Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.
Prime hAd5 Spike plus Nucleocapsid Vaccination Induces Ten-Fold Increases in Mean T-Cell Responses in Phase 1 Subjects that are Sustained Against Spike Variants In response to the need for a safe, efficacious vaccine that elicits vigorous T cell as well as humoral protection against SARS-CoV-2 infection, we have developed a dual-antigen COVID-19 vaccine comprising both the viral spike (S) protein modified to increase cell-surface expression (S-Fusion) and nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown previously in cancer vaccine studies to be safe and effective in the presence of pre-existing hAd5 immunity. The findings reported here are focused on human T-cell responses due to the likelihood that such responses will sustain efficacy against emerging variants, a hypothesis supported by our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2  A strain and the B.1.351 strain K417N, E484K, and N501Y spike and T201I N variants. We demonstrate the hAd5 S-Fusion + N-ETSD vaccine antigens expressed by previously SARS-CoV-2-infected patient dendritic cells elicit Th1 dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential to elicit immune responses in previously infected patients. For participants in our open-label Phase 1b study of the vaccine (NCT04591717; https://clinicaltrials.gov/ct2/show/NCT04591717), the magnitude of Th-1 dominant S- and N-specific T-cell responses after a single prime subcutaneous injection were comparable to T-cell responses from previously infected patients. Furthermore, vaccinated participant T-cell responses to S were similar for A strain S and a series of spike variant peptides, including S variants in the B.1.1.7 and B.1.351 strains. The findings that this dual-antigen vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.
Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination Early in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of post-menopausal people reported breakthrough bleeding. We found increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever, fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon nor dangerous, yet attention to these experiences is necessary to build trust in medicine.

TeaserIncreased bleeding can occur post SARS-CoV-2 vaccines; this study investigates patterns in who experiences these changes. Chemosensory dysfunctions induced by COVID-19 can persist up to 7 months: A study of over 700 healthcare workers Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivity have improved. The energy balance theory: an unsatisfactory model of body composition fluctuations Differential weight and fat losses under isocaloric diets of distinct macronutrient composition are well-documented findings in obesity research.1-6 Such data are considered a result of inadequate methodology as it disagree with the energy balance theory.7 A recent mathematical analysis of this paradigm has found, however, serious analytical contradictions in its foundations.8 As an alternative, a mass balance model was proposed to explain the aforesaid body composition alterations. Here, we expand on this observation by contrasting both models. We show that mass balance explains a wide range of fending experiments including those concurring with the energy balance principle. The latter, however, is less flexible and results in poor forecasts in settings consistent with mass balance. The energy balance theory is thus an unsatisfactory model of body composition changes. Consequently, by shifting to a mass balance paradigm of obesity a much deeper understanding of this disease may follow in the near future. Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative data BackgroundColorectal cancer (CRC) is the third most common type of cancer in Scotland and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. Linked administrative datasets can provide a real-world representation of current care as a basis for evaluation of new interventions or policies and to understand variation in care and outcomes. In this study, we aim to provide up to date, population level evidence on CRC treatment and survival in Scotland for patients treated with curative or palliative intent as a basis for the understanding of variation, and to provide data to underpin the evaluation of new treatments.

MethodsWe conducted a retrospective analysis of adults with an incident CRC registered on the Scottish Cancer Registry (ICD-10 codes C18-20) between January 2006 and December 2018. Data on patients with incident CRC was linked to hospital inpatient records allowing description of their demographic, diagnostic and treatment characteristics. For a curative cohort (n = 26,204) Cox-Proportional Hazards regression models were used to assess the factors affecting overall survival (OS) and CRC specific survival (CRCS).

ResultsOverall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively. On average, patients with colorectal cancer had two hospital inpatient stays in the five-years pre-diagnosis. Chemotherapy was used in 42% with colon cancer and 30% with colon cancer. Radiotherapy use was 2% and 39% respectively. Five year OS (CRCS) within the curative cohort was 71% (81%) and 75% (82%) for patients with colon and rectal cancer respectively. After accounting for patient and tumour characteristics, survival outcomes demonstrated significant geographical variation.

ConclusionsNational linked administrative datasets have the ability to provide real-world representation of the treatments and outcomes for patients with cancer. In a Scottish population of curative patients with CRC, there was significant variation in survival depending on sex and geography. Genetic control of fetal placental genomics contributes to development of health and disease As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we performed distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At P < 2.5 x 10-6, we detected 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explained 4 early-life traits but no later-in-life traits. 89 GTAs showed significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells showed that knockdown of mediator gene EPS15 upregulated predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course. A Randomised Trial of a Wearable UV dosimeter for Skin Cancer Prevention BackgroundNon-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States, affecting 5 million people and costing $8.1 billion per year. Despite well-defined guidelines on ultraviolet radiation (UVR) avoidance, it remains difficult for people to assess their individual exposure, as UVR is invisible and the onset of symptoms due to UVR damage are delayed.

MethodsIn a prospective, randomized-controlled trial, 97 patients with a history of actinic keratoses were enrolled from March 2018 to July 2018 and followed over 6 months. 50 patients were given a wearable device that measured UV exposure and a smartphone application that provided both real-time and cumulative UV exposure information, and 47 patients were provided with UV protection counseling by a dermatologist.

ResultsWe observed a significant decrease in the incidence rate of NMSC in the intervention group compared to the control group over 3 months (p = 0.02). We did not observe a significant decrease in the incidence rate of actinic keratoses (AK) in the intervention group compared to the control group. The observed clinical benefit was not accompanied by psychological side effects such as anxiety and depression.

ConclusionsThis study suggests that providing real-time UV exposure data using a wearable UV dosimeter is a safe and effective behavioral change strategy to prevent NMSC. (Funded by the National Cancer Institute, contract HHSN261201700005C; ClinicalTrials.gov number NCT03315286.) Do school closures and school reopenings affect community transmission of COVID-19? A systematic review of observational studies BackgroundSchool closures are associated with significant negative consequences and exacerbate inequalities. They were implemented worldwide to control SARS-CoV-2 in the first half of 2020, but their effectiveness, and the effects of lifting them, remain uncertain. This review summarises observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission.

MethodsThe study protocol was registered on Prospero (ID:CRD42020213699). On 07 January 2021 we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index, and Google. We included observational studies with quantitative estimates of the effect of school closures/reopenings on SARS-CoV-2 community transmission. We excluded prospective modelling studies and intra-school transmission studies. We performed a narrative synthesis due to data heterogeneity. We used the ROBINS-I tool to assess risk of bias.

FindingsWe identified 7,474 articles, of which 40 were included, with data from 150 countries. Of these 32 studies assessed school closures, and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60%, and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission.

ConclusionsSchool closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures. Adaptation of HL7 FHIR for the exchange of patients' gene expression profiles High-throughput technologies, especially gene expression analyses can accurately capture the molecular state in patients under different conditions. Thus, their application in clinical routine gains increasing relevance and fosters patient stratification towards individualized treatment decisions. Electronic health records already evolved to capture genomic data within clinical systems and standards like FHIR enable sharing within, and even between institutions. However, FHIR only provides profiles tailored to variations in the molecular sequence, while expression patterns are neglected although being equally important for decision making. Here we provide an exemplary implementation of gene expression profiles of a microarray analysis of patients with acute myeloid leukemia using an adaptation of the FHIR genomics extension. Our results demonstrate how FHIR resources can be facilitated in clinical systems and thereby pave the way for usage for the aggregation and exchange of transcriptomic data in multi-center studies. I wanna live and not think about the future; What place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study BackgroundLittle is known about how people with multiple sclerosis and their families comprehend advance care planning (ACP) and its relevance in their lives.

AimTo explore under what situations, with whom, how, and why do people with MS and their families engage in ACP

MethodsWe conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families. Twenty-seven people with MS and 17 family members were interviewed between June 2019 and March 2020. Interviews and the ethical discussion group were audio-recorded and transcribed verbatim. Data were analysed using the framework approach.

ResultsParticipants narratives focused on three major themes :(i) planning for an uncertain future; (ii) perceived obstacles to engaging in ACP that included uncertainty concerning MS disease progression, negative previous experiences of ACP discussions and prioritising symptom management over future planning; (iii) Preferences for engagement in ACP included a trusting relationship with a health professional and that information then be shared across services. Health professionals accounts from the ethical discussion group departed from viewing ACP as a formal document to that of an ongoing process of seeking preferences and values. They voiced similar concerns to people with MS about uncertainty and when to initiate discussions. Some shared concerns of a lack of confidence when having ACP discussions.

ConclusionThese findings support the need for a whole systems strategic approach where information about the potential benefits of ACP in all its forms can be shared with people with MS. Moreover, they highlight the need for health professionals to be skilled and trained in engaging in ACP discussions and where information is contemporaneously and seamlessly shared across services. Uncovering Survivorship Bias in Longitudinal Mental Health Surveys During the COVID-19 Pandemic AimsMarkedly elevated adverse mental health symptoms were widely observed early in the coronavirus disease 2019 (COVID-19) pandemic. Unlike the U.S., where cross-sectional data indicate anxiety and depression symptoms have remained elevated, such symptoms reportedly declined in the U.K., according to analysis of repeated measures from a largescale longitudinal study. However, nearly 40% of U.K. respondents (those who did not complete multiple follow-up surveys) were excluded from analysis, suggesting that survivorship bias might partially explain this discrepancy. We therefore sought to assess survivorship bias among participants in our longitudinal survey study as part of The COVID-19 Outbreak Public Evaluation (COPE) Initiative.

MethodsSurvivorship bias was assessed 4,039 U.S. respondents who completed surveys including the assessment of mental health as part of The COPE Initiative in April 2020 and were invited to complete follow-up surveys. Participants completed validated screening instruments for symptoms of anxiety, depression, and insomnia. Survivorship bias was assessed for (1) demographic differences in follow-up survey participation, (2) differences in initial adverse mental health symptom prevalences adjusted for demographic factors, and (3) differences in follow-up survey participation based on mental health experiences adjusted for demographic factors.

ResultsAdjusting for demographics, individuals who completed only one or two out of four surveys had higher prevalences of anxiety and depression symptoms in April 2020 (e.g., one-survey versus four-survey, anxiety symptoms, adjusted prevalence ratio [aPR]: 1.30, 95% confidence interval [CI]: 1.08-1.55, P=0.0045; depression symptoms, aPR: 1.43, 95% CI: 1.17-1.75, P=0.00052). Moreover, individuals who experienced incident anxiety or depression symptoms had higher odds of not completing follow-up surveys (adjusted odds ratio [aOR]: 1.68, 95% CI: 1.22-2.31, P=0.0015, aOR: 1.56, 95% CI: 1.15-2.12, P=0.0046, respectively).

ConclusionsOur findings revealed significant survivorship bias among longitudinal survey respondents, indicating that restricting analytic samples to only respondents who provide repeated assessments in longitudinal survey studies could lead to overly optimistic interpretations of mental health trends over time. Cross-sectional or planned missing data designs may provide more accurate estimates of population-level adverse mental health symptom prevalences than longitudinal surveys. Development and validation of a multimodal neuroimaging biomarker for electroconvulsive therapy outcome in depression: a multicenter machine learning analysis BackgroundElectroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers.

ObjectiveTo develop and validate neuroimaging biomarkers for ECT outcome in a multi-center setting.

MethodsMultimodal data (i.e., clinical, sMRI and resting-state fMRI) was collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluated which data modalities or combinations thereof could provide the best predictions for treatment response ([&ge;]50% symptom reduction) or remission (HAM-D score [&le;]7) using a support vector machine classifier.

ResultsRemission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers, and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).

ConclusionsThese results show that multimodal neuroimaging data is able to provide good prediction of remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. This suggests that these biomarkers are robust, indicating that future development of a clinical decision support tool applying these biomarkers may be feasible. Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the pandemic course and disease features in individual patients. Here we report SARS-CoV-2 genome sequences from 12,476 patients in the Houston Methodist healthcare system diagnosed from January 1, 2021 through May 31, 2021. The SARS-CoV-2 variant designated U.K. B.1.1.7 increased rapidly and caused 63%-90% of all new cases in the Houston area in the latter half of May. Eleven of the 3,276 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals with B.1.1.7 had a significantly lower cycle threshold value (a proxy for higher virus load) and significantly higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly, although the magnitude was less than for B.1.1.7. We identified 22 patients infected with B.1.617 "India" variants; these patients had a high rate of hospitalization. Vaccine breakthrough cases (n=207) were caused by a heterogeneous array of virus genotypes, including many that are not variants of interest or concern. In the aggregate, our study delineates the trajectory of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston, and heralds the arrival and spread of B.1.617 variants in the metroplex. Prospectively validated disease-agnostic predictive medicine with augmented intelligence Despite numerous superhuman achievements in complex challenges1,2, standalone AI does not free life science from the long-term bottleneck of linearly extracting new knowledge from exponentially growing new data3, severely limiting the success rate of drug discovery4. Inspired by the state-of-the-art AI training methods, we trained a human-centric hybrid augmented intelligence5 (HAI) to learn a foundation model6 that extracts all-encompassing knowledge of human physiology and diseases. To evaluate the quality of HAIs extracted knowledge, we designed the public, prospective prediction of pivotal ongoing clinical trial outcomes at large scale (PROTOCOLS) challenge to benchmark HAIs real-world performance of predicting drug clinical efficacy without access to human data. HAI achieved a 10.5-fold improvement from the baseline with 99% confidence7 in the PROTOCOLS validation, readily increasing the average clinical success rate of investigational new drugs from 7.9%8 to 90% for almost any human diseases9,10. The validated HAI confirms that exponentially extracted knowledge alone is sufficient for accurately predicting drug clinical efficacy, effecting a total reversal of Erooms law4. HAI is also the worlds first clinically validated model of human aging that could substantially speed up the discovery of preventive medicine for all age-related diseases11. Our results demonstrate that disruptive breakthroughs necessitate the smallest team size to attain the largest HAI for optimal knowledge extraction from high-dimensional low-quality data space, thus establishing the first prospective proof of the previous discovery that small teams disrupt12. The global adoption of training HAI provides a well-beaten economic path to mass-produce scientific and technological breakthroughs via exponential knowledge extraction and better designs of data labels for training better-performing AI13. Deceased donor kidney degradomics indicates cytoskeletal proteolytic alterations impacting post-transplant function. BackgroundIn brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction.

Material & MethodsUsing mass spectrometry and immunoblotting analyses, we profiled degradation patterns of cytoskeletal proteins in deceased (n=55) and living (n=10) donor kidneys.

ResultsWe found that in DBD kidneys, key podocyte cytoskeletal proteins had been proteolytically cleaved. Generated degradation profiles were not associated to donor related demographic and clinical factors but were associated to suboptimal post-transplant function. Strikingly, -actinin -4 and Talin-1 degradation profiles were not observed in circulatory-death or living-donor kidneys. As Talin-1 is a specific proteolytic target of Calpain-1, we investigated a potential trigger of Calpain activation and Talin-1 degradation using ex-vivo precision-cut human kidney slices and in-vitro immortalised human podocytes. Notably, we found that Transforming-Growth Factor-{beta} (TGF-{beta}) activated Calpain-1 and proteolytically cleaved Talin-1 to generate distinct peptide fragments. These peptide fragments were of similar size and matched the degradation patterns observed in DBD kidneys. Talin-1 degradation was prevented in vitro by Calpain-1 inhibition.

ConclusionsHere, we provide initial evidence that DBD kidneys are susceptible to cytoskeletal protein degradation that impacts posttransplant kidney function. Subsequent studies should aim to further investigate the link between brain death and activation of proteolytic pathways exploring new therapeutic opportunities. Surgical interventions targeting the nucleus caudalis for craniofacial pain: a systematic and historical review. IntroductionChronic facial pain is a prevalent group of conditions and when refractory to common treatments poses a social and economic burden. The last decade has seen a multitude of advancements in the multimodal management of pain. Ablative or neuromodulatory interventions targeting the nucleus caudalis (NC) of the trigeminocervical complex is one such treatment that has remained underutilized.

MethodsHere we present a systematic review of the literature and historical perspective regarding interventions targeting the NC. We examine the various intervention techniques, clinical indications, and procedural efficacy. A novel outcome reporting scheme was devised to allow comparison between studies using differing outcome reporting methods.

ResultsA review of the literature revealed 49 retrospective studies published over the last 80 years, reporting on 858 patients. The most common technique was the open NC dorsal root entry zone nucleotomy/tractotomy (n=515, 60.0%); however, there has been an emergence of novel approaches such as endoscopic (n=6, 0.7%) and spinal cord stimulation (n=20, 2.3%) in the last 10 years. Regardless of intervention technique or preoperative diagnosis, 90.4% of patients demonstrated some improvement from treatment.

ConclusionThis systematic review highlights recent advancements in NC intervention technique and the wide range of facial pain syndromes for which these interventions show promising efficacy. New and less invasive techniques continue to emerge, however prospective studies remain absent in the literature. Future work should address efficacy comparisons between intervention type and preoperative diagnosis. The Ophthalmic Surgical Backlog caused by the COVID-19 Pandemic: A population-based and microsimulation modelling study BackgroundJurisdictions worldwide ramped down ophthalmic surgeries to mitigate the effects of coronavirus disease 2019 (COVID-19), creating a global surgical backlog. We sought to predict the long-term impact of COVID-19 on ophthalmology surgical care delivery.

MethodsThis is a population-based and a microsimulation modelling study. Provincial administrative data from January 2019 to May 2021 was used to estimate the backlog size and wait-times following the COVID-19 pandemic. For the post-pandemic recovery phase, we estimated the resources required to clear the backlog of patients accumulated on the waitlist during the pandemic.

ResultsA total of 56,923 patients were on the waitlist in the province of Ontario awaiting non-emergency ophthalmic surgery as of March 15, 2020. The number of non-emergency surgeries performed in the province decreased by 45-98% from March to May 2020, and 48-80% from April to May 2021 compared to the same months in 2019. By 2 years and 3 years, the overall estimated number of patients awaiting surgery grew by 129% and 150%, respectively. The estimated mean wait-time for patients for all subspecialty surgeries increased to 282 (SD 91) in March 2023 compared to 94 days (SD 97) in 2019. The provincial monthly additional resources required to clear the backlog by March 2023 was estimated to be a 34% escalation from the pre-pandemic volumes (4,626 additional surgeries).

InterpretationThe magnitude of the ophthalmic surgical backlog from COVID-19 has important implications for the recovery phase. The estimates from this microsimulation modelling can be adapted to other jurisdictions to assist with recovery planning for vision saving surgeries. The incidence of delirium in an acute geriatric community hospital: an observational cohort feasibility study. ObjectivesDelirium in hospitalised older adults is associated with negative health outcomes. Admission to an alternative care setting may lower the incidence of delirium. The Acute Geriatric Community Hospital (AGCH) was recently opened in the Netherlands and uses a multi-component non-pharmacological intervention strategy to prevent delirium. The objective of this study was to describe the incidence of delirium at the AGCH and compare this incidence to existing rates from literature. If a possible effect on delirium is seen in this comparison this would support conducting a larger prospectively controlled study on delirium in this new care setting.

DesignProspective cohort feasibility study; exploratory meta-analysis of proportions.

Setting and ParticipantsThe AGCH is an acute geriatric unit in a skilled nursing facility for patients aged >65 years with acute medical conditions.

MethodsDelirium assessment using the Confusion Assessment Method (CAM) upon admission and on day one, two and three or until delirium had resolved. Patients charts were reviewed if CAM was missing. In an linear mixed-effects model, the delirium incidence rate in AGCH was compared to pooled delirium incidence rates from six studies found in a high-quality review.

Results214 patients from the AGCH (mean age 81.9 years, 47% male, 12% with a history of dementia) were included in the analysis. Delirium developed in 8% (18/214) (95% confidence interval [CI] 5-13%) of patients during AGCH admission compared to 16% (95% CI 12-21%) in hospitals. Admission to the AGCH was associated with a decreased delirium incidence rate compared to the hospital control group (OR[odds ratio]= 0.49, 95% CI 0.24-0.98, p-value=0.044).

Conclusions and implicationsThe delirium incidence in the AGCH was low compared to those incidences found in general hospitals in literature. Based on these findings a controlled observational or randomized study measuring delirium in this care setting is recommended. Stability of the stroke code during the COVID-19 pandemic in the region of Madrid: a retrospective cohort study Acute Stroke (AS) is the most common time-dependent disease attended in the Emergency Medicine Service (EMS) of Madrid (SUMMA 112). Community of Madrid has been one of the most affected regions in Spain by the coronavirus disease 2019 (COVID19) pandemic. A significant reduction in AS hospital admissions has been reported during the COVID-19 pandemic compared to the same period one year before. As international clinical practice guidelines support those patients with suspected acute stroke should be accessed via EMS, it is important to know whether the pandemic has jeopardized urgent pre-hospital stroke care, the first medical contact for most patients. We aimed to examine the impact of the COVID-19 in stroke codes (SC) in our EMS among three periods of time: the COVID-19 period, the same period the year before, and the 2019-2020 seasonal influenza period. Methods: We compared the SC frequency among the periods with high cumulative infection rate (above the median of the series) of the first wave of COVID-19, seasonal influenza, and also with the same period of the year before. Results: 1,130 SC were attended during the three periods. No significant reduction in SC was found during the COVID-19 pandemic. The reduction of hospital admissions might be attributable to patients attending the hospital by their means. The maximum SC workload seen during seasonal influenza has not been reached during the pandemic. We detected a non-significant deviation from the SC protocol, with a slight increase in hospitals transfers to hospitals without stroke units. Preexisting diabetes and COVID-associated hyperglycaemia in patients with COVID-19 pneumonia AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSAimC_ST_ABSThe aim of the current study was to compare clinical characteristics, laboratory findings and major outcomes of patients hospitalized for COVID-19 pneumonia with COVID-associated hyperglycaemia or preexisting diabetes.

MethodsA cohort of 176 adult patients with a diagnosis of pre-existing diabetes (n=112) or COVID-associated hyperglycaemia (n=55) was studied. Clinical outcomes and laboratory findings were analysed according to the presence of the two conditions. The time to viral clearance was assessed during the follow-up after hospital discharge.

ResultPatients with COVID-associated hyperglycaemia had lower BMI, significantly less comorbidities and higher levels of inflammatory markers and indicators of multi-organ injury than those with preexisting diabetes. No differences between preexisting diabetes and COVID-associated hyperglycaemia were evident for symptoms at admission, humoral response against SARS-CoV-2 or autoantibodies to glutamic acid decarboxylase or interferon alpha-4. COVID-associated hyperglycaemia was independently associated with the risk of adverse clinical outcome defined as ICU admission or death (HR 2.11, 95% CI 1.34-3.31; p=0.001), even after adjustment for age, sex and other selected variables associated with COVID-19 severity. Furthermore, we documented a negative association (HR 0.661, 95% CI 0.43-1.02; p=0.063) between COVID-associated hyperglycaemia and the time to swab negativization.

ConclusionsThe recognition of hyperglycaemia as a specific clinical entity associated with COVID-19 pneumonia is relevant for early and appropriate patient management and close monitoring for the progression of disease severity. Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years Angelman syndrome (AS) is a severe neurodevelopmental condition associated with a significant socioeconomic impact. This is the first study to estimate the impact of AS on parental productivity in Australia using cost-of-illness modelling with simulated follow-up over a 10-year period using 2019 as the baseline year. Key data were obtained from a prospective cohort of AS families, peer-reviewed literature, and publicly-available sources. The base-case productivity burden borne by the estimated 330 living parents of the 428 prevalent-persons with AS totalled AUD$1.25 million, corresponding to a loss of 38.42% of PALYs per-parent. This shows that caring for a child with AS has a significant impact on the productivity of affected parents, with a large associated impact on the broader Australian economy. Prognostic association supports indexing size measures in echocardiography by body surface area Abstract and keywordsO_ST_ABSAimsC_ST_ABSBody surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) <18.5 kg/m2 or [&ge;]30 kg/m2, respectively). We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI.

Methods and ResultsAdult patients with no prior valve replacement were selected from the National Echo Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint. Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n=337,481] and mass [n=330,959], left atrial area [n=136,989], aortic sinus diameter [n=125,130], right atrial area [n=81,699], right ventricular diameter [n=3,575], right ventricular outflow tract diameter [n=2,841]) by BSA had better prognostic performance vs unindexed measures (healthy/overweight: C-statistic 0.656 vs 0.618, average change in Akaike Information Criteria ({Delta}AIC) 800; underweight: C-statistic 0.669 vs 0.654, {Delta}AIC 15; obese: C-statistic 0.630 vs 0.612, {Delta}AIC 113). Indexation by other body size metrics (lean body mass or height and/or weight raised to various powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase [&le;]0.01), with smaller differences in higher BMI subgroups.

ConclusionIndexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.