title: Optimizing antibiotic use in Indonesia: a systematic review and synthesis of current evidence to inform opportunities for intervention

abstract:
IntroductionA major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervention.

MethodsWe systematically searched five international and national databases for eligible peer-reviewed articles, in English and Indonesian, published between 1 January 2000 and 1 June 2021 including: 1) antibiotic consumption; 2) prescribing appropriateness; 3) antimicrobial stewardship (AMS); 4) perceptions among consumers and providers. Two independent reviewers included studies and extracted data. Study-level data were summarized using random-effects model meta-analysis for consumption and prescribing appropriateness, effect direction analysis for AMS interventions, and qualitative synthesis for perception surveys. (PROSPERO CRD42019134641)

ResultsOf 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 110.1 DDD/100 patient-days (95%CI98.5-121.6), with ceftriaxone, ampicillin and levofloxacin being most consumed. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (95%CI18.1-53.4%) in hospitals and 49.4% (95%CI23.7-75.4%) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (95%CI97.4-100%) for indication, 84.9% (95%CI38.5-98.0%) for drug choice, and 6.1% (95%CI0.2-63.2%) for overall appropriateness, and, in primary care, 98.9% (95%CI60.9-100%) for indication, 82.6% (95%CI50.5%-95.7%) for drug choice and 10.5% (95%CI0.8-62.6%) for overall appropriateness. The few AMS intervention studies conducted to date suggested potential to reduce antibiotic consumption and improve prescribing appropriateness. Key themes identified in perception surveys were lack of antibiotic knowledge among consumers and non-prescription antibiotic self-medication.

ConclusionsContext-specific strategies are urgently needed to improve rational antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning private and informal health providers.

KEY QUESTIONSWhat is already known? * Indonesia is a potential AMR hotspot, where, based on pharmaceutical sales data, antibiotic consumption increased 2.5-fold between 2000 and 2015, mostly driven by broad-spectrum penicillins, fluoroquinolones and cephalosporins.
* Representative contemporary data on antibiotic use are lacking, although anecdotal data suggest antibiotic overuse in the healthcare system, widespread over-the-counter use in communities, and high rates of AMR mostly among common Gram-negative bacteria.
* A comprehensive review on antibiotic use in human health in Indonesia has not been conducted to date.
What are the new findings? * Available data spanning the past 20 years, suggested that only 34% and 49% of antibiotics were appropriately prescribed in hospital and primary care settings, respectively, although the quality of the evidence was low.
* Publications evaluating AMS interventions have been sparse to date, demonstrating the need to strengthen the local research base to develop context-specific and sustainable AMS models.
* Community surveys suggested important gaps in antibiotic knowledge, and that non-prescription antibiotic self-medication is common practice, although data to quantify this problem and its drivers are lacking.
What do the new findings imply? * Available evidence synthesised in this Review provides important insights in the magnitude and patterns of antibiotic use, and associated patient and health system factors, which helps define opportunities for optimising responsible antibiotic use.
* Critical evidence gaps exist on informal and formal private health care providers, geographic areas outside of Java Island, as well as effective AMS models that consider country-specific socio-cultural, economic and political circumstances.
* Optimization of antimicrobial use as a means to tackle AMR should be a priority of the national agenda for universal health coverage.


title: Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

abstract:
The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection.

To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death.

In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.

category: infectious diseases


title: At least three doses of leading vaccines essential for neutralization of SARS-CoV-2 Omicron variant

abstract: Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.


title: At least three doses of leading vaccines essential for neutralisation of SARS-CoV-2 Omicron variant


title: Understanding the immunological landscape of England during SARS-CoV2 Omicron variant wave

abstract: Understanding the scale of the threat posed by SARS-CoV2 B.1.1.529, or Omicron, variant formed a key problem in public health in the early part of 2022. Early evidence indicated that the variant was more transmissible and less severe than previous variants. As the virus was expected to spread quickly through the population of England, it was important that some understanding of the immunological landscape of the country was developed. This paper attempts to estimate the number of people with good immunity to the Omicron variant, defined as either recent infection with two doses of vaccine, or two doses of vaccine with a recent booster dose. To achieve this, we use a process of iterative proportional fitting to estimate the cell values of a contingency table, using national immunisation records and real-time model infection estimates as marginal values. Our results indicate that, despite the increased risk of immune evasion with the Omicron variant, a high proportion of Englands population had good immunity to the virus, particularly in older age groups. However, low rates of immunity in younger populations may allow endemic infection to persist for some time.

category: public and global health


title: Effectiveness of targeted antenatal family planning information provision on early postpartum family planning uptake in Kisumu county: Study protocol for a Simple Randomized Control Trial

abstract: Overlooking the contraceptive needs of postpartum women constitutes missed opportunities in health system. Inter-birth interval of at least three years can prevent poor maternal, perinatal and neonatal outcomes and afford women socioeconomic benefits of family planning (FP). The unmet need for FP in the postpartum period remains unacceptably high and far exceeds the FP unmet need of other women. The Kenya Demographic and Health Survey (KDHS) estimate the unmet need for postpartum FP to be 74%. Maternal and Child Health (MCH) continuum provides a great opportunity for postpartum FP (PPFP) interventions integration especially Antenatal targeted FP information giving and gauging fertility intentions. However, there is no protocol for structured, targeted Antenatal FP information giving and behavioural contracting to influence postpartum fertility intentions of mothers before delivery. Knowledge gap regarding fertility intentions and best antenatal strategies for postpartum FP still exists. The available evidence differs across settings and demography. Equally, there has been inadequate exploration of operationally-feasible ways to integrate FP counselling into existing ANC services with limited number of methodologically rigorous trials. This study will therefore examine the effectiveness of antenatal family planning information provision on early postpartum FP uptake using a randomized control trial in Kisumu. The researcher will; assess socio-cultural beliefs towards of PPFP and perceived individual control of PPFP choice, analyze knowledge and intention for PPFP, compare and examine the determinants of PPFP uptake between study groups. A group of 246 antenatal mothers will be randomly assigned to control, community and facility intervention groups as per eligibility criteria in the study facilities that will be cluster sampled. After at least 3 months of intervention and 3 months of postpartum follow-up, clinical superiority will be used to gauge which invention was effective and the model superiority. Questionnaire and Case Report Forms will be the main source of data. The participant will form the unit of analysis which will be by intention to treat. Bivariate analysis will be done as the selection criteria for inclusion of predictors of intention and uptake with a P[≤] 0.05 in the final logistic regression model. P-values, [≤]0.05, Odds Ratios and 95% confidence interval (CI) will be used to demonstrate significance and the strength of association between selected variables. Dissemination will be through conference presentations and peer reviewed journals. The trial has been registered with the Pan African Clinical Trials Registry PACTR202109586388973 on the 28th September 2021.

category: sexual and reproductive health


title: Mesoamerican Nephropathy in Central Panama

abstract:
BackgroundIn the last three decades, there has been an increase in the frequency of patients diagnosed with chronic kidney disease of nontraditional causes (CKDnt) in the Mesoamerican region. A region with an increased frequency of patients with chronic kidney disease (CKD) has been identified in central Panama. The present study aims to characterize the clinical presentation of patients with CKDnt in an understudied population of the central region of Panama and compare them with patients with traditional CKD (CKDt).

MethodsA retrospective descriptive study was conducted in a nephrology reference hospital in the central provinces of Herrera and Los Santos, comparing a group of 15 patients with CKDnt to 91 patients with CKDt. Sociodemographic variables, personal history, laboratory parameters, and of renal ultrasound were compared.

ResultsCKDnt is more common among relatively younger male patients who engage in strenuous work activities at high temperatures. CKDnt is not associated with type 2 diabetes mellitus or chronic hypertension, as it is the case in patients with CKDt. Renal atrophy and hyperuricemia are significant clinical markers of CKDnt.

ConclusionTo our knowledge, this is the first study in Panama and one of the few in Central America and the world to address the clinical presentation of patients with CKDnt compared to patients with CKDt. Because CKDnt remains asymptomatic for a long time, early detection is important, and efforts should be directed at halting disease progression at an early stage. Current evidence can also inform policies addressing occupational and environmental risk factors associated with CKDnt.

category: nephrology


title: Integration of proteomics and metabolomics - insights into inflammation, metabolic dysregulation, and vascular aspects in AD

abstract: Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations in the context of metabolic disorders, including Alzheimer s disease. Using targeted metabolomics, we have previously profiled lipid mediators, including oxylipins, endocannabinoids, bile acids and steroids in 293 CSF and 202 matched plasma samples from AD cases and healthy controls, and identified both central and peripheral metabolites of the inflammation-regulating cytochrome p450/soluble epoxide hydrolase pathway as strong predictors for the AD pathology. Additionally, using proteomics, we have identified five cerebrospinal fluid protein panels, involved in regulation of energy metabolism, vasculature, myelin/oligodendrocyte, glia/inflammation, and synapses/neurons affected in AD, and reflective of AD-related changes in brain. In the current manuscript, using metabolomics-proteomics data integration, we describe new associations between peripheral and central lipid mediators, with the above-described cerebrospinal fluid protein panels. Particularly strong associations were observed between cytochrome p450/soluble epoxide hydrolase metabolites, bile acids and CSF proteins involved in glycolysis, blood coagulation and vascular inflammation and the regulators of extracellular matrix. Those metabolic associations were not observed at the gene-coexpression level in the central nervous system, showing the importance of pathway interaction investigation on the level of the terminal part of the biochemical " omic" cascade. In summary, this manuscript provides new information regarding the Alzheimer s disease, linking both central and peripheral inflammatory cascade of cytochrome p450/soluble epoxide hydrolase and bile acids metabolism with AD-affected processes and illustrates the necessity for the " omics" data integration to uncover associations beyond gene co-expression.

category: neurology


title: Development of Parkinson's disease and its relationship with incidentally-discovered white matter disease and covert brain infarction in a real world cohort

abstract:
ImportanceWhile a link between cerebrovascular disease and cerebrovascular risk factors and subsequent development of Parkinsons disease has been suggested, the association between covert cerebrovascular disease and subsequent Parkinsons disease has not been rigorously examined.

ObjectiveTo examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care and subsequent Parkinsons disease.

DesignEnrollment in this observational cohort study occurred between 2009 and 2019.

SettingKaiser Permanente Southern California health system.

ParticipantsPatients were [≥]50 years old and received neuroimaging for a non-stroke indication.

ExposureIncidental covert brain infarction and white matter disease identified by natural language processing of neuroimaging reports. Natural language processing also classified white matter disease severity.

Main OutcomesParkinsons disease.

Results230,062 patients were included with a total of 980,772 person-years of follow-up and a median follow-up time of 3.72 years. 1,941 cases of Parkinsons disease were identified, with a median time-to-event of 2.35 (IQR 0.90 to 4.58) years. Covert cerebrovascular disease was identified in 70,592 (30.68%) patients, 10,622 (4.62%) with covert brain infarction and 65,814 (28.61%) with white matter disease. After adjustment for known risk factors, white matter disease was found to be associated with Parkinsons disease, with an adjusted hazard ratio of 1.67 (1.44, 1.93) for patients <70 years and 1.33 (1.18, 1.50) for those [≥]70 years. Greater severity of white matter disease was associated with an increased incidence of Parkinsons disease per 1000 person-years, from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe white matter disease. Findings were robust when more specific definitions of Parkinsons disease were used. Covert brain infarction was not associated with Parkinsons disease (adjusted hazard ratio=1.05 [0.88, 1.24]).

Conclusions and RelevanceWhite matter disease was associated with subsequent Parkinsons disease, an association strengthened with younger age and increased white matter disease severity. Covert brain infarction did not appear to be associated with subsequent Parkinsons disease.


title: An approach to quantify parameter uncertainty in early assessment of novel health technologies

abstract: Health economic modeling of novel technology at the early stages of a product lifecycle has been used to identify technologies that are likely to be cost-effective. Such early assessments are challenging due to the potentially limited amount of data. Modelers typically conduct uncertainty analyses to evaluate their effect on decision-relevant outcomes. Current approaches, however, are limited in their scope of application and imposes an unverifiable assumption, i.e., uncertainty can be precisely represented by a probability distribution. In the absence of reliable data, an approach that uses the fewest number of assumptions is desirable. This study introduces a generalized approach for quantifying parameter uncertainty, i.e., probability bound analysis (PBA), that does not require a precise specification of a probability distribution in the context of early-stage health economic modeling. We introduce the concept of a probability box (p-box) as a measure of uncertainty without necessitating a precise probability distribution. We provide formulas for a p-box given data on summary statistics of a parameter. We describe an approach to propagate p-boxes into a model and provide step-by-step guidance on how to implement PBA. We conduct a case and examine the differences between the status-quo and PBA approaches and their potential implications on decision-making.

category: health economics


title: COVID infection rates, clinical outcomes, and racial/ethnic and gender disparities before and after Omicron emerged in the US

abstract:
BackgroundSARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of the Omicron variant. Currently, data on infection rates, severity and racial/ethnic and gender disparities from Omicron in the US is limited.

MethodWe performed a retrospective cohort study of a large, geographically diverse database of patient electronic health records (EHRs) in the US. The study population comprised 881,473 patients who contracted SARS-CoV-2 infection for the first time between 9/1/2021-1/16/2022, including 147,964 patients infected when Omicron predominated (Omicron cohort), 633,581 when Delta predominated (Delta cohort) and another 99,928 infected when the Delta predominated but just before the Omicron variant was detected in the US (Delta-2 cohort). We examined monthly incidence rates of COVID-19 infections stratified by age groups, gender, race and ethnicity, compared severe clinical outcomes including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use between propensity-score matched Omicron and Delta cohorts stratified by age groups (0-4, 5-17, 18-64 and [≥] 65 years), and examined racial/ethnic and gender differences in severe clinical outcomes.

FindingsAmong 147,964 infected patients in the Omicron cohort (average age: 39.1 years), 56.7% were female, 2.4% Asian, 21.1% Black, 6.2% Hispanic, and 51.8% White. The monthly incidence rate of COVID infections (new cases per 1000 persons per day) was 0.5-0.7 when Delta predominated, and rapidly increased to 3.8-5.2 when Omicron predominated. In January 2022, the infection rate was highest in children under 5 years (11.0) among all age groups, higher in Black than in White patients (14.0 vs. 3.8), and higher in Hispanic than in non-Hispanic patients (8.9 vs. 3.1). After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than in the Delta cohort: ED visits: 10.2% vs. 14.6% (risk ratio or RR: 0.70 [0.68-0.71]); hospitalizations: 2.6% vs. 4.4% (RR: 0.58 [0.55-0.60]); ICU admissions: 0.47% vs. 1.00% (RR: 0.47 [0.43-0.51]); mechanical ventilation: 0.08% vs. 0.3% (RR: 0.25 [0.20-0.31]). Similar reduction in disease severity was observed for all age groups. There were significant racial/ethnic and gender disparities in severe clinical outcomes in the Omicron cohort, with Black, Hispanic patients having more ED visits and ICU admissions than White and non-Hispanic patients, respectively and women had fewer hospitalization and ICU admission than men.

InterpretationThe incidence rate of COVID infection during the omicron predominant period (prevalence >92%) was 6-8 times higher than during the Delta predominant period that preceded it consistent with greater infectivity. The incidence rate was highest among those less than 5 years of age, and in Black and Hispanic patients. COVID infections occurring when the Omicron predominated were associated with significantly less frequent severe outcomes than in matched patients when the Delta variant predominated. There were significant racial, ethnic and gender disparities in severe clinical outcomes, with Black and Hispanic patients and men disproportionally impacted.


title: Bayesian Emulation and History Matching of JUNE

abstract: We analyse JO_SCPLOWUNEC_SCPLOW : a detailed model of Covid-19 transmission with high spatial and demographic resolution, developed as part of the RAMP initiative. JO_SCPLOWUNEC_SCPLOW requires substantial computational resources to evaluate, making model calibration and general uncertainty analysis extremely challenging. We describe and employ the Uncertainty Quantification approaches of Bayes linear emulation and history matching, to mimic the JO_SCPLOWUNEC_SCPLOW model and to perform a global parameter search, hence identifying regions of parameter space that produce acceptable matches to observed data.

category: epidemiology


title: Gamma connectivity predicts response to intermittent Theta Burst Stimulation in Alzheimer's disease: A randomised controlled trial.

abstract: Alzheimers disease is characterised by progressive cognitive decline for which there are currently no effective treatments. There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimers and, as such, may represent a promising therapeutic target. Here we investigated whether a course of intermittent Theta Burst Stimulation (iTBS) could modulate functional connectivity and cognitive function in mild to moderate Alzheimers disease. Fifty-eight participants were randomised to receive a course of either active or sham iTBS. Stimulation was applied to four brain sites sequentially in each treatment session: left DLPFC, right DLPFC, left PPC, and right PPC. Neurobiological (EEG), cognitive (CogState, ADASCog), and functional (QoL-AD, GDS) assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3-months (blinded) and 6-months (active group only) following end of treatment. Active iTBS resulted in a significant and large increase in resting state gamma connectivity as well as improved delayed recall on an episodic memory task. Both baseline gamma connectivity, and change in gamma connectivity, were found to be predictive of improved delayed recall following active treatment. These findings support future research into iTBS for the treatment of Alzheimers disease focussing on protocol optimisation.

category: psychiatry and clinical psychology


title: Using Best-Worst Scaling to investigate younger adult Canadians' preferences for COVID-19 vaccination and public health measures: an observational study

abstract: Containing the COVID-19 pandemic is dependent on compliance with public health recommendations and mandates which is lower in younger compared to older adults. Furthermore, younger adults have demonstrated lower uptake of COVID-19 vaccines. The aim of this study was to assess preferences for COVID-19 related preventive health measures and vaccination and to explore their association with COVID-19 vaccine acceptability. Canadians aged 18-39 years were invited to participate in a web-based survey in August 2021. We used the Best-Worst-Scale (BWS) methodology to collect and analyze preference data and multivariable binary logistic regression to estimate associations with vaccine acceptability. Based on 266 complete responses, we found strong preferences for physical distancing and wearing face masks, as compared to general hygiene and respiratory etiquette. High vaccine accessibility independent of the location, receiving successive doses of the same vaccine brand and higher vaccine uptake of people in younger adults social circle were highly preferred. Higher preferences for mandates requiring proof of vaccination and altruistic motives for vaccination were associated with vaccine acceptability. As the COVID-19 pandemic waxes and wanes, studies using larger, nationally representative samples are needed to replicate and validate these results to assess preferences for health behaviors corresponding to the latest recommendations. The use of this methodology could provide public health authorities with a unique opportunity to develop targeted, preference-based messaging that aligns with the latest guidelines to effectively encourage compliance and COVID-19 vaccine uptake.


title: Community-based Case Studies of Vaccine Hesitancy and the COVID-19 Response in South Africa; The VaxScenes Study

abstract:
BackgroundSouth Africa has reported more than half of all COVID-19 cases and deaths in Africa. The South African government has launched a large COVID-19 immunization campaign with the goal of reaching more than 40 million individuals. Nonetheless, certain international, largely internet-based surveys have shown a significant proportion of vaccine hesitancy in South Africa. This study aims to determine and co-create with local stakeholders a comprehensive understanding of vaccine hesitancy and opportunities to support the promotion of other COVID-19 health-promoting behaviours at community level.

Methods and designA mixed-methods, multiple case-study design; informed by the socio-ecological model of behaviour change. Four socio-economically diverse communities across South Africa will be selected and data collection will take place concurrently through three iterative phases. Phase 1 will provide insights into community experiences of COVID-19 (response) through desktop mapping exercises, observations, in-depth interviews, and focus group discussions (FGDs) designed as expression sessions with local stakeholders. Phase 2 will explore the extent and drivers of community acceptance of COVID-19 vaccines. This phase will comprise a quantitative survey based on WHOs Behavioural and Social Drivers of Vaccination tool as well as further FGDs with community members. Phase 3 will involve cross-case study syntheses and presentation of findings to national role-players.

DiscussionThis study will provide ground up, locally responsive, and timeous evidence on the factors influencing COVID-19 health-seeking behaviours to inform ongoing management and mitigation of COVID-19 in South Africa. It will also provide insights into the applicability of a novel vaccine hesitancy model in Africa.


title: Automated detection of speech timing alterations in autopsy-confirmed non-fluent/agrammatic variant primary progressive aphasia

abstract:
Background and ObjectivesMotor speech function, including speech timing, is a key domain for diagnosing non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments employ subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically-confirmed diagnoses. This study overcomes such caveats via automated speech timing analyses in a unique cohort of autopsy-proven cases.

MethodsIn a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed via cortical thickness and white matter atrophy analysis.

ResultsWe evaluated 22 persons with nfvPPA (mean age: 67.3; 13 females) and confirmed underlying four-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5; 8 females), and 10 healthy controls (HCs; 70 years; 5 females). All five speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. Articulation rate robustly discriminated individuals with nfvPPA from HCs (AUC = .95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying white matter. Articulation rate was associated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, n = 10). Articulation rate robustly discriminated between individuals in each subgroup (AUC = .82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.

DiscussionAutomated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability, this approach could support standard speech assessments.


title: Methylome analysis for prediction of long and short-term survival in glioblastoma patients from the Nordic trial

abstract:
Patients with glioblastoma (GBM) have a short survival, but even among patients receiving the same therapies and with good prognostic factors, one can find those with exceptionally short and long survival.

In the Nordic trial, patients with GBM, 60 years or older, were randomized between 2 radiotherapy arms or TMZ. We selected 59 patients, equally distributed between the 3 treatment arms and MGMT promoter methylation status, with good prognostic factors, but with short or long survival. We performed methylation profiling with the Illumina Infinium Methylation EPIC BeadChip arrays in conjunction with a methylation-based CNS tumor classifier, analysis of differentially methylated CpG sites (DMCs) and pathway enrichment analysis.

Samples classified as non-GBM IDH wildtype were excluded and in the analysis of long vs. short survivors with documented progression or tumor-related death, we found DMCs in the TMZ, MGMT promoter methylated group (123,510), as well as in the 60Gy, MGMT promoter unmethylated group (4,086) and 34Gy, MGMT promoter methylated group (39,649). The joint analysis of the RT arms revealed 319 DMCs in the MGMT unmethylated group but no differences for MGMT promoter methylated samples, or in any of the analyses independent of MGMT status. Interestingly, in the long-term survivors with methylated MGMT promoter treated with TMZ we found hypermethylation of the Wnt signaling and the platelet activation, signaling and aggregation pathways.

We identified DMCs for both TMZ and RT treated patients. Further systematic analysis of larger patient cohorts is necessary for confirmation of their predictive properties.

category: oncology


title: Interoperability Assessment of Emergency Department Processes Based on Multicriteria Decision-Making Methods

abstract: It is noticeable that, because of the amount and quality of information exchanged and the criticality of the decisions guided by them, hospitals are considered as some of the most complex organizations in modern society. Evidencing it, emergency departments in hospitals are examples of such complex environments that need perfect integration among systems, people, departments, and data. The processes behind the Emergency Department (ED) routine cause a set of critical and time-dependent decision-making, which must consider several criteria related to organizational and clinical attributes. Based on the literature and worldwide initiatives related to managing complex organizations, an ED can be interpreted through the enterprise interoperability (EI) lens, a concept related to the capability of different systems to work collaboratively within and throughout the organization. Thus, this paper proposes a framework focusing on interoperability assessment in ED processes, where different actors need to interoperate. The proposed framework for Enterprise Interoperability Assessment (EIA) is based on multicriteria decision analysis (MCDA) methods, considering organizational and clinical attributes of the ED. The Analytic Hierarchy Process (AHP) and Preference Ranking Organization Method for Enrichment Evaluation II (PROMETHEE II), in an integrated approach, were elected as the most appropriate multicriteria methods to support, respectively, diagnostic (interoperability assessment) and decisional (interoperability improvements) processes in this background. Last, to validate the framework proposed, a case study was carried out at a stroke unit in a University Hospital (UH) in the south of Brazil. The outcome inferred that the UH achieved the intermediate level of enterprise interoperability in stroke treatment, and Business and Information Technology concerns were found to be the priorities, which deserved greater efforts, to enhance interoperability.

category: health systems and quality improvement


title: Tackling the first COVID-19 wave at the Cape Town Hospital of Hope: Why was it such a positive experience for staff?

abstract:
BackgroundIn contrast to alarming reports of exhaustion and burnout amongst healthcare workers in the first wave of the COVID-19 pandemic, we noticed surprisingly positive staff experiences of working in a COVID-19 field hospital in South Africa. The 862-bed  Hospital of Hope was established at the Cape Town International Convention Centre specifically to cope with the effects of the first wave of the COVID-19 pandemic in Cape Town.

MethodsWe aimed to systematically describe and assess the effects on staff and the local health system. A cross-sectional descriptive study design was employed using mixed methods including record reviews and interviews with key informants.

ResultsQuantitative results confirmed high job satisfaction and low staff infection rates. The emerging themes from the qualitative data are grouped around a "bulls eye" of the common purpose of person-centredness, from both patient and staff perspectives, and include staff safety and support, rapid communication, continuous learning and adaptability, underpinned by excellent teamwork. The explanations for the positive feedback included good disaster planning, adequate resources, and an extraordinary responsiveness to the need.

ConclusionsThe  Hospital of Hope staff experience produced significant learnings for the design and management of routine health services outside of a disaster situation. The adaptability and responsiveness of the facility and its staff was largely a product of the unprecedented nature of the pandemic, but such approaches could benefit routine health services enormously, as individual hospitals and health facilities realize their place in a system that is  more than the sum of its parts.


title: Childhood Trauma Exposure Increases Long COVID Risk

abstract:
BackgroundA proportion of those who contract COVID-19 will develop long COVID (i.e., symptoms that persist for three months or more). Childhood trauma contributes to a pro-inflammatory state in adulthood evidenced by high morbidity and early mortality, but it has not yet been investigated as a risk factor for long COVID.

MethodsParticipants (N=338) completed online measures of premorbid health, COVID-19 positivity, symptoms, recovery, depression, anxiety, and post-traumatic stress disorder (PTSD). Questionnaires about childhood and recent traumatic experiences were completed by half of the sample (N=162).

ResultsFifty-three percent of participants developed long COVID, of whom over 60% endorsed exercise intolerance and protracted myalgias, headaches, brain fog, and shortness of breath. Participants who experienced at least one childhood traumatic event were 3-fold more likely to develop the syndrome (OR=3.11, 95% CI, 1.49 to 6.48), while risk was nearly 6-fold increased for two or more events (OR=5.67, CI, 2.44 to 13.13). Regression models showed childhood trauma (OR=5.32, CI, 1.44 to 19.68), older age (OR=1.11, CI, 1.06 to 1.16), female sex (OR=4.02, CI, 1.34 to 12.12), along with chest pain (OR=8.77, CI, 2.80 to 27.43), brain fog (OR=3.33, CI, 1.16 to 9.57) and phantosmia (OR=5.90, CI, 1.40 to 24.86) during acute illness accurately classified long COVID status in 87% of participants.

InterpretationsEarly adversity is a risk-factor for long COVID, likely due to altered immune response, central sensitization, and peripheral dysfunction. Childhood trauma, a crucial social determinant of health, should be routinely assessed in COVID-19 survivors and may aid in determining prognosis.


title: Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting

abstract:
BackgroundIt is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups.

MethodsWe conducted a retrospective study in patients [≥]12 years who underwent testing for the SARS-CoV-2 virus from April 1 - October 25, 2021 at urgent care centers in the New York City metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n=484,468), partially vaccinated (n=107,573), and unvaccinated (n=466,452) patients, adjusted for demographic factors and calendar time.

ResultsVE against symptomatic infection after 2 doses of mRNA vaccines was 96% (95% Confidence Interval [CI]: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12-15-year-olds (85%; [95% CI: 81%, 89%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex, race/ethnicity, and comorbidity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the mRNA-1273 vaccine (83% [95% CI: 81%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after the single-dose Ad26.COV2.S vaccine was the lowest compared to other vaccines (29% [95% CI: 26%, 32%]) in the delta period.

ConclusionsVE against infection after two doses of the mRNA vaccine was high initially, but significantly reduced against the delta variant for all three FDA-approved vaccines.


title: A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

abstract: COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has exhibited mixed results in the treatment of COVID-19. Given that the therapeutic effect of CCP may extend beyond the ability of SARS-CoV-2-specific antibody binding and neutralization to influence the evolution of the endogenous antibody response, we took a systematic and comprehensive approach to analyze SARS-CoV-2 functional antibody profiles of participants in a randomized controlled trial of CCP treatment of individuals hospitalized with COVID-19 pneumonia where CCP was associated with both decreased mortality and improved clinical severity. Using systems serology, we found that the clinical benefit of CCP is related to a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We found CCP had the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function, rather than S or N antibody levels or participant demographic features. Further, CCP induced immunomodulatory changes to recipient humoral profiles persisted for at least two months, marked by the selective evolution of anti-inflammatory Fc-glycan profiles and persistently expanded nucleocapsid-specific humoral immunity following CCP therapy. Together, our findings identify a novel mechanism of action of CCP, suggest optimal patient characteristics for CCP treatment, identify long-last immunomodulatory effects of CCP, and provide guidance for development of novel N-focused antibody therapeutics for severe COVID-19 hyperinflammation.


title: An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile

abstract:
BackgroundMultiple vaccines against SARS-CoV-2 have been evaluated in clinical trials, but very few include the pediatric population. The inactivated vaccine CoronaVac(R) has shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. This study is an interim safety and immunogenicity report of a phase 3 clinical trial for CoronaVac(R) in healthy children and adolescents in Chile.

MethodsParticipants aged 3 to 17 years old received two doses of CoronaVac(R) in a four-week interval. Local and systemic adverse reactions were registered in 699 participants that received the first dose and 381 that received the second dose until December 31st, 2021. Whole blood samples were collected from 148 participants for humoral and cellular immunity analyses.

ResultsThe primary adverse reaction reported after the first and second dose was pain at the injection site. The adverse reactions observed were primarily mild and local, and no severe adverse events were reported. Four weeks after the second dose, a significant increase in the levels of total and neutralizing antibodies was observed. Increased activation of specific CD4+ T cells was also observed four weeks after the second dose. Although antibodies induced by vaccination neutralize variants Delta and Omicron, titers were lower than the D614G variant. Importantly, comparable T cell responses were detected against these variants of concern.

ConclusionsCoronaVac(R) is safe and immunogenic in subjects aged 3-17 years old and is thus likely to confer protection against infection caused by SARS-CoV-2 variants in this target population.


title: Best of intent, worst of both worlds: why sequentially combining epidemiological designs does not improve signal detection in vaccine safety surveillance

abstract:
BackgroundVaccine safety surveillance commonly includes a serial testing approach with a sensitive method for "signal generation" and specific method for "signal validation." Whether serially combining epidemiological designs improves both sensitivity and specificity is unknown.

MethodsWe assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared Type I and II errors before and after empirical calibration for historical comparator, SCCS, and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes.

ResultsHistorical comparator mostly had lower Type II error than SCCS. SCCS had lower Type I error than the historical comparator. Before empirical calibration, serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, Type I errors returned to nominal; sensitivity was lowest when the methods were combined.

ConclusionWe recommend against the serial approach in vaccine safety surveillance. While serial combination produced fewer false positive signals compared to the most specific method, it generated more false negative signals compared to the most sensitive method. Using the noisy historical comparator in front of SCCS deteriorated overall performance in evaluating safety signals.

Key MessagesO_LIUsing the serial approach in vaccine safety surveillance did not improve overall performance: specificity increased but sensitivity decreased.
C_LIO_LIWithout empirical calibration, Type II errors exceeded 50%; after empirical calibration, Type I error rates returned to nominal with negligible change to Type II error rates.
C_LIO_LIWhile prior research has suggested high sensitivity of the historical comparator method in distinguishing true safety signals, there were cases when self-controlled case series was more sensitive.
C_LIO_LIVaccine safety surveillance is becoming increasingly important, so monitoring systems should closely consider the utility and sequence of epidemiological designs.
C_LI


title: MEDIAL FRONTAL CORTEX GAMMA-AMINOBUTYRIC ACID CONCENTRATIONS IN PSYCHOSIS AND MOOD DISORDERS: A META-ANALYSIS OF PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDIES

abstract:
BackgroundAbnormalities of gamma-aminobutyric acid-ergic (GABAegic) systems may play an important role in psychosis spectrum and mood disorders. Proton magnetic resonance spectroscopy allows for non-invasive in vivo quantification of GABA; however, studies of GABA in psychosis have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions.

MethodsWe searched the PubMed database for magnetic resonance spectroscopy studies of medial frontal cortex (MFC) GABA in patients with psychosis, bipolar disorder, depression, and individuals meeting ultra-high risk for psychosis criteria. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and random effects meta-analyses conducted for each group, for each MFC sub-region.

ResultsOf 341 screened articles, 23 studies of psychosis (752 patients,856 controls), 6 studies of bipolar disorder (129 patients, 94 controls), 20 studies of depression (463 cases, 449 controls) and 7 studies of ultra-high risk (229 patients, 232 controls) met inclusion criteria. Meta-analysis revealed lower mid-(SMD = -0.28, 95% confidence interval [CI] = -0.48 to -0.07, p < .01) and posterior (SMD = -0.29, 95% CI = -0.49 to -0.09, p <.01) MFC GABA in psychosis, and increased rostral GABA in bipolar disorder (SMD = 0.76, 95% CI = 0.25 to 1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = -0.36, 95% CI = -0.64 to -0.08, p = .01) did not survive correction for multiple comparisons.

ConclusionsThese results substantiate the relevance in the ethology of psychosis spectrum and mood disorders and underline the importance of voxel placement.


title: The efficacy, effectiveness and safety of SARS-CoV-2 disinfection methods (including ozone machines) in educational settings for children and young people

abstract:
While evidence for the importance of transmission of SARS-CoV-2 from contaminated surfaces is limited, ozone disinfection methods have been considered for surface cleaning as a response to stopping the spread of the virus in educational settings. This rapid evidence summary aimed to search the available literature and summarise findings on the surface survival of SARS-CoV-2, efficacy and effectiveness of ozone machines against SARS-CoV-2, and benefits and harms caused by using these cleaning technologies, including their impact on health. Alternative cleaning technologies, such as light-based technologies and hydrogen peroxide vapour, were also investigated. Findings indicate that gaseous ozone can inactivate different bacteria and viruses, although there is a lack of direct evidence investigating the effect of these cleaning methods on SARS-CoV-2 in real-world settings, specifically in schools. However, regarding harm, ozone is a highly reactive oxidising agent, and high concentrations can contribute to decay of building materials, and health issues (mainly respiratory) by direct exposure or by-product formation. Therefore, leading environmental health organisations do not recommend the use of ozone cleaning technologies in real-world settings, such as schools. Research and policy focus may need to shift towards other interventions that could help reduce transmission, and consequently minimise disruption to education.

Funding statementThe Wales Centre for Evidence Based Care was funded for this work by the Wales Covid-19 Evidence Centre, itself funded by Health & Care Research Wales on behalf of Welsh Government.

TOPLINE SUMMARYO_ST_ABSWhat is a Rapid Evidence Summary?C_ST_ABSThis Rapid Evidence Summary was completed in two weeks to inform policy- decision making. It is based on a systematic search of the literature, conducted in September 2021. Priority is given to studies representing robust evidence synthesis. No quality appraisal or evidence synthesis are conducted, and the summary should be interpreted with caution.

Background / Aim of Rapid Evidence SummarySeveral non-touch disinfectant methods including ozone, light-based technologies, and hydrogen peroxide are being considered to reduce the risk of SARS-CoV-2 virus transmission to children and young people in educational settings. Concerns have been raised about the evidence of efficacy, effectiveness and safety of these technologies in these settings. We aimed to address the following research questions: O_LIWhat is the evidence for the surface survival of SARS-CoV-2?
C_LIO_LIWhat is the evidence for the efficacy (in vitro) and real-life effectiveness (in situ) of ozone machines, light-based technologies and hydrogen peroxide vapour as air or surface disinfectants against SARS-CoV-2?
C_LIO_LIWhat are the potential health effects of ozone, in particular for children and young people and the benefits and harms of using ozone machines?
C_LI

Key FindingsO_ST_ABSExtent of the evidence baseC_ST_ABSA total of 82 tertiary, secondary and primary evidence sources was included

Recency of the evidence baseMost studies were published 2020-21, indirect evidence was included from earlier work from 2006 onwards

Summary of findingsO_LISARS-CoV-2 fragments can be found on surfaces up to seven days later in the community but there is a lack of evidence whether these are viable
C_LIO_LIWhen accounting for both surface survival data and real-world transmission factors, the risk of surface transmission after a person with COVID-19 has been in an indoor space is minor after 72 hours, regardless of last clean
C_LIO_LIThere is evidence from experimental settings that ozone machines, light-based technologies and hydrogen peroxide do inactivate coronaviruses, including SARS-CoV-2
C_LIO_LIThere is a lack of evidence for the effectiveness of ozone machines, light- based technologies and hydrogen peroxide in real-world settings
C_LIO_LIThere are uncertainties about training requirements for staff, methods for assurance of ozone removal and monitoring of occupational exposure
C_LIO_LIThere is strong evidence of a causal relationship between short term ozone exposure and respiratory health issues; these can occur at very low concentrations of ozone; children with asthma are more at risk
C_LIO_LIRooms using ozone machines need to be sealed off to avoid leakage of the ozone gas which is toxic at high concentrations
C_LIO_LIOzone may react with materials in the room to form secondary pollutants (e.g. formaldehyde)
C_LI

The best quality evidenceO_LIThe US EPA 2021 does not recommend ozone for air cleaning and the UK SAGE EMG 2020a does not recommend technologies that "may generate undesirable secondary chemical products that could lead to health effects such as respiratory or skin irritation (medium confidence). These devices are therefore not recommended unless their safety and efficacy can be unequivocally and scientifically demonstrated by relevant test data" (SAGE EMG 2020a).
C_LI

Policy implicationsO_LIThere is no direct evidence for the effectiveness and safety of using ozone machines to deactivate SARS-CoV-2 in real-world educational settings for children, young people and staff
C_LIO_LIThere is evidence for the risk of potential harm to children and young people of ozone machines from either ozone or secondary pollutants, in particular but not only, if used in uncontrolled ways in educational settings
C_LI

Strength of Evidence to dateO_LImoderate evidence for the surface survival of SARS-CoV-2
C_LIO_LIstrong evidence of causal relationship between short term ozone exposure and respiratory health issues
C_LI


title: Psychological and financial impacts of COVID-19-related travel measures: An international cross-sectional study

abstract:
BackgroundThe impact of COVID-19 international travel restrictions has to date, not been fully explored, and with the ongoing threat that new variants could potentially restrict movement further, it is important to consider the impacts that travel restrictions have on community members. This study aimed to evaluate the psychological and financial impact of COVID-19 travel restrictions on those separated from their partners or immediate families, as well as temporary visa holders who were unable to migrate.

MethodsBetween 4 November 2021 to 1 December 2021, we executed a cross-sectional online survey targeting three specific groups; (1) those stranded from their partners; (2) those stranded from immediate families; and (3) temporary visa holders unable to migrate or cross international borders. We collected data on respondents demographic profile; the nature of COVID-19-related travel impacts; depression, anxiety, and stress levels (using the validated DASS-21); and finally, data on respondents financial, employment and accommodation situation.

Results1363 respondents located globally completed the survey. 71.2% reported financial stress, 76.8% ([Formula], SD=5.94) reported moderate-to-extremely severe depression, 51.6% ([Formula], SD=5.49) moderate-to-extremely severe anxiety, and 62.6% ([Formula], SD=5.55) moderate-to-extremely severe stress levels. Statistically significant factors associated with moderate-to-extremely severe depression, anxiety, and stress included being female, chronic illness, and experiencing financial stress. Employment during COVID-19 - specifically essential services workers or unemployed - was associated with higher levels of anxiety and stress, with only essential workers being a predictor of higher stress severity. Factors that provided psychological protection included being older and having children.

ConclusionThis study is one of the first to explore the impact COVID-19-related international travel restrictions have had on the financial status and psychological health of affected individuals. It highlights the significant human cost associated with the restrictions and identifies psychologically vulnerable populations. These results will help the design of targeted health and social policy responses.


title: Hypomethylation of miR-17-92 cluster in lupus T cells and no significant role for genetic factors in the lupus-associated DNA methylation signature

abstract:
ObjectivesEpigenetic dysregulation plays an important role in the pathogenesis of lupus, a systemic autoimmune disease characterized by autoantibody production. Lupus T cells demonstrate aberrant DNA methylation patterns dominated by hypomethylation of interferon-regulated genes. The objective of this study was to identify additional disease-associated DNA methylation changes in naive CD4+ T cells from an extended cohort of lupus patients and determine the genetic contribution to epigenetic changes characteristic of lupus.

MethodsGenome-wide DNA methylation was assessed in naive CD4+ T cells isolated from a cohort of 74 lupus patients and 74 age-, sex-, and race-matched healthy controls. We applied a trend deviation analysis approach, comparing methylation data in our cohort to methylation data from over 16,500 samples to characterize lupus-associated DNA methylation patterns. Methylation quantitative trait loci (meQTL) analysis was used to determine genetic contribution to lupus-associated DNA methylation changes.

ResultsIn addition to the previously reported epigenetic signature in interferon-regulated genes, we observed hypomethylation of the promoter regions of microRNA (miRNA) genes in the miR-17-92 cluster in lupus patients. Members of this miRNA cluster play an important role in regulating T cell proliferation and differentiation. Expression of two miRNAs within this cluster, miR-19b1 and miR-18a, showed a significant positive correlation with disease activity in lupus patients. meQTL were identified by integrating genome-wide DNA methylation profiles with genotyping data in lupus patients and controls. Patient meQTL show overlap with genetic risk loci for lupus. However, less than 1% of differentially methylated CpG sites in lupus patients were associated with an meQTL, suggesting minimal genetic contribution to lupus-associated epigenotypes.

ConclusionThe lupus defining epigenetic signature, characterized by robust hypomethylation of interferon-regulated genes, does not appear to be determined by genetic factors. Hypomethylation of the miR-17-92 cluster that plays an important role in T cell activation is a novel epigenetic locus for lupus.

category: rheumatology


title: Accuracy of Attestation Among Mohs and Dermatologic Surgery Diplomates

abstract: Self-regulation is a key tenet of professionalism. We sought to assess the accuracy of self-attestation with respect to the administration of a newly defined field of board sub-specialization. One qualifying pathway to take the written examination for certification in Mohs and Dermatologic Surgery (MDS) is to self-attest to an active practice of Mohs Surgery. Utilizing publicly available data, we find that greater than 6% (111) of new diplomates did not complete an ACGME-approved fellowship or charge CMS in 2019 for greater than one Mohs case per week. In addition, 72 individuals did not complete a fellowship or charge CMS in 2019 for a single Mohs case. This discrepancy between the test qualifications and practice patterns evident from CMS data suggests concern for the reliability of self-regulation in this setting.

category: medical ethics


title: The application of Raman spectroscopy and chemometric methods for analysis healthy blood and blood with BRCA mutation

abstract:
Presented study included human blood from heathy patients and from patients with BRCA mutation. Raman spectroscopy can be used for BRCA mutation detection and bioanalytical characterization of pathologically changed samples. The aim of this study is to evaluate the Raman biomarkers to distinguish blood samples from healthy patients and from patient with BRCA mutation by Raman spectroscopy. We have proved that Raman spectroscopy is a powerful technique to distinguish between healthy blood and blood with BRCA mutation and to characterize biochemical composition of samples. Partial Least Squares Discriminant Analysis yielded effective and comparable samples classification based on vibrational features. The sensitivity and specificity obtained from PLS-DA have been over 86.5%. The obtained results confirm clinical potential of Raman spectroscopy in oncological diagnostics.

Graphical Abstract

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title: Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

abstract:
ObjectivesImmunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes.

MethodsUtilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes.

ResultsOf 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths.

ConclusionsIn IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.


title: Early emergence phase of SARS-CoV-2 Delta variant in Florida

abstract: SARS-CoV-2, the causative agent of COVID-19, emerged in late 2020. The highly contagious B.1.617.2 (Delta) Variant of Concern (VOC) was first identified in October 2020 in India and subsequently disseminated worldwide, later becoming the dominant lineage in the U.S. Despite considerable genomic analysis of SARS-CoV-2 in the U.S., several gaps in the understanding of the local dynamics during early introductions remain, which when elucidated could translate the results of viral genomic epidemiology to actionable mitigation efforts. Here, we explore the early emergence of the Delta variant in Florida, U.S. using phylogenetic analysis of representative Florida and globally sampled genomes. We find multiple independent introductions into Florida primarily from North America and Europe, with a minority originating from Asia. These introductions lead to three distinct clades that demonstrated varying relative rates of transmission and possessed five distinct substitutions that were 3-21 times more prevalent in the Florida sample as compared to the global sample. Our results underscore the benefits of routine viral genomic surveillance to monitor epidemic spread and support the need for more comprehensive genomic epidemiology studies of emerging variants. In addition, we provide a model of epidemic spread of newly emerging VOCs that can inform future public health responses.


title: SENSOR TECHNOLOGY FOR OPENING NEW PATHWAYS IN DIAGNOSIS AND THERAPEUTICS OF BREAST, LUNG, COLORECTAL AND PROSTATE CANCER

abstract: This study analyzes the interaction between sensor research and technology and different types of cancer (breast, lung, colorectal and prostate) that generates a high mortality in society with the goals of detecting new directions for improving diagnosis and therapeutics. This study develops an approach of computational scientometrics based on data of the Web of Science from 1991 to 2021 period. The results of this analysis show the vital role of biosensor and electrochemical biosensor applied in breast cancer, lung cancer, and prostate cancer research, except colorectal cancer for latter one. Instead, research of optical sensors is developing mainly in the directions of breast, prostate, and colorectal cancer for improving diagnostics. Finally, oxygen sensor research is developing for breast and lung cancer for applications in breath analysis in new treatment processes. Preliminary results presented here clearly illustrate the evolutionary paths of main sensor technologies that have a great potential in future diagnosis of cancer, but we also need additional examinations of other aspects and factors for supporting appropriate strategies of management of technology to foster the technology transfer of sensor technologies in cancer research for improving diagnosis and, whenever possible, reduce world-wide mortality of cancer ins society.

category: health informatics


title: Clinical severity of COVID-19 patients admitted to hospitals during the Omicron wave in South Africa

abstract:
BackgroundClinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa.

MethodsWeekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each wave. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. Disease severity was compared across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, intensive-care admission or death.

Results335,219 laboratory-confirmed SARS-CoV-2 admissions were analysed, constituting 10.4% of 3,216,179 cases recorded during the 4 waves. In the Omicron wave, 8.3% of cases were admitted to hospital (52,038/629,617) compared to 12.9% (71,411/553,530) in the D614G, 12.6% (91,843/726,772) in the Beta and 10.0% (131,083/1,306,260) in the Delta waves (p<0.001). During the Omicron wave, 33.6% of admissions experienced severe disease compared to 52.3%, 63.4% and 63.0% in the D614G, Beta and Delta waves (p<0.001). The in-hospital case fatality ratio during the Omicron wave was 10.7%, compared to 21.5%, 28.8% and 26.4% in the D614G, Beta and Delta waves (p<0.001). Compared to the Omicron wave, patients had more severe clinical presentations in the D614G (adjusted odds ratio [aOR] 2.07; 95% confidence interval [CI] 2.01-2.13), Beta (aOR 3.59; CI: 3.49-3.70) and Delta (aOR 3.47: CI: 3.38-3.57) waves.

ConclusionThe trend of increasing cases and admissions across South Africas first three waves shifted in Omicron fourth wave, with a higher and quicker peak but fewer admitted patients, who experienced less clinically severe illness and had a lower case-fatality ratio. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and prior infection levels.


title: Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities

abstract: Vascular, cardiovascular and neurovascular ageing processes contribute to cognitive impairment. However, the unique and synergistic contributions of cardiovascular factors to cognitive function remain unclear because they are often condensed into a single composite score or examined in isolation of each other. We hypothesized that vascular risk factors, electrocardiographic features and blood pressure indices reveal multiple latent vascular factors, with independent contributions to age differences in cognition. In a population-based deep-phenotyping study of cognition across the lifespan (n=708, age 18-88), path analysis revealed three latent vascular factors dissociating the autonomic nervous system response from two components of blood pressure. These three factors made unique and additive contributions to the variability in crystallized and fluid intelligence. The discrepancy in fluid relative to crystallized intelligence, indicative of cognitive decline, was associated with a latent vascular factor predominantly expressing pulse pressure, suggesting that higher pulse pressure is associated with cognitive decline from expected performance. This association varied with age, such that higher factor scores predicted a greater cognitive discrepancy in older individuals. Controlling pulse pressure may help to preserve cognitive function, particularly in older adults. Our findings highlight the need to better understand the multifactorial nature of vascular aging, its effects on neurocognitive function, and the modifiable risks of cognitive decline.

category: cardiovascular medicine


title: LARisk: An R package for lifetime attributable risk from radiation exposure

abstract: The lifetime radiation associated risk of cancer incidence has been of interest at least seventy years after atomic bombings of Hiroshima and Nagasaki in 1945. Since most of radiation epidemiological studies are retrospective, it is important to assess the potential magnitude of radiation-related cancer risk. The R-package so-call LARisk implements to easily calculate lifetime attributable risks (LAR) of radiation associated cancer incidence presenting bootstrap-based confidence intervals of the estimated risks. The main characteristics of the LARisk package are to flexibly compute the LAR-associated risks, effectively summarize large data, and promptly update domain-knowledge such as new regression coefficients for excess relative risk or excess absolute risk models, population information, etc. The manuscript provides a complete guide for usage of the LARisk package, which will enable to contribute the prospective studies in radiation epidemiology.


title: Knowledge, Attitude, and Practices of Health Professionals Working in A Major Health Care System Regarding Social Determinants of Health (SDOH) and Community Health Workers (CHWs)

abstract:
IntroductionSocial Determinants of Health (SDOH) play a key role in impacting the health outcomes of any population. Community Health Workers (CHWs) play an important role in health promotion, disease prevention, and management of chronic illnesses. This study aims at exploring the knowledge, attitude, and practices of health care professionals towards CHWs to fully integrate in them for mitigation of SDOH.

Materials and MethodsA cross-sectional study utilizing an anonymous survey questionnaire across 4 clinical sites was carried out from June 2016 to November 2017 in a major healthcare system (Presbyterian) in Albuquerque, New Mexico. Descriptive statistics (means, standard deviations, and proportions) were collected. Categorical variables were analyzed using Chi-squared and Fishers exact test; a p-value of <0.05 was considered statistically significant, using SAS 9.4 statistical software.

ResultsAlmost half of the health professionals had no knowledge about the social determinants of health. Almost a quarter of the health professionals did not know the role of CHWs in healthcare, however, 100% of the respondents across all clinic and practice locations and regardless of their role or scope of the practice believed that greater involvement of CHWs would improve patient outcomes.

ConclusionThere is a knowledge deficit among health care providers about the social determinants of health (SDOH).More educational and teaching opportunities on SDOH and CHWs to all health professionals should be provided to all health professionals so the clinical team can help manage SDOH in addition to providing clinical care.

category: primary care research


title: Accurate non-invasive mass and temperature quantifications with spectral CT

abstract: Spectral CT has been increasingly implemented clinically for its better characterization and quantification of materials through its multi-energy results. It also facilitates calculation of physical density utilizing the Alvarez-Macovski model without approximations. These spectral physical density quantifications allow for non-invasive mass measurements and temperature evaluations by manipulating the definition of physical density and thermal volumetric expansion, respectively. To develop the model, original and parametrized versions of the Alvarez-Macovski model and electron density-physical density model were validated with a phantom. The best physical density model was then implemented on clinical spectral CT scans of ex vivo bovine muscle to determine the accuracy and effect of acquisition parameters on mass measurements. In addition, the relationship between physical density and changes in temperature was evaluated by scanning and subjecting the tissue to a range of temperatures. A linear fit utilizing the thermal volumetric expansion was performed to assess the correlation. The parametrized Alvarez-Macovski model performed best in both model development and validation with errors within {+/-}0.02 g/mL. As observed with muscle, physical density was not significantly affected by dose and acquisition mode but was slightly affected by collimation. These effects were also reflected in mass measurements, which demonstrated accuracy with a maximum percent error of 0.34%, further validating the physical density model. Furthermore, physical density was strongly correlated (R of 0.9781) to temperature changes through thermal volumetric expansion. Accurate and precise spectral physical density quantifications enable non-invasive mass measurements for pathological detection and temperature evaluation for thermal therapy monitoring in interventional oncology.

category: radiology and imaging


title: Scottish COVID CAncer iMmunity Prevalence (SCCAMP) - a longitudinal study of patients with cancer receiving active anti-cancer treatment during the COVID-19 pandemic

abstract:
BackgroundCancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aims to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anti-cancer treatment during the COVID-19 pandemic and their antibody response following vaccination.

Patients and MethodsEligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome was obtained from routine electronic health records.

ResultsThe study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. The median age was 62.7 years, and 66.5% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the age-matched local general population until May 2021, after which population levels appeared higher. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality proportion was similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, comorbidities and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARS-CoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type.

ConclusionSCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.

Highlights- The SCCAMP dataset represents the largest longitudinal study of patients with cancer undergoing anti-cancer treatment during the COVID-19 pandemic
- Rates of infection in the cancer cohort mirrored those of the local age adjusted population
- Vaccination was effective in patients with cancer undergoing active treatment in terms of antibody response and SARS-CoV-2 PCR rates
- Treatment type did not impact the rate of SARS-CoV-2 antibody response


title: Tinnitus Subtyping with Subgrouping Within Group Iterative Multiple Model Estimation: An Ecological Momentary Assessment Study

abstract:
BackgroundTinnitus is a heterogeneous condition associated with moderate to severe disability, but the reasons why only a subset of individuals is burdened by the condition are not fully clear. Ecological momentary assessment (EMA) allows a better understanding of tinnitus by allowing individualized models and by capturing the fluctuations of tinnitus symptoms and other behavioral dynamics as they occur, and therefore minimizing the risk of recollection bias. The TrackYourTinnitus (TYT) mobile app provides a platform for collecting ecologically valid time series data from tinnitus users and can be used to address questions like how mood, concentration, tinnitus distress, or loudness relate over time. Whether any of those variables have an influence over the next day, that is, whether any of these variables are auto- or cross-correlated, is still unanswered.

ObjectivesAssess whether behavioral and symptom-related data from tinnitus users from the TYT app auto- and cross-correlate in different time lags, both within and between individuals.

MethodsAnonymized data was collected from 278 users of the iOS or Android TYT apps between 2014 and 2020. Tinnitus-related distress, tinnitus loudness, concentration level, overall mood, emotional arousal, and overall stress level were assessed using a 10-point visual analog scale via a daily survey. Auto- and cross-correlations were calculated for participants who used the app for at least 10 consecutive days. Lagged cross-correlation was used to investigate the dynamics of each of these variables over time at the group level, followed by linear regression with elastic net regularization for each user. Additionally, subgrouping within group iterative multiple model estimation (S-GIMME) was used to model the behavioral dynamics at the group, subgroup, and individual levels with data collected from 32 users.

ResultsNo autocorrelation or cross-correlation was observed at the group level between the variables assessed. However, application of the regression models with elastic net regularization identified individualized predictors of tinnitus loudness and distress for most participants, with the models including contemporaneous and lagged information from the previous day. The finding that a subset of users experienced lagged and contemporaneous dynamics was corroborated by the models from S-GIMME. The models had adequate fits, with both contemporaneous and lagged coefficients obtained for most individuals. Two subgroups were identified, the first consisting of users where both contemporaneous and lagged effects were observed, and a second subgroup consisting of users whose dynamics were mainly of contemporaneous effects.

DiscussionWe showed that tinnitus loudness and tinnitus distress are affected by the contemporaneous and lagged dynamics of behavioral and emotional processes measured through EMA. These effects were seen at the group, subgroup, and individual levels. The relevance EMA and the implications of the insights derived from it for tinnitus care are discussed, especially considering current trends towards the individualization of tinnitus care.


title: Impact of BNT162b2 mRNA Vaccination on the Development of Short and Long-term Vaccine-Related Adverse Events in Inflammatory Bowel Disease: A Multi-Center Prospective Study

abstract:
IntroductionSARS-CoV-2 vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data is lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD.

MethodThis is a prospective, observational cohort study investigating short- and long-term AEs related to BNT162b2 vaccine in patients with IBD (study group) after first and second dose compared to healthy participants (study group). Patients were recruited at the time of attendance to clinic or infusion rooms. Short term (<3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.

ResultsA total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study nor the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose (58 (57%) vs 38 (37%) respectively, P-value= 0.005). After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%), (P-value<0.001)]. At 20-24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire (196 (96.1%) in the study group vs 190 (93.1%) in the control group). In both groups, none of the patients reported local, systemic or severe adverse events (0 out of 386) at week 20-244 post second dose.

ConclusionThe BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with longer follow-up duration are needed to assess for possible rare adverse events.

category: gastroenterology


title: Pan-cancer analyses reveal genomics and clinical characteristics of the down regulated genes for recurrent myocardial infarction in cancer

abstract:
BackgrounEarly identification of the occurrence and progression of coronary ischemic events is particularly important for the diagnosis and treatment of coronary heart disease complicated with tumor. Therefore, it is of great significance to analyze biomarkers and regulatory factors of recurrent myocardial infarction after first myocardial infarction.In order to specify the regulatory factor of coronary heart disease or myocardial infarction on tumor occurrence and metastasis and clinical survival effect, we select from GEO database for the first time of recurrence after myocardial infarction, myocardial infarction, microarray data set, the comprehensive evaluation of the data set is the key cut genes and cancer, tumor prognosis, the tumor extends into the immune level of mutation, etc.The purpose of this study is to discover the role of myocardial infarction regulatory factors in cancer.

MethodsGSE48060 chip data set was downloaded from GEO database to obtain gene expression profiles of blood samples from normal cardiac function control and first AMI patients within 48 hours after the first myocardial infarction.GEO2R online tool and Excel software were used to screen the differential genes between the reinfarction samples and the normal samples in the GSE48060 chip data set.DAVID database was used for enrichment analysis of GO and KEGG of DEGs.The PPI network was constructed and visualized by Using The STRING database and Cytoscape software, and the key genes were screened by the CytoHubba plug-in of Cytoscape software.TIMER database and GEPIA2 website were used to analyze and verify the expression levels of key genes between tumor tissues and normal tissues in generalized carcinoma.GEPIA2 website was used to analyze the correlation between key genes and tumor prognosis.The correlation between key gene expression and tumor purity and each immune cell was analyzed by TIMER database.CBioPortal website was used to analyze the mutation and correlation of key genes in tumors.

ResultsThrough analysis, the difference genes of 17 GSE48060 chip data sets of reinfarction samples and normal samples were obtained, and the above genes were all down-regulated genes.Five key genes were obtained through constructing PPI network, which were GART, SOD2, KLRF1, ERAP2 and CXCL5.According to the TIMER result, The expression level of GART in BLCA, BRCA, CHOL, COAD, ESCA, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, PRAD, READ, STAD and THCA was significantly different from that in normal tissues (P < 0.001).The expression levels of SOD2 in BRCA, ESCA, KICH, KIRC, KIRP, LUSC, SKCM and STAD were significantly different from normal tissues (P < 0.001).The expression levels of KLRF1 in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, PRAD, READ, STAD and UCEC were significantly different from those in normal tissues (P < 0.001).The expression levels of ERAP2 in BRCA, KIRC and LUSC were significantly different from those in normal tissues (P < 0.001).The expression levels of CXCL5 in BRCA, COAD, ESCA, HNSC, KICH, KIRC, KIRP, LUAD, LUSC, PRAD, STAD, THCA and UCEC were significantly different from those in normal tissues (P < 0.001).The results of GEPIA2 showed that the expression levels of GART in CESC, CHOL, ESCA, KICH, LUSC, SARC and STAD showed significant differences between tumor tissues and normal tissues (P < 0.05).There were significant differences in the expression levels of SOD2 in BLCA, BRCA, ESCA, PAAD and PCPG between tumor tissues and normal tissues (P < 0.05), and there were significant differences in the expression levels of KLRF1 in LUAD and LUSC between tumor tissues and normal tissues (P < 0.05).There were significant differences in ERAP2 expression between tumor tissues and normal tissues in KICH and LUSC (P < 0.05), and there were significant differences in CXCL5 expression between tumor tissues and normal tissues in CHOL, COAD, ESCA, LUAD, LUSC, READ and STAD (P < 0.05).The results of tumor survival analysis indicated that the correlation between the overall tumor survival (OS) of GART and CESC, KIRC, LUAD, READ and SARC was statistically significant (P < 0.05).The correlation between SOD2 and TUMOR OS of SKCM was statistically significant (P < 0.05).The correlation of TUMOR OS between KLRF1 and HNSC was statistically significant (P < 0.05).The correlation between CXCL5 and TUMOR OS of KICH and KIRC was statistically significant (P < 0.05).There was statistically significant correlation between GART and LUADs tumor stage (P < 0.05), SOD2 and SKCMs tumor stage (P < 0.05), CXCL5 and KICH and KIRCs tumor stage (P < 0.05).The GART gene expression level is significantly correlated with various immune cells in CESC, KIRC, LUAD, READ and SARC.The expression level of SOD2 gene was significantly correlated with various immune cells in SKCM.The expression level of KLRF1 gene was significantly correlated with various immune cells in HNSC.The expression level of CXCL5 gene was significantly correlated with various immune cells in KICH and KIRC.The proportion of mutations in COAD, KICH, LIHC, READ, SKCM and THCA was the highest, the proportion of amplification in BRCA, ESCA, HNSC, KIRC, LUSC and STAD was the highest, and the proportion of severe deletion in LUAD and PRAD was the highest.

ConclusionThe key down-regulated genes of recurrent myocardial infarction after initial myocardial infarction are related to tumor genesis, metastasis, clinical survival and immune invasion.Key down-regulated genes in recurrent myocardial infarction may serve as important biomarkers for the diagnosis and treatment of cancer.

category: genetic and genomic medicine


title: Application of the Weight Self-Stigma Questionnaire (WSSQ) in Subjects with Overweight and Obesity living in Italy

abstract:
AimsAlthough weight-based stigmatization is widespread in everyday life, a suitable measure of weight self-stigma is currently unavailable for those with overweight/obesity whose primary language is Italian. The purpose of this study was to translate and test the psychometric properties of the Italian version of the Weight Self-stigma Questionnaire (I-WSSQ) to administer it to adults with overweight/obesity.

Materials and MethodsA cross-sectional study was conducted on 214 adults with overweight or obesity. Data including Body Mass Index (BMI), I-WSSQ, and Body Uneasiness Test (BUT) scores were collected from April the 2nd to July the 6th, 2021.

ResultsReliability was assessed through internal consistency: the Cronbach  of the I-WSSQ was  =.814, indicating good reliability. The exploratory factor analysis revealed a two-factor structure of I-WSSQ (self-devaluation and fear of enacted stigma, respectively) that explained 49,25% of the total variance. In addition, the I-WSSQ score directly correlated with BMI and BUT score, indicating an acceptable criterion-related validity.

ConclusionThe I-WSSQ shows adequate reliability and validity. Health professionals may use the I-WSSQ to assess the weight self-stigma of adults with overweight/obesity whose primary language is Italian.


title: Breast and colorectal cancer awareness in Malaysians and barriers towards screening: A systematic review

abstract:
BackgroundBreast cancer (BC) and colorectal cancer (CRC) are considered primary cancers that affect both male and females globally. In Malaysia, BC is the most commonly diagnosed cancer among women of all ethnic groups and CRC is the second most common cancer in males and the second most common cancer in females. This systematic review was carried out to assess cancer symptom awareness and barriers to undergoing cancer screening for BC and CRC.

MethodsA pre-defined search was conducted between January 2008 and December 2018 using the following databases: MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus and Cochrane Library for relevant articles. The search was updated in June 2020. Reviewers independently performed the data extraction and quality assessment of the included study according to the Joanna Briggs Institute assessment tools.

Result22 studies met the inclusion criteria (BC n=11; CRC n=11). Nine studies assessed symptom knowledge for BC and eight for CRC. Two studies described barriers towards cancer screening for BC and one for CRC. Four CRC studies assessed symptoms knowledge and cancer screening barriers. The most commonly reported BC symptoms were  painless breast lump(27.6% - 90.8%),  nipple discharge (1.6% - 74.5%) and  pain in breast/ breast region (11.5% - 82.8%) meanwhile CRC symptoms were  change in bowel habits (new-onset diarrhoea or constipation) (28.4% - 86.6%),  bleeding and/or bleeding from the back passage (11.5% - 71.9%) and  weight loss (9.3% - 83.4%).  Financial issue (10% - 17.5%) was the most frequent blockade identified towards BC screening meanwhile  fear of result (27.6% - 32.1%) for CRC screening by Malaysians. Overall the studies carried out in Malaysia, six studies on BC symptom knowledge and one study on BC screening barrier were scored as medium study quality while four studies on CRC symptom knowledge and three studies on CRC screening barriers were scored as medium study quality.

ConclusionStudies described varied and overall, limited, symptom awareness and barriers towards BC and CRC screening which likely contributes to the delayed presentation of cancers in Malaysia. There is a need for improving the awareness of BC and CRC symptoms as well as the importance of screening to encourage the early presentation of symptomatic cancer patients and down-staging of cancer.

category: public and global health


title: Using a transection paradigm to enhance the repair mechanisms of an investigational human cell therapy

abstract:
One promising strategy in cell therapies for Parkinsons Disease (PD) is to harness a patients own cells to provide neuroprotection in areas of the brain affected by neurodegeneration. No treatment exists to replace cells in the brain. Thus, our goal has been to support sick neurons and slow neurodegeneration by transplanting living repair tissue from the peripheral nervous system into the substantia nigra of those with PD. Our group has pioneered the transplantation of transection-activated sural nerve fascicles into the brain of human subjects with PD. Our experience in sural nerve transplantation through FDA-regulated clinical trials has supported the safety and feasibility of this approach. We are among the first to collect human sural nerve both before and after transection and to perform single nuclei RNA sequencing to determine the cell types present. We collected nerve tissue before and approximately 2 weeks after sural nerve transection for immunoassays from 15 participants, and collected from two additional participants for single nuclei RNA sequencing. We quantified the expression of key neuroprotective and anti-apoptotic genes along with their corresponding protein levels using immunoassays. The single nuclei data clustered into 10 distinctive groups defined on the basis of previously published cell type-specific genes. Transection-induced reparative peripheral nerve tissue showed RNA expression of neuroprotective factors and anti-apoptotic factors across multiple cell types after nerve injury induction. Key proteins of interest (BDNF, GDNF, beta-NGF, PDGFB, and VEGF) were significantly upregulated in reparative tissue compared to naive. These results provide insight on this repair tissues utility as a neuroprotective cell therapy.

Clinical TrialClinicaltrials.gov (Trial registration number NCT02369003)

https://clinicaltrials.gov/ct2/show/NCT02369003).


title: Spillover Benefit of Pre-Exposure Prophylaxis for HIV Prevention: Evaluating the Importance of Effect Modification using an Agent-Based Model

abstract: We developed an agent-based model using a trial emulation approach to quantify effect measure modification of key variables on spillover effects of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in Atlanta, GA. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomized trial with eligible components ([≥]3 agents and [≥]1 HIV+ agent) first randomized to intervention or control (no PrEP). Within intervention components, agents were randomized to PrEP with intervention coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component level characteristics and estimated spillover effects using an extension of randomization-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between [≥]2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.

category: hiv aids


title: Favourable vaccine-induced SARS-CoV-2 specific T cell response profile in patients undergoing immune-modifying therapies

abstract: Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the impact of such therapies on vaccine-induced T cell responses. Here, we longitudinally characterised humoral and Spike-specific T cell responses in inflammatory bowel disease (IBD) patients who are on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors and/or other biologic treatment (anti-integrin or anti-p40) after mRNA vaccination up to 3 months after completing two vaccine doses. We demonstrated that a Spike-specific T cell response is not only induced in treated IBD patients at levels similar to healthy individuals, but also sustained at higher magnitude, particularly in those treated with TNF inhibitor therapy. Furthermore, the Spike-specific T cell response in these patients is mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile. Thus, despite the humoral response defects, the favourable profile of vaccine-induced T cell responses might still provide a layer of COVID-19 protection to patients under immune-modifying therapies.

category: infectious diseases