title: Hepatitis B virus infection in the Lao PDR: A systematic review

abstract:
IntroductionEven though hepatitis B is endemic in the Lao PDR, the understanding of the epidemiology of hepatitis B infection is incomplete. This article reviews the available literature about hepatitis B seroprevalence, risk factors and genotypes in the Lao population in order to provide an up- to date summary of the HBV epidemiology in the Lao PDR, identify knowledge gaps and provide public health recommendations.

MethodsUsing PubMed/Medline and ScienceDirect, all studies reporting the prevalence of hepatitis B markers or genotype distribution in the Lao PDR published were systematically reviewed.

ResultsThe 21 studies included focused on the general population, blood donors, women, children, health care workers and garment factory workers. The studies varied extensively in sample size, target population, methods, study location and time periods. The prevalence of the hepatitis B surface antigen (HBsAg) in blood donors was reported to be 8.7%-9.6% in 2003-2006. In the years 2011-2012, the reported HBsAg prevalence among women (including pregnant women) ranged from 0%-9.5% and among children aged 5-9 years from 1.7%-8.7%, depending on study location and age. The majority of strains characterized in Lao PDR belonged to genotypes B and C.

ConclusionStudies displayed considerable heterogeneity in populations, design and laboratory methods. A high HBsAg prevalence was reported in adults including pregnant women. Low infant vaccination coverage and compromised vaccine immunogenicity were found. Only two studies focused on HBV in risk populations, emphasizing the need for further studies to characterize hepatitis B epidemiology in potentially vulnerable groups. Hepatitis B infection continues to represent a substantial public health threat in the Lao PDR and needs to be monitored to inform health authorities and to counteract over-burdening of the health care system. In order to end mother to child transmission, vaccination coverage with the hepatitis B birth dose should be increased.


title: Learnings from the Australian First Few X Household Transmission Project for COVID-19

abstract:
BackgroundFirst Few "X" (FFX) studies provide a platform to collect the required epidemiological, clinical and virological data to help address emerging information needs about the COVID-19 pandemic.

MethodsWe adapted the WHO FFX protocol for COVID-19 to understand severity and household transmission dynamics in the early stages of the pandemic in Australia. Implementation strategies were developed for participating sites; all household members provided baseline epidemiological data and were followed for 14 days from case identification. Household contacts completed symptom diaries and had respiratory swabs taken at baseline, day 7 and day 14, and day 28 where applicable. We modelled the spread of COVID-19 within households using a susceptible-exposed-infectious-recovered-type model, and calculated the household secondary attack rate and key epidemiological parameters.

Findings96 households with 101 cases and 286 household contacts were recruited into the study between April-October 2020. Forty household contacts tested positive for SARS-CoV-2 in the study follow-up period. Our model estimated the household secondary attack rate to be 15% (95% CI 8-25%), which scaled up with increasing household size. Children were less infectious than their adult counterparts but were also more susceptible to infection.

InterpretationOur study provides important baseline data characterising the transmission of early SARS-CoV-2 strains from children and adults in Australia, against which properties of variants of concern can be benchmarked. We encountered many challenges with respect to logistics, ethics, governance and data management that may have led to biases in our study. Continued efforts to invest in preparedness research will help to test, refine and further develop Australian FFX study protocols in advance of future outbreaks.

FundingAustralian Government Department of Health

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe emergence of SARS-CoV-2 was initially characterised by uncertainty over key epidemiological, clinical and virological characteristics of the pathogen. We conducted a prospective household transmission study of confirmed cases of COVID-19 and their household contacts to collect data to understand severity and household transmission dynamics in Australia and add to the emerging evidence base for decision making. Large systematic reviews and meta-analyses of severity and transmission dynamics of SARS-CoV-2 in households have since been published, although estimates vary by setting.

Added value of this studyThis is the first multi-jurisdictional prospective household transmission study of its kind for SARS-CoV-2 in Australia. Australia experienced low epidemic activity during the study period in 2020 due to robust public health and social measures including extensive PCR testing of symptomatic persons and isolation of all known contacts of confirmed cases. Hence, we describe the transmission dynamics in our cohort, i.e. in a low incidence setting and provide estimates of the household secondary attack rate, the relative susceptibility of children compared to adults, and transmission from children compared to adults.

Implications of all the available evidenceOur findings describe the epidemiology of COVID-19 in Australian households in 2020, and demonstrate the effectiveness of public health measures to limit transmission in this setting. Comparisons to other household transmission studies must be interpreted in light of the local epidemiology and context including study design, and sampling methods. Additional research is needed to incorporate genomic and serological data to further study transmission dynamics in our cohort. Continued development of the FFX study platform in Australia will enable integration into surveillance systems and help inform targetted public health responses to future infectious disease emergencies.

category: epidemiology


title: Sex differences in the influence of toxoplasmosis on stress and perceived anxiety: Evidence for the stress-coping hypothesis

abstract: Life-long infection with Toxoplasma, which affects 30% of the human population, has specific behavioral effects. The stress-coping hypothesis explains why the toxoplasmosis-associated behavioral changes go in opposite directions in men and women. It suggests that toxoplasmosis impairs the health of humans, which results in chronic stress. Men and women are known to cope with stress in opposite ways. The first presumption of the hypothesis, impaired health, was confirmed in many studies. The second, higher level of stress, was tested only rarely. Levels of stress and anxiety, measured with the Perceived Stress Scale, and the State-Trait Anxiety Inventory X-2, respectively, were compared in a population of 614 Toxoplasma-free and 162 Toxoplasma-infected subjects. Higher stress was detected in the infected men, but not women. We also found that physical health had a positive rather than negative effect on stress when mental health is controlled, which seems to contradict the prediction of the stress-coping hypothesis. No differences were found in the anxiety of infected and noninfected subjects. Subjects who have objective reasons for stress (those with worse physical health) are less stressed than those without such reasons.

category: psychiatry and clinical psychology


title: BASELINE METABOLIC PROFILING AND RISK OF DEATH FROM COVID-19

abstract:
ObjectiveTo derive a predicted probability of death (PDeathLabs) based upon complete value sets for 11 clinical measurements (CM) obtained on patients prior to their diagnosis of coronavirus disease (COVID-19). PDeathLabs is intended for use as a summary metric for baseline metabolic status in multivariate models for COVID-19 death.

MethodsCases were identified through the COVID-19 Shared Data Resource (CSDR) of the Department of Veterans Affairs. The diagnosis required at least one positive nucleic acid amplification test (NAAT). The primary outcome was death within 60 days of the first positive test. We retrieved all values for systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (O2SAT), body mass index (BMI), estimated glomerular filtration rate (EGFR), alanine aminotransferase (ALT), serum albumin (ALB), hematocrit (HCT), LDL cholesterol (LDL) hemoglobin A1c (A1C), and HDL cholesterol (HDL) if they were done at least 14 days prior to the NAAT. Clinicians evaluate several attributes of CM that are of critical importance: metabolic control, disease burden, chronicity, refractoriness, tendency to relapse, temporal trends, and lability. We derived 1-3 parameters for each of these attributes: the most recent value (metabolic control); time-weighted average and abnormal area under a severity versus time curve (disease burden); time and number of readings above or below goal (chronicity); longest abnormal cluster and time/number of consecutive readings above goal if the last value was abnormal (refractoriness); number of abnormal clusters (tendency to relapse); long- and short-term changes (temporal trends); and coefficient of variation and mean deviation between consecutive readings (lability). We created computer programs to derive cumulative values for these 13 parameters for all 11 CM as each new value is added. A fitted logistic model was developed for each CM to determine which of the 13 parameters contributed to the risk of death. A main logistic model was developed to determine which of the 13 x 11 = 143 metabolic parameters were independently predictive of death. The resulting model was used to derive PDeathLabs for each patient and the area under its receiver operating characteristic (ROC) curve calculated. Single variable logistic models were also derived for age at diagnosis, the Charlson 2-year (Charl2Yr) and lifetime (CharlEver) scores, and the Elixhauser 2-year (Elix2Yrs) and lifetime (ElixEver) scores. Stata was used to compare the ROCs for PDeathDx and each of the other metrics.

ResultsOn September 30, 2021, there were 347,220 COVID-19 patients in the CSDR. 329,491 (94.9%) patients had CM performed at least 14 days prior to the COVID-19 diagnosis and form the basis for this report. 17,934 (5.44%) died within 60 days of the diagnosis. On the subset regressions, the number of significant parameters ranged from all 13 for SBP to 7 for HDL. 239,393 patients had complete sets of data for developing the main model. Of 143 candidate predictors, 49 parameters were identified as statistically significant, independent predictors of death. The most influential domains were the most recent value, disease burden, temporal trends, and tendency to relapse. The ROC area for PDeathLabs was 0.785 +/- 0.002. No difference was found in the ROC areas of PDeathLabs and age at diagnosis (0.783 +/- 0.002; P = NS). However, the ROC area for PDeathLabs was significantly greater than that of Charl2Yrs (0.704 +/- 0.002; P < 0.001), CharlEver (0.729 +/- 0.002; P < 0.001), Elix2Yrs (0.675 {+/-} 0.002; P < 0.001), and ElixEver (0.707 +/- 0.002; P < 0.001). A poor prognosis was found for chronic systolic hypertension. On the other hand, a higher BMI was protective once SBP, DBP, HDL, LDL and A1C were considered.

ConclusionsOur study confirms that parameters derived for 11 CM are significant determinants of COVID-19 death. The most recent value should not be selected over other parameters for multivariate modeling unless there is a physiologic basis for doing so. PDeathLabs has the same discriminating power as age at diagnosis and outperforms comorbidity indices as a summary metric for pre-existing conditions. If validated by others, this approach provides a robust approach to handling CM in multivariate models.

category: infectious diseases


title: Life-long effects of malnutrition using semi-quantitative EEG analysis

abstract:
1The non-linear spatiotemporal features in the continuing EEG recordings could be helpful to infer the physio and pathological significance of early insults on the brain, such as early malnutrition and their long-term effects. A unique opportunity is opened with the Barbados Nutrition Study (BNS) dedicated to studying Protein-Energy Malnutrition (PEM) with two groups, children suffering an early PEM episode and their controls. We evaluated the resting-state EEG (N=108, PEM=46) in 1978, and we repeated the EEG (N=97, PEM=46) in 2018. We did a qualitative analysis of the EEG using a semi-quantitative scale (Grand Total EEG (GTE)) and an item response theory (IRT) approach to estimate a latent variable that is able to explain the subjacent neurophysiological status (NPS). Finally, we applied a mixed-effects model with a sensitivity index for ignorability to test differences between the controls and PEM groups while accounting for the missing data mechanisms (nlme (Pinheiro J. 2020) and the ISNI package in R(Xie et al., 2018). The fixed effects were group, age, gender, and socioeconomic status; the random effect was the variability inherent to each participant and evaluator.

ResultsThe simple visual inspection of the 1978 EEG recordings detected 39 participants with abnormalities (28 PEM and 11 Controls; p<0.05); in 2018, a total of 63 participants showed abnormalities in the EEG recordings (35 PEM and 28 Controls; p<0.01)).

The polytomous IRT analysis revealed that all items had been loaded well onto the latent factor, and the highest value of the Focal abnormality reached 0.97. The fixed effect of the groups (PEM vs. Control) was highly significant, with a p-value of 0 and the c index of 5.27. Age was also significant with a p-value of 0.0093 and the c index of 14.793, whereas Gender and SES were not significant. The contrasts at the two different time points (childhood (1978) mean age= 8.45, adulthood (2018) mean age=48.30) also showed highly significant differences between groups with a p-value of 0.

ConclusionsEEG abnormalities were seen in both PEM and control groups during the school years and later in middle adulthood, with a higher proportion of abnormalities in the previously malnourished BNS participants at both ages. The statistical significance of these differences was confirmed through a latent variable approach and a linear mixed-effect model, which discriminated successfully against the long-term effects of early malnutrition on the brain up to 50 years after the onset of malnutrition in the first year of life.

category: neurology


title: Evaluate the risk in conventional IVF frozen human blastocysts undergoing PGT using a new quantification method for parental contamination testing (qPCT)

abstract:
ObjectiveTo establish a method to assess risks associated with preimplantation genetic testing (PGT) in embryos simultaneously with adhered sperm and cumulus cells.

DesignA prospective pilot study.

SettingUniversity teaching hospital.

Patient(s)120 frozen blastocysts that could be biopsied from 34 patients who had experienced repeated implantation failure or abortion due to chromosomal abnormalities after embryos transfer in prior routine IVF cycles.

Intervention(s)Chromosome screening and parental DNA contamination testing was performed in the surplus frozen IVF blastocysts from 34 patients.

Main Outcome Measure(s)Parental DNA contamination rate and euploidy rate in biopsied blastocysts.

Result(s)A new quantification method for parental contamination testing (qPCT) in single-cell whole-genome amplification (WGA) products based on allelic ratio analysis was established and validated in an artificial model by comparing 22 results obtained before and after adding different numbers of sperm and cumulus cells to biopsied TE cells. The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and the risk of paternal contamination was negligible. The euploidy rate in these blastocysts was 47.50% (57/120), and 21 frozen embryo transfer (FET) cycles resulted in ten ongoing clinical pregnancies and four healthy births.

Conclusion(s)The evidence we provide in the study shows a low risk of PGT in embryos simultaneously with adhered sperm and cumulus cells. The qPCT assay can be used to detect the risk of potential contamination and ensure the accuracy of PGT results, thereby improving the clinical outcome of IVF.

CapsuleDuring PGT for human frozen conventional IVF embryos, paternal source pollution is negligible, while maternal pollution can not be ignored. qPCT method can effectively detect the parent DNA contamination in WGA products of biopsied TE cells.

category: sexual and reproductive health


title: Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics

abstract:
BackgroundTransmission has been proposed as a driver of tuberculosis (TB) epidemics in high-burden regions, with negligible impact in low-burden areas. Genomic epidemiology can greatly help to quantify transmission in different settings but the lack of whole genome sequencing population-based studies has hampered its use to compare transmission dynamics and contribution across settings.

MethodsWe generated an additional population-based sequencing dataset from Valencia Region, a low burden setting, and compared it with available datasets from different TB settings to reveal heterogeneity of transmission dynamics and its public health implications. We sequenced the whole genome of 785 M. tuberculosis strains and linked genomes to patient epidemiological data. We applied a pairwise distance clustering approach and phylodynamics methods to characterize transmission events over the last 150 years, in Valencia, Spain (low burden), Oxfordshire, United Kingdom (low burden) and a high-burden (Karonga, Malawi).

ResultsOur results revealed high local transmission in the Valencia Region (47.4% clustering), in contrast to Oxfordshire (27% clustering), and similar to a high-burden setting like Malawi (49.8% clustering). By modelling times of the transmission events, we observed that settings with high transmission are associated with uninterrupted transmission of strains over decades, irrespective of burden.

ConclusionsOur results underscore significant differences in transmission between TB settings even with similar burdens, reveal the role of past epidemic in on-going TB epidemic and highlight the need for in-depth characterization of transmission dynamics and specifically-tailored TB control strategies.

FundingEuropean Research Council under the European Unions Horizon 2020 research and innovation program (Grants 638553-TB-ACCELERATE, 101001038-TB-RECONNECT), and Ministerio de Ciencia e Innovacion (Spanish Government, SAF2016-77346-R and PID2019-104477RB-I00)


title: The Choice of Response Alternatives in COVID-19 Social Science Surveys

abstract: Social science research is key for understanding and for predicting compliance with COVID-19 guidelines, and much of this research relies on survey data. While much focus is on the survey question stems, less is on the response alternatives presented that both constrain responses and convey information about the assumed expectations of the survey designers. The focus here is on the choice of response alternatives for the types of behavioral frequency questions used in many COVID-19 and other health surveys. We examine issues with two types of response alternatives. The first are vague quantifiers, like "rarely" and  frequently." Using data from 30 countries from the Imperial COVID data hub, we show that the interpretation of these vague quantifiers (and their translations) depends on the norms in that country. If the mean amount of hand washing in your country is high, it is likely "frequently" corresponds to a higher numeric value for hand washing than if the mean in your country is low. The second type are precise numeric response alternatives and they can also be problematic. Using a US survey, respondents were randomly allocated to receive either response alternatives where most of the scale corresponds to low frequencies or where most of the scale corresponds to high frequencies. Those given the low frequency set provided lower estimates of the health behaviors. The choice of response alternatives for behavioral frequency questions can affect the estimates of health behaviors. How the response alternatives mold the responses should be taken into account for epidemiological modeling. We conclude with some recommendations for response alternatives for health behavioral frequency questions in surveys.


title: Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the coronavirus disease 2019 (Covid-19) pandemic. The detection and rapid spread of the SARS-CoV-2   Omicron variant (lineage B.1.1.529) in Botswana and South Africa became a global concern because it contained 15 mutations in the spike protein immunogenic receptor binding domain and was less neutralized by sera derived from vaccinees compared to the previously dominant Delta variant. To investigate if Omicron is more likely than Delta to cause infections in vaccinated persons, we analyzed 37,877 nasal swab PCR tests conducted from 12-26 December 2021 and calculated the test positivity rates for each variant by vaccination status. We found that the positivity rate among unvaccinated persons was higher for Delta (5.2%) than Omicron (4.5%). We found similar results in persons who received a single vaccine dose. Conversely, our results show that Omicron had higher positivity rates than Delta among those who received two doses within five months (Omicron = 4.7% vs. Delta = 2.6%), two doses more than five months ago (4.2% vs. 2.9%), and three vaccine doses (2.2% vs. 0.9%). Our estimates of Omicron positivity rates in persons receiving one or two vaccine doses were not significantly lower than unvaccinated persons but were 49.7% lower after three doses. In comparison, the reduction in Delta positivity rates from unvaccinated to 2 vaccine doses was 45.6-49.6% and to 3 vaccine doses was 83.2%. Despite the higher positivity rates for Omicron in vaccinated persons, we still found that 91.2% of the Omicron infections in our study occurred in persons who were eligible for 1 or more vaccine doses at the time of PCR testing. In conclusion, escape from vaccine-induced immunity likely contributed to the rapid rise in Omicron infections.


title: Identification of HBV and HCV transmission in multi-transfused Thalassemia patients of Azad Jammu and Kashmir, Pakistan

abstract:
BackgroundThalassemia patients need regular blood transfusion which saves their lives but increases the risk of acquiring viral infections like hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

Objective(s)This study aimed to screen out the HCV and HBV infections in Thalassemia patients receiving regular blood in three centers of Azad Jammu and Kashmir (AJK), Pakistan.

Materials and MethodsIt was a cross sectional, multicenter study involving 224 Thalassemia patients. The study was carried out from August 2019 to January 2020 in Thalassemia centers of Sheikh Khalifa Bin Zaid hospital Rawalakot, District Headquarters hospital (DHQ) Palandari, and Combined Military Hospital (CMH) Muzaffarabad, AJK. A total of 224 patients were screened out for HCV and HBV. Indirect ELISA was carried out to detect anti HCV antibodies while direct ELISA was carried out to detect the HBsAg from all the samples using commercially available ELISA kits.

ResultsOverall, 12 patients (5.36%) were found to be positive for HBV while 63 (28.1%) were positive for HCV. HBV positive patients included 7 (5.69%) males and 5 (4.95%) females while HCV positive patients included 26 (41.27%) males and 37 (58.73%) female patients. Both the viruses were more common among elder patients as compared to younger patients.

ConclusionPrevalence of HCV is very high and that of HBV is moderately high among Thalassemia patients of AJK.


title: Projection of Healthcare Demand in Germany and Switzerland Urged by Omicron Wave (January-March 2022)

abstract: After the implementation of broad vaccination programs, there is an urgent need to understand how the population immunity affects the dynamics of the COVID-19 pandemic in presence of the protection waning and of the emergence of new vari-ants of concern. In the current Omicron wave that is propagating across Europe, assessing the risk of saturation of the healthcare systems is crucial for pandemic management, as it allows us to support the transition towards the endemic course of SARS-CoV-2 and implement more refined mitigation strategies that shield the most vulnerable groups and protect the healthcare systems. We investigated the current pandemic dynamics by means of compartmental models that describe the age-stratified social-mixing, and consider vaccination status, vaccine types, and their waning efficacy. Our goal is to provide insight into the plausible scenarios that are likely to be seen in Switzerland and Germany in the coming weeks and help take informed decisions. Despite the huge numbers of new positive cases, our results suggest that the current wave is unlikely to create an overwhelming health-care demand: owing to the lower hospitalization rate of the novel variant and the effectiveness of the vaccines. Our findings are robust with respect to the plausible variability of the main parameters that govern the severity and the progression of the Omicron infection. In a broader context, our framework can be applied also to future endemic scenarios, offering quantitative support for refined public health interventions in response to recurring COVID-19 waves.


title: Development and validation of personalised risk prediction models for early detection and diagnosis of primary liver cancer among the English primary care population using the QResearch database: research protocol and statistical analysis plan

abstract:
Background and research aimThe incidence and mortality of liver cancer have been increasing in recent years in the UK. However, liver cancer is still under-studied. The Early Detection of Hepatocellular Liver Cancer (DeLIVER-QResearch) project aims to address the research gap and generate new knowledge to improve early detection and diagnosis of primary liver cancer from general practice and at the population level. There are three research objectives: (1) to understand the current epidemiology of primary liver cancer in England, (2) to identify and quantify the symptoms and comorbidities associated with liver cancer, and (3) to develop and validate prediction models for early detection of liver cancer suitable for implementation in clinical settings.

MethodsThis population-based study uses the QResearch(R) database (version 46) and includes patients aged 25-84 years old and without a diagnosis of liver cancer at the cohort entry (study period: 1 January 2008 to 31 December 2020). The team conducted a literature review (with additional clinical input) to inform the inclusion of variables for data extraction from the QResearch database. A wide range of statistical techniques will be used for the three research objectives, including descriptive statistics, multiple imputation for missing data, conditional logistic regression to investigate the association between the clinical features (symptoms and comorbidities) and the outcome, fractional polynomial terms to explore the non-linear relationship between continuous variables and the outcome, and Cox regression for the prediction model. We have a specific focus on the 1-year, 5-year, and 10-year absolute risks of developing liver cancer, as risks at different time points have different clinical implications. The internal-external validation approach will be used, and the discrimination and calibration of the prediction model will be evaluated.

DiscussionThe DeLIVER-QResearch project uses large-scale representative population-based data to address the most relevant research questions for early detection and diagnosis of primary liver cancer in England. This project has great potential to inform the national cancer strategic plan and yield substantial public and societal benefits.

Medical Subject Headings (MeSH)Liver Neoplasms; Carcinoma, Hepatocellular; Cholangiocarcinoma; Clinical Decision Rules; Early Detection of Cancer; Early Diagnosis; Symptom Assessment; Comorbidity


title: Use of magnetic resonance imaging in neuroprognostication after pediatric cardiac arrest: Survey of current practices

abstract:
BackgroundUse of MRI as a tool to aid in neuroprognostication after cardiac arrest (CA) has been described, yet details of specific indications, timing, and sequences are unknown. We aim to define the current practices in use of brain MRI in prognostication after pediatric cardiac arrest.

METHODSA survey was distributed to pediatric institutions participating in three international studies. Survey questions related to center demographics, clinical practice patterns of MRI after CA, neuroimaging resources, and details regarding MRI decision support.

RESULTSResponse rate was 31% (44/143). Thirty-four percent (15/44) of centers have a clinical pathway informing the use of MRI after CA. Fifty percent (22/44) of respondents reported that an MRI is obtained in nearly all CA patients and 32% (14/44) obtain an MRI in those who did not return to baseline neurological status. Sixty-four percent of centers (28/44) obtain an MRI greater than 72 hours after return of spontaneous circulation. Poor neurologic exam was reported as the most common factor (91% [40/44]) determining the timing of the MRI. Conventional sequences (T1, T2, FLAIR, and diffusion weighted imaging/apparent diffusion coefficient) are widely used. Advanced imaging techniques, such as MR spectroscopy, diffusion tensor imaging and resting state functional MRI are less commonly used.

CONCLUSIONSConventional brain MRI is a common practice for prognostication after CA. Advanced imaging techniques, are used infrequently. The lack of standardized clinical pathways and variability in reported practices support a need for higher-quality evidence regarding the indications, timing, and acquisition protocols of clinical MRI studies.

category: pediatrics


title: Systematic review of social determinants of childhood immunisation in low- and middle-income countries and equity impact analysis of childhood vaccination coverage in Nigeria

abstract:
BackgroundNigeria has a high proportion of underimmunised children in the world. We estimated the inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and healthcare characteristics among children aged 12-23 months in Nigeria using a social determinants of health perspective.

MethodsWe conducted a systematic review focused on inequities in childhood immunisation in low- and middle-income countries to identify the social determinants of childhood immunisation. Using these determinants, we analysed basic vaccination coverage in Nigeria (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3- dose polio, and 1-dose measles) of 6,059 children aged 12-23 months using the 2018 Nigeria Demographic and Health Survey.

ResultsWe identified social determinants of immunisation - household wealth, religion, and ethnicity (socioeconomic characteristics); region and place of residence (geographic characteristics); maternal age at birth, maternal education, and maternal household head status (maternal characteristics); sex of child, and birth order (child characteristics); antenatal care and birth setting (healthcare characteristics). While basic vaccination coverage was 31% (95% CI: 29-33), 19% (18-21) of children aged 12-23 months had received none of the basic vaccines. After controlling for background characteristics, there was a significant increase in the odds of basic vaccination by household wealth, living in an urban area, antenatal care, delivery in a health facility, maternal age and maternal education. Children of Fulani ethnicity in comparison to children of Igbo ethnicity had lower odds of receiving basic vaccinations.

DiscussionChildren of Fulani ethnicity, living in rural areas, born in home settings, with young mothers living in the poorest households with no formal education and no antenatal care visits were associated with lower rates of basic vaccination in Nigeria. We recommend a proportionate universalism approach with targeted vaccination programmes proportionate to the level of disadvantage for addressing the immunisation barriers.

HighlightsO_LISocial determinants of childhood immunisation were identified via a systematic review
C_LIO_LIVaccine equity in Nigeria were analysed from a social determinants of health perspective
C_LIO_LIBasic vaccination coverage was 31% among children aged 12-23 months
C_LIO_LI19% of children had received none of the basic vaccines given in the first year of life
C_LIO_LIVaccination coverage among even the most advantaged groups was below target levels
C_LI

category: public and global health


title: Lung Perfusion Disturbances Detected with MRI in Non-Hospitalized Post-COVID-19 Individuals with Dyspnea 3 -13 Months after the Acute Disease

abstract:
BackgroundDyspnea is a prevalent symptom in the post-COVID-19 condition, though its mechanisms are largely unknown. Lung perfusion abnormalities have been reported in acute COVID-19 and could be suspected in patients with lingering dyspnea after the acute phase.

ObjectivesTo detect pulmonary perfusion disturbances in non-hospitalized post-COVID condition with persistent dyspnea 4-13 months after the disease onset.

MethodsNon-hospitalized individuals reporting persistent dyspnea after COVID-19 and matched healthy controls were prospectively recruited between October 2020 and May 2021 to undergo pulmonary dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), six-minute walk test, and self-reported scales questionnaires on dyspnea and physical activity. The DCE-MRI perfusion images were quantified into two parametric values: mean time-to-peak (TTP) and TTP ratio.

ResultsTwenty-eight persons with post-COVID condition and persistent dyspnea (mean age 46.5{+/-}8.0 years, 75% women) and 22 healthy controls (mean age 44.1{+/-}10.8 years, 73% women) were included. The post-COVID group had higher mean pulmonary TTP (0.43{+/-}0.04 vs. 0.41{+/-}0.03, P=0.011) and higher TTP ratio (0.096{+/-}0.052 vs. 0.068{+/-}0.027, P=0.032). Notably, post-COVID males had the highest values (mean TTP 0.47{+/-}0.02, TTP ratio 0.160{+/-}0.039, P<0.001 for both values compared to male controls and post-COVID females). Correlation between dyspnea and perfusion parameters was demonstrated in the males (r=0.83, P<0.001 for mean TTP; r=0.76, P=0.003 for TTP ratio), but not in females.

ConclusionsLung perfusion disturbances were detected in males reporting post-COVID dyspnea using perfusion parameters from DCE-MRI. The distinct sex difference has implications for understanding the perplexing post-COVID pathophysiology and warrants future studies. DCE-MRI could provide biomarkers for such studies.

category: radiology and imaging


title: Evaluating clinical acceptability of organ-at-risk segmentation In head & neck cancer using a compendium of open-source 3D convolutional neural networks

abstract: Deep learning-based auto-segmentation of organs at risk (OAR) holds the potential to improve efficacy and reduce inter-observer variability in radiotherapy planning; yet training robust auto-segmentation models and evaluating their performance is crucial for clinical implementation. Clinically acceptable auto-segmentation systems will transform radiation therapy planning procedures by reducing the amount of time required to generate the plan and therefore shortening the time between diagnosis and treatment. While studies have shown that auto-segmentation models can reach high accuracy, they often fail to reach the level of transparency and reproducibility required to assess the models generalizability and clinical acceptability. This dissuades the adoption of auto-segmentation systems in clinical environments. In this study, we leverage the recent advances in deep learning and open science platforms to reimplement and compare the performance of eleven published OAR auto-segmentation models on the largest compendium of head-and-neck cancer imaging datasets to date. To create a benchmark for current and future studies, we made the full data compendium and computer code publicly available to allow the scientific community to scrutinize, improve and build upon. We have developed a new paradigm for performance assessment of auto-segmentation systems by giving weight to metrics more closely correlated with clinical acceptability. To accelerate the rate of clinical acceptability analysis in medically oriented auto-segmentation studies, we extend the open-source quality assurance platform, QUANNOTATE, to enable clinical assessment of auto segmented regions of interest at scale. We further provide examples as to how clinical acceptability assessment could accelerate the adoption of auto-segmentation systems in the clinic by establishing  baseline clinical acceptability threshold(s) for multiple organs-at-risk in the head and neck region. All centers deploying auto-segmentation systems can employ a similar architecture designed to simultaneously assess performance and clinical acceptability so as to benchmark novel segmentation tools and determine if these tools meet their internal clinical goals.


title: Incontinence and Healthcare Utilization of Medicare Patients

abstract:
PurposeClaims data are used to directly measure the prevalence of incontinence and incontinence-related events within a large Medicare population.

DesignRetrospective analysis.

Subjects and SettingsThe study relied on administrative claims data from the CMS Medicare Limited Data Set (5% sample) in 2018. The analysis was limited to fee-for-service (FFS) Medicare beneficiaries with minimum of 3-month enrollment in Parts A & B and at least 65 years old.

MethodsWe used diagnosis codes to identify members with incontinence in their 2018 claims experience and grouped these members into 3 categories (urinary incontinent only, fecal incontinent only, and dual incontinent (DI)) and four sites-of-service (nursing home, Skilled-nursing Facility (SNF), home health, and self-care). We then determined the incidence of four types of incontinence-related events for each cohort: 1) Urinary Tract Infections (UTIs), 2) Incontinence-Associated Dermatitis (IAD), 3) Slips and falls, and 4) Behavioral disruptions.

ResultsWe found that 11.2 percent of Medicare members had a claims-based diagnosis of incontinence in 2018. This result falls below the estimated share of the over-65 population who are incontinent, as reported in the literature. The prevalence of the four incontinence-related events is significantly higher (between 2 percentage points to 17 percentage points) for members who experience dual incontinence relative to those with only urinary incontinence. On average, those diagnosed with incontinence experienced 5 times more UTIs, two times as many dermatitis events, more than twice as many slips and falls, and 2.8 times more behavior disruptions compared to those without an incontinence diagnosis.

ConclusionsAlthough we find that the prevalence of incontinence is under-reported relative to the literature, our results show that those who are diagnosed as incontinent experience a much higher prevalence of UTIs, IAD, slips and falls, and behavioral deterioration compared to those who are not diagnosed as incontinent. Our results suggest that incontinence may be an important indicator diagnosis of many other conditions and, if not well-managed, may challenge the desire for those who are incontinent to age at home.

category: urology


title: Hilab system, a new point-of-care hematology analyzer supported by the Internet of Things and Artificial Intelligence

abstract:
The complete blood count (CBC) is one of the most requested tests by physicians. Mostly realized in conventional hematological analyzers, CBC tests are restricted to centralized laboratories, due to frequent maintenance, size of devices, and expensive costs that these analyzers require. On the other hand, most handheld CBC devices commercially available present high costs and are not liable to calibration or control procedures, which results in poor quality compared to standard hematology instruments. The Hilab system is a small-handed novel hematological platform that uses microscopy and chromatography techniques for blood cells and hematimetric parameters analysis. Combining artificial intelligence, machine learning, and deep learning techniques, provides the main parameters evaluated in the CBC test and four-part differential WBC. For clinical evaluation, accuracy, precision, method comparison, and flagging capabilities of the Hilab System were compared with the Sysmex XE-2100 (Sysmex, Japan) results. Over the entire measuring range, a strong correlation (r > 0.9) between both methodologies was obtained for most parameters evaluated. Also, high accuracy (> 0.85), and adequate precision values were observed. The anticoagulant influence and the sample source (venous and capillary) effect were also evaluated, and no significant differences were observed (p > 0.05). Thus, considering the need for blood count point-of-care tests, especially for quickly patient management, the study indicated that the Hilab system provides fast, accurate, low cost, and robust blood cell analysis for reliable clinical use.

Key pointsO_LIThe Hilab system presents a high correlation with a standardized reference analyzer for all evaluated CBC parameters;
C_LIO_LIThe flagging capabilities of the Hilab system present high accuracy compared to results provided by specialized hematologists.
C_LI

category: hematology


title: Massive covidization of research citations and the citation elite

abstract: Massive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020-2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations received to papers published in 2020-2021 and >30% of citations received in 36 of the 174 disciplines of science (up to 79.3% in General and Internal Medicine). Across science, 98 of the 100 most-cited papers published in 2020-2021 were related to COVID-19. 110 scientists received >=10,000 citations for COVID-19 work, but none received >=10,000 citations for non-COVID-19 work published in 2020-2021. For many scientists, citations to their COVID-19 work already accounted for more than half of their total career citation count. Overall, these data show a strong covidization of research citations across science with major impact on shaping the citation elite.


title: Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time

abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the childrens sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.


title: Establishment of human post-vaccination SARS-CoV-2 standard reference sera

abstract: As SARS-CoV-2 variants emerge, there is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines. A reference reagent comprised of post-vaccination sera from recipients of different vaccines allows evaluation of in vitro variant neutralization, and provides a reference for comparing assay results across laboratories. We prepared and pooled >1 L serum from donors who received the SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), a replication-incompetent adenovirus type 26 vaccine (Ad26.COV2.S, Johnson and Johnson), or recombinant spike protein expressed by baculovirus incorporated into a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). Twice frozen sera were aliquoted and are available for distribution to the research community (BEI Resources). The calculated WHO titer of pooled sera to spike protein was 1,312, 1,447, 1,936, and 587 and the reciprocal RBD binding to ACE-2 IC90-titers were 60, 64, 118, and 46 for BNT162b2, mRNA1273, Ad26.CoV2373, and NVX-CoV2373 sera, respectively.


title: mRNA-1273 Vaccine-elicited Neutralization of SARS-CoV-2 Omicron in Adolescents and Children

abstract:
BackgroundThe highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant is a global concern. This study assessed the neutralization activity of two-dose regimens of mRNA-1273 vaccination against Omicron in adults, adolescents and children.

MethodsNeutralizing activity against the Omicron variant was evaluated in serum samples from adults ([≥]18 years) in the phase 3, Coronavirus Efficacy (COVE) and from adolescents (12-17 years) in the TeenCOVE trials following a two-dose regimen of 100 {micro}g mRNA-1273 and from children (6-<12 years) in the KidCOVE trial administered two doses of 50 {micro}g mRNA-1273. Neutralizing antibody geometric mean ID50 titers (GMT) were measured using a lentivirus-based pseudovirus neutralizing assay at day 1 and 4 weeks (day 57) following the second mRNA-1273 dose, compared with wild-type (D614G).

ResultsAt 4 weeks following a second dose of mRNA-1273 (100 {micro}g), the GMT was reduced 28.8-fold compared with D614G in adults ([≥]18 years). In adolescents (12-17 years), the GMT was 11.8-fold lower than D614G, 4 weeks after a second dose of mRNA-1273 (100 {micro}g), and compared with adults, were 1.5- and 3.8-fold higher for D614G and the Omicron variant, respectively. In children (6-<12 years), 4 weeks post-second dose of 50 {micro}g mRNA-1273, Omicron GMTs were reduced 22.1-fold versus D614G and were 2.0-fold higher for D614G and 2.5-fold higher for Omicron compared with adults.

ConclusionsA two-dose regimen of 100 {micro}g mRNA-1273 in adolescents and of 50 {micro}g in children elicited neutralization responses against the Omicron variant that were reduced compared with the wild-type D614G, and numerically higher than those in adults.


title: A Novel Barrier Device and Method for Protection against Airborne Pathogens During Endotracheal Intubation

abstract:
BackgroundThe risk of SARS-CoV-2 transmission to healthcare workers increases during aerosol-generating procedures such as endotracheal intubation.

ObjectivesWe tested the effectiveness of a novel barrier mouthpiece in reducing clinician exposure to aerosols and droplets during endotracheal intubation.

DesignA prospective case control study was carried out, with a single operator performing eight simulated intubations with and without the device on two different high-fidelity manikin models which produced aerosols and droplets.

SettingThe study was performed during June 2020, at the Clinical Skills Development Service, Brisbane, Australia.

InterventionsSimulated scenarios included 1) intubation during cardiopulmonary resuscitation 2) intubation while pre-oxygenating via high flow nasal cannula. Photographic images were obtained during each intubation and digitally analyzed using ImageJ v2.1.0/1.53c.

PatientsNot applicable.

Main outcome measuresAerosol and droplets were quantified using pixel counts. Overall results were expressed as means ({+/-} SD), with comparisons between groups made using a two-tailed Students T-test under the assumption of unequal variances. A P value of [≤] 0.05 was considered as statistically significant.

ResultsFirst pass intubation was achieved in all scenarios, with and without the barrier device. Pixel counts demonstrated significant overall reduction in aerosol and droplet exposure when the barrier device was used during intubation [Mean (SD) count:509 (860) vs 10169 (11600); P=0.014]. The highest exposure risk to airborne particles was observed during simulated induction, prior to laryngoscopy and intubation.

ConclusionsThe novel barrier device was effective in reducing environmental exposure to aerosols and droplets during intubation without negatively affecting first pass intubation. The highest risk of exposure to airborne particles was during induction, before intubation takes place. Clinical trials are indicated to further test the feasibility and efficacy of this device.

Trial registrationNot applicable.

KEY POINTSO_LIThis prospective, preclinical study represents a pilot trial of a novel barrier mouthpiece for reducing clinician exposure to aerosols and droplets during endotracheal intubation.
C_LIO_LIIn eight simulated intubations with and without the barrier mouthpiece, the device proved effective in reducing environmental exposure to aerosols and droplets (measured in pixels) during intubation, without negatively affecting first pass intubation.
C_LIO_LIThe novel barrier mouthpiece represents a possible solution for reducing the risk of respiratory pathogen transmission during endotracheal intubation without hampering the procedure itself, although larger preclinical and clinical trials are necessary.
C_LI

category: intensive care and critical care medicine


title: The MU Study of Seropositivity and Risk for SARS-CoV-2 and COVID-19: Crucial Behavioral and Immunological Data from Midwestern College Students

abstract:
ObjectiveWe describe our Fall 2020 study of college students COVID-19 related behaviors, attitudes, and antibody test results.

ParticipantsThe study included 1,446 randomly selected and self-enrolled undergraduate and graduate students from a midwestern university.

MethodsAn online survey was distributed to a sample of students, between September and December 2020. A sub-group also participated in a SARS-CoV-2 antibody blood draw.

ResultsNearly half of students reported a prior COVID-19 test with 22% indicating a positive test, which represents an 11% positivity rate across all student participants. Of those who participated in antibody testing, 15.1% tested positive for SARS-CoV-2 antibodies. Seventy-seven percent of participants said they would get vaccinated. One-third of students reported moderate to severe generalized anxiety disorder and 13% reported moderate to severe depression.

ConclusionsThis study informed campus decisions in Fall 2020. The importance of effective public health messaging on campus should continue in the future.


title: Patients' satisfaction and quality of clinical laboratory services provision at public health facilities in northeast Ethiopia

abstract: Patient satisfaction is a key element of quality measures that has increasingly become acknowledged as an important tool for service improvement. This study aimed to assess the level of patients satisfaction and associated factors with clinical laboratory services provided at public health facilities. A cross-sectional study was conducted from May-June 2019 among clients attending 24 health centers and 8 hospitals, northeast Ethiopia. A total of 502 patients were selected using systematic random sampling. Patients satisfaction towards multiple aspects of laboratory services was assessed using structured exit interview questionnaire, on a rating scale of 1 (very dissatisfied) to 5 points (very satisfied). We assessed test availability and laboratory practices using facility inventory, stepwise accreditation audit checklist and blinded slide rechecking. Data were entered and analyzed using EpiData ver3.1 and STATA ver14.1. Multivariable logistic regression analysis was used to determine the association of factors with overall satisfaction. Overall, majority of the respondents (73.5%) were found to be satisfied. Lowest mean ratings were obtained for waiting area (3.3), and information provided on specimen collection (3.5) and on how and when to receive results (3.7). Patients were more likely to be satisfied in health centers (75.2%) than in hospitals (68.6%) (AOR=1.9, 95%CI: 1.0-3.6, p=0.036). Patients timely receipt of results (p=0.005) and laboratories accuracy of results (p< 0.025) also showed significant positive associations with satisfaction. In conclusion, there were specific areas of deficiency that were driving dissatisfaction, particularly in the larger hospital laboratories. Therefore, more and balanced emphasis should be given to the patients experiences, alongside technical quality improvements, to reduce the disparities and enhance the overall quality of care.

category: health systems and quality improvement


title: Functional proteomic profiling links deficient DNA clearance to mortality in patients with severe COVID-19 pneumonia

abstract: Hyperinflammation, coagulopathy and immune dysfunction are prominent in patients with severe infections. Extracellular chromatin clearance by plasma DNases suppresses such pathologies in mice but whether severe infection interferes with these pathways is unclear. Here, we show that patients with severe SARS-CoV-2 infection or microbial sepsis exhibit low extracellular DNA clearance capacity associated with the release of the DNase inhibitor actin. Unlike naked DNA degradation (DNase), neutrophil extracellular trap degradation (NETase) was insensitive to G-actin, indicating distinct underlying mechanisms. Activity-based proteomic profiling of severely ill SARS-CoV-2 patient plasma revealed that patients with high NETase and DNase activities exhibited 18-fold higher survival compared to patients with low activity proteomic profiles. Remarkably, low DNA clearance capacity was also prominent in healthy individuals with chronic inflammation, suggesting that pre-existing inflammatory conditions may increase the risk for mortality upon infection. Hence, functional proteomic profiling illustrates that non-redundant DNA clearance activities protect critically ill patients from mortality, uncovering protein combinations that can accurately predict mortality in critically ill patients.


title: Acquired neutralizing breadth against SARS-CoV-2 variants including Omicron after three doses of mRNA COVID-19 vaccination and the vaccine efficacy

abstract: To investigate the induction of neutralizing antibodies against Omicron after two and three vaccine doses in recipients of different ages. Physicians at Kobe University Hospital who had received the second dose of the BNT162b2 mRNA vaccine. At 2 months after the second vaccinations, the positive rate of neutralizing antibody against Omicron was 28%, and the titer was significantly lower than those against other variants, 11.8-fold and 3.6-fold lower than those against D614G and Delta, respectively. Unlike Delta, that positive rates of neutralizing antibody against Omicron were low in all age groups, and there was no significant difference in titers among age groups. Seven months after the 2nd dose, the positive rate of neutralizing antibody against Omicron decreased to 6%, but after the booster,3rd vaccination, it increased to 100%, and the titer was much higher than those at 2 and 7 months post-vaccination, 32-fold and 39-fold respectively. The booster vaccination effect was also observed in the younger at 41-fold, middle-aged at 43-fold, and older at 27-fold groups compared to the 7-month titers. Surprisingly, higher-than-predicted titers of the neutralizing antibodies against Omicron were induced after the booster vaccination regardless of recipient age, while this effect was not observed after two doses, indicating the induction of antibodies against common epitopes by the booster vaccination. Three doses can be confidently recommended to suppress the pandemic.


title: Immunogenetics of Gastrointestinal Cancers: A Systematic Review of Inborn Errors of Immunity in Humans

abstract:
Background/AimsThe immune system plays a key role in cancer surveillance and modulation of the tumor microenvironment. Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be prone to recurrent mucosal bacterial and viral infections and chronic inflammation, associated with intrinsic or secondary epithelium dysfunction, a potential risk factor for early-onset gastrointestinal (GI) cancer.

MethodsWe systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed.

ResultsOf the 149 patients with IEIs, 95 presented with gastric cancer, 13 with small bowel cancer, 35 with colorectal cancer, and six with unspecified cancer or cancer at another site. Gastric and colonic adenocarcinoma was the most common. For both gastric and colorectal cancer, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immune deficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, CTLA4. Impaired humoral immunity and Epstein-Barr virus (EBV) infection were frequently reported as the factors potentially underlying early-onset GI malignancy in patients with IEIs.

ConclusionPatients with IEIs should be considered at risk of early-onset GI cancers, and should therefore undergo cancer screening at an earlier age. Surveillance guidance based on stratifications for genetic risk should be revised to take into account the immunogenetic contribution to GI cancers.

category: gastroenterology


title: Effects of vaccination against COVID-19 on the emotional health of Peruvian older adults

abstract:
BackgroundCOVID-19 vaccination may reduce anxiety and depression. However, the pandemic significantly impacted the elderly from low-middle-income countries. Therefore, we aimed to estimate the effect of vaccination against COVID-19 on the emotional health of older adults.

MethodsWe selected a nationally stratified sample of non-hospitalized adults aged 60 to 79 years who intended to receive the COVID-19 vaccine or had already received it during recruitment. We assess the fear, anxiety, and worry about COVID-19, general anxiety, and depression at baseline and after a month. We estimated the adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for each altered emotional health outcomes in those who had one and two doses, compared with those who were not vaccinated using multilevel logistic regression with mixed effects.

ResultsWe recruited 861 older adults. Loss to follow-up was 20.8%. At baseline, 43.9% had only one dose of the vaccine, and 49.1% had two doses. In the analysis during follow-up, those who had two doses had less fear (ORa: 0.19; CI95%: 0.07 to 0.51) and anxiety to COVID-19 (ORa: 0.45; CI95%: 0.22 to 0.89), compared to non-vaccinated. We observed no effects in those with only one dose.

LimitationsInability to obtain the planned sample size for primary analysis. There is a selection bias during recruitment and a measurement bias because of self-reported vaccination.

ConclusionsCOVID-19 vaccination with two doses in elders improves the perception of COVID-19 infection consequences. This information could be integrated into the vaccination campaign as its beneficial effect.

HighlightsO_LIUp to 90% of elders in a Peruvian sample had at least one dose of COVID-19 vaccine
C_LIO_LITwo doses of COVID-19 vaccine reduced the levels of fear and anxiety for COVID-19
C_LIO_LIOnly one dose of vaccine didnt had effect in any emotional mental outcome
C_LI


title: Who Develops Pandemic Fatigue?

abstract: According to the World Health Organization, pandemic fatigue poses a serious threat for managing COVID-19. The cardinal feature of pandemic fatigue is a progressive decline in adherence to social distancing (SDIS) guidelines, which is associated with pandemic-related emotional burnout. Little is known about the nature of pandemic fatigue; for example, it is unclear who is most likely to develop pandemic fatigue. We sought to evaluate this issue based on data from 5,812 American and Canadian adults recruited during the second year of the COVID-19 pandemic. Past-year decline in adherence to SDIS had a categorical latent structure according to Latent Class Analysis, consisting of an SDIS adherent group (Class 1: 92% of the sample) and a group reporting a progressive decline in adherence to SDIS (i.e., pandemic fatigue; Class 2: 8% of the sample). Class 2, compared to Class 1, was associated with greater pandemic-related burnout, pessimism, and apathy about the COVID-19 pandemic. They also tended to be younger, perceived themselves to be more affluent, tended to have greater levels of narcissism, entitlement, and gregariousness, and were more likely to report having been previously infected with SARSCOV2, which they regarded as an exaggerated threat. People in Class 2 also self-reported higher levels of pandemic-related stress, anxiety, and depression, and described making active efforts at coping with SDIS restrictions that they perceived as unnecessary and stressful. People in Class 1 generally reported that they engaged in SDIS for the benefit of themselves and their community, although 35% of this class also feared they would be publicly shamed if they did not comply with SDIS guidelines. The findings suggest that pandemic fatigue affects a substantial minority of people and even many SDIS-adherent people experience emotionally adverse effects (i.e., fear of being shamed). Implications for the future of SDIS are discussed.


title: Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

abstract:
BackgroundInterstitial lung disease (ILD) is the most important pulmonary manifestation of the connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD.

MethodsA literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews and meta-analyses that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. Methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I2, and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons.

DiscussionWhile many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing risks versus benefits of the available therapies by providing high-quality evidence to support informed decision making and may contribute to future guideline development.

Systematic review registrationpending

category: rheumatology


title: Comprehensive analysis of Histone deacetylases genes in the prognosis and immune infiltration of glioma patients

abstract: The occurrence and development of tumors are closely related to histone deacetylases (HDACs). However, the overall biology and prognosis are still unknown in glioma. In the present study, we comprehensively explored the biology function and prognosis of eleven HDAC genes in glioma, which may contribute the more understanding of molecular mechanisms and potential therapeutic targets for glioma patients.We systematically described the expression files, molecular subtypes, prognostic value, immune filtration and tumor microenvironment and gene alteration, function and pathways enrichment, and drug sensitivity using TCGA and CGGA datasets. We developed and validated the prognostic model based on HDACs genes in glioma using LASSO, univariate, and multivariate cox regression. Receiver operating characteristic analyses were used for model evaluating. We also validated the expressions of HDACs genes included in the model in non-tumor and glioma tissues samples. Glioma patients can be divided into two subclasses based on eleven HDAC genes, and patients from two subclasses had markedly different survival outcomes. Then, using six HDAC genes (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), we established a prognostic model in glioma patients, and this prognostic model was well validated in an independent cohort population. Furthermore, the calculated risk score from six HDACA genes expression was suggested to be an independent prognostic factor, which can predict the five-year overall survival of glioma patients well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low-risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, we identified several small molecular compounds that could be favorable for glioma patients treatment. And finally, the expression levels of HDAC genes from prognostic model were validated in glioma and non-tumor tissues samples.Our results revealed the clinical utility and potential molecular mechanisms of HDAC genes in glioma. Model based on six HDAC genes can predict the overall survival of glioma patients well, which can be served as potential therapeutic targets.

category: oncology


title: One minute Multiple Pupillary Frequency Tagging test to assess visual field defects

abstract: Pupillary responses to light offer a convenient and objective way to quickly assess the functional health of the anterior afferent visual pathways. We here present a proof of concept of an innovative one minute pupillary test consisting in 9 visual sub-regions simultaneously modulated in luminance at 9 different temporal frequencies. The spectral power of the sustained pupillary responses evoked by this display over 45 seconds of passive fixation distinguishes patients with retinal and optic nerve diseases from healthy participants with remarkable sensitivity and specificity, at both global and local scales. Reliable and fast, this test could ease patient care and allow screening for, and following-up, chronic ophthalmic diseases whose prevalence worryingly increases worldwide.

category: ophthalmology


title: Emotion-Mind Dynamic (EMD): Face-to-face and online blended-learning life coaching for a social prescribing intervention to support mental health and wellbeing: Protocol for a Social Return on Investment evaluation.

abstract:
IntroductionThe NHS is experiencing increased pressures due to an ageing population and rising health inequalities. GPs spend almost a fifth of their patient facing time addressing non-medical problems such as social isolation, financial struggles, and bereavement. Recent research suggests that holistic approaches linking social care to primary care may be cost-effective in supporting patients. Social Prescribing (SP) is an approach which could help individuals by sign posting and referral to non-clinical services, which can promote improvements in mental health and wellbeing, building resilience using community assets. The EmotionMind Dynamic (EMD) is a lifestyle coaching programme that supports individuals suffering from anxiety or depression referred from the health and social care sectors. EMD offers a unique, non-clinical mixed-modality approach combining coaching, mentoring, counselling skills, teaching and mindfulness. EMD is an adaptable, guided self-help tool that can be used as a preventative, supportive or reactive measure for improving mental health and wellbeing.

MethodsSROI methodology will be used to evaluate the EMD service. The aim of the SROI analysis is to develop a programme-level theory of change to establish how inputs (e.g. costs, staffing) are converted into outputs (e.g. numbers of clients seen), and subsequently into outcomes that matter to clients impacted by EMD coaching (e.g. improved mental wellbeing). Fifty participants will be recruited including clients who have completed the EMD programme and new clients participating in the online blended learning format. Face-to-face and blended learning formats will offer six sessions over a three-month period. A mixed-method approach will collect quantitative and qualitative from questionnaires and interviews. Outcomes will measure improvements in mental wellbeing and self-efficacy. Wellbeing valuation will be applied to quantify and value outcomes. Social value ratios will be generated from two value sets, one from the Social Value Bank and the other from the Short Warwick Edinburgh Mental Wellbeing Scale.

Ethics and disseminationEthical approval of this proposed study has been granted by the Medical and Health Sciences ethics committee, Bangor University. A final report will be presented to key stakeholders and research findings will be published in peer reviewed journals

Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThe first study to undertake a SROI analysis on lifestyle coaching to improve mental wellbeing resilience
C_LIO_LIApplies a mixed-method approach using both quantitative and qualitative data, using valid and reliable outcome measures
C_LIO_LIResearchers working with the same data may arrive at different SROI ratios
C_LIO_LIThe matching of outcomes from proposed study data with the most appropriate SVB value will depend on the research teams discretion and agreement. This could potentially introduce researcher bias and the likelihood that potential estimates of social value generated could be upward-biased
C_LI

category: health economics


title: Breast Cancer Survival Prediction using Machine Learning and Gene Expression Profiles

abstract: Breast cancer is one of the most common cancers with a high mortality rate among women. It is also the most frequent cause of cancer death in this population, with an estimated 684,996 deaths for that year (15.5% of cancer deaths in women) (IARC, 2020). In Brazil, breast cancer is also the most common type of cancer in women from all regions, after non-melanoma skin cancer. Therefore, an accurate and reliable system is needed for the early diagnosis of this cancer. Machine learning explores the study and construction of algorithms that can learn from their mistakes and make predictions about data. The results here are excellent with an accuracy and precision level of around 79%.

category: health informatics


title: Brain Tumor Detection Using Deep Learning

abstract: A brain tumor is understood by the scientific community as the growth of abnormal cells in the brain, some of which can lead to cancer. The traditional method to detect brain tumors is nuclear magnetic resonance (MRI). Having the MRI images, information about the uncontrolled growth of tissue in the brain is identified. In several research articles, brain tumor detection is done through the application of Machine Learning and Deep Learning algorithms. When these systems are applied to MRI images, brain tumor prediction is done very quickly and greater accuracy helps to deliver treatment to patients. These predictions also help the radiologist to make quick decisions. In the proposed work, a set of Artificial Neural Networks (ANN) are applied in the detection of the presence of brain tumor, and its performance is analyzed through different metrics.


title: Designing isolation guidelines for COVID-19 patients utilizing rapid antigen tests: a simulation study using viral dynamics models

abstract: Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adapted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation (thus they are redundantly isolated), whereas others may still be infectious. Utilizing viral test results to determine ending isolation would minimize both the risk of ending isolation of infectious patients and the burden due to redundant isolation of noninfectious patients. In our previous study, we proposed a computational framework using SARS-CoV-2 viral dynamics models to compute the risk and the burden of different isolation guidelines with PCR tests. In this study, we extend the computational framework to design isolation guidelines for COVID-19 patients utilizing rapid antigen tests. Time interval of tests and number of consecutive negative tests to minimize the risk and the burden of isolation were explored. Furthermore, the approach was extended for asymptomatic cases. We found the guideline should be designed considering various factors: the infectiousness threshold values, the detection limit of antigen tests, symptom presence, and an acceptable level of releasing infectious patients. Especially, when detection limit is higher than the infectiousness threshold values, more consecutive negative results are needed to ascertain loss of infectiousness. To control the risk of releasing of infectious individuals under certain levels, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation, and the length of prolonged isolation increases when the detection limit is higher than the infectiousness threshold values, even though the guidelines are optimized for given conditions.


title: COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins

abstract: The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naive to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.


title: SARS-CoV-2 antibody profile of naturally infected and vaccinated individuals detected using qualitative, semi-quantitative and multiplex immunoassays

abstract: Antibody profiling of vaccinated versus naturally infected individuals is important in evaluating immunity and aiding diagnosis and booster strategies. This study measured antibodies against different antigen targets in healthcare workers (HCW) who have been fully vaccinated with mRNA vaccines, recovered from natural infection, or patients during active infection. All vaccinated individuals were positive for anti-RBD, anti-S1, and anti-S2 antibodies. The median index and interquartile range (IQR) by the Atellica IgG assay were 179 and 140-291 respectively. Among the different antigen targets within the Bioplex assay, the levels of anti-RBD were highest (median >3200 U/mL; IQR >3200 to >3200 U/mL), followed by anti-S1 (median 2132 U/mL; IQR 1649->3200 U/mL) and anti-S2 (median=42 U/mL; IQR=24-76 U/mL). The non-vaccinated recovered cohort showed 90% seropositivity (median index >10; IQR 3.6->10) by Atellica total antibody, 73% by Atellica IgG (median index 3.3; IQR 0.9-9.4), 84% by Bioplex anti-RBD (median 62; IQR 12-269 U/mL), 77% by Bioplex anti-S1 (median 45; IQR 10-83 U/mL), 37% by Bioplex anti-S2 (median 7; IQR 1-12 U/mL), and 79% by Bioplex anti-nucleocapsid (median 69; IQR 20-185U/mL) respectively. The active infection cohort exhibited a similar pattern as the recovered cohort. About 88% and 78% of the recovered and active infection cohort produced both anti-spike and anti-N antibodies with Anti-S1/anti-N ratios ranging from 0.07-16.26. In summary, fully vaccinated individuals demonstrated an average of 50-fold higher antibody levels than naturally infected unvaccinated individuals with immune reactivity strongly towards RBD/S1 and a weak response to S2. The results support vaccination regardless of previous COVID-infection status.


title: Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): a point-of-care PCR test for rapid detection of SARS-CoV-2 infection

abstract:
BackgroundRapid and accurate testing for SARS-CoV-2 is an essential tool in the medical and public health response to the COVID-19 pandemic. An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR combined with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing.

MethodsTo evaluate the performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC PCR (sample insertion to result time of 16 minutes), we conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites. We collected two bilateral anterior nasal swabs from each participant and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard."

ResultsWe enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received [≥]2 doses of mRNA COVID-19 vaccine, and 16% currently COVID-19 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R=0.89 [95% CI 0.81, 0.94]).

ConclusionsDASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR. Its compact design and ease of use are optimal for a variety of healthcare, and potentially community settings, including areas with lack of access to central laboratory-based PCR testing.

SummaryDASH is an accurate, easy to use, and fast point-of-care test with applications for diagnosis and screening of SARS-CoV-2 infection.


title: Gasdermin-D activation by SARS-CoV-2 trigger NET and mediate COVID-19 immunopathology

abstract:
The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. Using a single-cell transcriptome analysis we observed that the expression of GSDMD and inflammasome-related genes were increased in neutrophils from COVID-19 patients. Furthermore, high expression of GSDMD was found associated with NETs structures in the lung tissue of COVID-19 patients. The activation of GSDMD in neutrophils requires live SARS-CoV-2 and occurs after neutrophil infection via ACE2 receptors and serine protease TMPRSS2. In a mouse model of SARS-CoV-2 infection, the treatment with GSDMD inhibitor (disulfiram) reduced NETs release and organ damage. These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology, and suggests that GSDMD inhibitors, can be useful to COVID-19 treatment.

In BriefHere, we showed that the activation of the Gasdermin-D (GSDMD) pathway in neutrophils controls NET release during COVID-19. The inhibition of GSDMD with disulfiram, abrogated NET formation reducing lung inflammation and tissue damage. These findings suggest GSDMD as a target for improving the COVID-19 therapy.

category: allergy and immunology


title: Empirical Calibration of a Simulation Model of Opioid Use Disorder

abstract: Simulation models of opioid use disorder (OUD) aim at evaluating the impact of different treatment strategies on population-level outcomes. Researching Effective Strategies to Prevent Opioid Death (RESPOND) is a dynamic population state-transition model that simulates Massachusetts (MA) OUD population synthesizing data from the MA Public Health Data Warehouse, published survey studies, and randomized trials. We implement an empirical calibration approach to fit RESPOND to multiple calibration targets, including yearly counts of fatal overdoses and detox admissions in 2013-2015, and 2015 OUD population counts in MA. We used capture-recapture analysis to estimate the OUD population and to quantify uncertainty around calibration targets.1 The empirical calibration approach involves Latin hypercube sampling for a parameter search of the multidimensional space, comprising demographics of "arrivals", overdose rates, treatment transition rates, and substance use transition probabilities. The algorithm accepts proposed parameter values when the respective model outputs are "close" to the observed calibration targets based on uncertainty ranges of targets. Calibration provided an excellent fit to the model calibration targets. The flexibility of the algorithm also allowed us to identify certain "questionable" parts of the model structure and explore the underlying relationships between the model parameters in an efficient manner. The calibrated model also provided a good fit to validation targets: non-overdose related deaths, percentage of active OUDs, and all types of overdose counts (fatal and non-fatal). In addition, the resulting set of values for the calibrated parameters will inform the priors of a more comprehensive Bayesian calibration. The calibrated RESPOND model will be employed to improve shared decision-making for OUD.

category: epidemiology


title: Exploring the application of behaviour change technique taxonomies in childhood obesity prevention interventions: A systematic scoping review

abstract: Behaviour change technique (BCT) taxonomies provide one approach to unpack the complexity of childhood obesity prevention interventions. This scoping review sought to examine how BCT taxonomies have been applied to understand childhood obesity prevention interventions targeting children aged 12 years or under and/or their caregivers. A systematic search was conducted in Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and PROSPERO. Eligible studies included any study design that applied a BCT taxonomy and evaluated behavioural childhood obesity prevention interventions targeting children aged 12 years or under and/or their parents or caregivers. Sixty-three records, describing 54 discrete studies were included; 32 applied a BCT taxonomy prospectively (i.e., to design interventions) and 23 retrospectively (i.e., to assess interventions), 1 study did both. There was substantial variation in the methods used to apply BCT taxonomies and to report BCT-related methods and results. There was a paucity of detail reported in how BCTs were selected in studies applying BCT taxonomies prospectively. Our review provides important insight into the application of BCT taxonomies in childhood obesity prevention and several ongoing challenges, pointing to the need for best practice reporting guidance.


title: Impaired alpha and beta modulation in response to social stimuli in children with autism spectrum disorder

abstract:
BackgroundEarly preferential attention to biological motion is a fundamental mechanism priming the development of sophisticated skills to detect and react to social stimuli. Children diagnosed with autism spectrum disorders (ASD) demonstrate reduced visual orientation towards biological motion, however, the underlying neurobiological mechanisms are unknown.

MethodsWe measured the neural oscillations in children with ASD (n=34, mean age 3.43 years) and age and gender matched typically developing children (TD, n=27) while watching videos of social biological (BM) and geometrical motion (GM). Their visual interest in BM stimuli was measured with eye-tracking techniques. Neural oscillations were measured as amplitude modulation of the frequency bands with the electroencephalogram and calculated as the power ratio between BM and GM conditions using scalp and brain source reconstruction analyses.

ResultsWe observed a reduced visual exploration of the BM stimuli along with (1) unchanged sensorimotor mu rhythm and (2) altered cortical alpha and beta power ratio in widespread right prefrontal areas associated with default mode and fronto-parietal networks in young children with ASD as compared to their TD peers. Furthermore, we measured significant correlations between prefrontal and posterior cingulate regions of the default mode network with the developmental quotient in both the ASD and TD groups.

ConclusionWe observed abnormal alpha and beta modulation of the fronto-parietal and default mode networks along with altered visual exploration of the social biological motion. These deficits represent core impairments of the disorder and may be informative in developing future behavioural and neuroregulation interventions, such as neurofeedback.

category: psychiatry and clinical psychology


title: Mitigating isolation: further comparing the effect of LFD testing for early release from self-isolation for COVID-19 cases

abstract: In a recent paper, we described how lateral flow device (LFD) testing might be used to reduce the amount of excess time individuals spend in isolation following confirmation of a COVID-19 infection. Through the work presented here, we look to expand upon this and explore in more detail the benefit that such an approach might provide. We use our previously described model to study scenarios through the metrics "proportion released still infectious", "excess time spent in isolation" (time isolated while no longer infectious), and "time spent infectious after early release". We also look to consider the effect on these metrics by comparing values obtained when a single negative LFD test is required for early release, versus requiring two and three sequential negative LFD tests. Results show that jointly employing self-isolation and LFD testing may deliver sizeable reductions to the proportion of individuals being release while still infection, the average amount of excess time spent in isolation by those no longer a public health threat, and the average amount of time spent infectious by those released early. These effects considered in conjunction could provide a considerable decrease in the public health risk posed by still infectious individuals being released back into the population by actively monitoring their infection status throughout their isolation period. Such an approach could also help lighten the impact incurred on the individual by reducing the amount of time spent in isolation while posing no further public health risk, in addition to alleviating pressures on the economy and in healthcare settings caused by mass isolation in times of high prevalence.


title: A circuit-based approach to repair hypersexuality in Parkinson's disease

abstract:
One common neuropsychiatric complication in patients with Parkinsons disease treated with dopamine replacement therapy is impulse control disorders. A proportion of patients under dopamine agonist exhibit excessive desire towards appetitive cues accompanied by lost control over behaviour in forms of pathological gambling, hypersexuality or binge eating. The balance between enhanced desire towards sexual cues and cognitive control changes has been hypothesized to be biased toward the former in individuals with hypersexuality and impulse control disorders. Yet, some studies report no behavioural differences in cognitive control differences between impulsive patients and general Parkinsons disease, suggesting possible functional changes along the mesocorticolimbic cortico-subcortical circuitry. Here, we provide evidence for this hypothesis by comparing the neurobiological substrate of sexual disturbance over response inhibition associated to medication states in Parkinsons disease patients with a specific subtype of impulse control disorders (i.e., hypersexuality).

We assessed the impact of sexual cues on response inhibition using a novel erotic stop signal task inside an fMRI. A total of 50 participants were included divided in 16 hypersexual and 17 non-hypersexual Parkinsons disease patients and 17 healthy controls. Task-related activations, functional and anatomical connectivity models were performed. Additionally, a separate sample of 20 hypersexual Parkinsons disease patients received excitatory neuromodulation (sham-controlled) over the pre-supplementary motor area (based on fMRI group-based results) aiming to improve response inhibition when exposed to sexual cues.

Compared with their non-hypersexual peers, medication perturbed response inhibition upon presentation of sexual cues in patients with hypersexuality, recruiting a network involving caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex. Dynamic causal modelling revealed distinct best models to account for cortico-subcortical interactions with reduced task-related inputs in pre-supplementary motor area and descending connectivity to caudate in hypersexual compared to non- hypersexual Parkinsons disease patients (while medicated). This was sustained by enhanced fractional anisotropy and reduced mean diffusivity in the pre-supplementary motor area-caudate pathway. Importantly, stimulation over the pre-supplementary motor area improved response inhibition when exposed to sexual cues in hypersexual Parkinsons disease.

We identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual behaviours in Parkinsons disease induced by medication, with recovery options by applying neuromodulation.

category: neurology


title: Comprehensive Quantitative Evaluation of Inter-observer Delineation Performance of MR-guided Delineation of Oropharyngeal Gross Tumor Volumes and High-risk Clinical Target Volumes: An R-IDEAL Stage 0 Prospective Study

abstract:
PurposeTumor and target volume manual delineation remains a challenging task in head and neck cancer radiotherapy. The purpose of this study is to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation MR scans of oropharyngeal cancer (OPC) patients.

MethodsPre-treatment T1-weighted (T1w), T1-weighted with Gadolinium contrast (T1w+C) and T2-weigted (T2w) MRI scans were retrospectively collected for 4 OPC patients under an IRB-approved protocol. The scans were provided to twenty-six radiation oncologists from seven international cancer centers who participated in this delineation study. In addition, each patients clinical history and physical examination findings along with a medical photographic image and radiological results were provided. The contours were compared using overlap and distance metrics using both STAPLE and pair-wise comparisons. Lastly, participants completed a brief questionnaire to assess personal experience and CTV delineation institutional practices.

ResultsLarge variability was measured between observers delineations for both GTVs and CTVs. The mean Dice Similarity Coefficient values across all patients delineations for GTVp, GTVn, CTVp, and CTVn where 0.77, 0.67, 0.77, and 0.69, respectively, for STAPLE comparison and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap and distance metrics. The median radiation oncology clinical experience was 7 years and the median experience delineating on MRI was 3.5 years. The GTV-to-CTV margin used was 10 mm for six of seven participant institutions. One institution used 8 mm and three delineators (from three different institutions) used a margin of 5 mm.

ConclusionThe data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of MR-based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing inter-observer delineation variation and ensure standardization of target design across clinical practices.

SummaryWith the rapid increase of MR imaging use in radiotherapy, MRI presents with endogenous contrast greater than CT for tumor and target definition; however, reports on delineation variability for these volumes on MRI are limited. In this prospective manual segmentation challenge of 26 radiation oncologists, we formally quantify human performance and heterogeneity in physician tumor and target delineations based on MRI scans of oropharyngeal cancer patients.


title: Algorithmic Fairness in Computational Medicine

abstract:
Machine learning models are increasingly adopted for facilitating clinical decision-making. However, recent research has shown that techniques may result in unintentional biases towards gender, race, and/or ethnicity. Such bias can lead to unexpected social implications, especially detrimental effects on the health and well-being of disadvantaged groups such as racial-ethnic minorities. In recent years, extensive studies on such algorithmic fairness have been conducted in machine learning in general. Yet, the understanding of how algorithmic bias will impact medicine and how to mitigate such bias still remains limited. The goal of this survey is to fill in this gap by providing a comprehensive review of algorithmic fairness within the scope of computational medicine, which aims at improving medicine with computational approaches. We first overview the three types of computational bias: data bias, measurement bias, and model bias. Then we summarize the fairness quantification metrics that are used in various literature. Finally, we present two types of bias mitigation methods, namely, data-based and model-based ones. We also summarize the popular software libraries and tools for bias evaluation and mitigation, followed by open questions and future directions.

O_TEXTBOXSearch strategy and selection criteria

We searched PubMed and Google Scholar from inception of the database to Jul 30, 2021, for research articles using the search terms ("bias" OR "disparity" OR "fairness" OR "fair" OR "inequality" OR "equality") AND ("machine learning" OR "artificial intelligence") AND ("medical" OR "medicine" OR "healthcare") in English. We independently reviewed the title and abstracts for inclusion. We also reviewed the reference lists of eligible texts.

C_TEXTBOX