To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment.

A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis.

The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease.

The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.

Hearing consists of peripheral components (outer and middle ear, cochlea) and the central auditory system (cochlear nuclei to the auditory cortex). Speech perception relies on peripheral hearing abilities (i.e., pure-tone thresholds) and central auditory processing (CAP) and cognitive functioning. Specifically, working memory, executive function, attention, and verbal functioning allow for speech understanding. As a result, CAP deficits are also influenced by peripheral hearing sensitivity and cognitive functioning. Assessing CAP deficits can be difficult because of these complex interactions. Prior work has shown persons living with HIV (PWH) are at higher risk for sensorineural hearing loss compared to persons living without HIV (PWOH) after adjusting for age, sex, and noise exposure. Further, HIV is a risk factor for cognitive impairment, one example being Alzheimer's disease (AD) and its precursor, Mild Cognitive Impairment (MCI), with auditory dysfunction occurring in earlier stages of AD. Therefore, the purpose of this study was to evaluate: 1) the peripheral hearing sensitivity and CAP in PWH and PWOH; and 2) the association between cognitive function measures and CAP in PWH and PWOH.

Participants included 59 PWH (39 men and 20 women, mean age=66.7 years [SD=4.4 years]) and 27 PWOH (13 men and 14 women, mean age=71.9 years [SD=7.1 years]). Participants completed a standard neuropsychological battery assessing the domains of learning, recall, executive function, working memory, verbal fluency, processing speed and motor. Raw scores were transformed to demographically corrected, domain T-scores. Cognitive function was normal for 39 (66.1%) PWH and 16 (59.3%) PWOH while 43 (72.9%) PWH and 17 (63.0%) PWOH were determined to have MCI. Participants with dementia were excluded. Participants also completed a hearing assessment, a portion of which consisted of pure-tone thresholds, peripheral hearing measure, and dichotic digits testing (DDT), a CAP measure. Pure-tone air-conduction thresholds were obtained at octave frequencies from 0.25 through 8 kHz, including 3 and 6 kHz. A pure-tone average (PTA) was calculated from 0.5, 1, 2, and 4 kHz thresholds for each ear. The DDT involves the presentation of numbers from 1 to 10, excluding 7, in which two different digits are presented to one ear while two other digits are simultaneously presented to the opposite ear. The outcome of DDT is percent correct.

PWH had slightly lower (i.e., better) mean PTAs in both ears compared to PWOH, but this was not statistically significant. Conversely, PWH had lower percent correct DDT results compared to PWOH, but this difference was also not statistically significant. Participants with impairment in verbal fluency, executive functioning, and working memory had significantly worse DDT results by approximately 10%, but only for right ear data.

PWH in our sample had better hearing than PWOH, which can be explained by PWH having a lower mean age. PWH had poorer DDT results, however, indicative of CAP deficits rather than peripheral hearing problems. Poor right ear DDT was associated with impairments specifically in frontal-based cognitive processes with an executive component.

We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.

The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.

We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.

It is often assumed, that adult patients with CHD (ACHD) have impairments regarding their cognitive function (CF) and health-related quality of life. In particular, it seems reasonable to assume that cyanosis may have a potential impact on CF as well as surgical or drug treatment into adulthood. This study assesses neuromental health aspects such as CF and health-related quality of life in ACHD patients.

Seventy-eight ACHD patients (female n = 39 (50%); 34.1 ± 12.9 years; cyanotic CHD n = 49 (62.8%) with a cyanosis duration of 159.8 ± 196.2 month) who underwent open heart surgery as first intervention were asked to participate during routinely follow-up in 2018. Wechsler Intelligence Scale IV was used for CF and the Short Form 36 Health Survey to assess health-related quality of life.

Intelligence quotient measures showed significant differences comparing never cyanotic and with a cyanotic phase in verbal comprehension (p = 0.013). There was no association of CF with cyanosis duration, number of surgery or catheter, CHD severity, and time of first surgery. The group of early surgery showed significantly better results in physical function (p = 0.040) of health-related quality of life, and in comparison with their assigned reference, both groups showed significantly reduced results in all domains except in bodily pain and mental health. Full-Scale intelligence quotient correlates with physical function of health-related quality of life.

The results show normal CF in ACHD. Health-related quality of life was weak in comparison with the reference. There is a need to improve the well-being of our ACHD with structured programmes, including physical activity programmes. This growing ACHD population should be focused in order of their needs, medical ones on one hand and on the other hand psychosocial matters.

Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.

This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.

A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.

The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Individuals living with severe mental illness can have significant emotional, physical and social challenges. Collaborative care combines clinical and organisational components.

We tested whether a primary care-based collaborative care model (PARTNERS) would improve quality of life for people with diagnoses of schizophrenia, bipolar disorder or other psychoses, compared with usual care.

We conducted a general practice-based, cluster randomised controlled superiority trial. Practices were recruited from four English regions and allocated (1:1) to intervention or control. Individuals receiving limited input in secondary care or who were under primary care only were eligible. The 12-month PARTNERS intervention incorporated person-centred coaching support and liaison work. The primary outcome was quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA).

We allocated 39 general practices, with 198 participants, to the PARTNERS intervention (20 practices, 116 participants) or control (19 practices, 82 participants). Primary outcome data were available for 99 (85.3%) intervention and 71 (86.6%) control participants. Mean change in overall MANSA score did not differ between the groups (intervention: 0.25, s.d. 0.73; control: 0.21, s.d. 0.86; estimated fully adjusted between-group difference 0.03, 95% CI −0.25 to 0.31; P = 0.819). Acute mental health episodes (safety outcome) included three crises in the intervention group and four in the control group.

There was no evidence of a difference in quality of life, as measured with the MANSA, between those receiving the PARTNERS intervention and usual care. Shifting care to primary care was not associated with increased adverse outcomes.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Lung function and cardiac function are naturally correlated by sharing the thoracic cage and handling the whole cardiac output sequentially. However, lung function studies are rare in patients with CHD, although results worthy of investigation could be expected. This review summarises existing studies with the lung function parameters (spirometry and body plethysmography) in CHD patients during the last decade.

A systematic review was performed in the relevant database (PubMed, Cochrane, and Scopus) in studies including paediatric and adult patients with CHD where lung parameters (spirometry, body plethysmography) were investigated from January 2010 to December 2020. Two independent reviewers evaluated the studies according to the Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute

Eight studies investigated patients with Fontan palliation including 704 patients (306 female). Four studies included patients after repaired tetralogy of Fallot examining 219 patients (103 female), with one study using double. Further six studies included 3208 (1324 female) children and adults with various CHDs. Overall, four studies were categorised as “good”, ten as “fair”, and four as “poor”. While the measurements were consistently standardised, references to calculate %predicted differed substantially across all studies. All evaluated studies showed reduced forced vital capacity in the majority of CHD patients.

Many CHD patients have a reduced forced vital capacity independent of their underlying defect. Spirometry should not only follow a standardised measure according to ATS (update 2019) but also stick to the 2012 GLI reference values

Impairments and developmental delay are often reported in infants and young children with CHD. However, currently, there is no data regarding cognitive abilities assessed by standardised intelligence tests in adults with CHD. This study assesses the cognitive function in Fontan patients compared with acyanotic CHD patients whether restrictions in cognitive function are present in adulthood and its association with health-related quality of life.

Forty-four adult CHD (female n = 21 (47.7%); mean age 34.7 ± 11.9 years), 22 with Fontan circulation and 22 with acyanotic CHD, underwent the Wechsler Intelligence Scale for adults as patients during routine follow-up in 2018. The Medical Outcomes Study Questionnaire Short-Form 36 Health Survey (SF-36) assessed health-related quality of life.

Fontan patients showed significantly better results in the FSIQ (p = 0.020) and perceptual reasoning (p = 0.017) in comparison with patients with acyanotic CHD. All adult CHD patients showed normal IQ in subscales and full-scale IQ (FSIQ). In health-related quality of life, no association with cognitive function was found and no significant difference between both CHD groups, but trends to reduced values in acyanotic adult CHD.

Interestingly, our study results in adult Fontan patients showed that it is possible to live an adult life with normal cognitive function and good health-related quality of life with a univentricular heart. Thus, this study could be a guidepost for more in-depth studies on cognitive function in Fontan survivors. In addition, the focus should be on health-related quality of life of adult CHD with simple CHD in particular, since a reduced health-related quality of life is not only medically based.

To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.

Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.

Community settings and care homes in 26 UK centers.

People with probable or possible Alzheimer’s disease and agitation.

Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.

One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.

On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

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.