title: Telemedicine for surgical site infection diagnosis: a systematic review protocol

abstract:
1Since the COVID-19 pandemic there has been a rapid uptake and utilisation of telemedicine in all aspects of healthcare. This presents a key opportunity in surgical site infection surveillance. Remote follow up methods have been used via telephone, with photographs and questionnaires for post-operative reviews with varying results.

This review therefore aims to comprehensively synthesise available evidence for the diagnostic accuracy of all forms of SSI telemedicine monitoring. The protocol has been established as per both PRISMA-P and the Cochrane handbook for reviews of diagnostic test accuracy.

Medline, Embase, CENTRAL and CINAHL will be searched using a complete search strategy developed with librarian input, in addition to google scholar and hand searching. All study designs with patients over 18 and undergone a primarily closed surgical procedure will be eligible. Index tests will include all forms of telemedicine and a subgroup analysis performed for each of these. Comparative tests must include face to face review, and all reference standards will be included again for sub-group analyses. Search results will be screened by two investigators independently with a third providing consensus review on disagreements. Methodological quality will be assessed using the QUADAS-2 tool, first validated by two investigators as per the Cochrane handbook.

Exploratory analysis will formulate summary receiver operating characteristic curves and forest plots with estimates of sensitivity and specificity of the included studies. Sources of heterogeneity will be identifying and investigated through further analysis.

Potential benefits of telemedicine integration in surgical practice will reduce cost and travel time to patients in addition to avoiding wasted clinic appointments, important considerations in a peri-pandemic era. To avoid missed or further complications, there must be confidence in the ability to diagnose infection. This review will systematically determine whether telemedicine is accurate for surgical site infection diagnosis, which methods are well established and if further research is indicated.

AmendmentsProtocol version number will be annotated on the title page and thereby footer of each page. A list of major amendment changes to the protocol will be kept in the table below.

O_TBL View this table:
org.highwire.dtl.DTLVardef@6d6ef7org.highwire.dtl.DTLVardef@90477borg.highwire.dtl.DTLVardef@451a13org.highwire.dtl.DTLVardef@b2fa76org.highwire.dtl.DTLVardef@5971f4_HPS_FORMAT_FIGEXP  M_TBL C_TBL Important Dates

O_TBL View this table:
org.highwire.dtl.DTLVardef@48660corg.highwire.dtl.DTLVardef@123b383org.highwire.dtl.DTLVardef@de9a90org.highwire.dtl.DTLVardef@758950org.highwire.dtl.DTLVardef@89ea9a_HPS_FORMAT_FIGEXP  M_TBL C_TBL DefinitionsSurgical Site Infection An infection occurring after surgery in the part of the body where surgery took place

Telemedicine The remote diagnosis and treatment of patients by means of communications technology

Telehealth The delivery of healthcare services, where patients and providers are separated by distance.

eHealth The use of information communication technology for health.

mHealth A component of eHealth where medical and public health practices are supported by mobile devices.

Virtual Care All the ways healthcare providers remotely interact with their patients


title: The impact of retracted randomised controlled trials on systematic reviews and clinical practice guidelines: a meta-epidemiological study

abstract:
ObjectivesTo investigate whether and when the correction is done in Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) when their included Randomised Controlled Trials (RCTs) have been retracted.

DesignA meta-epidemiological study.

Data sourcesThe Retraction Watch Database.

Eligibility criteria for selecting studiesSRs and CPGs citing the retracted RCTs on Web of Science.

Review methodsWe investigated how often the retracted RCTs were cited in SRs and CPGs. We also investigated whether and when such SRs and CPGs corrected themselves by visually inspecting their current web pages. We summarized the proportion of correction and the time from retraction to correction.

ResultsWe identified 98 retracted RCTs as well as 360 articles (335 SRs and 25 CPGs) citing them. Among the 360 articles, 157 (44%) were published after the retraction, 203 (56%) were published before retraction. Among 77 articles published citing already retracted RCTs in their evidence synthesis without caution, none corrected themselves after publication. Of 203 articles published before retraction, 149 included RCTs that were later retracted in their evidence synthesis. Among them, one SR was retracted due to plagiarism. Only 5% of SRs (6/130) and 11% of CPGs (2/18) corrected their results.

ConclusionsA large number of SRs and CPGs included already retracted RCTs without caution and never corrected themselves. When SRs and CPGs had included RCTs which were later retracted, only a small minority corrected their evidence syntheses. The scientific community, including publishers and researchers, should make systematic and concerted efforts to remove the impact of retracted RCTs.

What is already known on this topic- Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) aggregating randomised controlled trials (RCTs) are important sources of information for clinical decision making.
- There are anecdotal reports of publications citing retracted RCTs and point to the problem of their continued citation after retraction.
- However, there are no studies that comprehensively examined the fate of retracted RCTs on SRs and CPGs in their evidence synthesis.

What this study adds- A considerable number of SRs and CPGs cited already retracted RCTs and none corrected themselves later.
- Only a small minority of SRs (5%, 6/130) and CPGs (11%, 2/18) which cited RCTs that were later retracted corrected their findings after the retraction was announced.
- The results indicate that publishers and researchers should make efforts to remove the impact of retracted RCT.

category: medical ethics


title: Synaptic loss in behavioural variant frontotemporal dementia revealed by UCB-J PET

abstract: Synaptic loss is an early feature of neurodegenerative disease models, and is often severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) imaging with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synapses in vivo. This study used [11C]UCB-J PET in people with behavioural variant frontotemporal dementia (bvFTD), testing the hypothesis that synaptic loss is severe and related to clinical severity. We performed a cross-sectional observational study of bvFTD, versus healthy controls, in which participants underwent neurological examination, neuropsychological assessment, magnetic resonance imaging (MRI) and [11C]UCB-J PET. Patients were recruited from the Cambridge Centre for Frontotemporal Dementia at the University of Cambridge, and healthy volunteers from the UK National Institute for Health Research Join Dementia Research register. Eleven people with a clinical diagnosis of probable bvFTD and 25 age- and sex-matched healthy controls were included. All participants underwent dynamic [11C]UCB-J PET imaging, structural MRI and a neuropsychological battery, including the Addenbrookes cognitive examination (ACE-R), and INECO frontal screening (IFS). General linear models were used to compare [11C]UCB-J binding potential maps between groups, and correlate synaptic density with cognitive performance and clinical features in patients. Group-comparison and correlation analyses were also performed using partial-volume corrected [11C]UCB-J binding potential from regions of interest (ROIs). Patients with bvFTD showed severe synaptic loss compared to controls. In particular, [11C]UCB-J binding was significantly reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insular cortex and medial temporal lobe. Synaptic loss in the left frontal and cingulate regions correlated significantly with cognitive impairments as assessed with ACE-R and IFS. Results from ROI-based analyses mirrored the voxel-wise results. In keeping with preclinical models, and human post mortem data, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to disease severity. [11C]UCB-J PET could support translational studies and experimental medicines strategies for new disease-modifying treatments for neurodegeneration.

category: neurology


title: Task-based fMRI in early Multiple Sclerosis: what is the best head motion correction approach?

abstract:
Functional MRI (fMRI) is one of the most common brain imaging modalities used for understanding brain organization and connectivity abnormalities associated with multiple sclerosis (MS). The fMRI signal is highly perturbed by head motion, which degrades data quality and influences all image-derived metrics. Numerous correction approaches have been proposed over the years to overcome the problems induced by head motion, however, despite a few efforts, there are still current and persistent controversies regarding the best correction strategy. The lack of a systematic comparison between different correction approaches motivates the search for optimal correction models, particularly in studies with clinical populations prone to characterize by higher motion. Moreover, motion correction strategies gain more relevance in task-based designs, which are less explored compared to resting-state and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes.

We acquired fMRI data from a group of patients with early MS and matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and compared the most used motion correction methods. We compared task-activation metrics obtained from models without motion correction, models containing 6 or 24 motion parameters (MPs) as nuisance regressors, models containing 6 or 24 MPs and motion outliers detected with FD or DVARS as nuisance regressors (scrubbing) and models with 6 or 24 MPs where motion outliers were corrected through volume interpolation. To our knowledge, volume interpolation is a frequently used approach but was never compared with other existent methods.

Our results showed that there were no differences in motion between groups, suggesting that recently diagnosed MS patients do not present problematic motion. In general, models with 6 MPs present higher Z-scores than models with 24 MPs, suggesting the 6 MPs as the best trade-off between motion correction and preservation of valuable information. However, correction approaches differ between groups, regarding the combination of MPs with correction of motion outliers. Models with 6 MPs and outliers volume interpolation or scrubbing with FD presented higher Z-scores in the MS group, while models with 6 MPs and scrubbing with DVARS or volume interpolation were the best combinations for the HC group. Differences between groups in motion correction strategies draw attention to the intrinsic impact of MS on fMRI analyses, which should be carefully addressed.

This work paves the way towards finding an optimal motion correction strategy, which is required to improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other patient populations.


title: Vaginal microbiome is associated with endometrial cancer grade and histology

abstract:
BackgroundThe vaginal microbiome is an underexplored environment which may yield insights about endometrial cancer (EC) pathophysiology and serve as an early marker of disease. Our objective was to evaluate the preoperative vaginal microbiome in women undergoing hysterectomy for benign conditions and EC to identify patterns which could segregate benign disease from EC, and to assess if the microbiome distinguishes low-grade (LG) from high-grade (HG) histologies.

MethodsVaginal microbiome samples were prospectively collected at the time of hysterectomy, and clinicopathologic data collected. Extracted DNA underwent shotgun metagenomics sequencing. Microbial diversity was calculated using the Shannon Index (-diversity) and PERMANOVA ({beta}-diversity). Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Machine learning was utilized to assess the predictive value of grade and histology based on relative bacterial abundance.

Results61 patients participated: 1) benign gynecologic disease (n=11), 2) LG EC (n=30), and 3) HG EC (n=20). 40 (62.5%) were White, 22 (34.3%) were Black, and 37 (57.8%) were Hispanic. Both - and {beta}-diversity were associated with tumor grade (p{square}={square}0.026 and p{square}={square}0.035, respectively). Four CST were identified that associated with grade of disease (p=0.036). Different histologies demonstrated variation in CST even within tumor grades (p=0.017). Markers at the species level informed models that predicted benign vs cancer (AUC 0.878), HG versus benign (AUC=0.803), and HG versus LG (AUC=0.771) with high accuracy.

ConclusionsThe vaginal microbiome segregates benign disease from EC, and is predictive of histology and grade, suggesting it may be an effective tool for screening.

category: oncology


title: Anterior Segment Optical Coherence Tomography in Pediatric Ocular Pathology

abstract:
BackgroundTo assess the pediatric anterior segment characteristics in ocular pathology, using spectral domain optical coherence tomography (SD-OCT).

MethodsOur case series follows 115 eyes of 78 children aged 2-17 years of age with anterior segment pathology in an academic facility. A thorough eye examination and investigations were performed for each child. The anterior segment optical coherence tomography (AS-OCT) analysis was done using the Optopol Revo 80(R) high resolution SD-OCT (840 nm, axial resolution of 5 {micro}m) using an imaging adapter. All pathological features visible on imaging were observed, studied, tabulated, and analyzed.

Results115 eyes of 78 children with anterior segment pathology were imaged. The average age was 11.84 years, with 44 males and 34 females. The primary clinical diagnosis was cataract (congenital and acquired) in 40 (34.8%) eyes, followed by corneal disease (congenital, inflammatory, and traumatic) in 28 (24.3%) eyes, glaucoma (juvenile and secondary) in 18 (15.7%) and trauma in 15 (13%) eyes. Systemic diseases were associated in 20.9%. The commonest imaging pathology observed was lens opacification (any morphology/location) in 43 (37.4%), increased reflectivity of the cornea in 31 (28.2%), corneal stromal thinning in 34 (29.6%), increased corneal thickness in 28 (24.3%), shallow anterior chamber in 17 (14.8%), and cells in anterior chamber in18 (15.7%) eyes, along with a multitude of other findings.

ConclusionsOur study demonstrates that anterior segment optical coherence tomography is a useful non-contact technique used without sedation for the detailed anatomic and pathologic assessment, imaging, diagnosis, and monitoring of pediatric ocular diseases.

category: ophthalmology


title: Assessing the Value of Education-Focused Laws in Reducing Child Sexual Abuse

abstract:
I.We investigated the impact of new state laws requiring or encouraging education on Child Sexual Abuse ("CSA") in schools. From 2005 through June, 2019, 31 states enacted such laws. By comparing the states with and without those laws using a difference-in-differences calculation, and controlling for changes in population, wages, employment and other relevant CSA laws, we conclude that most likely such laws: O_LIIncreased the number of CSA reports made to state departments of child services each year, and
C_LIO_LIDecreased the number of CSA cases that those departments were able to substantiate from the reported cases.
C_LI We had hypothesized, however, that effective educational content would cause more reported cases to be substantiated as people learn what to report, but implementation of the new laws apparently instead increased the proportion of unsubstantiated reports of CSA.

Our research does not tell us whether that is good or bad. In the best scenario, children are helped, but at the expense of potentially hurting those who are wrongly accused. In another scenario, children and the wrongly accused are hurt. In arguably the worst scenario, child are hurt and perpetrators are helped.

We recommend that policymakers support research to learn why the laws are shifting more cases to unsubstantiated. Depending on the answer, the laws may be worthwhile to continue but with a modification to how the reporting is done, creating a new path for reporting troublesome but lawful activity. Such a modification would preserve the benefit to children while avoiding the harm to adults.

category: health policy


title: Side Effects of COVID-19 Vaccines and Perceptions about COVID-19 and Its Vaccines in Bangladesh

abstract:
IntroductionOne of the primary reasons for hesitancy in taking COVID-19 vaccines is the fear of side effects. This study primarily aims to inspect the potential side effects of the COVID-19 vaccines circulated in Bangladesh.

MethodsThe study was a cross-sectional anonymous online survey conducted across Bangladesh. Data were collected from December 2 to December 26, 2021. The study included consenting (informed) Bangladeshi individuals aged 12 and above who had received at least one dose of the COVID-19 vaccines. Analyses were carried out through exploratory analysis, Chi-square test, and logistic regression.

ResultsA total of 1,180 (males-63.89%, age 50 years or over-65.4%, rural-52.86%) vaccinated people participated in the study. Less than half of the participants (39.48%) reported at least one side effect after receiving their COVID-19 vaccine. Injection-site pain, fever, headache, redness/swelling at the injection site, and lethargy were the most commonly reported adverse effects, all of which were mild and lasted 1-3 days. Side effects were most prevalent (about 80%) among individuals who received Pfizer-BioNTech and Moderna vaccines and were least common among those who received Sinopharm and Sinovac vaccines (21%-28%). When compared to the Sinopharm vaccines, the OxfordAstraZeneca, Pfizer-BioNTech, and Moderna vaccines were 4.51 (95% CI: 2.53-8.04) times, 5.37 (95% CI: 2.57-11.22) times, and 4.28 (95% CI: 2.28-8.05) times likelier to produce side effects. Furthermore, males, those over 50 years old, urban dwellers, smokers, and those with underlying health issues had a considerably increased risk of developing side effects. A lack of confidence in vaccines efficacy and a substantial level of hesitancy in allowing children (age five years or over) and older people (70 years or over) to receive COVID-19 vaccines were also observed.

ConclusionSide effects of COVID-19 vaccines are minimal, demonstrating their safety. Further studies are required to establish the efficacy of the vaccines.

What is already known?Significant COVID-19 vaccine hesitancy has been observed globally, mainly due to vaccine safety and efficacy concerns. Until now, most of the data on COVID-19 vaccine safety and efficacy have been published in manufacturer-funded trials that adhere to regulatory criteria and are monitored by third parties. A lack of independent studies on vaccine safety may have a detrimental effect on vaccine acceptance, which should be intensified to combat the deadly virus.

What are the new findings?After receiving the COVID-19 vaccines, less than half of the subjects experienced at least one side effect. The side effects were mild and regular and lasted 1-3 days only. Side effects were most prevalent among individuals who received Pfizer-BioNTech and Moderna vaccines and were least common among those who received Sinopharm and Sinovac vaccines. A lack of confidence in vaccines efficacy and a substantial level of hesitancy in allowing children (age five years or over) and older people (70 years or over) to receive COVID-19 vaccines were also observed.

What do the new findings imply?Side effects of COVID-19 vaccines are minimal and regular, demonstrating their safety. Efforts should be made to disseminate such findings among marginalized people worldwide who showed greater vaccine hesitancy.

category: infectious diseases


title: Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes

abstract:
The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum cytokine levels and standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays ([≥] 6 days). Based on this definition, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity, patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Immunophenotyping revealed a clear measure of clinical outcome in COVID-19 and a highly sensitive and specific prognostic test that could prove useful in guiding clinical resource allocation, treatment regimens and assessment of new therapeutic interventions.

Graphical abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/22270208v3_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@1dbe088org.highwire.dtl.DTLVardef@7227a0org.highwire.dtl.DTLVardef@87a2a2org.highwire.dtl.DTLVardef@c67679_HPS_FORMAT_FIGEXP  M_FIG C_FIG


title: The course of COVID-19 in patients with chronic spontaneous urticaria receiving omalizumab treatment

abstract:
IntroductionAlthough there are case reports and guideline recommendations that states omalizumab can be used in chronic spontaneous urticaria (CSU) patients during SARS-CoV-2 pandemic, there are scarce studies showing the course of Coronavirus disease 2019 (COVID-19) in CSU patients receiving omalizumab.

Materials and MethodsA total of 370 patients with chronic urticaria were included in the study between June 2020 and December 31, 2020.

ResultsSixty patients (16.2%) became infected with the SARS-CoV-2. The rate of pneumonia and hospitalization were 4.1% and 1.9%. There was no significant difference was determined between the CSU patients with omalizumab treatment and the non-receivers in regard to the rate of SARS-CoV-2 (+) (p: 0.567) and in regard to the rate of SARS-CoV-2 related pneumonia and hospitalization (p: 0.331 and p: 0.690). Gender, duration of CSU, serum IgE levels, omalizumab treatment, and atopy were not found to be associated with an increased risk for SARS-CoV-2 positivity in patients with CSU.

ConclusionOur study shows that the use of omalizumab does not increase the risk of COVID-19 infection, COVID-19-related pneumonia and hospitalizations in CSU patients and supports the views that omalizumab can be used safely in patients with CSU during the COVID-19 pandemic.

category: allergy and immunology


title: Patterns of Medication Use and Prescription Fills for Cardioprotective Anti-Hyperglycemic Agents in the United States

abstract:
ImportanceSelected glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT2i) have cardioprotective effects in patients with type 2 diabetes and elevated cardiovascular risk. Prescription of these agents by clinicians and their consistent use by patients are essential to realize their benefits.

ObjectiveTo assess the patterns of use and prescription fills of GLP-1RAs and SGLT-2i.

DesignCross-sectional for medication use and prospective for prescription fills in 2018-2020

SettingNationwide de-identified US administrative claims database of Medicare Advantage and commercially insured adults.

ParticipantsIndividuals 18 years of age and older with type 2 diabetes

ExposuresComorbidities representing guideline-directed indications of atherosclerotic cardiovascular disease (ASCVD) for GLP-1RAs, and ASCVD, heart failure, and diabetic nephropathy for SGLT2i.

Main Outcomes and MeasuresMedication use and monthly fill rates for 12 months following initiation of therapy by calculating the proportion of days with consistent medication use.

ResultsAmong 587,657 individuals with type 2 diabetes, 80,196 (13.6%) were prescribed GLP-1RAs and 68,149 (11.5%) SGLT2i during 2018-2020. This represented 12.9% and 10.5% of individuals with indications for each medication, respectively. Based on monthly counts of new prescriptions, there were no changes in the uptake of either drug class during 2019-2020. Among new initiators, fill rate was 52.5% for GLP-1RAs and 52.9% for SGLT2i one year after initiation. One-year fill rates were higher for patients with commercial insurance than those with Medicare Advantage plans for both GLP-1RAs (59.3% vs 51.0%, p-value<0.001) and SGLT2i (63.4% vs 50.3%, p-value<0.001). After adjusting for comorbidity profile, there were higher prescription fills for patients with commercial insurance (versus Medicare Advantage, OR 1.17, 95% CI [1.06-1.29] for GLP-1RAs, and 1.59 [1.42-1.77] for SGLT2i); and higher income (top quartile versus others, OR 1.09 [1.06-1.12] for GLP-1RAs, and 1.06 [1.03-1.10] for SGLT2i).

Conclusions and RelevanceIn 2018-2020, use of GLP-1RAs and SGLT2i remained limited to fewer than 1 in 8 individuals with type 2 diabetes meeting criteria for evidence-based guideline and professional society recommendations, with one-year fill rates around 50%. The low and inconsistent use of these medications compromises their longitudinal health outcomes benefits in a period of expanding indications for their use.

category: cardiovascular medicine


title: Multispecialty multidisciplinary input into comorbidities in heart failure reduces hospitalisation and clinic attendance

abstract:
AimsHeart failure (HF) is associated with multiple co-morbidities which independently influence response to treatment as well as outcomes. This retrospective observational study (January 2020-June 2021) analysed the impact of monthly virtual HF multi-specialty multi-disciplinary team (MDT) meetings to address the management of associated comorbidities and thereby upon provision, cost of care and HF outcomes.

MethodsPatients acted as their own controls, with outcomes compared for equal periods (for each patient) pre versus post-MDT meeting. The MDT comprised of HF cardiologists (primary, secondary, tertiary care), HF specialist nurses (hospital, community), nephrologist, endocrinologist, palliative care specialist, chest physician, pharmacist, clinical pharmacologist and geriatrician. Outcome measures were 1) all-cause hospitalisations, 2) outpatient clinic attendances, and 3) cost.

Results334 patients (mean age 72.5{+/-}11 years) were discussed virtually through MDT meetings and follow-up duration was 13.9 {+/-} 4 months. The mean age-adjusted Charlson Co-morbidity Index was 7.6 {+/-} 2.1 and Rockwood Frailty Score was 5.5 {+/-} 1.6. The mean number of clinic attendances prevented was 1.6 {+/-} 0.4. The total cost of funding monthly meetings for the duration of the study was {pound}32400 and the 64 clinic appointments generated cost {pound}9600. The MDT meetings prevented 534 clinic appointments (cost saving {pound}80,100) and reduced all-cause hospitalisations (pre-MDT meeting 1.1{+/-}0.4 vs. 0.6{+/-}0.1 post-MDT meeting; p<0.001), reduction of 1586 hospital bed-days and cost-savings of {pound}634,400. The total cost-saving to the healthcare system was {pound}672,500.

ConclusionThe HF multispecialty virtual MDT model provides integration of care across all tiers of healthcare for HF management and a holistic approach addressing associated co-morbidities. This approach can reduce the need for out-patient attendances and all-cause hospitalisations, leading to significant cost-savings.

Key questionsO_ST_ABSWhat is already known about this subject?C_ST_ABSHeart failure is associated with several co-morbid health conditions (multi-morbidity) which independently influence outcomes as well as response to treatment.

What does this study add?This study assesses the impact of multispecialty multi-morbidity input into the management of co-morbidities and thereby the effect upon all-cause outcomes.

How might this impact on clinical practice?Results of this study illustrate that multi-speciality management of comorbidities associated with heart failure, may not only improve all-cause outcomes but could also prove to be cost-beneficial.


title: An outbreak of SARS-CoV-2 in a public-facing office in England, 2021

abstract: Between August-September 2021, an outbreak of SARS-CoV-2, with an attack rate of 55% (22/40 workers), occurred in a public-facing office in England. To identify workplace and worker-related risk factors, a comprehensive investigation involving surface sampling, environmental assessment, molecular and serological testing, and worker questionnaires was performed in September - October 2021. The results affirm the utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

category: epidemiology


title: Protection by 4th dose of BNT162b2 against Omicron in Israel

abstract:
BACKGROUNDOn January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine (Pfizer-BioNTech) to people aged over 60 years and at-risk populations, who had received a third dose of vaccine at least 4 months earlier. The effect of the fourth dose on confirmed coronavirus 2019 disease (Covid-19) and severe illness are still unclear.

METHODSWe extracted data for the Omicron-dominated period January 15 through January 27, 2022, from the Israeli Ministry of Health database regarding 1,138,681 persons aged over 60 years and eligible for the fourth dose. We compared the rate of confirmed Covid-19 and severe illness between those who had received a fourth dose at least 12 days earlier, those who had received only three doses, and those 3 to 7 days after receiving the fourth dose. We used Poisson regression after adjusting for possible confounding factors.

RESULTSThe rate of confirmed infection was lower in people 12 or more days after their fourth dose than among those who received only three doses and those 3 to 7 days after vaccination by factors of 2.0 (95% confidence interval [CI], 2.0 to 2.1) and 1.9 (95% CI, 1.8 to 2.0), respectively. The rate of severe illness was lower by factors of 4.3 (95% CI, 2.4 to 7.6) and 4.0 (95% CI, 2.2 to 7.5).

CONCLUSIONSRates of confirmed Covid-19 and severe illness were lower following a fourth dose compared to only three doses.


title: COVID-19 contact tracing during first delta wave, Lebanon, 2021

abstract:
BackgroundOn the 11th March, the WHO has declared COVID-19 pandemic. Officially, the virus was introduced in Lebanon on the 21st February 2020. Since then, the national curve has drawn several waves. From July to September 2021, Lebanon has experienced the first delta wave. As part of the investigation, contact tracing was enhanced to limit virus transmission. The objective is to describe close tracing approach and profile of close contacts identified during the first delta wave.

MethodsCOVID-19 surveillance is integrated within the national communicable diseases surveillance. The case definitions are adopted from WHO guides. Laboratories report positive cases on daily basis to the Ministry of Public Health, on DHIS2 platform directly or indirectly via excel files importation. Once reported, case investigation is initiated. It includes contact tracing with: 1) identification of close contacts, 2) advice on quarantine and self-monitoring, 3) contact testing. Referral to field testing is made available free of charge for close contacts. Collected data is updated on DHIS2 platform. Later, data is cleaned and analyzed to generate the daily report including description of close contacts. The report is shared with decision makers, professionals, media and public.

ResultsFrom week 2021W27 to week 2021W40, 85490 cases were reported. Case investigation rate reached 78.8% of the cases were investigated within 24 hours. 66.5% of investigated cases shared lists of contacts, with 3.6 as average number of contacts per case.

We identified a total of 161805 close contacts, 95% were from family members, 71% were not vaccinated and 10 % had prior COVID-19 infection.

As for contact testing, 65% had RT-PCR test upon investigation, with 32% positive result. Furthermore, 19205 were referred and tested via field testing, with 25% positivity rate. Of all identified contacts, the reported positive tests reached 56,904 representing 35.2% of all contacts.

ConclusionDuring community transmission and mitigation strategy, contact tracing contributes to increase awareness to the contacts and importance to abide to quarantine measures and thus to slow down the virus circulation.

Current close contacts are characterized with new profile of prior infection, vaccination history and testing behavior. There is need to adapt the quarantine measures to close contacts based on their profile, and to ensure easy access to free testing.


title: Predicting animal to human translation: A proof of concept study using qualitative comparative analysis

abstract:
Drug development suffers from high attrition rates; promising drug candidates fail in clinical trials. Low animal-to-human translation may impact attrition. We previously summarised published translational success rates, which varied from 0% to 100%. Based on analyses of individual factors, we could not predict translational success.

Several approaches exist to analyse effects of combinations of potential predictors on an outcome. In biomedical research, regression analysis (RGA) is common. However, with RGA it is challenging to analyse multiple interactions and specific configurations ({approx} combinations) of variables, which could be highly relevant to translation.

Qualitative comparative analysis (QCA) is an approach based on set theory and Boolean algebra. It was successfully used to identify specific configurations of factors predicting an outcome in other fields. We reanalysed the data from our preceding review with a QCA. This QCA resulted in the following formula for successful translation:

O_FD O_INLINEFIG[Formula 1]C_INLINEFIGM_FD(1)C_FD

Which means that within the analysed dataset, the combination of relative recency ([~] means not; >1999), analyses at event or study level (not at intervention level), n<75, inclusion of more than one species and quantitative (instead of binary) analyses always resulted in successful translation (>85%). Other combinations of factors showed less consistent or negative results. An RGA on the same data did not identify any of the included variables as significant contributors.

While these data were not collected with the QCA in mind, they illustrate that the approach is viable and relevant for this research field. The QCA seems a highly promising approach to furthering our knowledge on animal-to-human translation and decreasing attrition rates in drug development.

category: pharmacology and therapeutics


title: Analysis of COVID-19 infection amongst healthcare workers in Rivers State, Nigeria

abstract:
Background/aimsHealthcare workers (HCWs) are at an increased risk of infection and mortality associated with the COVID-19 pandemic. This study determined the illness severity and mortality amongst COVID-19 infected healthcare workers.

MethodsThe current study was a retrospective cohort study using population-level data. Secondary analysis was conducted on collated data from the Public Health Emergency Operations Centre (PHEOC) at the State Ministry of Health. The cohort included all documented healthcare workers with confirmed COVID-19 infection (diagnosed by Polymerase Chain Reaction). Data were gathered from the COVID-19 patient database of the PHEOC, on demographics, place of work, illness severity and outcome. Descriptive statistics were reported on the cohort characteristics. Adjusted odds ratio was used to report the measure of association between illness severity and risk factors.

ResultsThe mean age was 43 years and 50.5% of the cohort were female. Of the 301 healthcare workers, 187 patients were symptomatic with 32 requiring hospitalisation. From the available data, seven infected HCWs died of their COVID-19 infection, resulting in a case fatality ratio of 2.3%. A subgroup analysis was conducted on the health professionals infected -doctors (71.7%), nurses (27.3%), others (1%). Symptomatic cases were more inclined to progress to severe illness. Predictors of mortality assessed included age, sex, case class and illness severity. The logistic regression model was statistically significant,{chi} 2(9) = 16.965,  = 0.049.

ConclusionFrontline healthcare workers are at an increased risk of exposure to COVID-19 infections. In Nigeria, there is a higher risk of experiencing a severe disease if symptomatic while infected with COVID-19. It is imperative that preventive strategies, proper education, and awareness are put in place to protect healthcare workers.

Summary BoxHealthcare workers as first responders, are vulnerable to workplace infections. It is manifest in the COVID-19 pandemic where deaths of healthcare workers resulted in further shortage of the already compromised human resource; consequently compromising effective healthcare delivery. As the pandemic progresses, studies have been conducted globally on this topic and scientific evidence continues to show higher mortality and disease severity of COVID-19. Nevertheless, it is important to understand the effect of COVID-19 on healthcare workers in Nigeria-a developing country.

This study highlights the illness severity and mortality associated with COVID-19 among the study population; its results presented a higher case fatality rate than both national and subnational rates. The results also further emphasises the need to protect healthcare workers; ensure they are knowledgable in both infection prevention and control, and that the healthcare space is safe against nosocomial infections

The study adds to the scientific evidence on the severity and mortality associated with COVID-19 in Nigeria. A national research is needed to extrapolate the findings from this study to the nation. Hence, expatiate on the global fight against coronaviruses such as COVID-19.

category: public and global health


title: Determining the Origins of Repeat Trichomonas vaginalis Infections Using Clinical Versus Genotype-Informed Criteria

abstract:
BackgroundHigh rates of repeat infections post-treatment are reported in women infected with Trichomonas vaginalis (TV). Determining the origin of repeat infections is generally limited to clinical queries of adherence to treatment and sexual exposure. The purpose of this study was to add micro-satellite (MS) genotype data to classification criteria for origin of repeat TV infection, and examine if the addition of TV genotype changes classification as treatment failure, re-infection, or new infection

MethodsWomen were enrolled at clinics in Birmingham, AL; Jackson, MS; and New Orleans, LA as part of a randomized clinical trial comparing single-dose (2 g) and multi-dose (500 mg twice daily x 7 days) metronidazole (MTZ) treatment regimens. Participants provided vaginal swabs and completed a behavioral audio-computer assisted self-interview (ACASI). TV specimens were genotyped at 11 microsatellite (MS) loci. Women with repeat TV infections at TOC, were classified as treatment failure, re-infection or new infections using behavioral and genotype data; classifications were compared.

ResultsData were available for 45 women. Genotype concordance was defined as <4 MS loci different and genotype discordance was defined as [≥] 4 MS loci different. Clinical criteria vs. genotype-informed criteria classifications were treatment failure (66.7% vs 64.4%) re-infection (26.7% vs. 17.8%) and new infections (6.7% vs. 17.8%) respectively; Bowkers test of symmetry had X2=16.00 p=0.0011, indicating differences in results.

ConclusionsThe majority of women, using either criteria, were classified as treatment failure. Clinical assessment may overestimate reinfections and underestimate new infections. Patient counseling should be adapted accordingly.

SummaryTo more precisely determine the origin of repeat Trichomonas vaginalis infection, we compared genotype microsatellite size polymorphism data to clinical criteria and found that clinical data overestimated reinfection and underestimated new infections. Patient counselling should consider new partners.

category: sexual and reproductive health


title: Using the app '' Injurymap (C) '' to provide exercise rehabilitation for people with acute lateral ankle sprains seen at the Hospital Emergency Department: a mixed-method pilot study

abstract:
BackgroundAcute lateral ankle sprains (LAS) account for 4-5% of all Emergency Department (ED) visits. Few patients receive the recommended care of exercise rehabilitation. A simple solution is an exercise app for mobile devices, which can deliver tailored and real-time adaptive exercise programs.

PurposeThe purpose of this pilot study was to investigate the use and preliminary effect of an app-based exercise program in patients with LAS seen in the Emergency Department at a public hospital.

Materials and methodsWe used an app that delivers evidence-based exercise rehabilitation for LAS using machine-based learning. Participants were recruited from the ED and followed for four months. Data on app-use and preliminary effect were collected continuously through the exercise app and weekly text-messages. Baseline and follow-up data were collected though an online questionnaire. Semi-structured interviews were performed after participants stopped using the app.

ResultsHealth care professionals provided 485 patients with study information and exercise equipment. Of those, 60 participants chose to enroll in the study and 43 became active users. The active users completed a median of 7 exercise sessions. Most of the active users were very satisfied or satisfied (79%-93%) with the app and 95.7% would recommend it to others. The interviews showed that ankle sprains were considered an innocuous injury that would recover by itself. Several app users expressed they felt insufficiently informed from the ED health care professionals. Only 39% felt recovered when they stopped exercising, and 33% experienced a recurrent sprain in the study period.

ConclusionIn this study, only few patients with LAS became active app users after receiving information in the ED about a free app-based rehabilitation program. We speculate the reason for this could be the perception that LAS is an innocuous injury. Most of the patients starting training were satisfied with the app, although few completed enough exercise sessions to realistically impact clinical recovery. Interestingly more than half of the participants did not feel fully recovered when they stopped exercising and one third experienced a recurrent sprain.

Trial-identifiershttps://clinicaltrials.gov/ct2/show/NCT03550274, preprint (open access): doi/xxx.

category: sports medicine


title: Extension of Community Healthcare Outcomes in Parkinson Disease (Parkinson ECHO): A Feasibility Study

abstract: Parkinsons disease is the second most common neurodegenerative disorder and presents with a heterogeneous group of symptoms. Managing these symptoms requires coordinated care from a neurology specialist and a primary care provider. Access to neurology care is limited for those patients with Parkinsons disease who reside in rural areas given financial and mobility constraints along with the rarity of specialty providers. To close this gap, we developed and implemented a telehealth-based Project ECHO(R) (Extension for Community Healthcare Outcomes) program, "Parkinson ECHO," to provide education and support for rural clinicians and allied health members. We assessed the feasibility of this tele-mentoring educational offering and the effect it had on clinician confidence in diagnosing and treating Parkinsons disease. Participants from across Oregon (n=33), of whom 70% served rural and/or medically underserved communities, attended the biweekly sessions. The sessions focused on a topic within Parkinsons disease diagnosis or management followed by case discussions. We assessed clinician confidence and acceptability using surveys before and after their participation in the program. The COVID-19 pandemic was an unexpected obstacle in executing this project, delaying the program by several months and likely accounting for a lower number of attendees for the last two sessions. Nevertheless, we found Parkinson ECHO did significantly increase participant confidence levels in diagnosing and managing Parkinsons disease.

category: medical education


title: Blood transcriptomes of SARS-CoV-2 infected kidney transplant recipients demonstrate immune insufficiency

abstract:
BackgroundKidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.{square}

MethodsClinical data were collected by chart review. PAXgene blood RNA was poly-A selected and RNA sequencing was performed to evaluate transcriptome changes.

ResultsA total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis) and 33 post-acute cases (>4 weeks). In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of T-cell and adaptive immune-activation pathways proportional to severity score. This finding was independent of lymphocyte count and despite reduction in immunosuppression (IS) in most KTRs. Comparison with post-acute cases showed "normalization" of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity score and lymphocyte count. DEGs associated with worsening disease severity in a non-KTR cohort with COVID-19 (GSE152418) showed significant overlap with KTRs in these identified enriched pathways.

ConclusionBlood transcriptome of KTRs affected by COVID-19 shows decrease in T-cell and adaptive immune activation pathways during acute disease that associate with severity despite IS reduction and show recovery after acute illness.

Significance statementKidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of maintenance immunosuppression is pursued. Surprisingly, reported rates of acute rejection have been low despite reduced immunosuppression. We evaluated the peripheral blood transcriptome of 64 KTRs either during or after acute COVID-19. We identified transcriptomic signatures consistent with suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease, even after adjustment for lymphocyte number. Our transcriptomic findings of immune-insufficiency during acute COVID-19 provide an explanation for the low rates of acute rejection in KTRs despite reduced immunosuppression. Our data support the approach of temporarily reducing T -cell-directed immunosuppression in KTRs with acute COVID-19.

category: nephrology


title: Monitoring tubular epithelial cell damage in AKI via urine flow cytometry

abstract:
IntroductionAcute kidney injury (AKI) is associated with significant morbidity and mortality. The diagnosis is currently based on urine output and serum creatinine and there is a lack of biomarkers that directly reflect tubular damage. Here, we establish flow cytometric quantification of renal epithelial cells as a potential biomarker for quantifying the severity of tubular kidney damage and for predicting AKI outcome.

MethodsA total of 84 patients with AKI were included in this study, divided into an exploratory cohort (n=21) and confirmatory cohort (n=63), as well as 25 controls. Urine of patients was collected and processed within 72 hours after AKI onset. Different urinary tubular epithelial cell (TEC) populations were identified and quantified by flow cytometry (FACS). Urinary cell counts were analyzed regarding AKI severity defined by KDIGO stage as well as renal recovery, length of hospital stay and occurrence of MAKE-30 events.

ResultsUrinary TEC counts correlated with stages of AKI based on KDIGO classification and were significantly enriched in patients with AKI compared to healthy donors and inpatient controls in both cohorts. Furthermore, both proximal and distal TEC (pTEC, dTEC) counts performed well in identification of patients with AKI regardless of stage. Urinary amounts of pTEC and dTEC showed a strong correlation, with predominance of dTEC. Higher numbers of TEC were associated with extended length of hospital stay, while elevated pTEC counts were associated with the occurrence of MAKE-30 events. Follow-up measurements showed decreasing amounts of urinary TEC after AKI recovery over several days.

ConclusionThe amount of urinary TEC directly reflects severity of tissue damage in human AKI. Our protocol furthermore provides a basis for a deeper phenotypic analysis of urinary TEC populations.


title: Number of plasma exchanges and outcome in myasthenic crisis

abstract:
BackgroundPlasma exchange is an effective therapy for myasthenic crisis (MC); yet the number of exchanges needed is unknown. We set out to examine the relationship between the number of plasma exchanges and clinical outcome in patients experiencing MC.

MethodsWe retrospectively reviewed patient episodes with ICD 9 and ICD 10 codes for myasthenia gravis and myasthenia gravis exacerbation/crisis in patients admitted to a single center tertiary care referral center from July 2008 to July 2017. These episodes were screened for patients with impending myasthenia gravis crisis and manifest crisis who received plasmapheresis during their hospital course. We performed statistical analyses to determine if increased number of plasma exchanges improves the primary outcome (hospital length of stay), as well as the secondary outcome (disposition to home, skilled nursing facility, long term acute care hospital, or death).

ResultsThere is neither clinically observable nor statistically significant improvement in length of stay or disposition on discharge in patients who received six or greater sessions of plasmapheresis.

ConclusionsThis study provides class IV evidence that extending the number of plasma exchanges beyond five does not correlate with decreased hospital length of stay or improved discharge disposition in patients experiencing myasthenic crisis.


title: The benefits and harms of adjuvant chemotherapy for non-small cell lung cancer in patients with major comorbidities: A simulation study

abstract:
BackgroundRandomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of stage IB-IIIA non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however.

MethodsWe used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in stage IB-IIIA NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases.

ResultsAdjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with stage IB cancers. For patients with CHF and stage IB disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for stages II-IIIA for younger patients with CHF. In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts.

ConclusionsOlder, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.


title: High-Throughput Clinical Trial Emulation with Real World Data and Machine Learning: A Case Study of Drug Repurposing for Alzheimer's Disease

abstract: Clinical trial emulation, which is the process of mimicking targeted randomized controlled trials (RCT) with real-world data (RWD), has attracted growing attention and interest in recent years from the pharmaceutical industry. Different from RCTs which have stringent eligibility criteria for recruiting participants, RWD are more representative of real-world patients to whom the drugs will be prescribed. One technical challenge for trial emulation is how to conduct effective confounding control with complex RWD so that the treatment effects can be objectively derived. Recently many approaches, including deep learning algorithms, have been proposed for this goal, but there is still no systematic evaluation and practical guidance on them. In this paper, we emulate 430, 000 trials from two large-scale RWD warehouses, covering both electronic health records (EHR) and general claims, over 170 million patients spanning more than 10 years, aiming to identify new indications of approved drugs for Alzheimers disease (AD). We have investigated the behaviors of multiple different approaches including logistic regression and deep learning models, and propose a new model selection strategy that can significantly improve the performance of confounding balance of the participants in different arms of emulated trials. We demonstrate that regularized logistic regression-based propensity score (PS) model outperforms the deep learning-based PS model and others, which contradicts with our intuitions to a certain extent. Finally, we identified 8 drugs whose original indications are not AD (pantoprazole, gabapentin, acetaminophen, atorvastatin, albuterol, fluticasone, amoxicillin, and omeprazole), hold great potential of being beneficial to AD patients.

category: health informatics


title: Comparison of BinaxNOW TM and SARS-CoV-2 qRT-PCR detection of the Omicron Variant from Matched Anterior Nares Swabs

abstract: The COVID-19 pandemic has increased the use of rapid antigen tests such as the Abbott BinaxNOW COVID-19 Antigen Self-Test. In winter of 2021-2022, the omicron variant surge made it quickly apparent that although rapid diagnostic tests (RDTs) are less sensitive than qRT-PCR, the accessibility, ease of use, and rapid read-outs of RDTs made them a sought after and often sold-out item at local suppliers. Here, we sought to qualify the BinaxNOW test for use in our university testing program as a method to rule-in positive or rule-out negative individuals quickly when they seek care at our priority qRT-PCR testing site. To perform this qualification study, we collected matched additional swabs from individuals attending this test site for standard of care qRT-PCR testing. All matched swabs were tested using the BinaxNOW RDT. Initially as part of a feasibility study, test period 1 (n=110) samples were put in cold storage prior to testing. In follow-on test period (n=209), we tested samples real-time at the test facility. Combined, 102 of 319 samples tested positive for SARS-CoV-2. All samples for which genome sequence could be collected were omicron (n=92). We observed a calculated sensitivity of 53.9%, specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 82.2% for the BinaxNOW tests (n=319). Sensitivity improved (75.3%) by changing the qRT-PCR positivity threshold from a CT of 40 to a CT of 30. The ROC curve shows that for qRT-PCR positive CT values between 24-40, the BinaxNOW test is of limited value diagnostically. Our results suggest that RDT tests could be used in our setting to confirm SARS-CoV-2 infection in individuals with substantial viral load, but that a significant fraction of infected individuals would be missed if we used RDT tests exclusively to rule out infection.


title: Ethiopian Healthcare Workers' Experiences During the COVID-19 Pandemic

abstract:
BackgroundThe COVID-19 pandemic has caused widespread health and socioeconomic disruptions around the world. Understanding the impact that this crisis has had on health workers and the delivery of routine health care services within countries provides evidence on pandemic preparedness and response. Here, we conduct an investigation into these factors for the Ethiopian context.

Methods and findingsWe conducted an online cross-sectional survey with Ethiopian health care professionals between August 27 and October 10, 2020 via existing research networks. The variables of interest were confidence in COVID-19 related knowledge, training and experience, the adoption of precautionary health practices, risk perceptions, and respondent concerns. The majority of surveyed health care professionals in Ethiopia reported seeing fewer patients than usual during the COVID-19 crisis, gaps in pandemic training, inadequate access to personal protective equipment (PPE) and barriers to accessing COVID-19 testing. Most health care professionals were also deeply concerned and worried about their own COVID-19 risks and the likelihood that they would transmit the disease to others.

ConclusionsOur study findings point to a possible reduction in routine health care services during the COVID-19 pandemic and gaps in pandemic preparedness in Ethiopia. The ministry of health and other stakeholders should work towards improving access to PPE and testing, and identify approaches to ensure that essential healthcare provision (such as immunizations) is not disrupted during crises akin to the COVID-19 outbreak.


title: Deep learning-based approach for detecting signs of atrial septal defect on chest radiographs: a proof of concept study

abstract: Many patients with atrial septal defects (ASD) are asymptomatic and undiagnosed during the first few decades of life, but have overt heart failure, arrhythmias, cerebral infarction, and increased mortality in adults with advancing age. To provide a non-invasive, easy-to-use, and effective method for detecting ASD, we aimed to develop and validate a deep learning-based algorithm to diagnose ASD on chest radiographs. The ASD dataset was created from 173 chest radiographs of 74 patients with ASD and 170 chest radiographs of 100 patients without ASD. Convolutional neural network models (VGG16, ResNet50, DenseNet121, and Xception) for diagnosing ASD were pretrained using two different datasets, the large-scale real-world ImageNet dataset and the ChestX-ray14 dataset released by National Institutes of Health, followed by a round of training using the training set of the ASD dataset. Model performance was evaluated by five-fold stratified cross-validation. The best performance in ImageNet pretraining was achieved by ResNet50 model, and the cross-validation area under the curve (AUC) was 0.95, with sensitivity of 0.86, specificity of 0.87, and overall accuracy of 0.87. The best performance in ChestX-ray pretraining was achieved by Xception, and the cross-validation AUC was 0.93, with sensitivity of 0.85, specificity of 0.85, and overall accuracy of 0.85. The diagnostic performances of these models were comparable to those of cardiologists. Gradient-weighted Class Activation Mapping showed that the ImageNet-pretrained model focused on bilateral hilar regions, while the ChestX-ray14-pretrained model focused on areas around cardiac silhouette and lower lung fields. Our deep learning-based algorithms made a diagnosis of ASD on the input chest radiographs with high accuracy, and had potential to help clinicians make accurate diagnosis of ASD from routine chest radiography, leading to improvement of prognosis and quality of life in patients with ASD.


title: Principles and test methods of non-contact body thermometry

abstract:
SignificanceFar infrared (IR) has a long history in thermometry and febrile screening. Concerns have been raised recently over the accuracy of non-contact body thermometry. Clinical testing with febrile individuals constitutes the standard performance assessment. This is challenging to replicate, which may have inadvertently allowed approval of IR systems that are unable to detect fevers. The ability to test performance without relying on febrile participants would have ramifications for public health, especially if this discovered undisclosed differences in accuracy in widely used devices.

AimTo identify foundational issues in, demonstrate principles of, and develop test methods for non-contact body thermometry.

ApproachWe review foundational literature and identify confounds impeding performance of IR thermography (IRT) and non-contact IR thermometry (NCIT) for febrile screening and demonstrate corrections for their effects, which would otherwise be unacceptable. Almost none of the devices we are aware of compensate for these confounds. We reverse-engineer surface-to-body temperature relations for several FDA-cleared NCITs. We note their similarity to recently reported bias-to-normal behavior in other devices and determine range of body temperatures for which the device would produce a "normal" (non-febrile) output. Finally, we generate predictable elevated face temperatures in healthy subjects and demonstrate this in several devices.

ResultsThe surface-to-body relationships for two IRT and one NCIT were linear, while all others exhibited nonlinear bias-to-normal behavior that produce normal temperatures when presented with surface temperatures ranging from hypothermia to moderate-to-severe fever. The test method was used in healthy, non-febrile subjects to generate elevated temperatures corresponding to body temperatures from 97.35F to 102.45F. Three out of five systems had negligible sensitivity.

ConclusionsThis demonstrates an alternative evaluation method without the limitations and risks of febrile patients. These results indicate many devices may be unusable for body thermometry and may be providing a false sense of security for public health surveillance.


title: Environmental pollutants and essential elements as regulators of miR-30b, miR-223 and Let-7a microRNAs expression in maternal sera from the NEHO cohort

abstract:
BackgroundBirth cohorts of women living in highly industrialized areas provide an ideal setting for studying the correlation between environmental exposure and health.

ObjectivesTo evaluate serum microRNA expression in response to environmental contaminants in 68 healthy pregnant women from the NEHO birth cohort.

MethodsSerum contaminants were determined by GC-MS/MS and ICP-MS/MS. Serum microRNA expression was determined by qPCR. Associations between miRNA {Delta}CTs and single serum element levels were tested by linear regression models, while whole mixture effect was studied by WQS regression analysis.

ResultsIn separate regression models, a positive association was found between miR-223 {Delta}CT and concentrations of Se and Zn, while a negative association between miR-30b and Hg levels was observed. Similar regression models were also conducted using tertiles of each chemical as independent variables. In this setting, the Let-7a {Delta}CT was decreased in the comparison between medium and low tertiles of Se. The highest tertiles of Zn and p,p-DDE showed a significant association with increasing levels of miR-223 {Delta}CT with respect to the lower tertile; moreover, miR-30b {Delta}CT was reduced in the comparison between high and low tertiles of Hg. The observed data were confirmed by fold-change analysis. A WQS analysis built on tertiles of contaminant distribution revealed a significant mixture effect on the expression of the analyzed miRNAs. The inverse association between Let-7a {Delta}CT and the WQS index was dominated by Zn, Se, Cu, Hg and HCB. Moreover, miR-223 {Delta}CT was positively associated with the WQS index, where p,p-DDE, Zn and Se showed the greatest contributions to the association. Conversely, the reduction of miR-30b {Delta}CT was mainly driven by Hg and Se.

DiscussionThis study allowed us to characterize the role of prolonged exposure to environmental contaminants influencing the expression of circulating miRNAs in the serum of women in the last trimester of pregnancy.


title: Blood Gene Expression Risk Profiles and Interstitial Lung Abnormalities: COPDGene and ECLIPSE cohort studies

abstract:
RationaleInterstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown.

ObjectivesTo evaluate if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality.

MethodsIn COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE.

Measurements and Main ResultsIn 1,469 COPDGene (training n=734; testing n=735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2-1.6]) and mortality (HR 1.25 [95% CI: 1.12-1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated).

ConclusionsAn ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.

Key messagesO_ST_ABSWhat is the key questionC_ST_ABSInterstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Do blood gene expression profiles that predict IPF mortality also associate with ILA?

What is the bottom lineAn ILA gene expression score, derived from IPF mortality-associated genes, was associated with ILA and all-cause mortality. This score identified genes with concordant and discordant effects on IPF mortality and ILA. Our results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.

Why read onOur results lend insight into how gene expression profiles and biological pathways associated with IPF prognosis relate to ILA and all-cause mortality

category: respiratory medicine


title: Phospholipase D3 contributes to Alzheimer's disease risk via disruption of Aβ clearance and microglia response to amyloid plaques

abstract: Alzheimers disease (AD) is characterized by the accumulation of amyloid-{beta} (A{beta}) plaques and neurofibrillary tangles in the brain. AD is also the result of complex genetic architecture that can be leveraged to understand pathways central to disease processes. We have previously identified coding variants in the phospholipase D3 (PLD3) gene that double the late-onset AD risk. However, the mechanism by which PLD3 impacts AD risk is unknown. One AD risk variant, PLD3 p.A442A, disrupts a splicing enhancer-binding site and reduces PLD3 splicing in human brains. Using differentiated induced pluripotent stem cells from a PLD3 p.A442A carrier and CRISPR-reverted, isogenic control, we show that PLD3 p.A442A cortical neurons exhibit a PLD3 splicing defect and a significant increase in A{beta}42 and A{beta}40, both of which are corrected upon reversion of the risk allele in isogenic control neurons. Thus, PLD3 p.A442A is sufficient to alter PLD3 splicing and A{beta} metabolism. While the normal function of PLD3 is poorly understood, PLD3 is highly expressed in neurons and brain regions most susceptible to amyloid pathology. PLD3 expression is significantly lower in AD brains than controls, suggesting that PLD3 may play a role in sporadic AD. Thus, we sought to determine whether PLD3 contributes to A{beta} accumulation in AD. In a mouse model of amyloid accumulation, loss of Pld3 increases interstitial fluid (ISF) A{beta} and reduces A{beta} turnover. AAV-mediated overexpression of PLD3 in the hippocampus decreased ISF A{beta} levels and accelerated A{beta} turnover. To determine whether PLD3-mediated reduction of ISF A{beta} impacts amyloid accumulation, we measured amyloid plaque abundance and size after significant A{beta} deposition. We found that in the absence of Pld3, amyloid plaques were less compact and more diffuse. Additionally, we observed reduced recruitment of microglia to amyloid plaques in the absence of Pld3. PLD3 may impact amyloid accumulation and AD risk through disrupted microglia function as PLD3 is enriched in disease associated microglia in human brains. Together, our findings demonstrate that PLD3 regulates A{beta} clearance through cell-autonomous and non-cell-autonomous pathways in a manner that likely contributes to AD risk.


title: Behavioural Activation for Social IsoLation (BASIL+) trial (Behavioural activation to mitigate depression and loneliness among older people with long-term conditions): Protocol for a fully-powered pragmatic randomised controlled trial

abstract:
IntroductionDepression is a leading mental health problem worldwide. People with long-term conditions are at increased risk of experiencing depression. The COVID-19 pandemic led to strict social restrictions being imposed across the UK population. Social isolation can have negative consequences on the physical and mental wellbeing of older adults. In the Behavioural Activation in Social IsoLation (BASIL+) trial we will test whether a brief psychological intervention (based on Behavioural Activation), delivered remotely, can mitigate depression and loneliness in older adults with long-term conditions during isolation.

MethodsWe will conduct a two-arm, parallel-group, randomised controlled trial across several research sites, to evaluate the clinical and cost-effectiveness of the BASIL+ intervention. Participants will be recruited via participating general practices across England and Wales. Participants must be aged [≥]65 with two or more long-term conditions, or a condition that may indicate they are within a  clinically extremely vulnerable group in relation to COVID-19, and have scored [≥]5 on the Patient Health Questionnaire (PHQ9), to be eligible for inclusion. Randomisation will be 1:1, stratified by research site. Intervention participants will receive up to eight intervention sessions delivered remotely by trained BASIL+ Support Workers and supported by a self-help booklet. Control participants will receive usual care, with additional signposting to reputable sources of self-help and information, including advice on keeping mentally and physically well.

A qualitative process evaluation will also be undertaken to explore the acceptability of the BASIL+ intervention, as well as barriers and enablers to integrating the intervention into participants existing health and care support, and the impact of the intervention on participants mood and general wellbeing in the context of the COVID-19 restrictions. Semi-structured interviews will be conducted with intervention participants, participants caregivers/supportive others and BASIL+ Support Workers.

Outcome data will be collected at one, three, and 12 months post-randomisation. Clinical and cost-effectiveness will be evaluated. The primary outcome is depressive symptoms at the three-month follow up, measured by the PHQ9. Secondary outcomes include loneliness, social isolation, anxiety, quality of life, and a bespoke health services use questionnaire.

DiscussionThis study is the first large-scale trial evaluating a brief Behavioural Activation intervention in this population, and builds upon the results of a successful external pilot trial.

Trial RegistrationClinicalTrials.Gov identifier ISRCTN63034289, registered on 5th February 2021.

FundingThis study was funded by National Institute for Health Research (NIHR) Programme Grants for Applied Research (PGfAR) RP-PG-0217-20006

category: psychiatry and clinical psychology


title: Partnering with Athletes to Assess Risk of COVID-Related Myocarditis

abstract:
BackgroundMyocarditis in athletes is a feared complication of SARS-CoV-2, yet guidelines for screening with cardiac magnetic resonance imaging are lacking. Further, stakeholder involvement in the research is rare.

HypothesisWe sought to determine the rates of cardiac magnetic resonance imaging evidence of SARS-CoV-2 related myocarditis in student athletes. We hypothesized that rates of myocarditis were lower than initially reported and that including athletes on the research team would enhance participant satisfaction and scientific integrity.

MethodsAccordingly, when members of a hockey team were infected with SARS-CoV-2, we invited them and their team physicians to be part of the design of a study assessing the incidence of myocarditis. We performed cardiac magnetic resonance imaging on participating hockey players infected with SARS-CoV-2 and compared them to a healthy lacrosse cohort. Participants were given an optional survey to complete at the end of the study to assess their satisfaction with it.

ResultsFour hockey players and two team physicians joined the study team; eight hockey players and four lacrosse players participated in the study. Zero athletes met imaging criteria for myocarditis; delayed enhancement was observed in seven cases and three controls. Athletes supported sharing the findings with the participants. No athletes reported feeling uncomfortable participating, knowing other athletes participated on the research team.

ConclusionRates of SARS-CoV-2 myocarditis in young athletes appears to be lower than initially reported. Partnered research is important, especially in populations with more to lose, such as collegiate athletes; future studies should include stakeholders in the study design and execution.

Key pointsCardiac MRI findings of myocarditis after COVID infection in young athletes is rare. Subjects of research studies appreciate involvement in the development of the study, and this also builds trust with the research team.


title: Three decades of hospital evacuations in the Netherlands: a scoping review

abstract:
BackgroundHospitals are expected to provide their essential services under all circumstances, including disasters and crisis situations. However, crises and disasters may disrupt essential hospital functions, and necessitate evacuation of the facility. Data on the prevalence and causes of hospital evacuations is limited, whilst realistic evacuation planning will make hospitals more resilient during future crises and disasters. The aim of this study was to develop a systematic understanding of hospital evacuation frequency, causes and characteristics in the Netherlands.

MethodsA systematic scoping review of news articles retrieved from the LexisNexis database, Google, Google News, PubMed and EMBASE between 1990 and 2020. All articles mentioning a hospital evacuation in the Netherlands were analyzed.

ResultsA total of 67 hospital evacuations were identified in a 30-year time period. The most common primary incidents were internal fire (33%), technological failure (21%) and hazardous materials (12%). Cascading events transpired in 37% of all events. As a result, internal fire (34%), internal power failure (19%) and hazardous materials (16%) were the most important reasons to evacuate a medical facility. The number of evacuees ranged from 1 to 339 patients (median 10.5, interquartile range 36), and there were 13 (19%) complete hospital evacuations. The frequency of hospital evacuations increased over time, with a more diverse etiology during later years.

ConclusionsHospital evacuations do occur, and hospitals are vulnerable to both internal and external hazards. Internal fire, internal power failure, hazardous materials and flooding incidents were the most important reasons to (partly) evacuate a hospital. Our findings suggest that facility-specific evacuation guidelines are necessary, and that evacuation preparedness will benefit if the most relevant evacuation scenarios are planned and practiced.

category: emergency medicine


title: The Nicaraguan Pediatric Influenza Cohort Study, 2011-2019: influenza incidence, seasonality, and transmission

abstract:
BackgroundChildren account for a large portion of global influenza burden and transmission, and a better understanding of influenza in children is needed to improve prevention and control strategies.

MethodsTo examine the incidence and transmission of influenza we conducted a prospective community-based study of children aged 0-14 years in Managua, Nicaragua between 2011 and 2019. Participants were provided with medical care through study physicians and symptomatic influenza was confirmed by RT-PCR. Wavelet analyses were used to examine seasonality. Generalized growth models (GGMs) were used to estimate effective reproduction numbers.

ResultsFrom 2011-2019, 3,016 children participated, with an average of [~]1,800 participants per year and median follow-up time of 5 years per child, and 48.3% of the cohort in 2019 had been enrolled their entire lives. The overall incidence rates per 100 person-years were 14.5 symptomatic influenza cases (95%CI: 13.9-15.1) and 1.0 influenza-associated ALRI case (95%CI: 0.8-1.1). Symptomatic influenza incidence peaked at age 9-11 months. Infants born during peak influenza circulation had lower incidence in the first year of their lives. The mean effective reproduction number was 1.2 (range 1.02-1.49), and we observed significant annual patterns for influenza and influenza A, and a 2.5-year period for influenza B.

ConclusionsThis study provides important information for understanding influenza epidemiology and informing influenza vaccine policy. These results will aid in informing strategies to reduce the burden of influenza.

SummaryIn this long-running influenza cohort, we found a substantial incidence of RT-PCR-confirmed influenza, and report by subtype/lineage. Infants born during influenza epidemics were protected from infection that first year. The mean effective reproduction number across years was 1.2.


title: Detection of prevalent SARS-CoV-2 variant lineages in wastewater and clinical sequences from cities in Quebec, Canada

abstract: Wastewater-based epidemiology has emerged as a promising tool to monitor pathogens in a population, particularly when clinical diagnostic capacities become overwhelmed. During the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), several jurisdictions have tracked viral concentrations in wastewater to inform public health authorities. While some studies have also sequenced SARS-CoV-2 genomes from wastewater, there have been relatively few direct comparisons between viral genetic diversity in wastewater and matched clinical samples from the same region and time period. Here we report sequencing and inference of SARS-CoV-2 mutations and variant lineages (including variants of concern) in 936 wastewater samples and thousands of matched clinical sequences collected between March 2020 and July 2021 in the cities of Montreal, Quebec City, and Laval, representing almost half the population of the Canadian province of Quebec. We benchmarked our sequencing and variant-calling methods on known viral genome sequences to establish thresholds for inferring variants in wastewater with confidence. We found that variant frequency estimates in wastewater and clinical samples are correlated over time in each city, with similar dates of first detection. Across all variant lineages, wastewater detection is more concordant with targeted outbreak sequencing than with semi-random clinical swab sampling. Most variants were first observed in clinical and outbreak data due to higher sequencing rate. However, wastewater sequencing is highly efficient, detecting more variants for a given sampling effort. This shows the potential for wastewater sequencing to provide useful public health data, especially at places or times when sufficient clinical sampling is infrequent or infeasible.


title: Coagulation abnormalities in children with uncorrected congenital heart defects seen at a teaching hospital in a developing country

abstract:
BackgroundCoagulation abnormality is a significant complication and cause of mortality in children with uncorrected congenital heart defects (CHD). The aim of this study was to determine the prevalence of coagulation abnormalities and the associated factors in children with uncorrected CHD.

MethodA cross sectional study conducted to determine the prevalence of coagulation abnormalities among 70 children with uncorrected CHD aged six months to 17 years and 70 age and sex matched apparently healthy controls. Coagulation abnormality was determined using complete blood count, prothrombin time, activated partial thromboplastin time and D-dimer assay.

ResultsThe prevalence of coagulation abnormalities among children with CHD and controls was 37.1% and 7.1% respectively. Children with Cyanotic CHD had a significantly higher prevalence of coagulation abnormalities compared to children with Acyanotic CHD (57.1% versus 17.1%). Haematocrit and oxygen saturation levels were significantly associated with coagulation abnormalities.

ConclusionThis study affirms that coagulation abnormality is high in children with uncorrected CHD. Oxygen saturation and haematocrit are factors of coagulation abnormalities. Routine coagulation screening is recommended especially in children with cyanotic congenital heart defects to improve their quality of life and reduce morbidity and mortality while awaiting definitive surgeries.

category: pediatrics


title: Robotic-Assisted Gait for lower-limb Rehabilitation: Evidence of Altered Neural Mechanisms in Stroke

abstract: Robotic-Assisted Gait training (RAGT) offers an innovative therapeutic option for restoration of functional gait in stroke survivors, complementing existing physical rehabilitation strategies. However, there is a limited understanding of the neurophysiological response induced by this training in end-users. Neural desynchronization and Cortico-Muscular Coherence (CMC) are two biomarkers that define the level of muscle-cortex association during gait phases and can be used to estimate induced users adaptation during RAGT. In this study, we measure Event-Related Spectral Perturbation (ERSP) and CMC from three healthy individuals and three stroke survivors during overground-gait with and without an exoskeleton. Results show that (1) the use of the exoskeleton in healthy individuals is associated with a different and more refined motor-control represented in a high{theta} -desynchronization, (2) altered and noisy ERSP and lower and non-focal {beta}-CMC patterns are observed in Stroke patients when performing overground-gait both with and without the Exoskeleton, and (3) Exoskeleton use in stroke survivors is associated with a reduction in swing-time during gait-cycle, but this effect is not correlated with an increment of{theta} -desynchronization and/or {beta}-CMC. ERSP and CMC demonstrated evidence of neural modulation in able-bodied users during RAGT, which could not be detected in subacute stroke survivors during RAGT. These results suggest that the gait-parameters changes observed during exoskeleton use in subacute stroke survivors are unlikely to be neurally driven.

category: rehabilitation medicine and physical therapy


title: Noninvasive Epileptogenic Signal Direction Determination by Effective Connectivity of Resting State Functional MRI - Independent of EEG

abstract:
The goal of this study was to determine resting state fMRI effective connectivity (RSEC) capacity, agnostic of epileptogenic events, in distinguishing seizure onset zones (SOZ) from propagation zones (pZ). Consecutive patients (2.1-18.2 years old), with epilepsy and hypothalamic hamartoma, pre-operative rs-fMRI-directed surgery, post-operative imaging, and Engel class I outcomes were collected. Cross-spectral dynamic causal modelling (DCM) was used to estimate RSEC between the ablated rs-fMRI-SOZ to its region of highest connectivity outside the HH, defined as the propagation zone (pZ). RSEC between the SOZ and PZ was characterized as positive (excitatory), negative (inhibitory), or null. It was hypothesized that connectivity from the SOZ would be excitatory and connectivity from the pZ would be inhibitory. Sensitivity, accuracy, positive predictive value were determined for node-to-node connections. A Parametric Empirical Bayes (PEB) group analysis was performed to identify effects of Engel class outcome and age. RSEC strength was also evaluated for correlation with percent seizure frequency improvement, sex, and region of interest size. Of the SOZs RSEC, only 3.6% had no connection of significance to the pZ when patient models were individually reduced. Among remaining, 96% were in expected (excitatory signal found from SOZ[->]pZ and inhibitory signal found from pZ[->]SOZ) versus 3.6% reversed polarities. Both polarity signals were equivalently as expected, with one false signal direction out of 26 each (3.7% total). Sensitivity of 96%, accuracy of 93%, and positive predictive value of 96% in identifying and differentiating the SOZ and pZ. Groupwise PEB analysis confirmed SOZ[->]pZ EC was excitatory, and pZ[->]SOZ EC was inhibitory. Patients with better outcomes (Engel Ia vs. Ib) showed stronger inhibitory signal (pZ[->]SOZ). Age was negatively associated with absolute RSEC bidirectionally, but had no relationship with Directionality SOZ identification performance. This study demonstrates the accuracy of Directionality to identify the origin of excitatory and inhibitory signal between the surgically confirmed SOZ and the region of hypothesized propagation zone in children with DRE due to a HH. Thus, this method validation study in a homogenous DRE population may have potential in narrowing the SOZ-candidates for epileptogenicity in other DRE populations and utility in other neurological disorders.

HighlightsO_LIDirectional rs-fMRI connectivity identifies seizure onset zone independent of EEG
C_LIO_LISignal from seizure onset zone to propagation zone is excitatory
C_LIO_LISignal from propagation zone to seizure onset zone is inhibitory
C_LIO_LIGreater inhibition from propagation zone is associated with better surgical outcome
C_LI

category: neurology


title: Early colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative data

abstract:
BackgroundColorectal cancer (CRC) is the third most common type of cancer in Scotland and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. Linked administrative datasets can provide a real-world representation of current care as a basis for evaluation of new interventions or policies and to understand variation in care and outcomes. In this study, we aim to provide up to date, population level evidence on CRC treatment and survival in Scotland for patients treated with curative or palliative intent as a basis for the understanding of variation, and to provide data to underpin the evaluation of new treatments.

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

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

ConclusionsNational linked administrative datasets have the ability to provide real-world representation of the treatments and outcomes for patients with cancer. In a Scottish population of curative patients with CRC, there was significant variation in survival depending on sex and geography.

category: oncology


title: Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative data


title: Unravelling the population structure and transmission patterns of Mycobacterium tuberculosis in Mozambique, a high TB/HIV burden country

abstract:
Genomic studies of Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. We applied Whole-genome sequencing (WGS) to characterize the local population of MTBC, unravel potential transmission links and evaluate associations with host and pathogen factors.

MethodsA one-year prospective study was conducted in Mozambique, a high HIV/TB burden country. WGS was applied to 295 positive cultures. We combined phylogenetic, geographical and clustering analysis, and investigated associations between risk factors of transmission.

FindingsA significant high proportion of strains were in recent transmission (45.5%). We fully characterized MTBC isolates by using phylogenetic approaches and dating evaluation. We found two likely endemic clades, comprised of 67 strains, belonging to L1.2, dating from the late XIX century and associated with recent spread among PLHIV.

InterpretationOur results unveil the population structure of MTBC in our setting. The clustering analysis revealed an unexpected pattern of spread and high rates of progression, suggesting the failure of control measures. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB coinfected patients, hint at possible coevolution with sympatric host populations and challenge the role of HIV in TB transmission.

FundingMinistry of Enterprise and Knowledge (Government of Catalonia & European Social Fund, AGAUR fellowship); European Research Council (ERC) European Unions Horizon 2020.

category: genetic and genomic medicine


title: SARS-CoV-2 Variant Surveillance Using Tandem Targeted RT-PCR-based Genotyping Assays and Whole Genome Sequencing

abstract: Genomic surveillance is critical for tracking SARS-CoV-2 Variants of Concern (VOC) and for rapid detection of emerging variants. Whole genome sequencing (WGS) is the predominant method for genomic surveillance; but it is a laborious process for large-scale testing. The aim of this study was to assess the performance of a PCR-based mutation panel for the discrimination of 5 known VOC; Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529). Genotyping analysis was performed on 128 SARS-CoV-2 positive samples collected at the Life Science Testing Center at Northeastern University from April-December 2021. RNA extraction was performed using MagMax Viral/Pathogen II Nucleic Acid Isolation Kit. SARS-CoV-2 detection was confirmed using the TaqPath COVID-19 Combo Kit. Variant determination was conducted using a panel of TaqMan SARS-CoV-2 single nucleotide polymorphism (SNP) assays. On November 25, 2021, the emerging VOC (Omicron) was reported by South Africa and the panel was quickly modified to detect Omicron by substituting P681H and K417N assays. Based on the SNP panel analysis, variant identification in 128 samples were as follows: Alpha (N=34), Beta (N=1), Gamma (N=7), Delta (N=41) and Omicron (N=21). The genotyping panel accurately assigned lineages to 104 samples, confirmed by Ion Torrent GeneStudio S5 WGS. VOC discrimination using RT-PCR genotyping is a rapid, versatile method for detecting known and emerging SARS-CoV-2 variants. The versatility of SNP panels allows monitoring of emerging strains by simple layout adaptations. RT-PCR genotyping assays can expedite variant identification, enable high-throughput variant surveillance, and support WGS prioritization for detection of new variants.

category: infectious diseases


title: Predictors of mortality, ICU admission and intubation among hospitalized COVD-19 patients in Jordan.

abstract:
IntroductionSeveral studies characterized COVID-19 patients and revealed the factors associated with COVID-19 mortality and severity. However, few studies were conducted in the Middle East, hence we decided to conduct this study to characterize COVID-19 patients, identify the factors associated with COVID-19 mortality and severity and to compare the patients outcomes in the two waves of the pandemic.

MethodWe conducted a retrospective single center cohort study among COVID-19 patients admitted to our hospital. The primary outcomes were COVID-19 related death, ICU admission and invasive intubation. Whereas, the secondary outcome was the length of hospital stay. In addition, the patients were divided into two cohorts to represent the two waves of the pandemic, to compare between them based on the outcomes.

ResultsThe total number of COVID-19 patients included in our study was 745. The overall rates of COVID-19 related mortality, ICU admission and invasive intubation were 23.0%, 28.3% and 10.8%, respectively. CKD, troponin, LDH and O2 saturation <90% were significant predictors for mortality. Moreover, the significant predictors for ICU admission were HF and remdesivir use. Whereas, O2 saturation<90% and GI symptoms were the only significant predictors for invasive intubation. Additionally, the second wave had significantly higher rates of ICU admission compared to the first one.

ConclusionOur study showed that several factors predicted COVID-19 mortality, ICU admission and invasive intubation. Additionally, our study revealed that the second wave of the pandemic had significantly higher rates of ICU admission but not mortality or invasive intubation compared to the first wave.


title: Spatial Growth Rate of Emerging SARS-CoV-2 Lineages in England, September 2020-December 2021

abstract: This paper uses a robust method of spatial epidemiological analysis to assess the spatial growth rate of multiple lineages of SARS-CoV-2 in the local authority areas of England, September 2020-December 2021. Using the genomic surveillance records of the COVID-19 Genomics UK (COG-UK) Consortium, the analysis identifies a substantial (7.6-fold) difference in the average rate of spatial growth of 37 sample lineages, from the slowest (Delta AY.4.3) to the fastest (Omicron BA.1). Spatial growth of the Omicron (B.1.1.529 and BA) variant was found to be 2.81x faster than the Delta (B.1.617.2 and AY) variant and 3.76x faster than the Alpha (B.1.1.7 and Q) variant. In addition to AY.4.2 (a designated variant under investigation, VUI-21OCT-01), three Delta sublineages (AY.43, AY.98 and AY.120) were found to display a statistically faster rate of spatial growth than the parent lineage and would seem to merit further investigation. We suggest that the monitoring of spatial growth rates is a potentially valuable adjunct to routine assessments of the growth of emerging SARS-CoV-2 lineages in a defined population.

category: epidemiology