To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Consumers, public officials, and even managers of health care and insurance are unhappy about care quality, access, and costs. This book shows that is because efforts to do something about these problems often rely on hope or conjecture, not rigorous evidence of effectiveness. In this book, experts in the field separate the speculative from the proven with regard to how care is rendered, how patients can be in control, how providers should be paid, and how disparities can be reduced – and they also identify the issues for which evidence is currently missing. It provides an antidote to frustration and a clear-eyed guide for forward progress, helping health care and insurance innovators make better decisions on deciding whether to go ahead now based on current evidence, to seek and wait for additional evidence, or to move on to different ideas. It will be useful to practitioners in hospital systems, medical groups, and insurance organizations and can also be used in executive and MBA teaching.
COVID-19 spread globally, including across Europe, resulting in different morbidity and mortality outcomes. The aim of this study was to explore the progression of the COVID-19 pandemic over 18 months in relation to the effect of COVID-19 vaccination at a population level across 35 nations in Europe, while evaluating the data for cross-border epidemiological trends to identify any pertinent lessons that can be implemented in the future.
Epidemiological data was obtained from European Centre for Disease Prevention and Control and Our World in Data databases while Ministry of Health websites of each respective country and local newspapers were utilized for COVID-19-related vaccination strategies. Case, mortality, and vaccination incidence comparative analyses were made across neighbouring countries.
Similar morbidity and mortality outcomes were evident across neighbouring countries over 18 months, with a bidirectional relationship evident between cumulative fully vaccinated population and case fatality rates.
Countries’ COVID-19 outcome is related on national mitigative measures, vaccination rollouts, and neighbouring countries’ actions and COVID-19 situations. Mass population vaccination appeared to be effective in reducing COVID-19 case severity and mortality rates. Vaccination equity and pan-European commitment for cross-border governance appear to be the way forward to ensure populations’ return to “normality”.
People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.
People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012–2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.
The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: ‘substance related’ (24.9%), ‘atopic’ (24.2%), ‘pure affective’ (30.4%), ‘cardiovascular’ (14.1%), and ‘complex multimorbidity’ (6.4%). Patients had on average 7–9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the ‘pure affective’. Compared to the largest cluster (‘pure affective’), the ‘substance related’ and the ‘atopic’ clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98–1.00) and 0.96 (0.95–0.97) respectively], and the ‘cardiovascular’ and ‘complex multimorbidity’ clusters were older (ORs 1.09 (1.07–1.10) and 1.16 (1.14–1.18) respectively). The ‘substance related’ cluster was more likely to be White, the ‘cardiovascular’ cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10–2.79), and both more likely to have schizophrenia, compared to other clusters.
The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.
In March 2020, New York City (NYC) became the epicenter of the COVID-19 pandemic in the United States (US). As healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation’s largest alternate care site (ACS): Javits New York Medical Station (Javits). Protecting healthcare workers during a global shortage of personal protective equipment (PPE) in a non-traditional healthcare setting posed unique challenges. We describe components of the healthcare worker safety program implemented at Javits.
Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps (USPHS) and the Department of Defense (DoD).
Healthcare Worker Safety Methods:
Key strategies included ensuring one-way flow of traffic on and off the patient floor; developing a matrix detailing PPE required for each work activity and location; PPE extended use and reuse protocols; personnel training; and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) test.
A well-designed and implemented healthcare worker safety plan can minimize the risk of SARS-CoV-2 infection for healthcare workers. The lessons learned from operating the nation’s largest COVID-19 ACS can be adapted to other environments during public health emergencies.
Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other).
Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness.
A total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55 years; 50% male; 6.4 years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60 years; 35% male; 4.6 years since diagnosis; 50% taking DRA). At week 145, mean ± SE dose was 40.4 ± 1.1 mg/day for schizophrenia/schizoaffective disorder (n = 88) and 38.5 ± 1.2 mg/day for mood disorders (n = 72). Mean ± SE change from baseline in AIMS score at week 145 was −6.3 ± 0.49 and −7.1 ± 0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05).
Long-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Tardive dyskinesia (TD) is an involuntary movement disorder that can result from exposure to dopamine-receptor antagonists (DRAs). Deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores in the 12-week pivotal trials (ARM-TD/AIM-TD). This post hoc analysis assessed the long-term efficacy and safety of deutetrabenazine by baseline DRA use.
Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse event (AE) rates were analyzed in subgroups by baseline DRA use.
Of 337 patients in the OLE study, 254 were taking DRAs at baseline (mean age, 56 years; 48% male; 6.0 years since diagnosis) and 83 were not (mean age, 60 years; 31% male; 4.9 years since diagnosis). Mean ± SE dose at week 145 was 39.9 ± 1.0 mg/day in patients taking DRAs (n = 108) and 38.5 ± 1.5 mg/day in patients not taking DRAs (n = 53). At week 145, mean ± SE change from baseline in AIMS score was −6.1 ± 0.43 and −7.5 ± 0.71; 64% and 62% achieved PGIC treatment success; and 69% and 81% achieved CGIC treatment success, respectively. Overall AE incidence was low (exposure-adjusted incidence rates [incidence/patient-years]: any, 1.08 and 1.97; serious, 0.10 and 0.12; leading to discontinuation, 0.06 and 0.05).
This analysis suggests that deutetrabenazine for long-term treatment of TD is beneficial, with a favorable safety profile, regardless of concomitant DRA use.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
We honour a great man and a true giant. Lodewyk H.S. van Mierop (March 31, 1927 – October 17, 2021), known as Bob, was not only a Paediatric Cardiologist but also a dedicated Scientist. He made many significant and ground-breaking contributions to the fields of cardiac anatomy and embryology. He was devoted as a teacher, spending many hours with medical students, Residents, and Fellows, all of whom appreciated his regularly scheduled educational sessions. Those of us who were fortunate to know and spend time with him will always remember his great mind, his willingness to share his knowledge, and his ability to encourage spirited and fruitful discussions. His life was most productive, and he will long be remembered by many through his awesome and exemplary scientific contributions.
His legacy continues to influence the current and future generations of surgeons and all providers of paediatric and congenital cardiac care through the invaluable archive he established at University of Florida in Gainesville: The University of Florida van Mierop Heart Archive. Undoubtedly, with these extraordinary contributions to the fields of cardiac anatomy and embryology, which were way ahead of his time, Professor van Mierop was a true giant in Paediatric Cardiology. The invaluable archive he established at University of Florida in Gainesville, The University of Florida van Mierop Heart Archive, has been instrumental in teaching medical students, Residents, Medical Fellows, and Surgical Fellows. Only a handful of similar archives exist across the globe, and these archives are the true legacy of giants such as Dr. van Mierop. We have an important obligation to leave no stone unturned to continue to preserve these archives for the future generations of surgeons, physicians, all providers of paediatric and congenital cardiac care, and, most importantly, our patients.
OBJECTIVES/GOALS: a) Explore topics related to AMC CRP job titles, descriptions, and pre-requisites for hire b) Describe impact of COVID-19 on the AMC CRP workforce c) Discuss opportunities for improving diversity in the CRP workforce d) Discuss opportunities to enhance institutional staffing culture to retain CRP workforce METHODS/STUDY POPULATION: Qualitative data from a series of workshop breakout sessions and open-text survey materials focusing on AMC CRP recruitment, retention and diversity were analyzed to inform content and recommendations for clinical research job titles and descriptions, pre-requisites, diversity, and current needs. RESULTS/ANTICIPATED RESULTS: While certain institutions have established competency-based frameworks for job descriptions and career ladders, standardization remains generally lacking across CTSA hubs. Significant hiring needs have reached exponential proportions across hubs, unable to meet current and projected clinical research goals. Data confirmed an urgent need for closing gaps in clinical research workforce at AMCs, especially for improving diversity and equity of personnel. Improved collaboration with human resource departments, engagement with principal investigators, and overcoming both organizational and resource challenges were suggested strategies, as well as pipeline development via outreach to universities, community colleges, and high schools to raise awareness of the professional pathways for CRPs. DISCUSSION/SIGNIFICANCE: Based on input from 130 CRP leaders at 38 CTSA hubs and 4 IDeA sites evaluating data from 23 breakout transcripts and ~92 surveys from the Collaborative Conversations Unmeeting, new opportunities emerged during the analysis. The findings will be summarized in a 2022 Synergy manuscript including best practice benchmarking recommendations.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Most psychiatric disorders are associated with several risk factors, but a few underlying psychopathological dimensions account for the common co-occurrence of disorders. If these underlying psychopathological dimensions mediate associations of the risk factors with psychiatric disorders, it would support a trans-diagnostic orientation to etiological research and treatment development.
An analysis was performed of the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a US nationally representative sample of non-institutionalized civilian adults, focusing on respondents who were aged ⩾21 (n = 34 712). Structural equation modeling was used to identify the psychopathological dimensions underlying psychiatric disorders; to examine associations between risk factors, psychopathological dimensions and individual disorders; and to test whether associations of risk factors occurring earlier in life were mediated by risk factors occurring later in life.
A bifactor model of 13 axis I disorders provided a good fit (CFI = 0.987, TLI = 0.982, and RMSEA = 0.011) including an overall psychopathology factor as measured by all 13 disorders and 2 specific factors, one for externalizing disorders and one for fear-related disorders. A substantial proportion of the total effects of the risk factors occurring early in life were indirectly mediated through factors occurring later in life. All risk factors showed a significant total effect on the general psychopathology, externalizing and fear-related factors. Only 23 of 325 direct associations of risk factors with psychiatric disorders achieved statistical significance.
Most risk factors for psychiatric disorders are mediated through broad psychopathological dimensions. The central role of these dimensions supports trans-diagnostic etiological and intervention research.
This note describes improvements of UV oxidation method that is used to measure carbon isotopes of dissolved organic carbon (DOC) at the National Ocean Sciences Accelerator Mass Spectrometry Facility (NOSAMS). The procedural blank is reduced to 2.6 ± 0.6 μg C, with Fm of 0.42 ± 0.10 and δ13C of –28.43 ± 1.19‰. The throughput is improved from one sample per day to two samples per day.
Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.
Posttraumatic stress disorder (PTSD) is traditionally understood as a disorder that occurs more commonly in women than in men, and in younger age groups than in older age groups. The objective of this study was to determine if these patterns are also observed in relation to International Classification of Diseases (ICD-11) PTSD and complex PTSD (CPTSD).
Secondary data analysis was performed using data collected from three nationally representative samples from the Republic of Ireland (N = 1,020), the United States (N = 1,839), and Israel (N = 1,003), and one community sample from the United Kingdom (N = 1,051).
Estimated prevalence rates of ICD-11 PTSD were higher in women than in men in each sample, and at a level consistent with existing data derived from Diagnostic and Statistics Manual of Mental Disorders (DSM)-based models of PTSD. Furthermore, rates of ICD-11 PTSD were generally lower in older age groups for men and women. For CPTSD, there was inconsistent evidence of sex and age differences, and some indication of a possible interaction between these two demographic variables.
Despite considerable revisions to PTSD in ICD-11, the same sex and age profile was observed to previous DSM-based models of PTSD. CPTSD, however, does not appear to show the same sex and age differences as PTSD. Theoretical models that seek to explain sex and age differences in trauma-related psychopathology may need to be reconsidered given the distinct effects for ICD-11 PTSD and CPTSD.
The current study was conducted to examine the types of adjustments used to support students with special educational needs in mainstream classrooms and how schools monitored the effectiveness of the adjustments they use. A range of stakeholders were interviewed in 22 mainstream schools across New South Wales, Australia, and the interviews were analysed for key themes. Some schools had a narrow focus on a few key areas, with teaching assistants being the most commonly reported adjustment. Few schools used formal formative monitoring to evaluate the effectiveness of adjustments. Options for improvement schools could consider include examining the breadth of adjustments, establishing clear measurable goals, considering alternative strategies for use of teaching assistants, and ensuring adjustments are monitored.
Radiocarbon (14C) is an isotopic tracer used to address a wide range of scientific research questions. However, contamination by elevated levels of 14C is deleterious to natural-level laboratory workspaces and accelerator mass spectrometer facilities designed to precisely measure small amounts of 14C. The risk of contaminating materials and facilities intended for natural-level 14C with elevated-level 14C-labeled materials has dictated near complete separation of research groups practicing profoundly different measurements. Such separation can hinder transdisciplinary research initiatives, especially in remote and isolated field locations where both natural-level and elevated-level radiocarbon applications may be useful. This paper outlines the successful collaboration between researchers making natural-level 14C measurements and researchers using 14C-labeled materials during a subglacial drilling project in West Antarctica (SALSA 2018–2019). Our strict operating protocol allowed us to successfully carry out 14C labeling experiments within close quarters at our remote field camp without contaminating samples of sediment and water intended for natural level 14C measurements. Here we present our collaborative protocol for maintaining natural level 14C cleanliness as a framework for future transdisciplinary radiocarbon collaborations.
Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined.
We harmonized data from 1489 participants (9–27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood.
Three dimensions of antisociality were uncovered: ‘callous-unemotional (CU)/manipulative traits’, ‘intentional aggression/conduct’, and ‘reactivity/impulsivity/irritability’. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age.
Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations.
This chapter considers issues of investment treaties and human rights through the prism of the transboundary haze pollution which has recurred throughout South East Asia for decades, arising from forest and peat fires in Indonesia. There have been a range of responses, which have included action within Indonesia and by individual States, such as Singapore, as well as by the Association of Southeast Asian Nations. This chapter analyses the responsibility of States to prevent transboundary pollution and to protect the human rights of those within their jurisdiction, as well as those residing in neighbouring States. As there are limited means to compel States to comply with international law in this area, this chapter explores two other avenues of enforcement. It considers whether claims could be brought against a State under a relevant investment treaty when an investor’s investment has been affected by the haze pollution. It also examines whether a claim could be brought against those companies which have caused or contributed to human rights violations by their own actions in relation to haze pollution or by actions of third parties with whom they have a business relationship.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.