolescents (e.g., stress psychobiology, physiological development, microbial exposures) and strategies for mitigating such effects to reduce STB.
Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.
Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many “omics” factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.
Rapid Acceleration of Diagnostics (RADx®) Tech was the key diagnostics component of a three-pronged national strategy, including vaccines and therapeutics, to respond to the COVID-19 pandemic. Unprecedented in the scale of its mission, its budget, its accelerated time frame, the extent of cross-government agency collaboration and information exchange, and the blending of business, academic, and investment best practices, RAD Tech successfully launched dozens of US Food and Drug Administration Emergency Use Authorization diagnostic tests, established a new model for rapidly translating diagnostic tests from the laboratory to the marketplace, and accelerated public acceptance of home-based diagnostic tests. This chapter provides an overview of the processes utilized by RADx Tech during the COVID-19 pandemic to improve clinical laboratory tests and identify, evaluate, support, validate, and commercialize innovative point-of-care and home-based tests that directly detected the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.
People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31–36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25–30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Understanding spatial variation in origination and extinction can help to unravel the mechanisms underlying macroevolutionary patterns. Although methods have been developed for estimating global origination and extinction rates from the fossil record, no framework exists for applying these methods to restricted spatial regions. Here, we test the efficacy of three metrics for regional analysis, using simulated fossil occurrences. These metrics are then applied to the marine invertebrate record of the Permian and Triassic to examine variation in extinction and origination rates across latitudes. Extinction and origination rates were generally uniform across latitudes for these time intervals, including during the Capitanian and Permian–Triassic mass extinctions. The small magnitude of this variation, combined with the possibility of its attribution to sampling bias, cautions against linking any observed differences to contrasting evolutionary dynamics. Our results indicate that origination and extinction levels were more variable across clades than across latitudes.
Many clinical trials leverage real-world data. Typically, these data are manually abstracted from electronic health records (EHRs) and entered into electronic case report forms (CRFs), a time and labor-intensive process that is also error-prone and may miss information. Automated transfer of data from EHRs to eCRFs has the potential to reduce data abstraction and entry burden as well as improve data quality and safety.
Methods:
We conducted a test of automated EHR-to-CRF data transfer for 40 participants in a clinical trial of hospitalized COVID-19 patients. We determined which coordinator-entered data could be automated from the EHR (coverage), and the frequency with which the values from the automated EHR feed and values entered by study personnel for the actual study matched exactly (concordance).
Results:
The automated EHR feed populated 10,081/11,952 (84%) coordinator-completed values. For fields where both the automation and study personnel provided data, the values matched exactly 89% of the time. Highest concordance was for daily lab results (94%), which also required the most personnel resources (30 minutes per participant). In a detailed analysis of 196 instances where personnel and automation entered values differed, both a study coordinator and a data analyst agreed that 152 (78%) instances were a result of data entry error.
Conclusions:
An automated EHR feed has the potential to significantly decrease study personnel effort while improving the accuracy of CRF data.
To describe inpatient fluoroquinolone use and susceptibility data over a 10-year period after the implementation of an antimicrobial stewardship program (ASP) led by an infectious diseases pharmacist starting in 2011.
Design:
Retrospective surveillance study.
Setting:
Large community health system.
Methods:
Fluoroquinolone use was quantified by days of therapy (DOT) per 1,000 patient days (PD) and reported quarterly. Use data are reported for inpatients from 2016 to 2020. Levofloxacin susceptibility is reported for Pseudomonas aeruginosa and Escherichia coli for inpatients from 2011 to 2020 at a 4 adult-hospital health system.
Results:
Inpatient fluoroquinolone use decreased by 74% over a 5-year period, with an average decrease of 3.45 DOT per 1,000 PD per quarter (P < .001). Over a 10-year period, inpatient levofloxacin susceptibility increased by 57% for P. aeruginosa and by 15% for E. coli. P. aeruginosa susceptibility to levofloxacin increased by an average of 2.73% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = −0.99 (P = .002). E. coli susceptibility to levofloxacin increased by an average of 1.33% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = −0.95 (P = .015).
Conclusions:
A substantial decrease in fluoroquinolone use and increase in P. aeruginosa and E. coli levofloxacin susceptibility was observed after implementation of an antimicrobial stewardship program. These results demonstrate the value of stewardship services and highlight the effectiveness of an infectious diseases pharmacist led antimicrobial stewardship program.
Presidents may react to Supreme Court decisions by supporting or opposing them in their public rhetoric and by calling on Congress to take action to alter or implement the Court’s decisions. We investigate this unique form of lawmaking using an original database of presidential calls to Congress and congressional reactions. We find that presidents call for congressional action to pursue their policy goals and enhance the power of the presidency; we also find that Congress reacts when it is asked to do so by both the Court and the president, as well as when presidents support the implementation of the Court’s decisions.
Sealings recovered from the Omo M10 temple, a provincial center of the Andean Tiwanaku state (AD 500–1100), and from the Muru Ut Pata neighborhood of the Tiwanaku capital, as well as a signet ring from the Akapana East complex of Tiwanaku's highland capital, shed light on the hitherto undocumented use of seals and sealings in Central Andean complex society. The identification of Tiwanaku sealings related to the signet ring seal has implications for understanding the transmission of identity, authority, and authenticity over time and distance in early Andean states.
Suicide in later life is a pressing public health concern, which has likely been exacerbated by the COVID-19 pandemic. Many older adults who need mental health treatment do not have access to necessary services and training for mental health providers to support older adults experiencing suicidality is limited. One solution is developing interventions based in a public health approach to suicide prevention, whereby natural helpers who provide community services are mobilised to respond to older persons-at-risk. Home-delivered meal (HDM) services, for example, are one effective means to reach older adults who are isolated due to being homebound and may be instrumental in preventing suicide. This study examined the experiences of 20 HDM volunteers who received Applied Suicide Intervention Skills Training (ASIST), an evidence-based suicide intervention programme. Phenomenological analysis yielded findings centred on three areas demonstrating the impact of the ASIST training on HDM volunteers: putting asist skills into practice; response to ASIST skills; and role transformation. Implications for integrating suicide prevention efforts with HDM services and directions for future research are discussed.
Hospitalized coronavirus disease 2019 (COVID-19) patients receiving antibiotics (n = 173) were retrospectively assigned to the early or late discontinuation groups. The length of therapy was shorter in the early discontinuation group (3 vs 7 days; P < .0001). Mortality rates (14.3% vs 20.7%; P = .316) and length of stay (7 vs 9 days; P = .063) were similar.
An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
Methods
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
Results
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
Conclusions
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.
Aims
To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.
Method
Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.
Results
Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.
Conclusions
These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of $<\!\!1\,\mu\text{s}$ in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.