title: DBS for substance use disorders? An exploratory qualitative study of perspectives of people currently in treatment

abstract:
Background and AimsDeep brain stimulation (DBS) has shown promise as a treatment option for substance use disorders (SUDs), but may have unique ethical risks due to stigma and other factors. Previous studies have elicited researcher and clinician opinions on those risks, but none have studied perspectives of people living with SUDs.

MethodsParticipants were recruited through a national inpatient treatment network employing purposive sampling for representation of minoritized groups and diversity of substances. Participants viewed a short video introducing DBS, followed by a 1.5 hour semi-structured interview on their experiences with SUDs and their perspectives on DBS as a future treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes.

ResultsWe interviewed 20 people in 12-step based, inpatient treatment programs (10 [50%] white/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 11 [45%] women). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks). The majority of respondents expressed interest in DBS as a future treatment option, emphasizing the importance of exploring novel treatment options and keeping individual treatment goals as key guiding considerations.

ConclusionsThe perspectives of people with lived experience of SUDs contrasted with previous surveys of provider attitudes on DBS for SUDs. Individuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS. These differences derived largely from their experiences living with an often-fatal disease, encountering limitations of current treatment options, and their familiarity with 12-step treatment paradigms that prioritize having multiple therapeutic "tools." These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates.

category: addiction medicine


title: Ribavirin antiviral combination therapy in COVID 19, a single-center experience

abstract:
BackgroundCOVID 19 infection has a similar clinical spectrum of disease presentation such as SARS and MERS in the past. These led to the assumption of the possibility to treat COVID 19 infection with antivirals which had been used to treat SARS and MERS.

MethodsA retrospective analysis was done on the data of SEV COVID Trial in symptomatic adult patients of COVID 19 infection with objectives to explore whether ribavirin antiviral combinations reduces the need of both noninvasive and invasive ventilators in treatment of COVID 19 infections.

ResultsThe patients were categorized as "Cohort A" consisting of 40 patients and "Cohort B" of 61 patients as Cohort A being the group of patients who received the standard therapy and Cohort B the group of patients who received the ribavirin combination therapy.

ConclusionThe study concluded that there was no statistically significant difference in regard to the need of noninvasive ventilation and invasive ventilation and also the development of multi-organ dysfunction in between the two Cohorts. Also, with progress of time, the proportion of patients with single organ dysfunctions in the two cohorts showed gradual recovery without any statistically significant differences.

category: infectious diseases


title: Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and its potential application to disease diagnosis

abstract: Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls. In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis. With this purpose, we re-analysed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could be used to distinguish patients from healthy controls. A similar finding was obtained when comparing patients with noninfectious or unknown disease trigger to healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070). Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients. When a bioinformatic analysis was performed on these epitopes, it revealed a potential molecular mimicry with several human proteins. To confirm these promising findings, a follow-up study will be conducted in a separate cohort of patients.


title: Heme Oxygenase-1 Promoter (GT)n Alleles and Neurocognitive Functioning in Thai Youth with Perinatally-Acquired HIV: A Pilot Study

abstract:
BackgroundHeme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may modify HIV-associated neurocognitive impairment (HIV-NCI) risk. Among adults, short HO-1 (GT)n alleles associate with greater HO-1 antioxidant enzyme inducibility and lower rates of HIV-NCI. This pilot study examined associations between HO-1 (GT)n alleles and neurocognitive outcomes in a sample of Thai youth (13-23 years) with perinatally-acquired HIV (PHIV) and demographically-matched HIV-negative controls.

MethodsParticipants completed neurocognitive testing and provided blood samples for DNA extraction and sequencing of HO-1 promoter (GT)n dinucleotide repeat lengths. Allele lengths were assigned based on number of (GT)n repeats: <27 Short (S); 27-34 Medium (M); >34 Long (L). Relationships between HO-1 (GT)n repeat lengths and neurocognitive measures were examined, and differences by HO-1 (GT)n allele genotypes were explored.

ResultsNearly half (48%) of all HO-1 (GT)n promoter alleles were short. Longer repeat length of participants longest HO-1 (GT)n alleles significantly associated with poorer processing speed (Total sample: r=-.36, p=.01; PHIV only: r=-.69, p<.001). Compared to peers and controlling for covariates, SS/SM genotypes performed better in processing speed, and SS genotypes performed worse in working memory.

ConclusionsA high frequency of short HO-1 (GT)n alleles was found among these Thai youth, as previously observed in other cohorts of people of Asian ancestry. In contrast to previous adult studies, the presence of a short allele alone did not associate with better neurocognitive performance, suggesting additional modifying effects among the different alleles. Research is needed to determine whether HO-1 (GT)n promoter genotypes differentially influence neurocognitive functioning across the lifespan and different ethnic backgrounds.

category: hiv aids


title: Anti SARS-CoV2 seroprevalence in Zanzibar in 2021 before the Omicron wave

abstract:
ObjectivesFor Tanzania including Zanzibar, The development of the COVID-19 pandemic has remained unclear, since reporting cases was suspended during2020/21. The present study provides first data on the COVID-19 seroprevalence among Zanzibari before the omicron variant wave starting in late 2021.

DesignDuring August through October 2021 representative cross-sectional data were collected from randomly selected households in 120 wards of the two main islands, Unguja and Pemba. Participants voluntarily provided blood samples to test their sera for antibodies against SARS-CoV2 in a semiquantitative enzyme-linked immunosorbant assay (ELISA).

Results57% of the 2080 sera analysed were positive without significant differences between Unguja and Pemba or between rural and urban areas, similar to observations from other sub-Saharan Africa countries.

ConclusionsThe antibody levels observed are most likely to previous infections with SARS-CoV2, since vaccination was basically not available before the survey. Therefore, this study provides first insight, how many Zanzibari have had COVID-19 before the Omicron variant. Further, it provides the appropriate basis for a follow-up survey addressing how this seroprevalence influenced the susceptibility to the Omicron variants, given harmonised methodologies are used.


title: Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents

abstract:
BackgroundAdministration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell depleting agents that hinder the endogenous humoral response. However, little is known on the impact of anti-CD20 pre-exposition and the use of different sources of plasma (convalescent versus vaccinated) on the kinetics of SARS-CoV-2-specific antibodies and viral evolution after plasma therapy.

MethodsEligible COVID-19 patients (n = 36), half of them after anti-CD20 targeted therapy, were treated with therapeutic plasma from convalescent (n = 17) or mRNA-vaccinated (n = 19) donors. Each plasma-transfused patient was thoroughly monitored over time by anti-S IgG quantification and whole-genome SARS-CoV-2 sequencing.

ResultsThe majority of anti-CD20 pre-exposed patients (15/18) showed progressive declines of anti-S protein IgG titers following plasma therapy, indicating that they mostly relied on the passive transfer of anti-SARS-CoV-2 antibodies. Such antibody kinetics correlated with prolonged infection before virus clearance, contrasting with the endogenous humoral response predominantly present in patients who had not received B-cell depleting agents (15/18). No relevant differences were observed between patients treated with plasma from convalescent and/or vaccinated donors. Finally, 4/30 genotyped patients showed increased intra-host viral evolution and 3/30 included 1 to 4 spike mutations, potentially associated to immune escape.

ConclusionsConvalescent and/or vaccinated plasma therapy may provide anti-SARS-CoV-2 antibodies and clinical benefit to B-cell depleted COVID-19 patients. Only a limited number of patients acquired viral mutations prior to clinical recovery, yet our study further emphasizes the need for long-term surveillance for intra-host variant evolution, to guide best therapeutic strategies.


title: Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta and Delta-plus variants

abstract:
As SARS-CoV-2 continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses, and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta or Delta variants, we show that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta plus (Delta+) which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+ and Omicron, which all possess the N417 residue. We isolated a N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D mAb utilized the IGHV3-23*01 germline gene and had similar somatic hypermutations compared to previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targetting escape mutations such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines.

ImportanceThe evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring varying immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants, and to define shared epitopes. We show that Beta and Delta infection resulted in antibody responses that were more cross-reactive compared to the original D614G variant, but each with differing patterns of cross-reactivity. We further isolated an antibody from Beta infection, which targeted the N417 site, enabling cross-neutralization of Beta, Delta+ and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.


title: Safety, tolerability and immunogenicity of Biological Es CORBEVAX vaccine in children and adolescents: A Prospective, Randomised, Double-blind, Placebo controlled, Phase-2/3 Study.

abstract:
BackgroundAfter establishing safety and immunogenicity of Biological Es CORBEVAX vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.

MethodsThis is a phase-2/3 prospective, randomised, double-blind, placebo controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX vaccine in children and adolescents of either gender between <18 to [≥]12 years of age in Phase-II and <18 to [≥]5 years of age in Phase-III with placebo as a control. This study has two age sub groups; age subgroup-1 with subjects <18 to [≥]12 years of age and age subgroup-2 with subjects <12 to [≥]5 years of age. In both age sub groups eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX vaccine or Placebo in 3: 1 ratio.

FindingsThe safety profile of CORBEVAX vaccine in both pediatric cohorts was comparable to the placebo control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all the reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers against Ancestral Wuhan and Delta strains. Significantly high interferon gamma immune response (cellular) was elicited by CORBEVAX vaccinated subjects with minimal effect on IL-4 cytokine secretion.

InterpretationsThe safety profile of CORBEVAX vaccine in <18 to [≥]5 years children and adolescents was found to be safe and tolerable. The adverse event profile was also found to be acceptable. Significant increase in anti-RBD IgG and nAb titers and IFN-gamma immune responses were observed post vaccination in both pediatric age sub groups. Both humoral and cellular immune responses were found to be non-inferior to the immune responses induced by CORBEVAX vaccine in adult population. This study shows that CORBEVAX vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old.

The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066


title: Oral Cancer Prevalence, Mortality, and Costs in Medicaid and Commercial Insurance Claims Data

abstract:
ObjectivesThis study compared prevalence, incidence, mortality rates, treatment costs, and risk factors for oral and oropharyngeal cancer (OC/OPC) between two large cohorts of adults in 2012-2019.

MethodsMedicaid and commercial claims data were from the IBM Watson Health MarketScan Database. Logistic regression analyses estimated incidence and risk factors for OC/OPC. Mortality was calculated by merging deceased individuals Medicaid files with those of the existing cancer cohort. Costs were calculated by summing costs of outpatient and inpatient services.

ResultsThe prevalence of OC/OPC in the Medicaid cohort decreased each year (129.8 cases per 100,000 enrollees in 2012 to 88.5 in 2019); commercial enrollees showed a lower and more stable prevalence (64.7 per 100,000 in 2012 and 2019). Incidence trended downward in both cohorts, with higher incidence in the Medicaid (51.4-37.6 cases per 100,000) than in the commercial cohort (31.9-31.0 per 100,000). OC/OPC mortality rates decreased in the Medicaid cohort during 2012-2014 but increased in the commercial cohort. Total OC/OPC treatment costs were higher for commercial enrollees by an average of $8.6 million during 2016-2019. In both cohorts, incidence of OC/OPC was higher among adults who were older, male, white, used tobacco or alcohol, or had prior HIV/AIDS diagnosis, and lower among those who had seen a dentist within the prior year.

ConclusionsMedicaid enrollees experienced higher OC/OPC incidence, prevalence, and mortality compared with commercially insured adults. Having seen a dentist within the prior year was associated with a lower risk of OC/OPC diagnosis.

category: dentistry and oral medicine


title: Excess all-cause mortality across counties in the United States, March 2020 to December 2021

abstract:
Official Covid-19 death tallies have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county-level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare these estimates with the observed numbers of deaths to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial urban mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths were still not assigned to Covid-19 during 2021.

SIGNIFICANCEDeaths during the Covid-19 pandemic have been primarily monitored through death certificates containing reference to Covid-19. This approach has missed more than 170,000 deaths related to the pandemic between 2020 and 2021. While the ascertainment of Covid-19 deaths improved during 2021, the full effects of the pandemic still remained obscured in some regions. County-level estimates of excess mortality are useful for studying geographic inequities in the mortality burden associated with the pandemic and identifying specific regions where the full mortality burden was significantly underreported (i.e. Southeast). They can also be used to inform resource allocation decisions at the federal and state levels and encourage uptake of preventive measures in communities with low vaccine uptake.

category: epidemiology


title: Coronavirus and incomes: the COVID-19 pandemic dynamics in Africa in February 2022

abstract: The relative accumulated and daily characteristics of the COVID-19 pandemic dynamics in Africa were used to find links with the gross domestic product per capita (GDP), percentages of fully vaccinated people and daily numbers of tests per case. A simple statistical analysis of datasets corresponding to February 1, 2022 showed that accumulated and daily numbers of cases per capita, daily numbers of deaths per capita and vaccination levels increase with the increase of GDP. As in the case of Europe, the smoothed daily numbers of new cases per capita in Africa increase with the increasing of the vaccination level. But the increase of the accumulated numbers of cases and daily number of deaths with increasing the vaccination level was revealed in Africa. In comparison with Europe, no significant correlation was revealed between the vaccination level and the number of deaths per case. As in the case of Europe, African countries demonstrate no statistically significant links between the pandemic dynamics characteristics and the daily number of tests per case. It looks that countries with very small GDP are less affected by the COVID-19 pandemic. The cause of this phenomenon requires further research, but it is possible that low incomes limit the mobility of the population and reduce the number of contacts with infected people. In order to overcome the pandemic, quarantine measures and social distance should not be neglected (this also applies to countries with a high level of income and vaccination).


title: A systematic review of the reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank

abstract:
BackgroundMendelian randomisation (MR) is a method of causal inference that uses genetic variation as an instrumental variable (IV) to account for confounding. While the number of MR articles published each year is rapidly rising (partly due to large cohort studies such as the UK Biobank making it easier to conduct MR), it is not currently known whether these studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them.

MethodsWe conducted a systematic review of reporting and analysis quality of MR studies using only individual level data from the UK biobank to calculate a causal estimate. We reviewed 64 eligible articles on a 25-item checklist (based on the STROBE-MR reporting guidelines and the Guidelines for performing Mendelian Randomisation investigations). Information on article type and journal information was also extracted.

ResultsOverall, the proportion of articles which reported complete information ranged from 2% to 100% across the different items. Palindromic variants, variant replication, missing data, associations between the IV and variables of exposure/outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%).

There was no clear evidence that Journal Impact Factor, word limit/recommendation or year of publication predicted percentage of article completeness (for the eligible analyses) across items, but there was evidence that whether the MR analyses were primary, joint-primary or secondary analyses did predict completeness.

ConclusionsThe results identify areas in which the reporting and conducting of MR studies needs to be improved and highlights that this is independent of Journal Impact Factor, year of publication or word limits/recommendations.


title: Prevalence and characteristics of hazardous and harmful drinkers receiving general practitioners' brief advice on and support with alcohol consumption in Germany: results of a population survey

abstract:
ObjectiveThe German treatment guideline on alcohol-related disorders recommends that general practitioners (GPs) offer brief advice on, and support with, reducing alcohol consumption to hazardous (at risk for health events) and harmful (exhibit health events) drinking patients. We aimed to estimate the implementation of this recommendation using data from the general population in Germany.

DesignCross-sectional analysis of data (2021/2022) of a nationally representative household survey.

SettingPopulation of Germany.

ParticipantsRepresentative sample of 2,247 adult respondents (>18 years) who reported hazardous or harmful drinking according to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; score females: 4-12, males: 5-12).

Main outcome measureEver receipt of "brief GP advice on, or support with, reducing alcohol consumption". Differences in the likelihood of ever receiving advice and/or support (yes/no) relative to respondents sociodemographic, smoking, and alcohol consumption characteristics were estimated using logistic regressions.

ResultsEver receipt of GP advice on/support with reducing alcohol was reported among 6.3% (95%CI=5.3%-7.4%), and the offer of support among 1.5% (95%CI=1.1%-2.1%) of the hazardous and harmful drinking respondents. The likelihood of having ever received advice/support was positively associated with being older (odds ratio (OR)=1.03 per year, 95%CI=1.01-1.04), a current or former (versus never) smoker (OR=2.36, 95%CI=1.46-3.80; OR=2.17, 95%CI=1.23-3.81), and with increasing alcohol consumption (OR=1.76 per score, 95%CI=1.59-1.95). One in two harmful drinking respondents (AUDIT-C score 10-12) reported appropriate advice/support. The likelihood was negatively associated with being female (e.g., OR=0.32, 95%CI=0.21-0.48), having a medium and high (versus low) education, and with increasing household income.

ConclusionsA small proportion of people drinking at hazardous and harmful levels in Germany report having ever received brief GP advice on, or support with, reducing alcohol consumption. The implementation of appropriate advice or support seems to be strongly linked to specific sociodemographic characteristics, tobacco smoking, and the alcohol consumption level.

Strengths and limitations of this studyO_LIThe principal strength of this study is the large, nationally representative population sample.
C_LIO_LIThe cross-sectional study design and temporality issues with our measures (alcohol consumption was measured with reference to the present and the outcome as "ever receipt of GP advice or support") limited our ability to explore causal relationships.
C_LIO_LIThe outcome measure had a complex, not entirely hierarchical structure, which may have led to respondents being unsure of which response option to select.
C_LIO_LIData were collected during the COVID-19 pandemic, during which alcohol consumption in Germany seemed to have changed. It is unclear how this might have influenced GPs behaviour.
C_LIO_LIDue to the socially loaded topic, respondents may not have answered truthfully or repressed a previous conversation with their GP on their alcohol consumption. We did not assess the GPs view on the topic.
C_LI

category: primary care research


title: Global burden of mental health problems among children and adolescents during COVID-19 pandemic: A systematic umbrella review

abstract: Mental health problems among children and adolescents are increasingly reported amidst the coronavirus disease (COVID-19) pandemic. In this umbrella review, we aimed to synthesize global evidence on the epidemiologic burden and correlates of child and adolescent mental health (CAMH) problems during this pandemic from existing systematic reviews and meta-analyses. We evaluated 422 citations and identified 17 eligible reviews on the epidemiology of CAMH in the context of COVID-19. Most of the reviews reported a high prevalence of anxiety, depression, sleep disorders, suicidal behavior, stress-related disorders, attention-deficit/hyperactivity disorder, and other mental health problems. Also, factors associated with CAMH such as age, gender, place of residence, educational attainment, household income, sedentary lifestyle, social media and internet use, comorbidities, family relationships, parents psychosocial conditions, COVID-19 related experiences, closure of schools, online learning, and social support were reported across reviews. As most studies were cross-sectional and used nonrepresentative samples, future research on representative samples adopting longitudinal and intervention designs is needed. Lastly, multipronged psychosocial care services, policies, and programs are needed to alleviate the burden of CAMH problems during and after this pandemic.

category: psychiatry and clinical psychology


title: Allogeneic Hematopoietic Cell Transplants as Dynamical Systems: Effect of Early-Term Immune Suppression Intensity on Long-Term T Cell Recovery

abstract: Reduced intensity conditioning (RIC) is fraught with risk for disease relapse. This may be overcome by donor T cell alloreactivity. Reducing the duration of intense immune suppression in the early term following transplantation may create an immunologic environment favoring rapid T cell reconstitution to influence longer term transplant outcomes. Twenty-six patients were adaptively randomized based on donor-derived T cell recovery, between 2 different dosing schedules of mycophenolate mofetil (MMF): MMF for 30 days post-transplant, with filgrastim for cytokine support (MMF30 arm, 11 patients), or MMF for 15 days post-transplant, with sargramostim (MMF15 arm, 15 patients). All patients were treated with anti-thymocyte globulin at a dose of 1.7 mg/kg/day from day - 9 through day -7 and total body irradiation, 450 cGy given in 3 fractions. Patients were well matched between the study arms and underwent HLA matched related and unrelated donor hematopoietic cell transplantation (HCT). The MMF15 arm demonstrated superior T cell recovery in the first month. This difference persisted through the first year for total T cells, T cell subsets and NK cells. T cell repertoire tended to be more diverse in the MMF15 arm. The long term superior immune recovery in the MMF15 arm is consistent with a disproportionate impact of early interventions in HCT. Clinically, shorter course MMF post-transplant was not associated with increased risk of acute or chronic graft vs. host disease (GVHD), and relapse and there was a trend toward improved overall survival in the MMF15 arm. Reducing the duration of intense immunosuppression in the early term and the use of sargramostim following allogeneic HCT is feasible and leads to superior long-term T cell recovery. This regimen should be studied to improve immune recovery in large cohorts of patients undergoing HCT with RIC.

category: oncology


title: Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG

abstract:
ObjectivesAlthough often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. The UK recommendations are that varicella immunoglobulin (VZIG) is administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG is recommended if exposure occurs at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox.

MethodsWe identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes.

Results171/186 (91.9%) of these women received either VZIG or oral aciclovir. 53 of the 145 (36.6%) women who received VZIG went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p=0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p=0.751).

ConclusionsThese findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed at 20+ weeks, (and possibly second-line <20 weeks) as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG.


title: Medical Students Perception of Anatomage: A 3D Interactive (Virtual) Anatomy Dissection Table

abstract:
IntroductionThe rising number of Medical Schools and the increasing demand for cadavers, amid its scarcity, has prompted the search for alternatives in Anatomy Education. This study assessed students thought of the use of Anatomage as an Anatomy teaching and learning tool in medical school.

MethodsA five-point scale questionnaire with a free hand comment section was completed by 50 medical students exposed to the use of Anatomage alongside the traditional cadaveric dissection for 2 academic sessions.

ResultsOur results findings showed that there were preference pattern variations in the use of the Anatomage for various fields of anatomy such as Gross Anatomy (48%), Histology (46%), and Neuroanatomy (2%) respectively. Furthermore, 66% opined that Anatomage and Cadaveric dissection should be complementary in teaching and learning anatomy. However, been satisfied with Anatomage was 76% (52% completely and 24% generally agreed respectively), while Anatomage increasing their interest in Anatomy was 66% (40% completely agreed and 26% generally agreed) and 74% (40% completely agreed and 34% generally agreed) of learning outcomes been achieved using Anatomage. Also, 68% stated that the micrographs were well displayed for histology teaching. Overall, 60% of the students agreed that Anatomage should be encouraged in teaching and learning Anatomy, along with other teaching aids.

DiscussionAnatomage increased students interest in Anatomy as its 3D-image display enabled better visualization of relevant anatomical structures. Anatomage has the potential to be a beneficial supplement to standard learning methods in the acquisition of 3D anatomy information.

category: medical education


title: Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: a pilot study

abstract:
ObjectivePharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide.

Materials and MethodsFour healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration.

ResultsThere were 3,076 human, 332 S. mitis, 102 G. haemolyans and 42 G. adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and [~]300 proteins that had a p<0.05 between the pre-and post-octreotide groups [~]50 proteins with an FDR-corrected p<0.05 between pre-and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment.

ConclusionThis pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotides effects on saliva and reports of improved PCF healing.

category: otolaryngology


title: Impact of HIV and recreational drugs on cognitive functions in young men having sex with men.

abstract:
ObjectivesThis study characterizes the structural and metabolic cerebral correlates of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in a preclinical setting that considers the lifestyle of young European men exposed to HIV, including recreational drugs.

DesignProspective inclusion of participants.

MethodsSimultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men with HIV+ (mean age: 33.6 years, age range: 23-60 years; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of a group of 26 young HIV-men, highly well matched for what concerns age, lifestyle, named pre-exposure prophylaxis users (HIV-PrEP), and to a group of 23 undifferentiated matched young men (i.e., healthy controls). A comprehensive neuropsychological assessment was also administered to the HIV+ and HIV-PrEP subjects.

ResultsHIV+ subjects had lower performances in executive, attentional and working memory functions compared to HIV-PrEP subjects. No structural or metabolic differences were found between those two groups. Compared to healthy controls, HIV+ and HIV-PrEP exhibited a common frontal hypometabolism in the right prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found.

ConclusionA dynamic prevention of recreational drugs use in HIV+ and HIV-PrEP subjects is mandatory to cope with their negative impact on brain function and their neurocognitive consequences. A complex interplay between recreational drugs and HIV might be involved in the development of neurocognitive disorders in young men with HIV.


title: Barriers to access to HIV care services in host countries: views and experiences of Indonesian male ex-migrant workers living with HIV

abstract: This study aimed to understand barriers to accessing HIV care services in host countries among Indonesian, male, former (returned) migrant workers living with HIV. The study utilised a qualitative design employing in-depth interviews to collect data from twenty-two returned migrant workers from Eastern Indonesia, recruited using the snowball sampling technique. A qualitative data analysis framework was used to guide a step-by-step analysis of the findings. Findings demonstrated that limited host-country language proficiency, lack of knowledge regarding healthcare systems in host countries and having  undocumented worker status were barriers to accessing HIV care services. Data also revealed unavailability of HIV care services nearby migrants work locations, long distance travel to healthcare facilities, and challenges in accessing public transportation as barriers that impeded their access to the services. Other factors limiting the participants access to HIV services were identified as the transient and mobile nature of migrant work requiring frequent relocation and disrupting work life stability. Additionally, in lieu of formal HIV services, many participants self-medicated by using over-the-counter herbal or  traditional medicines, often because of peer or social group influence regarding selection of informal treatment options. Recommendations arising from this study demonstrate the need to improve pre-departure information for migrant workers regarding healthcare system and access procedure in potential host countries. Data from this study also indicate that social services should be available to assist potential migrants to access legal channels for migrant work overseas, to ensure that Indonesian migrants can safely access healthcare services in the countries for which they are providing migrant labour. Future studies to understand barriers to accessing HIV care services among various migrant groups living with HIV are warranted to build evidence for potential social policy change.


title: Impact of the additional/booster dose of COVID-19 vaccine against severe disease during the epidemic phase characterized by the predominance of the Omicron variant in Italy, November 2021 - March 2022

abstract: Despite the stunning speed with which highly effective and safe vaccines have been developed, increasingly transmissible variants are emerging. Using surveillance data from Italy (November 2021-March 2022), during the epidemic phase characterized by the predominance of the Omicron variant, vaccination with additional/booster dose significantly reduces the risk at all ages for hospitalization (relative risk (RR): 0.16; 95% confidence interval (CI): 0.13-0.19), admission to ICU (RR: 0.08; 95% CI: 0.06-0.09) and death (RR: 0.13; 95% CI: 0.10-0.16). Results support the importance of receiving a third dose of mRNA COVID-19 vaccine.


title: Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden

abstract: Background Analyses of COVID-19 suggest specific risk factors make communities more or less vulnerable to pandemic related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics. Methods We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality. Results We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100,000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden. Conclusion These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.


title: SARS-CoV-2 detection in wastewater as an early warning: the case of metropolitan area of the city of Buenos Aires (AMBA).

abstract:
Agua y Saneamientos Argentinos S.A. (AySA) delivers essential services as drinking water production and wastewater treatment for more than 14.5 million inhabitants of Buenos Aires Metropolitan Area (AMBA), Argentina, and collects residual liquids of 8.5 million through 16,178 km network. Since the very moment the World Health Organization (WHO) declared the COVID-19 pandemic, AySA developed a methodology to determine SARS-CoV-2 viral genetic load in untreated wastewater as an epidemiological surveillance tool, based on international experiences. In order to monitor viral load in the representative areas of the sewage collection system, more than 1500 samples where concentrated, by using an adapted ultracentrifugation method followed by RNA extraction and quantitative reverse transcription polymerase chain reaction (RT-qPCR), to measure the target Orf1ab gene of SARS-CoV-2 in our molecular microbiology laboratory.

This research was developed for a period that lasted from January 01 to June 02, 2021, in order to anticipate to the current second wave. The results achieved have demonstrated that changes in SARS-CoV-2 RNA are satisfactorily related to local epidemiological data for COVID-19. The association of variables is statistically significant when analyzing data from four large wastewater treatment plants, (R2 > 0.5 and p-value < 0.05), obtaining significant correlations between log10 viral genomic load and log10 positive cases reported one and two weeks later after samples were analyzed.

From the results obtained, it is concluded that the virus sewage system levels were a good predictor of clinical cases to be diagnosed in the immediate future and it is feasible to use this methodology, at local level, as an additional tool for decision-making in public health strategy.

Highlights Development of an integrated molecular sampling, analysis and detection system that can alert about the circulation of SARS-CoV-2.
 Early warning of infected population.
 First laboratory in a public water company to develop a monitoring method in Argentina.
 Use of poly aluminum chloride (PAC) as a coagulant in the viral concentration stage.


title: Real-world study of the effectiveness of BBIBP-CorV (Sinopharm) COVID-19 vaccine in the Kingdom of Morocco

abstract:
The Kingdom of Morocco approved BBIBP-CorV (Sinopharm) COVID-19 vaccine for emergency use on 22 January 2021 in a two-dose, three-to-four-week interval schedule. We conducted a case-control study to determine real-world BBIBP-CorV vaccine effectiveness (VE) against serious or critical hospitalization of individuals RT-PCR-positive for SARS-CoV-2 during the first five months of BBIBP-CorV use in Morocco.

The study was conducted among adults 18-99 years old who were tested by RT-PCR for SARS-CoV-2 infection between 1 February and 30 June 2021. RT-PCR results were individually linked with outcomes from the COVID-19 severe or critical hospitalization dataset and with vaccination histories from the national vaccination registration system. Individuals with partial vaccination (<2 weeks after dose two) or in receipt of any other COVID-19 vaccine were excluded. Unadjusted and adjusted VE estimates against hospitalization for serious or critical illness were made by comparing two-dose vaccinated and unvaccinated individuals in logistic regression models, calculated as (1-odds ratio) * 100%.

There were 348,190 individuals able to be matched across the three databases. Among these, 140,892 were fully vaccinated, 206,149 were unvaccinated, and 1,149 received homologous BBIBP-CorV booster doses. Unadjusted, full-series, unboosted BBIBP-CorV VE against hospitalization for serious or critical illness was 90.2% (95%CI: 87.8% - 92.0%). Full-series, unboosted VE, adjusted for age, sex, and calendar day of RT-PCR test, was 88.5% (95%CI: 85.8% - 90.7%). Calendar day- and sex-adjusted VE ranged from 93.9% to 100% for individuals <60 years, and was 53.3% for individuals 60 years and older. There were no serious or critical illnesses among BBIBP-CorV-boosted individuals.

Effectiveness of Sinopharms BBIBP-CorV was consistent with phase III clinical trial results. Two doses of BBIBP-CorV was highly protective against COVID-19-associated serious or critical hospitalization in working-age adults under real-world conditions and moderately effective in older adults. Booster dose VE should be evaluated, as booster doses of BBIBP-CorV are recommended and are being used.

category: public and global health


title: Implementation of a pediatric telemedicine and medication delivery service in a resource-limited setting: A pilot study of clinical safety and feasibility

abstract:
ObjectiveDetermine the clinical safety and feasibility of implementing a telemedicine and medication delivery service (TMDS) to address gaps in nighttime healthcare access for children in low-resource settings.

MethodsWe implemented a TMDS in Haiti called  MotoMeds: (i) A parent/guardian of a child [≤]10 years contacted the call center (6pm-5am). (ii) A provider used paper clinical decision support tools to triage the case as mild, moderate, or severe. Severe cases were referred to emergency care. For non-severe cases, call center providers gathered clinical findings to generate an assessment and plan. (iii) For households within the delivery zone, a provider and driver were dispatched with medications/fluids; the provider performed a paired in-person exam. For households outside the delivery zone, the family received phone consult alone. All families received a follow-up call at 10-days. Data were analyzed for clinical safety and feasibility.

ResultsA total of 391 cases were enrolled from September 9th, 2019 to January 19th, 2021; 89% (347) received a household visit. Most cases were triaged as mild or moderate (92%; 361). Among the severe cases, 83% (20) sought subsequent referred care. The most common complaint was a respiratory problem (63%; 246). At 10-days, 95% (329) of parents reported their childs condition as "improved" or "recovered". Ninety-nine percent (344) rated the TMDS as "good" or "great". The median phone consultation was 20 minutes, time to arrival at the household was 73 minutes and total workflow per case was 114 minutes.

ConclusionThe TMDS was a feasible healthcare delivery model with high rates of improved clinical status at 10-days.

Study registration (clinicaltrials.gov)NCT03943654


title: Analytical performance of 17 commercially available point-of-care tests for CRP to support patient management at lower levels of the health system

abstract: Accurate and precise point-of-care (POC) testing for C-reactive protein (CRP) can help support healthcare providers in the clinical management of patients. Here, we compared the analytical performance of 17 commercially available POC CRP tests to enable more decentralized use of the tool. The following CRP tests were evaluated. Eight quantitative tests: QuikRead go (Aidian), INCLIX (Sugentech), Spinit (Biosurfit), LS4000 (Lansionbio), GS 1200 (Gensure Biotech), Standard F200 (SD Biosensor), Epithod 616 (DxGen), IFP-3000 (Xincheng Biological); and nine semi-quantitative tests: Actim CRP (ACTIM), NADAL Dipstick (nal von minden), NADAL cassette (nal von minden), ALLTEST Dipstick (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-40-80 (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-30 (Hangzhou Alltest Biotech), Biotest (Hangzhou Biotest Biotech), BTNX Quad Line (BTNX), BTNX Tri Line (BTNX). Stored samples (n=660) had previously been tested for CRP using Cobas 8000 Modular analyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland (reference standards). CRP values represented the clinically relevant range (10-100 mg/L) and were grouped into four categories (<10 mg/L, 10-40 mg/L or 10-30 mg/L, 40-80 mg/L or 30-80 mg/L, and > 80mg/L) for majority of the semi-quantitative tests. Among the eight quantitative POC tests evaluated, QuikRead go and Spinit exhibited better agreement with the reference method, showing slopes of 0.963 and 0.921, respectively. Semi-quantitative tests with the four categories showed a poor percentage agreement for the intermediate categories and higher percentage agreement for the lower and upper limit categories. Analytical performance varied considerably for the semi-quantitative tests, especially among the different categories of CRP values. Our findings suggest that quantitative tests might represent the best choice for a variety of use cases, as they can be used across a broad range of CRP categories.


title: Epidemiological behavior of the contamination curve by COVID-19 in Brazil: a time series study

abstract: The Brazil is experiencing the greatest episode of sanitary collapse ever known in the countrys history. Therefore, the relevance of this study is highlighted for the scientific advance on the epidemiological behavior of the virus in Brazil, enabling the development of analyses and discussions on the factors that influenced the high rates of contamination by SARS-CoV-2 in the country. Given the above, the study in question aims to analyze the epidemiological behavior of the contamination curve by COVID-19 by epidemiological week (EW), in the years 2020-2021, in Brazil. This is an ecological study of time series, prepared using information collected through secondary means. The country of origin of the study is Brazil, and its main theme is the number of those infected during the pandemic of COVID-19, this being the dependent variable of the study. The data been analyzed from February 23, 2020, when the first case was confirmed in Brazil, to January 1, 2022. In 2021, the countrys graph shows an exorbitant growth, reaching a peak of approximately 250 new cases per 100,000 inhabitants in the 12th EW. This data became the highest rate of the pandemic in Brazil, and did not vary significantly for the next twelve weeks. Thus, it was identified that Brazil was severely impacted by the new coronavirus, considering the high rates of confirmed cases of the virus in the country, the low adhesion of the population to preventive measures, the late start of mass vaccination in the Brazilian population, and the lack of structure in the health system, which was not properly prepared for the high demand generated by COVID-19.


title: Clinical characteristics and outcome of immunocompromised patients with COVID-19 caused by the Omicron variant: a prospective observational study

abstract:
BackgroundIn the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants. Data on the disease burden of Omicron in immunocompromised patients are lacking. We investigated the clinical characteristics and outcome of a cohort of immunocompromised patients with COVID-19 caused by Omicron.

MethodsSolid organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients on immunosuppressive therapy infected with the Omicron variant, were included. Patients were contacted regularly until symptom resolution. Clinical characteristics of consenting patients were collected through their electronic patient files. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed.

ResultsA total of 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received three mRNA vaccinations. While only one patient died, 23 (20%) required hospital admission for a median of 11 days. A low SARS-CoV-2 IgG antibody response (<300 BAU/mL) at diagnosis, higher age, being a lung transplant recipient, more comorbidities and a higher frailty were associated with hospital admission (all p<0.01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of them, of which one died.

ConclusionsWhile the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. Besides vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

SummaryCOVID-19-associated morbidity and mortality in immunocompromised patients is unknown for the SARS-CoV-2 Omicron variant. This prospective registry, demonstrated low COVID-19-associated mortality in these vulnerable patients. However, morbidity remained substantial. Other interventions to abate COVID-19 severity are needed.


title: Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities

abstract:
BackgroundStudies have shown that those with certain high-risk comorbidities such as diabetes, chronic kidney disease (CKD), chronic lung disease, or those with immunocompromising conditions have increased risk of hospitalization from COVID-19. Here we estimate the elevated risks of breakthrough infection and hospitalization in fully vaccinated individuals with comorbidities.

MethodsUsing a population of fully-vaccinated patients in the de-identified Truveta Platform of electronic health records from January 1, 2019, to January 10, 2022, we used logistic regression to estimate risk of 1) a patient experiencing a breakthrough COVID-19 infection after being fully vaccinated, and 2) rate of hospitalization in those experiencing breakthrough infection. Potential confounding was adjusted with inverse probability weighting for each comorbidity by age, race, ethnicity, and sex. We present ORs and percentages of breakthrough infections by comorbidity status.

ResultsOf 3,424,965 fully vaccinated patients, 2.79%, 2.63%, 2.38%, 1.83% with CKD, chronic lung disease, diabetes, and those in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.95% in the overall population. All cormorbidities were associated with significantly increased odds of breakthrough infections and subsequent hospitalizations. Breakthrough infection hospitalizations in populations with comorbidities ranged from 26.43% for CKD to 10.23% for chronic lung disease, with corresponding ORs of 2.22 (95% CI: 1.88 - 2.63) and 1.37 (95% CI: 1.21 - 1.55), respectively.

ConclusionsFully-vaccinated individuals with certain comorbidities experienced increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the general population. Individuals with comorbidities should remain vigilant against infection even if vaccinated.

HighlightsO_LICOVID-19 infection has greater severity in those with comorbidities.
C_LIO_LIHere we investigate the risk of breakthrough infections and hospitalizations in fully-vaccinated individuals with and without comorbidities.
C_LIO_LIWe find increased rates of breakthrough infections with all comorbidities, with CKD having the greatest risk.
C_LIO_LIIndividuals with chronic lung disease had the highest rate of breakthrough infection, but the lowest subsequent risk of hospitalization.
C_LIO_LIIndividuals with comorbidities should remain vigilant against infection even if vaccinated.
C_LI


title: A systematic review of the experiences of minority language users in health and social care research

abstract:
To obtain the most rigorous results in health and social care research (HSCR), it is important to have a representative sample. Culture can sometimes be overlooked but can be important to the individual concerned. Ethnic minorities are often not accounted for in HSCR. Migration, equality, and diversity issues are now important priorities and therefore need to be considered by researchers. Therefore, it is important to explore the literature examining the experiences of minority language users in HSCR. A systematic review (SR) of the literature was conducted to answer the research question. SPIDER framework and Cochrane principles were utilized for the SR. Five databases were searched, yielding 5311 papers initially. A SR protocol was developed and published in PROSPERO. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020225114analysis. Following the title and abstract review by two authors, 74 papers were included, and a narrative account was provided. Six themes were identified: 1. Disparities in health care; 2. Maternal health; 3. Mental health; 4. Methodology in health research; 5. Migrant and minority health care; 6. Racial and ethnic gaps in health care. It was evident that language barriers (including language proficiency) and cultural barriers still exist in terms of recruitment, possibly effecting the validity of the results. Several papers acknowledged language barriers but did not act on this information. Ethnic minorities needs are not completely addressed in HSCR. Despite research acknowledging different cultures over the past 40 years, there is a need for this to be fully acknowledged and embedded in the research process. We propose that future research should include details of ethnicity and languages spoken so that readers can understand the sample composition to be able to interpret the results in the best way, recognising the significance of culture and language.

2-4 Key messages, detailing the main points made in the paperO_LIEthnic minorities needs are not completely addressed in health and social care research. Despite research acknowledging different cultures over the past 40 years, there is a need for this to be fully acknowledged and embedded in the research process.
C_LIO_LIEthnic background and languages spoken by the research participants should be identified and addressed throughout the research process (from design of the study to dissemination of findings).
C_LIO_LILanguage and cultural preferences should be appropriately considered/included in the analysis.
C_LIO_LIFuture research should include details of ethnicity and languages spoken so that readers can understand the sample composition to be able to interpret the results in the best way, recognising the significance of culture and language.
C_LI

category: health systems and quality improvement


title: Spatio-temporal dynamics of malaria in Zanzibar, 2015-2020

abstract:
BackgroundDespite the continued high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. The aims of the analyses presented here were to (i) assess the spatio-temporal dynamics of malaria in Zanzibar between 2015 and 2020, and (ii) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting, thereby allowing for more effective programmatic resource allocations.

MethodsData routinely collected by Zanzibars Malaria Case Notification (MCN) system were analyzed. The system collects detailed socio-demographic and epidemiological data from all malaria cases who are passively detected and reported at the islands 313 public and private health facilities (defined as primary index cases), as well as through case follow-up and reactive case detection (defined as secondary cases). Using these data, spatio-temporal analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons and its correlation with 2015-2020 rainfall.

ResultsFrom January 1, 2015, to April 30, 2020, 22,686 index cases were notified by health facilities and reported through the MCN system. Number of cases reported showed declining trends from 2015 to 2017, followed by an increase from 2018 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed-up index cases was approximately 70% for all years. Change point analysis identified 10 distinct periods of malaria transmission across the study period, and the seasonality of reported index cases was significantly correlated to the amount of precipitation that occurred during the previous rainy season. Out of Zanzibars 388 shehias, 79 (20.3%) were identified as malaria hotspots in any given year between 2015 and 2020; these hotspots reported 52% of all index cases during the study period. Of the 79 shehias identified as hotspots, 12 (3% of all shehias) were hotspots in more than four years, i.e., considered temporally stable, reporting 14.5% of all index cases.

ConclusionsOur findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006, with mean annual shehia incidence being 3.8 cases per 1,000 over the 2015-2020 study period. Spatio-temporal analyses identified hotspots, some of which were stable across multiple years. From a programmatic perspective, malaria efforts should progress from an approach that is based on universal coverage of interventions to an approach that is more tailored and nuanced, with resources prioritized and allocated to a select number of hotspot shehias.


title: Recent advances in efficacy of corticosteroids as adjunct therapy for the treatment of community-acquired pneumonia in children: a systematic review and meta-analysis.

abstract: It has been recently shown that the adjunct use of corticosteroids in the treatment of community-acquired pneumonia shorten the time taken to reach clinical stability (time to clinical stability) in patients with community-acquired pneumonia (CAP). Considering the hyperglycemic effects of corticosteroids, there are concerns about the efficacy and safety of this therapy for children with CAP. Our objective is to evaluate the influence of recent advances in adjunct corticosteroid use and/or aerosolized antibiotic administration on admission to hospital with our main outcome being duration of fever and hospital stay, and additional outcomes as the time to clinical stability therapeutic efficacy, C-reactive protein and defervescence at 24, 48, and 72 hours after starting treatment in a well-defined cohort of children with community-acquired pneumonia. Therapeutic efficacy is defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough, and improved or normal laboratory values. Five academic literature databases will be searched using Boolean keyword searches. Articles eligible for inclusion are those that present original research with the study topic as CAP, the study was designed as a randomized controlled trial (RCT) or clinical trial (CT) or an observational study with controls. The review will result in a narrative synthesis that summarizes the effectiveness of corticosteroid use in children.

category: pediatrics


title: Application and reflection of blended learning in theoretical and practice courses of periodontology education

abstract:
BackgroundBlended learning mode has been widely applied in medical education, especially during the current COVID-19 pandemic. This study is to evaluate the effectiveness of blended learning mode in periodontal education for further promotion.

MethodsThe blended learning mode consists of face-to-face classes and SPOCs built on the Xfaike online course platform. The preparation before the courses included the optimization of teaching calendar, establishment of online learning platform, integration of the online and offline content. The feedback was evaluated by a questionnaire involving instruction method, instruction content and learning outcomes.

ResultsAll of the participants (n=65) answered the questionnaire. According to the questionnaire, the blended learning mode has been approved by all of the students. More than 95% of students convinced that blended learning mode can improve their self-learning ability. About 84.62% of students could finish the preview and review task of online courses. All of the students believed that they can exchange their questions with teachers more pertinently in offline classes after online learning, and online learning videos can be viewed smoothly and repeatedly at any time.

ConclusionsThe blended learning mode has been highly accepted among students, as the learning platform could provide abundant learning materials, improve self-learning ability, and provide a deeper understanding of knowledge. Thus, the blended learning could be considered as a promising educational mode for medical students to meet higher educational requirements.


title: Digital therapy to improve stuttering symptoms in patients with a deficit of spectral power in the EEG beta frequency band

abstract:
BackgroundStuttering is a speech disorder that affects more than 70 million people worldwide, limiting their ability to communicate and socialize. In recent decades, several studies have demonstrated a link between stuttering and a deficit of {beta} electroencephalographic (EEG) power.

Aim and MethodsThis study investigates the efficacy of a novel auditory neuro modulating technology that leverages euphonic music tracks with broad-spectrum binaural beats to induce selective EEG spectral power changes. Adults with stuttering (AWS, n=6) and participants from the control group (n=6) were exposed to euphonic binaural stimuli for 5 minutes. The EEG and electrocardiographic (ECG) bio-signals were recorded prior, during, and after exposure.

ResultsDuring standard reading tasks without stimulation, {beta}-power in the left hemisphere in the adults without stuttering and with stuttering differed. The left-right hemisphere asymmetry in {beta}-wave power was observed in the control group but not in AWS. After the stimulation, the power of {beta}-band in AWS participants in the left hemisphere increased 1.54-fold, while changes in the right hemisphere activity were not significant. Average {beta}-band power within left frontotemporal area and temporoparietal junction after stimulation in AWS participants shows an increase of {beta}-band in left frontotemporal junction by 1.65-fold and in left temporoparietal by 1.72-fold. The changes in the quality of speech were assessed based on the speech rate and the rate of speech disfluencies evaluated by speech therapists. The rate of disfluencies dropped significantly after the stimulation (median 74.70% of the baseline rate), but the effect was not significantly different from the baseline 10 min later (median 65.51% of the baseline rate). Similarly, the speech rate significantly increased immediately after the stimulation (median 133.15%) but was not significantly different 10 min later (median 126.63% of the baseline rate). In this study, we found significant correlations of {beta}-activation level in left temporoparietal projection (Spearman{rho} =-0.54,) and left frontotemporal area (Spearman{rho} =-0.58) with disfluency rate of speech.

ConclusionsWe show for the first time that auditory binaural beats stimulation can substantially improve speech fluency in AWS and its effect is related to boost of EEG {beta}-band power in speech-production centers. The changes in {beta} power are detected immediately after the exposure and persist 10 min later. Additionally, these effects are accompanied by a reduction in stress level as monitored by ECG markers. This suggests that auditory binaural beats stimulation temporarily improves speech quality in AWS by increasing {beta}-band power of EEG in speech centers of the brain.

category: neurology


title: Intra-myonuclear inclusions are diagnostic of oculopharyngeal muscular dystrophy

abstract: The pathologies of oculopharyngeal muscular dystrophy (OPMD) and oculopharyngodistal myopathy (OPDM) are indistinguishable. We found that p62-positive intra-nuclear inclusions (INIs) in myonuclei (myo-INIs) were significantly more frequent in OPMD (11.4 {+/-} 4.1%, range 5.0- 17.5%) than in OPDM and other rimmed vacuolar myopathies (RVMs) (1-2% on average, range 0.0-3.5%, p<0.0001). In contrast, INIs in nonmuscle cells (nonmuscle-INIs) were present in OPDM, but absent in other RVMs, including OPMD. These results indicate that OPMD can be differentiated from OPDM and other RVMs by the frequent presence of myo-INIs ([≥]5%) and the absence of nonmuscle-INIs in muscle pathology.


title: Patient Experience with Amputation or Limb Loss: Literature Review

abstract:
BackgroundsAmputation which is the removal of body parts, the reality faced by patients who must be amputated raises various responses ranging from rejection to acceptance. The process of each patient is certainly different according to the experience experienced by each patient.

MethodsThis literature review uses articles published from 2018-2022 with source from databased ScienceDirect, Pubmed, Scopus, Sage Journals, EBSCO-Host, BMC Journal, Springer Link, Taylor and Francis, and ProQuest. The keywords used are patient experience, perspectives of patients, amputations, limb loss, low extremity amputation, qualitative, qualitative study. Article selection follows "PRISMA" flow.

ResultsThis systematic review have a total of 6 articles meet the criteria for analysis. Respondents involved in this qualitative research amounted to 109 respondents who had undergone the amputation process. There are several themes that are used to explore the patients experience, the themes used are divided into several aspects in the form of aspects of physical changes, aspects of psychological changes, and also aspects of social adaptation that patients must go through after undergoing the amputation process.

ConclusionThrough a qualitative study, it was found that the average patient expressed feelings of worry, fear, anxiety, feeling useless, no longer liking his body, feeling lost in self-confidence, and no longer wanting to interact socially because of the negative response from the surrounding environment towards the patients.

category: nursing


title: Weight-Normative Messaging Predominates on TikTok - A Qualitative Content Analysis

abstract: Tiktok is a social media platform with many adolescent and young adult users. Food, nutrition, and weight-related posts are popular on TikTok, yet there is little understanding of the content of these posts, and whether nutrition-related content is presented by experts. The objective was to identify key themes in food, nutrition, and weight-related posts on TikTok. 1000 TikTok videos from 10 popular nutrition, food, and weight-related hashtags each with over 1 billion views were downloaded and analyzed using template analysis. The one-hundred most viewed videos were downloaded from each of the ten chosen hashtags. Two coders then coded each video for key themes. Key themes included the glorification of weight loss in many posts, the positioning of food to achieve health and thinness, and the lack of expert voices providing nutrition information. The majority of posts presented a weight-normative view of health, with less than 3% coded as weight-inclusive. Most posts were created by white, female adolescents and young adults. Nutrition-related content on TikTok is largely weight normative, and may contribute to disordered eating behaviors and body dissatisfaction in the young people that are TikToks predominant users. Helping users discern credible nutrition information, and eliminate triggering content from their social media feeds may be strategies to address the weight-normative social media content that is so prevalent.

category: nutrition


title: Leg ulcers are associated with an increased risk of Sickle eye disease in Lagos.

abstract:
Key PointPatients with sickle cell Leg ulcers are 5.9 times more likely to develop sickle retinopathy.

Leg ulcers are a common sign in Sickle Cell Disease. But to what extent are they indicative of Sickle cell eye disease in these patients? This short communication assesses to what extent leg ulcers predict the presence of sickle eye disease in Nigerian patients.

This was a clinic based, comparative non-interventional study, conducted at both the Hematology Clinic and Eye clinic in Lagos University Teaching Hospital (LUTH). One hundred consecutive cases of Sickle Cell Disease (SCD) patients (HbSS and HbSC) attending the Haematology Clinic were compared with 100 age and sex matched non-SCD HbAA controls. The presence of leg ulcers was sought in both groups, and all had assessment for ocular anterior and posterior signs of SCD. Cases and controls were comparable in age and sex. Amongst 100 Cases, 85 were HbSS and 15 HbSC. Leg ulcers were present in 18 patients. Eighty-two cases had either anterior or posterior SCD related ocular manifestations. Patients with leg ulcer were found to be at higher risk of developing Conjunctival Sickle Sign, Retinal Venous Tortuosity and Proliferative Sickle Retinopathy with an increased likelihood of 22.9, 7.1 and 5.9 times respectively. We believe this is the first study to quantify this association.

ConclusionsThis study suggests that sickle cell eye disease is more likely to develop in sickle cell disease patients with leg ulcers. Internists managing SCD patients are advised to refer patients with leg ulcers for early ocular assessment in order to prevent complications.

category: ophthalmology


title: A mesocorticolimbic dopamine gene network moderates the effect of early adversity on the risk for psychiatric and cardio-metabolic comorbidities

abstract: Psychiatric and cardio-metabolic conditions are commonly comorbid, being a leading cause of disability. Early adversity is a risk factor for both conditions, however, biological pathways remain unknown. The dopamine (DA) system is sensitive to early adversity and influences the development of comorbidities. We hypothesized that early life adversity would functionally link these conditions with the mesocorticolimbic dopamine system as a critical moderator pathway. We computed a co-expression based polygenic score (ePRS) reflecting variations in the function of the dopamine transporter (DAT) gene network in the prefrontal cortex and striatum, the final targets of the mesocorticolimbic pathway. We explored the interaction effects of the ePRS with a score of early life adversity on presence of psychiatric and cardio-metabolic comorbidities in adults (UK Biobank, N= 60016) and adolescents (ALSPAC, N= 910). In adults we also explored genetic and environment effects on gray matter density variations. As predicted, the mesocorticolimbic DAT1 ePRS significantly moderated the impact of early life adversity on the risk for both psychiatric (schizophrenia, neuroticism, mood and substance use disorders) and cardio-metabolic (type 2 diabetes, atherosclerosis, cardiovascular disease) comorbidities in adults and adolescents. Brain gray matter densities in the insula and prefrontal cortex were significantly associated with SNPs from the DAT1 ePRS implicating these regions as critical dopaminergic targets for psychiatric/cardio-metabolic comorbidities. These results reveal that psychiatric and cardio-metabolic comorbidities share common developmental pathways and underlying biological mechanisms.

category: genetic and genomic medicine


title: Using genotyping and whole-exome sequencing data to improve genetic risk prediction in deep venous thrombosis

abstract:
BackgroundDeep Vein Thrombosis (DVT) is a common disease that can lead to serious complications such as pulmonary embolism and in-hospital mortality. More than 60% of DVT risk is influenced by genetic factors, such as Factor V Leiden (FVL) and prothrombin G20210A mutations (PTM). Characterising the genetic contribution and stratifying participants based on their genetic makeup can favourably impact risk prediction. Therefore, we aimed to develop and evaluate a genetic-based prediction model for DVT based on polygenic risk score (PRS) in the UK Biobank cohort.

MethodsWe performed a genome-wide association study (GWAS) and constructed a PRS in the 60% (N=284,591) of the UK Biobank cohort. The remaining 40% (N=147,164) was employed to evaluate the PRS and to perform gene-based tests on exome-sequencing data to identify effects by rare variants.

ResultsIn the GWAS, we discovered and replicated a novel variant (rs11604583) near TRIM51 gene and in the exome-sequencing data, and we identified a novel rare variant (rs187725533) located near CREB3L1, associated with 2.2-fold higher risk of DVT. In our PRS model, the top decile is associated with 3.4-fold increased risk of DVT, an effect that is 2.3-fold, when excluding FVL carriers. In the top PRS decile, cumulative risk of DVT at age of 80 years is 10% for FVL carriers, contraposed to 5% for FVL non-carriers.

ConclusionWe showed that common and rare variants influence DVT risk and that the PRS improves risk prediction on top of FVL. This suggests that individuals classified with high PRS scores could benefit from early genetic screening.


title: Machine learning approaches for electronic health records phenotyping: A methodical review

abstract:
ObjectiveAccurate and rapid methods for phenotyping are a prerequisite to realizing the potential of electronic health records (EHRs) data for clinical and translational research. This study reviews the literature on machine learning (ML) approaches for phenotyping with respect to the phenotypes considered, the data sources and methods used, and the contributions within the wider context of EHR-based research.

Materials and MethodsWe searched for relevant articles in PubMed and Web of Science published between January 1, 2018 and April 14, 2022. After screening, we collected data on 52 variables across 106 selected articles.

ResultsML-based methods were developed for 156 unique phenotypes, primarily using EHR data from a single institution or health system. 72 of 106 articles leveraged unstructured data in clinical notes. In terms of methodology, supervised learning is the most prevalent ML paradigm (n = 64, 60.4%), with half of the articles employing deep learning. Semi-supervised and weakly-supervised approaches were applied to reduce the burden of obtaining gold-standard labeled data (n = 21, 19.8%), while unsupervised learning was used for phenotype discovery (n = 20, 18.9%). Federated learning has been applied to develop algorithms across multiple institutions while preserving data privacy (n = 2, 1.9%).

DiscussionWhile the use of ML for phenotyping is growing, most articles applied traditional supervised ML to characterize the presence of common, chronic conditions.

ConclusionContinued research in ML-based methods is warranted, with particular attention to the development of advanced methods for complex phenotypes and standards for reporting and evaluating phenotyping algorithms.

category: health informatics


title: Systematic Review of Supervised Machine Learning Models in Prediction of Medical Conditions

abstract:
Machine learning (ML) models for analyzing medical data are critical for both accelerating development of novel diagnostic and treatment strategies and improving the accuracy of medical care delivery. Our objective was to comprehensively review supervised ML models for diagnosis or treatment prediction. Publications indexed in PubMed were reviewed to identify articles utilizing supervised predictive ML models in medicine. Articles published between 01/01/2020-01/01/2022 were included in this review. Initially, PubMed was searched using MeSH major terms, and if more extensive search results were needed, a broader search was applied (titles/abstracts).

PubMed indexed 21,268 published articles (MeSH Major topic) describing ML methods implemented in medicine. Of those, 11,726 articles were published within the last 2 years. Most of the published ML models in medicine in the last two years were different types of deep learning models (about 75%). Fifty articles were included in this review.

Almost all categories of disease were subjects of ML predictions. Positive and negative factors in each of the scenarios need to be evaluated before the most optimal ML model is selected. Domain knowledge and collaborations between physicians and ML experts can improve the selection and prediction performance of ML models in medicine and facilitate implementation in clinical practice. Predictive ML models could provide recommendations to recruit suitable patients for clinical trials. Prediction ML models may contribute to development of more effective diagnostic and therapeutic choices, founded on evidence-based medicine. A broad range of methodological approaches have been taken toward this goal, and those approaches are presented here with their various advantages and disadvantages.

AUTHOR SUMMARYOver the last decade, there has been rapid development of Machine learning (ML) methods to analyze Big Data in medicine. ML is aimed to make the computer learn from past experiences and make predictions by recognizing patterns in medical data. We performed a comprehensive systematic literature review of recent publications (last two years), indexed in PubMed/MEDLINE that have described either traditional or deep supervised prediction ML models in medicine. We identified 21,268 articles describing ML implementation in medicine. 11,726 articles were published in the last 2 years. We presented the number of publications describing each of the most often ML methods to show current trends in development of these models. Most of the recently published ML models in medicine were deep learning models. We found that the understanding of disease is likely to lead to more accurate prediction. An important dilemma is the selection of optimal ML models for a specific task, considering amount and type of available data. Domain knowledge and collaborations between physicians and ML experts can improve the prediction performance of ML models, which could help clinicians to select the most effective diagnostic and therapeutic choices available and decrease medical errors.


title: Towards Equitable Patient Subgroup Performance by Gene-Expression-Based Diagnostic Classifiers of Acute Infection

abstract: Host-response gene expression measurements may carry confounding associations with patient demographic characteristics that can induce bias in downstream classifiers. Assessment of deployed machine learning systems in other domains has revealed the presence of such biases and exposed the potential of these systems to cause harm. Such an assessment of a gene-expression-based classifier has not been carried out and collation of requisite patient subgroup data has not been undertaken. Here, we present data resources and an auditing framework for patient subgroup analysis of diagnostic classifiers of acute infection. Our dataset comprises demographic characteristics of nearly 6500 patients across 49 studies. We leverage these data to detect differences across patient subgroups in terms of gene-expression-based host response and performance with both our candidate pre-market diagnostic classifier and a standard-of-care biomarker of acute infection. We find evidence of variable representation with respect to patient covariates in our multi-cohort datasets as well as differences in host-response marker expression across patient subgroups. We also detect differences in performance of multiple host-response-based diagnostics for acute infection. This analysis marks an important first step in our ongoing efforts to characterize and mitigate potential bias in machine learning-based host-response diagnostics, highlighting the importance of accounting for such bias in developing diagnostic tests that generalize well across diverse patient populations.


title: The nature and extent of enterprise virtual care physician services in Canada: an environmental scan

abstract:
BackgroundEmployers in Canada are increasingly offering physician services to their employees, often through enterprise virtual care platforms. To date however, little work has been done to understand this method of organizing and delivering care.

ObjectiveTo understand the nature, extent and implications of enterprise virtual care in Canada.

MethodsWe conducted structured internet and database searches to identify enterprise virtual care platforms and their public websites. To answer our research question, we extracted data from their websites, and linked company documents, including investor reports, and information from Mergent Intellect, a web-based application with business data on Canadian companies.

FindingsWe identified nine companies offering enterprise virtual care physician services to employees in Canada on behalf of their employers. According to enterprise virtual care company claims, over four million Canadian employees and their family members have access to enterprise virtual care services. All platforms offer virtual physician services to employees and four also offer in person visits arranged through their platforms. Eight of the platforms provide primary care services and one offers only addiction medicine services. Four of the platforms offer to communicate and share information with an employees regular primary care provider. Four state they share aggregate or de-identified health data with employers.

ImplicationsEnterprise virtual care companies provide millions of Canadian employees and their families with access to physician services. These services appear to disrupt continuity of care (care by the same provider over time) and pose risks to privacy. As other Canadians do not have access to these services, enterprise virtual care is also introducing two-tiered health care broadly across Canada.

category: health policy


title: Estimates of Cross-Border Menthol Cigarette Sales Following the Comprehensive Tobacco Flavor Ban in Massachusetts

abstract: On June 1, 2020, Massachusetts became the first state in the US to ban all flavored tobacco product sales, including menthol cigarettes. Recent research has estimated the reduction in cigarette sales in Massachusetts following the comprehensive tobacco flavor ban, but noted that missing data on border states was a major limitation of the findings. This letter replicates the procedures of Asare et al. with 1540 state-months and then adds Asare et al.s missing states with 2420 total observations for the period January 2017 to July 2021. The replication confirms Asare et al.s adjusted estimate for the reduction in menthol cigarettes, which falls within their 95% confidence interval. However, assigning Massachusetts and its bordering states as a single treatment group leads to an increase of 191.95 (95% CI, 96.82 to 287.09) total cigarette packs sold per 1000 people in the six-state region. In the 12-month period following the comprehensive flavor ban in Massachusetts, the state sold 29.96 million fewer cigarette packs compared to the prior period. However, a total of 33.36 million additional cigarette packs were sold during the same post-ban period in the counties that bordered Massachusetts. Given decreasing rates of smoking in all five bordering states between 2019 and 2020, the increase in border-state cigarette sales following the comprehensive flavor ban should be interpreted as a lower-bound estimate for cigarettes that were ultimately consumed in Massachusetts.


title: GroceryDB: Prevalence of Processed Food in Grocery Stores

abstract: The offering of grocery stores is a strong driver of consumer decisions, shaping their diet and long-term health. While processed food has been increasingly associated with unhealthy diet, information on the degree of processing characterising an item in a store is virtually impossible to obtain, limiting the ability of individuals to make informed choices. Here we introduce GroceryDB, a database with over 50,000 food items sold by Walmart, Target, and Wholefoods, unveiling the degree of processing characterizing each food. GroceryDB indicates that 73% of the US food supply is ultra-processed, and on average ultra-processed foods are 52% cheaper than minimally-processed alternatives. We find that the nutritional choices of the consumers, translated as the degree of food processing, strongly depend on the food categories and grocery stores. We show that there is no single nutrient or ingredient "bio-marker" for ultra-processed food, allowing us to quantify the individual contribution of over 1,000 ingredients to ultra-processing. GroceryDB and the associated http://TrueFood.Tech/ website make this information available, aiming to simultaneously empower the consumers to make healthy food choices, and aid policy makers to reform the food supply.


title: Do panic values cause panic? Reporting of critical laboratory results in a tertiary hospital in Kenya

abstract: Prompt communication of critical laboratory results is important for patient safety. Various standardisation bodies have proposed procedures for handling critical results, with notification parameters outlined. However, few studies exist in low- and middle-income countries (LMIC) to document how critical results are handled. We tracked 12 types of laboratory tests over a three-week period in December 2018 and documented if and how critical test results were communicated, the time-frame for communication, and evidence of action taken on the results. During the period, 331 of 5,500 (6.1%) test results were identified as critical. Only 71 (21%) of the critical results were documented as having been communicated to the destination departments. Of the communicated results, clinicians were unaware of 21 (29.6%). Of the 12 test types, critical results were only communicated for three tests namely: potassium, haemoglobin and positive malaria tests. Communication of critical results to inpatient settings was significantly higher than to outpatient settings (p <0.05), with communication rates decreasing as the week progressed, during weekends and around holidays. The observed poor communication of critical results in an LMIC setting raise significant patient safety concerns. Laboratories in these settings need to adhere to international standards, like ISO 15189:2009, to assure safe practice. Training of staff, establishment of standard operating procedures guiding these results, and implementation of fail-proof critical result dissemination mechanisms are essential. It is important that all critical results are communicated within one hour of availability. Implementation of Order Entry and Laboratory systems should be highly considered.


title: Clinical evaluation of an automated, rapid mariPOC(R) antigen test in screening of symptomatics and asymptomatics for SARS-CoV-2 infections

abstract: A novel automated mariPOC(R) SARS-CoV-2 antigen test was evaluated in a Health care center laboratory among symptomatic and asymptomatic individuals seeking SARS-CoV-2 testing. According to the national testing strategy, RT-PCR was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS-CoV-2 RT-PCR positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC(R) SARS-CoV-2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct value <30. The mariPOC(R) SARS-CoV-2 test detected 2/6 PCR positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC(R) SARS-CoV-2 test was 100% (916/916). The evaluation showed that the mariPOC(R) SARS-CoV-2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious.

category: infectious diseases


title: Vaping preferences of individuals who vaporise dry herb cannabis, cannabis liquids and cannabis concentrates

abstract: In 2019 an estimated 200 million people aged 15-64 used cannabis, making cannabis the most prevalent illicit substance worldwide. The last decade has seen a significant expansion in the cannabis vaporiser market, introducing cannabis vaporisation as a common administration method alongside smoking and ingestion. Despite reports of increased prevalence of cannabis vaporisation there has been little research into the use of these devices. To remedy the current dearth of data in this area this study utilised an anonymous online survey of individuals who self-reported past cannabis vaporisation. The respondents (N=557) were predominantly young (<35 years) and male. Most (91.4%) stated they had ever vaped dry herb cannabis, 59.1% reported vaporisation of cannabis oil or liquids, and 34.0% reported vaporisation of cannabis concentrates. This study identifies the types of vaporisation devices (including brands and models) employed by cannabis vapers, as well as the vaporisation temperatures and puff durations commonly used for dry herb, cannabis liquids and cannabis concentrates. To the best of our knowledge, this is the first time the usual operating temperatures of these vaporisation devices and user specific consumption patterns such as puff duration have been reported for cannabis vaping. This information will allow for more realistic experimental conditions in research settings.

category: addiction medicine


title: Delayed booster dosing improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine

abstract:
BackgroundAntibodies are crucial for vaccine-mediated protection against many pathogens. Modifications to vaccine delivery that increase antibody magnitude, longevity, and/or quality are therefore of great interest for maximising efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6mo) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared to monthly dosing (0-1-2mo; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing was unclear.

MethodsImmunokinetics of PfRH5-specific Ig across multiple isotypes were compared between DFx and monthly regimen vaccinees. Peak responses were characterised in-depth with a systems serology platform including biophysical and functional profiling. Computational modelling was used to define the humoral feature set associated with DFx dosing. PfRH5-specific B cells were quantified by flow cytometry and sorted for single cell RNA sequencing (scRNA-seq). Differential gene expression between DFx and monthly dosing regimens was explored with Seurat, DESeq2 and gene set enrichment analysis.

ResultsDFx dosing increases the frequency of circulating PfRH5-specific B cells and longevity of PfRH5-specific IgG1, as well as other isotypes and subclasses. At the peak antibody response, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn-binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. At the same time point, scRNA-seq of PfRH5-specific B cells revealed enriched plasma cell and Ig / protein export signals in the monthly dosing group as compared to DFx vaccinees.

ConclusionsDFx dosing of the RH5.1/AS01B vaccine had a profound impact on the humoral response. Our data suggest plausible mechanisms relating to improved FcRn-binding (known to improve Ig longevity) and a potential shift from short-lived to long-lived plasma cells. Recent reports of the positive impact of delayed boosting on SARS-CoV-2 vaccine immunogenicity highlight the broad relevance of these data.

category: allergy and immunology