title: Predictive and analysis of COVID-19 cases cumulative total：ARIMA model based on machine learning

abstract: At present, COVID-19 poses a serious threat to global human health, and the cumulative confirmed cases in America, Brazil and India continue to grow rapidly. Therefore, the prediction models of cumulative confirmed cases in America, Brazil and India from August 1, 2021 to December 31, 2021 were established. In this study, the prevalence data of COVID-19 from 1 August 2021 to 31 December 2021 were collected from the World Health Organization website. Several ARIMA models were formulated with different ARIMA parameters. ARIMA (7,2,0), ARIMA (3,2,1), and ARIMA (10,2,4) models were selected as the best models for America, Brazil, and India, respectively. Initial combinations of model parameters were selected using the automated ARIMA model, and the optimized model parameters were then found based on Bayesian information criterion (BIC). The analytical tools autocorrelation function (ACF), and partial autocorrelation function (PACF) were used to evaluate the reliability of the model. The performance of different models in predicting confirmed cases from January 1, 2022 to January 5, 2022 was compared by using root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE). This study shows that ARIMA models are suitable for predicting the prevalence of COVID-19 in the future. The results of the analysis can shed light on understanding the trends of the outbreak and give an idea of the epidemiological stage of these regions. Besides, the prediction of COVID-19 prevalence trends of America, Brazil, and India can help take precautions and policy formulation for this epidemic in other countries.


title: Predictive and analysis of COVID-19 cases cumulative total;ARIMA model based on machine learning

category: public and global health


title: TNFα-producing CD4+ T cells dominate the SARS-CoV-2-specific T cell response in COVID-19 outpatients and are associated with durable antibodies

abstract: SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection and specific features that correlate with the maintenance of neutralizing antibodies remains limited. We characterized SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients. The quality of the SARS-CoV-2-specific CD4+ response shifted from cells producing IFN{gamma} to TNF+ from five days to four months post-enrollment, with IFN{gamma}-IL21-TNF+ CD4+ T cells the predominant population detected at later timepoints. Greater percentages of IFN{gamma}-IL21-TNF+ CD4+ T cells on day 28 correlated with SARS-CoV-2 neutralizing antibodies measured seven months post-infection ({rho}=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosted both IFN{gamma} and TNF producing, spike protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

category: infectious diseases


title: Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

abstract: Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity to Delta and Omicron SARS-CoV-2 variants in 239 samples from 125 fully vaccinated individuals. In uninfected, non-boosted individuals, VLP neutralization titers to Delta and Omicron were reduced 2.7-fold and 15.4-fold, respectively, compared to wild-type (WT), while boosted individuals (n=23) had 18-fold increased titers. Delta breakthrough infections (n=39) had 57-fold and 3.1-fold titers whereas Omicron breakthrough infections (n=14) had 5.8-fold and 0.32-fold titers compared to uninfected non-boosted and boosted individuals, respectively. The difference in titers (p=0.049) was related to a higher proportion of moderate to severe infections in the Delta cohort (p=0.014). Correlation of neutralizing and spike quantitative antibody titers was decreased with Delta or Omicron compared to WT. Neutralizing antibodies in Delta and Omicron breakthrough infections increase overall, but the relative magnitude of increase is greater in more clinically severe infection and against the specific infecting variant.


title: Comparative immunogenicity of heterologous versus homologous 3rd SARS-CoV-2 vaccine doses in kidney transplant recipients

abstract:
BackgroundSolid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2.

Methods700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3rd doses were BNT162b2. All participants had serological testing performed post-2nd vaccination at a median time of 34 (IQR 26-46) days following the 2nd inoculation, and at least once prior to their 1st dose of vaccine.

Results366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection naive participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3rd vaccine (V3); 54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, p<0.0001.

Cellular responses were investigated in 30 infection naive participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77.

ConclusionA significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

category: transplantation


title: Estimating Under-diagnosis of Patients in Chronically-ill Populations

abstract: Diagnosis coding in administrative data is known to be inconsistent and incomplete, introducing inaccurate assessment of patients health outcomes. The under-diagnosis of members with a target chronic condition reduces the correlation of that chronic condition with associated events. Yet, only a few studies have evaluated the extent of under-reporting of chronic conditions in administrative data. In this study, we developed a novel framework to identify latent members, or those who have not yet been identified with a target chronic condition through claims-based diagnosis but are likely to have some degree of the condition. We applied our innovative approach to estimate the prevalence of a chronic-related event, based on the population of observed and latent members. We provided a detailed illustration that treats incontinence as our target chronic condition while examining four types of incontinence-related events: urinary-tract infections (UTIs), slips and falls, dermatitis, and behavioral disruptions. All analysis relied on the 5% Medicare sample for a continuously enrolled cohort between 2014-2018. Using our novel approach, we were able to increase our identification of incontinence from the 11.2% diagnosed in 2018 to an estimated prevalence in 2018 of 34.7% among fee-for-service Medicare beneficiaries over the age of 65. Similarly, our estimation of UTIs associated with those with incontinence increased from 38% to 68%, from 20% to 41% for IAD, 22% to 54% for slips and falls, and from 26% to 57% for behavior disruptions.

category: urology


title: Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in patients receiving haemodialysis

abstract:
BackgroundEmerging data suggest a reduction in SARS-CoV-2 vaccine effectiveness against Omicron SARS-CoV-2 infection. There is also evidence to show that Omicron is less pathogenic than previous variants. For clinically vulnerable populations, a less pathogenic variant may still have significant impact on morbidity and mortality. Herein we assess the clinical impact of Omicron infection, and vaccine effectiveness, in an in-centre haemodialysis (IC-HD) population.

MethodsOne thousand, one hundred and twenty-one IC-HD patients were included in the analysis, all patients underwent weekly screening for SARS-CoV-2 infection via RT-PCR testing between 1st December 2021 and 16th January 2022. Screening for infection via weekly RT-PCR testing and 3-monthly serological assessment started prior to the vaccine roll out in 2020.

ResultsOmicron infection was diagnosed in 145/1121 (12.9%) patients over the study period, equating to an infection rate of 3.1 per 1000 patient days. Vaccine effectiveness (VE) against Omicron infection in patients who had received a booster vaccine was 58 (23-75)%, p=0.002; VE was seen in patients who received either ChAdOx1, VE of 47(2-70)%, p=0.034, or BNT162b2, VE of 66 (36-81)%, p=0.0005, as their first two doses. No protection against infection was seen in patients who were partially vaccinated (2-doses), p=0.83. Prior infection was associated with reduced likelihood of Omicron infection, HR 0.69 (0.50-0.96), p=0.0289. Four (2.8%) patients died within 28 days of infection diagnosis, with no excess mortality was seen in patients with infection.

Conclusion3-doses of SARS-CoV-2 vaccines are required in ICHD to provide protection against Omicron infection.

category: nephrology


title: Adverse events following COVISHIELD (ChAdOx1nCoV-19) vaccination among health care workers in Sri Lanka; a multi-centre cross sectional survey

abstract:
IntroductionA community vaccination programme is the best approach to combat the COVID-19 pandemic. Post-vaccine surveillance is important to identify adverse events (AE) following COVID -19 vaccination in the population.

MethodsA multicentre cross-sectional survey was conducted in six provinces to estimate the prevalence of AE following the first dose of COVISHIELD (ChAdOx1nCoV-19) among all categories of health care workers (HCWs). A self-administered questionnaire was used to gather demographic data and AE.

ResultsOf 5140 participants 67.8% were females. The mean (SD) age was 40.69 ({+/-}9.85) years. At least one comorbidity was reported in 15.4%. At least one AE was reported in 86.6% and 49.3% had local AE. Fever (67.2%), headaches (57.3%), body aches (54.4%), chills (51.2%), fatigue (37.5%) and arthralgia (36%) were the most reported systemic AE. The majority of AE lasted less than 24 hours. Pain and redness at the site were the most reported local AE. Mean duration of onset of fever and pain at injection site from the time of the vaccination was 6.65 and 9.67 hours respectively.

When participants were divided into two groups by mean age ([≤]40 and >40 years) and parameters were compared, most systemic (fever, nausea, fatigue, itching) and all local AE were significantly more prevalent in the [≤]40 age group.

Two percent had reactions within the first 20 minutes. Anaphylaxis developed in 12 participants. Past history of anaphylaxis, drug or food allergy were reported in 0.6%, 2.8% and 6.7% respectively. However, previous history of allergy was not significantly related to immediate reactions or anaphylaxis following vaccination. Despite having minor AE, 71.1% attended routine work while 0.2% required hospitalisation.

ConclusionsWhile 86.6% reported minor AE, only a few serious AE were reported. Overall, the first dose of the vaccine was well-tolerated by HCWs.


title: The McGill Approach to Core Stabilization in the Treatment of Chronic Low Back Pain: A Review

abstract:
IntroductionLow back pain (LBP) is a major cause of disability and is progressively becoming worse on a global scale. [1,2] The prevention and rehabilitation of LBP lacks clarity in part due to the heterogeneity of the exercise programs prescribed to treat low back pain. Some authors have proposed stabilizing exercises for lower back pain which exert minimal loads on the spine. [3,4,5] Despite a multitude of existing exercise therapies, McGill has introduced three exercises for rehabilitating lower back pain, termed the McGill Big Three (MGB3). [6,7,8,9,10] These include the curl-up, side plank and bird-dog. The purpose of this review is to investigate the clinical outcomes from prescribing the MGB3 to individuals with chronic LBP.

MethodsInclusion criteria were randomized control trials that involved an intervention with MGB3 core stabilization exercises for patients with chronic low back pain. The research included articles published during any period in full English text. Studies were critically reviewed by two authors EL and GG independently and collaboratively.

ResultsIn total, four randomized control trials were included in this review. Multiple cohorts, with varying age, demographics and occupation were studied. Outcomes studied included various pain scores, patient reported functional and performance measures.

DiscussionControlled clinical trials employing this method in low back pain treatment showed low quality data with mixed statistical significance, and little to no clinical significance irrespective of the measure used or even when compared to baseline. Limitations of these trials are detailed herein.

ConclusionCurrently there is limited data supporting the clinical benefit of the McGill approach for the treatment of low back pain based on the available randomized clinical trials. More study is required prior to widespread adoption into clinical practice.

category: rehabilitation medicine and physical therapy


title: Efficacy and Safety of a Plant-Based Virus-Like Particle Vaccine for COVID-19 Adjuvanted with AS03

abstract:
BackgroundSeveral COVID-19 vaccines are currently being deployed but supply constraints, concerns over durability of immune responses, solidifying vaccine hesitancy/resistance and vaccine efficacy in the face of emerging variants mean that new vaccines continue to be needed to fight the ongoing pandemic. The vaccine described here is an enveloped, coronavirus-like particle produced in plants (CoVLP) that displays the prefusion-stabilized spike (S) glycoprotein of SARS-CoV-2 (ancestral Wuhan strain) and is adjuvanted with AS03 (CoVLP+AS03).

MethodsThis Phase 3 randomized, observer-blind, placebo-controlled trial was conducted at 85 centers in Argentina, Brazil, Canada, Mexico, the UK, and the USA. Adults [≥]18 years of age including those at high risk for COVID-19 complications were randomly assigned 1:1 to receive two intramuscular injections of CoVLP (3.75 g) adjuvanted with AS03 or placebo, 21 days apart. The primary efficacy endpoint was prevention of symptomatic ([≥] 1 symptom), PCR-confirmed SARS-CoV-2 infection with onset at least 7 days after the second injection and was triggered by the identification of [≥]160 virologically-confirmed cases. Tolerability and safety of CoVLP+AS03 were also determined.

ResultsA total of 24,141 volunteers were randomly assigned 1:1 to receive vaccine or placebo (N= 12,074 and 12,067, respectively: median age 29, range 18 to 86 years). Overall, 83% received both doses. 14.8% were SARS-CoV-2 seropositive at baseline. Symptomatic SARS-CoV-2 infection was confirmed in 165 study participants in the intention to treat (ITT) set and 157 in the per-protocol population (PP) set. Of the 157 in the PP set, 118 COVID-19 cases were in the placebo group and 39 COVID-19 cases were in the CoVLP+AS03 group for an overall vaccine efficacy (VE) of 71.0% (95% confidence interval (CI) 58.6, 80.0). Moderate-to-severe COVID-19 occurred in 8 and 32 participants in the CoVLP+AS03 and placebo groups, respectively: VE 78.1% (95% CI: 53.9, 90.5) in the PP set overall and 84.5% (95% CI: 62.0, 94.7) in those seronegative at recruitment.

To date, 100% of the sequenced strains (122/165 cases: 73.39%) were variants, dominated by Delta (45.9%) and Gamma (43.4%) strains. Vaccine efficacy by variant was 75.3% (95% CI 52.8, 87.9) against Delta and 88.6% (95% CI 74.6, 95.6) against Gamma. Cross-protection was also observed against Alpha, Lambda and Mu variants; although fewer cases were identified, all were in the placebo group. At diagnosis, viral loads in the CoVLP+AS03 breakthrough cases were >100-fold lower than in the placebo cases. Reactogenicity data for solicited adverse events (AEs) was analysed for a subset (N=4,136 in vaccine arm and N=3,683 for placebo) of participants. Reactogenicity was mostly mild to moderate, and transient, and occurred more frequently in the CoVLP+AS03 group. The safety analysis set used for unsolicited AE assessment comprised 24,076 participants who received at least one study injection: 12,036 received CoVLP+AS03 and 12,040 received placebo. All serious adverse events were assessed as unrelated, except two events reported in the same subject in the placebo group. No significant imbalance or safety concern was noted in medically attended AEs (MAAEs), adverse event of special interest (AESIs), AEs leading to withdrawal, deaths, or adverse events potentially associated with currently authorized vaccines.

ConclusionsThe CoVLP+AS03 vaccine candidate conferred an efficacy of 71.0% in preventing symptomatic SARS-CoV-2 infection caused by a spectrum of variants. Vaccine efficacy of 78.1% was observed against moderate and severe disease, while variant-specific efficacy ranged from 75.3% to 100%. Markedly lower viral loads in the CoVLP+AS03 group at the time of diagnosis suggests a significant virologic impact of vaccination even in the breakthrough cases. CoVLP+AS03 vaccine candidate was well tolerated, and no safety concerns were identified during the study. If approved by regulators, this more traditional protein+adjuvant vaccine produced using the novel plant-based platform may be able to make an important contribution to the global struggle against the increasingly complex family of SARS-CoV-2 viruses (Funded by Medicago with grants from the governments of Quebec and Canada; NCT04636697).


title: Seroepidemiological and genomic investigation of COVID-19 spread in North East region of India

abstract: Seroepidemiology and genomics are valuable tools to investigate the transmission of COVID-19. We utilized qRT-PCR, serum antibody immunoassays, and whole genome sequencing to examine the spread of SARS-CoV-2 infections in North East (NE) region of India during the first and second pandemic waves (June 2020 to September 2021). qRT-PCR analysis was performed on a selected population from NE India during June 2020 to July 2021, and metadata were collected for the region. Seroprevalence and neutralizing antibody immunoassay were studied on selected individuals (n=2026) at three time points (August 2020, February 2021 and June 2021), as well as in a cohort (n=35) for a year (August 2020 to August 2021). SARS-CoV-2 genomes of 914 qRT-PCR positive samples (June 2020 to September 2021) were sequenced and assembled, and those obtained from the sequence databases were analyzed. Test positivity rates in first and second waves were 6.34% and 6.64% in the state of Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in August 2020, February 2021, and June 2021 were 10.63%, 40.3% and 46.33% respectively, and neutralizing antibody prevalence were 90.91%, 52.14%, and 69.30% respectively. The cohort group showed the presence of stable neutralizing antibody throughout the year. Normal variants dominated the first wave, while the variant of concerns (VOCs) B.1.617.2 and AY-sublineages dominated the second wave, and identified mostly among vaccinated individuals. All eight states of NE India reported numerous incidences of SARS-CoV-2 VOCs, especially B.1.617.2 and AY sublineages, and their prevalence co-related well with high TPR and seropositivity rate in the region. High infection and seroprevalence of COVID-19 in NE India during the second wave was associated with the emergence of VOCs. Natural infection prior to vaccination provided higher neutralizing activity than vaccination alone.

category: epidemiology


title: Wearable technology for health monitoring during pregnancy: an observational cross-sectional survey study

abstract:
ObjectiveTelemedicine has advanced to the forefront of healthcare delivery, including maternal-fetal medicine. Smart wearable electrocardiogram (ECG) devices can enable pregnant women to monitor their health and that of their fetuses. Such technology would be a logical extension of the telemedicine ecosystem. However, it is not known how pregnant women perceive the ability to use such technologies.

DesignObservational cross-sectional study.

SettingOnline survey in the United States in 2019.

PopulationA representative sample of 507 women aged 18-45 were polled from 45 states.

MethodsStudy participants were recruited using the SurveyMonkey Audience Polling system and responded virtually.

Main Outcome MeasuresWomen were asked to identify willingness to use a wearable ECG device the size of a patch-sized large band-aid on their abdomen. Ten binary or multiple-choice questions were used to gauge population interest and related demographics towards the usage of a wearable ECG device.

Results91% of women expecting to become pregnant in the next five years accept wearable ECG technology as a mechanism for increased frequency of monitoring of maternal and fetal health throughout the pregnancy outside the hospital. 78% of women demonstrated a willingness to wear devices day and night or at least during sleep and 42% of women would spend up to $200 on such a device.

ConclusionsEven though conducted prior to the COVID-19 pandemic, this study clearly indicates a high degree of readiness of prospective pregnant women for telemedicine with continuous health monitoring of the mother-fetus dyad during the entire antepartum period.

Fundingn/a

category: obstetrics and gynecology


title: Comparative diagnostic performance of the new chromatographic Affimer(R)-based rapid antigen detection against SARS-CoV-2 and other standard antigen tests for COVID-19 in a clinical setting.

abstract: The availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. In this context, researchers in the UK have started testing a new Lateral Flow Device (LFD) based on proprietary Biotinylated anti SARS-CoV-2 S1 Affimer(R) technology that binds to the SARS-CoV2-S1 protein in anterior nasal swab samples, generating an ultra-sensitive method for detection. This international study aimed to compare its performance against other available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world clinical setting. The study was completed under the frame of Project SENSORNAS RTC-20176501 in collaboration with MiRNAX Biosens Ltd. and Hospital Carlos III, it was documented internally and deposited in agreement to the ISO 13485 norm. All the data obtained are currently under submission and review from the Ethics Committee of Universidad Autonoma de Madrid.


title: Identification of eight novel variants across PAX3, SOX10, EDNRB and MITF genes in Waardenburg syndrome with next-generation sequencing

abstract: Waardenburg syndrome (WS) is a hereditary, genetically heterogeneous disorder characterized by variable presentations of sensorineural hearing impairment and pigmentation anomalies. This study aimed to investigate the clinical features of WS in detail and determine the genetic causes of patients with clinically suspected WS. A total of 24 patients from 21 Han Taiwanese families were enrolled and underwent comprehensive physical and audiological examination. We applied targeted next-generation sequencing (NGS) to investigate the potential causative variants in these patients and further validated the candidate variants through Sanger sequencing. We identified 18 causative variants of WS in our cohort. Of these variants, eight were novel and discovered in PAX3, SOX10, EDNRB, MITF genes, including missense, nonsense, deletion, and splice site variants. Several patients presented skeletal deformities, hypotonia, megacolon, and neurological disorders that were rarely seen in WS. This study revealed highly phenotypic variability in Taiwanese WS patients and demonstrated that targeted NGS allowed us to clarify the genetic diagnosis and extend the genetic variant spectrum of WS.

category: otolaryngology


title: Determinants of SARS-CoV-2 nasopharyngeal testing in a rural community sample: the CHRIS COVID-19 study

abstract:
BackgroundTo rapidly characterize COVID-19 epidemiology, numerous population-based studies have been undertaken to model the risk of SARS-CoV-2 infection. Less is known about what may drive the probability to undergo testing. Understanding how much testing is driven by contextual or individual conditions provides the basis for unbiased representation of testing figures and shaping of public health interventions and resource allocation.

MethodsIn the Val Venosta/Vinschgau district (South Tyrol, Italy), we conducted a population-representative longitudinal study on 697 individuals who completed 4,512 repeated online questionnaires at four week intervals between September 2020 and May 2021. Mixed-effects logistic regression models were fitted to investigate associations between self-reported SARS-CoV-2 testing and both individual characteristics (social, demographic, and biological) and contextual determinants.

ResultsTesting was associated with month of reporting, reflecting the timing of both the pandemic intensity and public health interventions, COVID-19-related symptoms (odds ratio, OR:8.26; 95% confidence interval, CI:6.04-11.31), contacts with infected individuals within home (OR:7.47, 95%CI:3.81-14.62) or outside home (OR:9.87, 95%CI:5.78-16.85), and being retired (OR:0.50, 95%CI:0.34-0.73). Within- and outside-home contacts were the leading determinants in the first and second half of the period, respectively, possibly reflecting later relaxation of social-distancing measures. Testing was not associated with age, sex, education, comorbidities, or lifestyle factors.

ConclusionsIn the study area, contextual determinants reflecting the course of the pandemic were predominant compared to individual sociodemographic characteristics in explaining the SARS-CoV-2 probability testing. Decision makers should evaluate whether the intended target groups were correctly prioritized by the testing campaign.

Research in Context box for Lancet Regional Health - EuropeO_ST_ABSEvidence before this studyC_ST_ABSSince the beginning of the COVID-19 pandemic, characterizing the epidemiological landscape of SARS-CoV-2 infections was an urgent need. Numerous population-based studies were undertaken to quantify infection risk. However, while such quantification critically depends on the availability and accessibility of swab tests, studies assessing SARS-CoV-2 nasopharyngeal swab-testing probability at population level are lacking. A PubMed search for "COVID-19" or "SARS-CoV-2" and "testing" and "probability" or "determinants", conducted on November 30, 2021, identified few, mostly non-European cross-sectional studies revealing that access to COVID-19 testing can be associated with deprivation, ethnicity, and age. A comprehensive assessment of how much testing might be driven by contextual rather than personal conditions is currently missing. This appears to be particularly relevant since, during the pandemic, the personal conduct of citizens, which depends on biological, social and cultural factors, seems to have played a role in various circumstances such as willingness to be tested or to be vaccinated. We addressed this question by investigating data from the CHRIS COVID-19 study, a rural population-based study that collected information on SARS-CoV-2 testing as well as biological, sociodemographic, lifestyle-related, and medical conditions from each participant longitudinally between September 2020 and May 2021.

Added value of this studyIn the studied region, which is ethnically and culturally more homogeneous than most other study contexts, contextual determinants reflecting the course of the pandemic and individual sociodemographic characteristics were assessed as determinants for undergoing testing. The only factors suggested to be associated with SARS-CoV-2 testing were the time period, presence of symptoms, and contacts with infected or symptomatic individuals within- and outside-home. The time period reflects the temporal evolution of the pandemic and mitigation policies. Contacts with other individuals reflect the social context, with stronger association found for within-home contact earlier in the period, when infection rates were higher and restrictions on social contact more rigid, and for outside-home contact later. When these factors were accounted for, no personal characteristic was associated with the probability to undergo a swab test, except being retired, which was associated with a lower probability of getting tested, probably because of the greater isolation of this group.

Implications of all the available evidenceThe study shows that, in this area, individuals largely followed the general recommendations for undertaking a test when they had symptoms and contacts with infected individuals. The study also implicates that citizens undertook SARS-CoV-2 testing regardless of their personal demographic, economic, cultural and medical condition. This could be reassuring to the healthcare system in terms of social equity. On the other hand, decision makers should evaluate whether the specific target groups, such as individuals with higher risk to develop severe COVID-19 disease, were correctly prioritized by the testing campaign, especially during the acute phase of the pandemic. Further research is needed to investigate additional reasons potentially related to SARS-CoV-2 testing, such as information about testing center accessibility or limited laboratory resources.


title: Performance of SARS-CoV-2 rapid antigen test compared with real-time RT-PCR in asymptomatic individuals

abstract: Screening, testing and contact tracing plays a pivotal role in the control of COVID-19 pandemic. To carry out this strategy it is necessary to increase the testing capacity. Here, we compared a SARS CoV-2 rapid antigen test (RAT) and RT-PCR in 842 asymptomatic individuals from Tarapaca, Chile. We report a sensibility of 69.86%, a specificity of 99.61%, PPV of 94.44% and NPP of 97.22% with Ct values (Ct > 27) that were significantly higher among individuals with false-negative RAT. These results support the fact that RAT might have a significant impact in the identification of asymptomatic carriers in areas that lack well-equipped laboratories to perform SARS-CoV-2 real -time RT-PCR diagnostics or the results take more than 24-48 hours, as well as zones with high traffic of individuals, such as border/customs, airports, interregional bus, train stations or in any mass testing campaign requiring rapid results.


title: FAMILY LIFE EXPERIENCES IN CARING FOR CHILDREN WITH LEUKEMIA: A LITERATURE REVIEW

abstract: Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer, and ALL is the leading cause of death in children. Chronic diseases, one of which is cancer suffered by children, can provide varied responses to families. Caring for children with cancer requires a very long and complex process, so it requires good coordination between children, parents, families and the health team. The purpose of this literature review is to obtain in-depth information on the experiences of parents in caring for children with cancer. The method of writing this article is a literature review of 40 articles with the year 2019-2021 published from electronic database, namely CINAHL, Web of Science, SAGE and Proquest. The method of searching and selecting articles used The Center for Review and Dissemination and the Joanna Briggs Institute Guideline and PRISMA diagram. Checklist with selection criteria using the PICOS approach. The results of a literature review show that while caring for children with cancer, parents experience stress, anxiety about losing a child, uncertainty in child treatment, difficulties in caring for children and family responsibilities. Support in the form of psychosocial, material, and social support is needed for parents. The declining health condition of children is the biggest obstacle for parents, material needs are needed to support the care of children suffering from cancer, and there is hope from parents for their childs recovery.

category: nursing


title: Do self-management interventions improve self-efficacy and quality of life in stroke survivors? A literarture review

abstract:
ObjectiveThe aim of this review was to assess the effectiveness of self-management interventions on the self-efficacy and quality of life of stroke survivors compared to usual care.

MethodArticle searches were performed using the same keywords in the Pubmed, CINAHL, Scopus and Science Direct databases published from January 2020 to October 16, 2021. A total of 8 articles in randomized controlled trials were identified in this study.

FindingsEight studies were taken, of which six discussed the effectiveness of self-management interventions on self-efficacy and two literatures measured the quality of life of stroke patients. Almost all participatory studies reported an increase in self-efficacy and quality of life after receiving the self-management intervention. The heterogeneity in this study is reported regarding the form of intervention, duration of implementation, instruments used, and outcomes

ConclusionsThere are various self-management interventions, which can be in the form of education, support, coaching, or empowerment. Self-management interventions are reported to improve self-efficacy and quality of life of stroke patients. Future studies are expected to measure the perceived burden of self and self-care in stroke patients


title: Association of Increased Fluvoxamine Use with Reports of Benefit for COVID

abstract:
IntroductionSeveral recent studies have found that fluvoxamine decreases the risk of serious disease progression among people with early SARS-CoV-2 infection. In this study, we examined changes in the total number of fluvoxamine tablets dispensed across retail pharmacies in the U.S.

MethodsWe hypothesized that fluvoxamine prescriptions would increase substantially since March 2021 as an option for the early treatment of SARS-CoV-2 infection. We used the IQVIA National Prescription Audit (NPA) Weekly nationally projected data for prescriptions dispensed from retail pharmacies for fluvoxamine from 27 December 2019 to 31 December 2021. We performed an interrupted-time series analyses on frequency of dispensing fluvoxamine tablets.

ResultsThe weekly rate of dispensed tablets of fluvoxamine increased throughout the study period. The weekly number of dispensed tablets of fluvoxamine increased (11.1%) from a baseline of 1,586,154 (95% confidence interval [CI]: 1,563,960 - 1,608,348) to 1,762,381 (95% CI: 1,735,682 - 1,789,080) by December 2021.

ConclusionOur findings are consistent with a modest increase in the use of fluvoxamine for the treatment of COVID-19 associated with the discovery and media dissemination of the potential clinical benefit of fluvoxamine use.


title: Cohort Profile: The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH)

abstract:
Key Features of the UK-REACH Cohort (Profile in a nutshell)

O_LIThe UK-REACH Cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared to their white ethnic counterparts in the United Kingdom (UK). Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data has been collected.
C_LIO_LIA total of 17891 HCWs aged 16-89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service (NHS) hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study.
C_LIO_LIData available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition, and opinions on COVID-19 vaccines, with baseline (n=15 119), 6 (n=5632) and 12-month follow-up data captured.
C_LIO_LIRequest data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing.
C_LI


title: Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects

abstract:
BackgroundUnderstanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination.

MethodsThis prospective study enrolled 208 healthcare workers from the Liege University Hospital (CHU) of Liege in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naive (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN-{gamma} on peripheral blood lymphocytes using the QuantiFERON Human IFN-{gamma} SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naive and experienced participants.

FindingsWe found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naive HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed.

ConclusionsOur data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses.


title: Nucleocapsid antigenemia is a marker of acute SARS-CoV-2 infection

abstract:
BackgroundReliable detection of SARS-CoV-2 infection is essential for diagnosis and treatment of disease as well as infection control and prevention during the ongoing COVID-19 pandemic. Existing nucleic acid tests do not reliably distinguish acute from resolved infection, as residual RNA is frequently detected in the absence of replication-competent virus. We hypothesized that viral nucleocapsid in serum or plasma may be a specific biomarker of acute infection that could enhance isolation and treatment strategies at an individualized level.

MethodsSamples were obtained from a retrospective serological survey using a convenience sampling method from adult inpatient and outpatient encounters from January through March 2021. Samples were categorized along a timeline of infection (e.g. acute, late presenting, convalescent) based on timing of available SARS-CoV-2 testing and symptomatology. Nucleocapsid was quantified by digital immunoassay on the Quanterix HD-X platform.

ResultsIn a large sample of 1860 specimens from 1607 patients, the highest level and frequency of antigenemia were observed in samples obtained during acute SARS-CoV-2 infection. Levels of antigenemia were highest in samples from seronegative individuals and in those with more severe disease. Using ROC analysis, we found that antigenemia exhibited up to 85.8% sensitivity and 98.6% specificity as a biomarker for acute COVID-19.

ConclusionsNucleocapsid antigenemia is a sensitive and specific biomarker for acute SARS-CoV-2 infection and may aid in individualized assessment of SARS-CoV-2 infection resolution or persistence, although interpretation is limited by absence of a diagnostic gold standard for active infection.


title: Single-Cell RNA Sequencing Reveals the Altered Landscape of Immune Cells in Immune Checkpoint Inhibitor Related Myocarditis

abstract:
BackgroundMyocarditis has emerged as a rare but lethal Immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism for ICI related myocarditis remains underexplored; and the specific therapeutic targets is still lacking. In this study, we used scRNA-seq to characterize the transcriptomic profiles of single cells from the peripheral blood mononuclear cell (PBMC) of ICI related myocarditis during fulminant myocarditis and disease recovery.

MethodsPBMC samples were taken from the patient during fulminant ICI related myocarditis and after disease remission. Cells were isolated from blood samples by density gradient centrifugation over Ficoll-Paque. Single-cell RNA sequencing with 10X genomics was performed. Subpopulation determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were carried out afterwards.

ResultsWe presented the altered landscape of immune cells and differential genes in ICI related myocarditis during the disease activity and remission using scRNA-seq. Substantial immune cell composition and intercellular communication were found to be altered. Monocyte, NK cell as well as B cell subpopulations contributed to the regulation of innate immunity and inflammation in ICI related myocarditis. T cell subpopulations highly expressed genes associated with PD-1 inhibitor resistance and hyper-progressor. At last, the intercellular communication in ICI related myocarditis was significantly dysregulated.

ConclusionBy identifying altered pathways and highlighting a catalog of marker genes, this study has revealed the diversity of cellular populations in ICI related myocarditis, marked by their distinct transcriptional profiles and biological functions. Our investigation would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI related myocarditis in continuous exploration.

category: allergy and immunology


title: Knowledge and aptitude of early childhood, primary and/or secondary education teachers referred to first aid measures in dental trauma in the province of Seville (Spain.)

abstract:
The high of childhood dental trauma requires childcare professionals to have basic notions of dental first aid. The aim of this study is to assess the level of knowledge and aptitude (defined as the ability to operate competently in a given activity) of early childhood, primary and/or secondary education teachers from Seville (Spain) referred to first aid measures in dental trauma. A descriptive study was made. The study sample consisted of 442 teachers (334 women and 108 men) coinciding proportionately with the study target population in terms of gender distribution, type of center and teaching level.

MethodsA specifically designed questionnaire was used.

ResultsMost of the participants (88.5%, n=391) exhibited poor knowledge and aptitude, 11.5% (n=51) showed medium level knowledge and aptitude, and none were categorized as having high knowledge and aptitude.

ConclusionThese findings could be explained by the fact that 98% of those surveyed had never received any training in this area.

category: dentistry and oral medicine


title: A re-examination of the impact of COVD-19 deaths on the computation of average life expectancy

abstract: It is natural to question the impact of COVID-19 on life expectancy. However, a newborn during the 2020-2021 period need not experience the same level of adult mortality found in 2020-2021 because there may be zero COVID-19 related deaths when the newborn reaches adulthood. Thus, life expectancy lost due to COVID-19 cannot be found simply by incorporating excess deaths due to COVID-19 and re-doing the life table computations because: (1) we know that the COVID-19 deaths need not occur every year for the next 20-25 years; and (2) once an adult, a newborn in 2021/2022 need not experience the same mortality rate that current middle and older aged COVID-19 patients experience. Using U.S. data as an example, we estimate an average of 29.68 years of life was lost to those aged 18-64 who died from COVID-19 in the U.S., noting that 74 % of the reported deaths of 18-64 occurred among 50-64 years and 10 % below 40 years. Instead of computing life expectancy years lost due to COVID-19, we recommend computing life years lost due to COVID-19.


title: Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: possible improvement by mycophenolate mofetil reduction

abstract:
BackgroundModification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs).

MethodsThis multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success.

Results18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels ([≤]206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76-353) BAU/ml and median neutralizing capacity titer of 1:10 (0- 1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09-1.76), graft function (OR 0.05, 95% CI 0.01-0.39), time after transplantation (OR 1.04, 95% CI 1.02-1.07) and MMF trough levels (OR 0.43, 95% CI 0.21-0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels [≥]35.2 BAU/ml than their matched KTRs (p=0.02).

ConclusionsTemporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.


title: Meditation practice, mindfulness and pain-related outcomes in mindfulness-based treatment for episodic migraine

abstract:
ObjectivesMindfulness-based interventions (MBIs) have emerged as promising prophylactic episodic migraine treatments. The present study investigated biopsychosocial predictors and outcomes associated with formal, daily-life meditation practice in migraine patients undergoing MBI, and whether augmented mindfulness mechanistically underlies change.

MethodsSecondary analyses of clinical trial comparing data 12-week mindfulness-based stress reduction (MBSR+; n = 50) to stress management for headache (SMH; n = 48) were conducted.

ResultsPre-treatment mesocorticolimbic system functioning (i.e., greater resting state ventromedial prefrontal cortex-right nucleus accumbens [vmPFC-rNAC] functional connectivity) positively predicted meditation practice duration over MBSR+ (r = .58, p = .001), and moderated change in headache frequency from pre to post-treatment (b = -12.60, p = .02) such that patients with greater vmPFC-rNAC connectivity showed greater reductions in headache frequency. Patients who meditated more showed greater increases in mindfulness (b = .52, p = .02) and reductions in the helplessness facet of pain catastrophizing (b = -.13, p = .01), but not headache frequency, severity or impact. Augmented mindfulness mediated reductions in headache impact resulting from MBSR+, but not headache frequency.

ConclusionsMesocorticolimbic system function is implicated in motivated behavior, and thus could be a target of augmentative interventions designed to enhance meditation practice engagement. Meditation practice appears to benefit pain-related cognitions, but not clinical pain, while mindfulness emerges as a mechanism of MBIs on headache impact, but not frequency. Further research is needed to investigate the day-to-day effects of meditation practice on pain, and continue to characterize the specific mechanisms of MBIs on headache outcomes.

category: pain medicine


title: "It affects every aspect of your life": A qualitative study of the impact of delaying surgery during COVID-19

abstract:
BackgroundThe COVID-19 pandemic has overwhelmed healthcare systems, leading many jurisdictions to reduce surgical services to create capacity (beds and staff) to care for the surge of patients with COVID-19. These decisions were made in haste, and little is known about the impact on patients whose surgery was delayed. This study explores the impact of delaying non-urgent surgeries on patients, from their perspective.

MethodsUsing an interpretative description approach, we conducted interviews with adult patients and their caregivers who had their surgery delayed or cancelled during the COVID-19 pandemic in Alberta, Canada. Trained interviewers conducted semi-structured interviews. Interviews were iteratively analyzed by two independent reviewers using an inductive approach to thematic content analysis to understand key elements of the patient experience.

ResultsWe conducted 16 interviews with participants ranging from 27 to 75 years of age with a variety of surgical procedures delayed. We identified four interconnected themes: individual-level impacts (physical health, mental health, family and friends, work, quality of life), system-level factors (healthcare resources, communication, perceived accountability/responsibility), unique issues related to COVID-19, and uncertainty.

InterpretationThe patient-reported impact of having a surgery delayed during the COVID-19 pandemic was diffuse and consequential. While the decision to delay non-urgent surgeries was made to manage the strain on healthcare systems, our study illustrates the consequences of these decisions. We advocate for the development and adoption of strategies to mitigate the burden of distress that waiting for surgery during and after COVID-19 has on patients and their family/caregivers.

category: surgery


title: Mucosal immunity against SARS-CoV-2 variants of concern including Omicron following vaccination

abstract: SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody (Ab) responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19 vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing Ab against D614G, Delta and Omicron in the BAL compared to COVID-19 convalescents, despite robust S-specific Ab responses in the blood. Further, mRNA vaccination induced significant circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using an animal immunization model, we demonstrate that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing Ab responses, especially against SARS-CoV-2 Omicron; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing Ab response, not only against the ancestral virus but also the Omicron variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during re-infection, but offer limited protection against breakthrough infection, especially by Omicron. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by Omicron and future variants.


title: Variation and impact of polygenic hematological traits in monogenic sickle cell disease

abstract: Several complications observed in sickle cell disease (SCD) are influenced by variation in hematological traits (HT), such as fetal hemoglobin (HbF) level and neutrophil count. Previous large-scale genome-wide association studies carried out in largely healthy individuals have identified 1000s of variants associated with HT, which have then been used to develop multi-ancestry polygenic trait scores (PTS). Here, we tested if these PTS associate with HT in SCD patients and can improve the prediction of SCD-related complications. In 2,056 SCD patients, we found that the PTS predicted less HT variance than in non-SCD African-ancestry individuals. This was particularly striking at the Duffy/DARC locus, where we observed an epistatic interaction between the SCD genotype and the Duffy null variant (rs2814778) that led to a two-fold weaker effect on neutrophil count. PTS for these routinely measured HT were not associated with complications in SCD. In contrast, we found that a simple PTS for HbF that includes only six variants explained a large fraction of the phenotypic variation (17.1-26.4%), associated with acute chest syndrome and stroke risk, and improved the prediction of vaso-occlusive crises. Using Mendelian randomization, we found that increasing HbF by 4.8% reduces stroke risk by 36% (P = 0.0008). Taken together, our results highlight the importance of validating PTS in large diseased populations before proposing their implementation in the context of precision medicine initiatives.

category: genetic and genomic medicine


title: Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity

abstract:
BackgroundThe Omicron variant of SARS-CoV-2 is now overtaking the Delta variant in many countries. Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron may indicate that the higher rate of transmission is due to evasion from vaccine-induced immunity. However, there is little information about activation of recall responses to Omicron in vaccinated individuals.

MethodsWe measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively.

FindingsInfection with Omicron or Delta led to a rapid and similar increase in antibodies to the SARS-CoV-2 spike and nucleocapsid proteins and spike peptide-induced interferon gamma in whole blood. Both the Omicron and the Delta infected patients had a mild and transient increase in inflammatory parameters.

InterpretationThe results suggest that vaccine-induced immunological memory yields similar coverage for the Omicron and Delta variants.


title: The impacts of increased global vaccine sharing on the COVID-19 pandemic; a retrospective modelling study

abstract:
BackgroundThe SARS-CoV-2 pandemic has generated considerable morbidity and mortality world-wide. While the protection offered by vaccines (and booster doses) offers a method of mitigating the worst effects, by the end of 2021 the distribution of vaccine was highly heterogeneous with some countries achieving over 90% coverage in adults by the end of 2021, while others have less than 2%. In part, this is due to the availability of sufficient vaccine, although vaccine hesitancy also plays a role.

MethodsWe use an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries, to investigate the global impact of different vaccine sharing protocols during 2021. We assume a direct relationship between the emergence of variants with increased transmissibility and the cumulative amount of global infection, such that lower global prevalence leads to a lower reproductive number within each country. We compare five vaccine sharing scenarios, from the current situation, through sharing once a particular within-country threshold is reached (e.g. all over 40s have received 2 doses), to full sharing where all countries achieve equal age-dependent vaccine deployment.

FindingsCompared to the observed distribution of vaccine uptake, we estimate full vaccine sharing would have generated a 1.5% (PI -0.1 - 4.5%) reduction in infections and a 11.3% (PI 0.6 - 23.2%) reduction in mortality globally by January 2022. The greatest benefit of vaccine sharing would have been experienced by low and middle income countries, who see an average 5.2% (PI 2.5% - 10.4%) infection reduction and 26.8% (PI 24.1% - 31.3%) mortality reduction. Many high income countries, that have had high vaccine uptake (most notably Canada, Chile, UK and USA), suffer increased infections and mortality under most of the sharing protocols investigated, assuming no other counter measures had been taken. However, if reductions in vaccine supply in these countries had been offset by prolonged use of non-pharmaceutical intervention measures, we predict far greater reductions in global infection and mortality of 64.5% (PI 62.6% - 65.4%) and 62.8% (PI 44.0% - 76.3%), respectively.

InterpretationBy itself, our results suggest that although more equitable vaccine distribution would have had limited impact on overall infection numbers, vaccine sharing would have substantially reduced global mortality by providing earlier protection of the most vulnerable. If increased vaccine sharing from high income nations had been combined with slower easing of non pharmaceutical interventions to compensate for this, a large reduction in both infection and mortality globally would be expected, confounded by a lower risk of new variants arising.


title: SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI)

abstract:
BackgroundGeneral population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations such as Long-Term Care Facility (LTCF) residents but published data are scarce.

MethodsVIVALDI is a prospective cohort study in England which links serial blood sampling in LTCF staff and residents to routine healthcare records. We measured quantitative titres of SARS-CoV-2 anti-spike antibodies in residents and staff following second vaccination dose with ChAdOx1 nCov-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). We investigated differences in peak antibody levels and rates of decline using linear mixed effects models.

ResultsWe report on 1317 samples from 402 residents (median age 86 years, IQR 78-91) and 632 staff (50 years, 37-58), [≤]280 days from second vaccination dose. Peak antibody titres were 7.9-fold higher after Pfizer-BioNTech vaccine compared to Oxford-AstraZeneca (95%CI 3.6-17.0; P<0.01) but rate of decline was increased, and titres were similar at 6 months. Prior infection was associated with higher peak antibody levels in both Pfizer-BioNTech (2.8-fold, 1.9-4.1; P<0.01) and Oxford-AstraZeneca (4.8-fold, 3.2-7.1; P<0.01) recipients and slower rates of antibody decline. Increasing age was associated with a modest reduction in peak antibody levels for Oxford-AstraZeneca recipients.

ConclusionsDouble-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.


title: Estimates of the impact on COVID-19 deaths of unequal global allocations of vaccines

abstract:
During 2021, COVID-19 vaccinations were delivered much more rapidly in some countries than in others. Ethical principles would have suggested allocating available vaccines to people by age, irrespective of where they live, because mortality risks from COVID-19 are much higher for older people. The World Health Organization recommended initial allocations of vaccines to countries based on their total population size, in part due to uncertainty about how COVID-19 would affect different countries.

This paper estimates how many people would have died from COVID-19 up to 31 October 2021 if either of these allocation rules had been applied, compared to estimates of actual COVID-19 deaths. The estimates suggest that allocating vaccines by age would have resulted in between 500,000 and 1,500,000 fewer deaths globally (with a best estimate of 1,090,000 fewer deaths), while allocating vaccines between countries based on national population sizes would have reduced total deaths globally by between 450,000 and 2,100,000 (with a best estimate of 1,440,000 fewer deaths).

Most low-and middle-income countries would have seen reductions in deaths, with the greatest absolute numbers in large middle-income countries (especially Bangladesh, India and Indonesia). More deaths would have taken place in many high-income countries, with the greatest absolute numbers in the United States and Turkey, and the greatest percentage changes in Arabian Peninsula countries, Israel and some island states. In most European Union countries, deaths would not have differed much if vaccines were allocated by age, because they would have received more vaccine doses during the early months of 2021 but fewer later in the year.

Although allocation of vaccines by age should intuitively lead to fewest deaths, the estimated deaths would have been even lower if vaccines were allocated based on population size. Allocation by population would have directed disproportionate numbers of vaccines to a set of countries - especially India, Bangladesh and Indonesia - which experienced large outbreaks due to the Delta variant in 2021 after having previously limited infections through " flattening the curve".

Sequencing of vaccination by age in national vaccination rollouts is critical to maximizing the numbers of lives saved. The estimated gains from fairer global vaccination allocation would be greater if high-income and upper-middle-income countries did not sequence vaccinations by age cohort, and would be lower if lower-middle-income and low-income countries did not vaccinate most of their elderly before the general population, whether due to policy choices or people not accepting vaccines made available to them or logistical difficulties in vaccine delivery.

The estimates correspond to a reduction of between 8.5% and 10.7% (with a best estimate of 10.4%) of the total estimated actual deaths from COVID-19 between 1 January and 31 October 2021, if vaccines were allocated by age, and between 7.8% and 15.0% (with a best estimate of 13.6%) of total estimated actual deaths, if vaccines were allocated based on national population sizes. These percentages are small, despite the large differences in vaccine deployment between countries, because the mostly high-income countries which vaccinated their populations faster have disproportionately large numbers of elderly people. If a future SARS-CoV-2 variant, or a future pandemic, were to have fatality rates that are similar across age groups, or that are higher for children and young adults, then unequal global allocation of vaccines would have a much more severe effect on overall global mortality than it has for COVID-19 so far.


title: Risk factors and survival in patients with COVID-19 in northeastern Brazil.

abstract:
BACKGROUNDCountries have focused research on developing strategies to fight COVID-19, prevent hospitalizations, and maintain economic activities.

OBJECTIVEThis study aimed to establish a survival analysis and identify risk factors for patients with COVID-19 in a upper middle-income city in Brazil.

METHODSWe performed a retrospective cohort study with 280 hospitalized patients with COVID-19. The eCOVID platform provided data used to monitor COVID-19 cases and help communication between professionals.

RESULTSSurvival analysis showed that age [≥] 65 years was associated with decreased survival (54.8%). Females had lower survival rate than males (p=0.01). Regarding risk factors, urea concentration (p<0.001), hospital LOS (p=0.002), oxygen concentration (p=0.005), and age (p=0.02) were associated with death.

CONCLUSIONAge, hospital LOS, high blood urea concentration, and low oxygen concentration were associated with death by COVID-19 in the studied population. These findings corroborate with studies conducted in research centers worldwide.

Key FindingsSome parameters assessed during hospital admission may identify patients with COVID-19 with high risk of progressing to severe conditions and early identification of risk factors and continuous monitoring of laboratory tests may prevent progression to severe disease.

Key ImplicationsKnowledge regarding main signs and symptoms of COVID-19 and associated risk factors helps the population manage and monitor the disease at home and identify early signs of severity. Also, more information about COVID-19, such as prevalence, specific characteristics in certain regions, and treatments, must become public to encourage the population to participate in the control and contingency of the pandemic.


title: Detection of SARS-CoV-2 Omicron, Delta, Alpha and Gamma variants using a rapid antigen test

abstract: Throughout the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged with different infection and disease dynamics. Testing strategies, including clinical diagnosis, surveillance, and screening, have been deployed to help limit the spread of SARS-CoV-2 variants. Rapid antigen tests, in particular, have been approved for self-testing in many countries and governments are supporting their manufacturing and distribution. However, studies demonstrating the accuracy of rapid antigen tests in detecting SARS-CoV-2 variants, especially the new Omicron variant, are limited. We determined the analytical sensitivity of a CE-marked rapid antigen test against the Omicron, Delta, Alpha and Gamma variants. The rapid antigen test had the most sensitive limit of detection (10 plaque forming units [PFU]/mL) when tested with the Alpha and Gamma variants, followed by the Omicron (100 PFU/mL) and Delta (1,000 PFU/mL) variants. Given the increasing numbers of breakthrough infections and the need to surveil infectiousness, rapid antigen tests are effective public health tools to detect SARS-CoV-2 variants.


title: SPATIAL HETEROGENEITY OF NEIGHBORHOOD-LEVEL WATER AND SANITATION ACCESS IN INFORMAL URBAN SETTLEMENTS: A CROSS-SECTIONAL CASE STUDY IN BEIRA, MOZAMBIQUE

abstract: Rapid urbanization, resulting in population growth within informal settlements, has worsened exclusion and inequality in access to water and sanitation (WASH) services in the poorest and most marginalized communities. In this study, we describe the heterogeneity in water service satisfaction and WASH access in low-income, peri-urban neighborhoods of Beira, Mozambique, and examine whether this heterogeneity can be explained by distance to water distribution mains. Using spatial statistics and regression analyses, we identified statistical spatial heterogeneity in household WASH access, as well as consumer-reported satisfaction with water services (services, pressure, quality, and sufficient quantity). We found that as distance from the water main increased, both access to an improved water source at the household and satisfaction with water pressure decreased, controlling for household density and socioeconomic status. The odds of a household having access to a water source at the household or on the compound decreased with every 100-meter increase in distance from a water main pipe (odds ratio [OR] 0.87, 95% confidence interval [CI]: 0.82, 0.92). Satisfaction with water services also decreased with every 100-meter increase in distance from a water main pipe (OR: 0.80; 95% CI: 0.69, 0.94). Findings from this study highlight the unequal household access to water and sanitation in urban informal settlements, even within low-income neighborhoods. Describing this heterogeneity of access to water services, sanitation, and satisfaction - and the factors influencing them - can inform stakeholders and guide the development of infrastructural solutions to reduce water access inequities within urban settings.


title: Patterns of treatment and outcome in patients with unresectable or inoperable esophageal cancer: A real world data

abstract:
BackgroundEsophageal cancer is the eighth most common cancer in the world with a high mortality rate. Surgery, radiation and chemotherapy have been tried in various combinations to improve on the survival rates. Our study provides real world data from a South Asian country on patterns of treatment and outcome in patients with unresectable or inoperable esophageal cancer.

Materials and MethodsThis study is a retrospective analysis of all consecutive esophageal cancer patients, with medically inoperable or unresectable disease, and treated with conformal radical radiotherapy at a tertiary cancer center from January, 2016 to December, 2017. Data regarding patients age, histology, location, pre-treatment imaging, disease stage, treatment details, compliance and response to treatment and status at last follow-up were retrieved from their file. Continuous and categorical variables were summarized by descriptive statistics.

ResultsA total of 100 esophageal cancer patients with a mean age of 60.24 years were included in the study. 60% of the patients were male and upper one-third was the most common site involved. Squamous cell carcinoma was reported in 83% of the patients. About 70% of the patients had a T3/T4 disease and 44% also had nodal metastasis. The radiation dose ranged from 45Gy - 63Gy (median = 59.4Gy). Further, 15% and 54% of the patients received neoadjuvant and concurrent chemotherapy respectively. Radiation compliance was seen in 90% of the patients. With a median follow-up of 7 months (range 3-58 months), 80% of the patients were alive with 32.22% having no evidence of disease. Distant metastases and loco regional failure was seen in 32.22% and 28% of the patients respectively.

ConclusionOur study showed that esophageal cancer is more common in elderly males. Adherence to a uniform treatment protocol using concurrent chemo radiation is difficult in clinical practice especially in resource constrained set up. Both distant metastases and loco regional failure continues to be a matter of concern. Further improvement in local control must be evaluated by either radiation dose escalation or novel combinations with chemotherapy and immunotherapy in large, multi centric trial settings.

category: oncology


title: Utility of 3D printing in the surgical management of intra-articular distal humerus fractures: A protocol for Systematic Review and Meta-analysis

abstract:
BackgroundThe quality of reduction in distal humerus fractures plays a crucial role in obtaining good postoperative functional outcomes. The use of 3D printed models for preoperative planning could help improve reduction and hence potentially influencing outcomes after surgery.

ObjectivesThis systematic review aims to compare the outcome of surgeries done with the help of 3D printing assistance to those done with conventional techniques in distal humerus intraarticular fractures.

MethodsA systematic review will be conducted according to the PRISMA guidelines. Electronic databases of PubMed, Embase, Scopus and Ovid will be searched with a pre-defined search strategy. Bibliography of included articles will also be searched for more potential studies. Original research articles published since inception till the date of search in English language that compare the outcomes of 3D print-assisted surgery with those done without the help of 3D printing will be included. Review articles, conference abstracts and animal studies will be excluded. Outcome measures will be extracted from the selected studies and analysed with the help of appropriate software.

category: orthopedics


title: TreatmentPatterns: An R package to analyze treatment patterns of a study population of interest

abstract:
Background and objectivesThere is an increasing interest to use real-world data to illustrate how patients with specific medical conditions are treated in real life. Insight in the current treatment practices helps to improve and tailor patient care. We aim to provide an easy tool to support the development and analysis of treatment pathways for a wide variety of medical conditions.

MethodsWe formally defined the process of constructing treatment pathways and developed an open-source R package TreatmentPatterns (https://github.com/mi-erasmusmc/TreatmentPatterns) to enable a reproducible and timely analysis of treatment patterns.

ResultsThe developed package supports the analysis of treatment patterns of specific populations of interest. We demonstrate the functionality of the package by analyzing the treatment patterns of three common chronic diseases (type II diabetes mellitus, hypertension, and depression) in the Dutch Integrated Primary Care Information (IPCI) database.

ConclusionTreatmentPatterns is a tool to make the analysis of treatment patterns more accessible, more standardized, and more interpretation friendly. This tool can facilitate and contribute to the accumulation of knowledge on real-world treatment patterns across disease domains. We encourage researchers to further adjust and add custom analysis to the package based on their research needs.

category: health informatics


title: Viral Cultures for Assessing Fomites Transmission of SARS-CoV-2: a Systematic Review Protocol

abstract:
This is a protocol for a systematic review to assess fomite transmission in SARS-CoV-2. Our research questions are as follows: O_LIAre fomite samples infectious?
C_LIO_LIIf so, what proportion are infectious, and what is the distance and duration of infectiousness in the air?
C_LIO_LIWhat is the relationship between fomites, infectiousness and PCR cycle threshold (Ct)?
C_LIO_LIIs there evidence of a chain of transmission that establishes an actual instance of fomite transmission of SARS-CoV-2?
C_LI

We will include studies of any design (and in any setting) that investigate fomite transmission (defined as any inanimate object that, when contaminated with or exposed to infectious agents, can transfer the agent to a new host). We will only include studies that performed viral culture which assessed cytopathic effect and verification techniques to ensure the cultured virus is SARS-CoV-2. We will assess the risk of bias using a checklist modified from the QUADAS-2 criteria.

category: infectious diseases


title: The inactivated NDV-HXP-S COVID-19 vaccine induces a significantly higher ratio of neutralizing to non-neutralizing antibodies in humans as compared to mRNA vaccines

abstract:
NDV-HXP-S is a recombinant Newcastle disease virus based-vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that employed for the production of influenza virus vaccines. Here we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a Phase I clinical study in Thailand.

The SARS-CoV-2 neutralizing and spike binding activity of NDV-HXP-S post-vaccination serum samples was compared to that of matched samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of individuals vaccinated with BNT162b2. Interstingly, the spike binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from individuals vaccinated with the mRNA vaccine. This let us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios similar to those of convalescent sera suggesting a very high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induces a very RBD focused response with little reactivity to S2. This explains the high proportion of neutralizing antibodies since most neutralizing epitopes are located in the RBD. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers comparable to those after mRNA vaccination.


title: CD38 expression by antigen-specific CD4 T cells correlates with sputum bacterial load at time of tuberculosis diagnosis and is significantly restored 5-months after treatment initiation.

abstract: T cell activation markers (TAM) expressed by antigen-specific T cells constitute promising candidates to attest the presence of an active infection by Mycobacterium tuberculosis (Mtb). Reciprocally, their modulation may be used to assess antibiotic treatment efficacy and eventually attest disease resolution. We hypothesized that the phenotype of Mtb-specific T cells may be quantitatively impacted by the load of bacteria present in a patient. We recruited 105 Tanzanian adult tuberculosis (TB) patients and obtained blood before and after 5 months of antibiotic treatment. We studied relationships between patients clinical characteristics of disease severity and microbiological as well as molecular proxies of bacterial load in sputum at the time of diagnosis. Besides, we measured by flow cytometry the expression of CD38 or CD27 on CD4+ T cells producing interferon gamma (IFN-{gamma}) and/or tumor necrosis factor-alpha (TNF-) in response to a synthetic peptide pool covering the sequences of Mtb antigens ESAT-6, CFP-10 and TB10.4. Reflecting the difficulty to extrapolate bacterial burden from a single end-point read-out, we observed statistically significant, but weak, correlations between Xpert MTB/RIF, MBLA and time to culture positivity. Unlike CD27, the resolution of CD38 expression by antigen-specific T cells was observed readily following 5 months of antibiotic therapy. In addition, only the intensity of CD38-TAM signals measured at diagnosis significantly correlated with Mtb 16S RNA recovered from patients sputa. Altogether, our data support CD38-TAM as an accurate marker of infection resolution and a sputum-independent proxy of bacterial load.


title: Long term effectiveness of inactivated vaccine BBIBP-CorV (Vero Cells) against COVID-19 associated severe and critical hospitalization in Morocco

abstract:
INTRODUCTIONWe provide national estimates of the real-world Vaccine effectiveness (VE) based on nationally available surveillance data. The study aimed to estimate the effectiveness of the inactivated Covid-19 vaccine BBIBP-CorV (Vero Cells) Sinopharm vaccine currently deployed in Morocco to reduce the risk of hospitalization from a severe infection of SARS- CoV-2 virus within 9 months after vaccination.

METHODSWe conducted a test-negative, case-control study among a population aged 18 years or older who were tested by rt-PCR for SARS-CoV-2 infection from February to October 2021 in Morocco. From the national laboratory COVID-19 database; we identified cases who were rt-PCR positive amongst severe and critical COVID-19 cases and controls who had a negative rt-PCR test for SARS-CoV-2. From the national vaccination register (NVR); individuals vaccinated with COVID-19 Vaccine (Vero Cell) and those unvaccinated were identified and included in the study. The linkage between databases was conducted for the study of Vaccination status based on the timing of the vaccine receipt relative to the SARS-CoV-2 rt-PCR test date. For each person, who tested positive for SARS-CoV-2, we identified a propensity score-matched control participant who was tested negative. We estimated vaccine effectiveness using conditional logistic regression.

RESULTSAmong 12884 persons who tested positive and 12885 propensity score-matched control participants, the median age was 62 years, 47.2% of whom were female. As a function of time after vaccination of second dose vaccination, vaccine effectiveness during the first month was 88% (95% CI, 84-91), 87% (95% CI: 83-90) during the second and third month, 75% (95% CI: 67-80) during the fourth month, 61% (95% CI: 54-67) during the fifth month, and 64% (95% CI: 59-69) beyond the sixth month. VE remained high and stable during the first three months in the two-age subgroup. In the fourth month, the VE in the older population aged 60 years and above (64%) was reduced by 20 points compared to VE in the younger population (84%).

CONCLUSIONA Sinopharm vaccine is highly protective against serious SARS-CoV-2 infection under real-world conditions. Protection remained high and stable during the first three months following the second dose and decreases slightly beyond the fourth month especially beyond 60 years.


title: Diagnostic accuracy of chest X-ray interpretation for tuberculosis by three artificial intelligence-based software in a screening use-case: an individual patient meta-analysis of global data

abstract:
BackgroundChest X-ray (CXR) screening is a useful diagnostic tool to test individuals at high risk of tuberculosis (TB), yet image interpretation requires trained human readers who are in short supply in many high TB burden countries. Therefore, CXR interpretation by computer-aided detection software (CAD) may overcome some of these challenges, but evidence on its accuracy is still limited.

We established a CXR library with images and metadata from individuals and risk groups that underwent TB screening in a variety of countries to assess the diagnostic accuracy of three commercial CAD solutions through an individual participant meta-analysis.

Methods and findingsWe collected digital CXRs and demographic and clinical data from 6 source studies involving a total of 2756 participants, 1753 (64%) of whom also had microbiological test information. All CXR images were analyzed with CAD4TB v6 (Delft Imaging), Lunit Insight CXR TB algorithm v4.9.0 (Lunit Inc.), and qXR v2 (Qure.ai) and re-read by an expert radiologist who was blinded to the initial CXR reading, the CAD scores, and participant information. While the performance of CAD varied across source studies, the pooled, meta-analyzed summary receiver operating characteristic (ROC) curves of the three products against a microbiological reference standard were similar, with area under the curves (AUCs) of 76.4 (95% CI 72.1-80.3) for CAD4TB, 83.3 (95% CI 78.4-87.2) for Lunit, and 76.4 (95% CI 72.1-80.3) for qXR. None of the CAD products, or the radiologists, met the targets for a triage test of 90% sensitivity and 70% specificity. At the same sensitivity of the expert radiologist (94.0%), all CAD had slightly lower point estimates for specificity (22.4% (95% CI 16.9-29.0) for CAD4TB, 34.6% (95% CI 25.3-45.1) for qXR, and 41.0% (95% CI 30.1-53.0) for Lunit compared to 45.6% for the expert radiologist). At the same specificity of 45.6%, all CAD products had lower point estimates for sensitivity but overlapping CIs with the sensitivity estimate of the radiologist.

ConclusionsWe showed that, overall, three commercially available CAD products had a reasonable diagnostic accuracy for microbiologically confirmed pulmonary TB and may achieve a sensitivity and specificity that approximates those of experienced radiologists. While threshold setting and cost-effectiveness modelling are needed to inform the optimal implementation of CAD products as part of screening programs, the availability of CAD will assist in scaling up active case finding for TB and hence contribute to TB elimination in these settings.


title: The impact of the COVID-19 pandemic on health service utilisation following self-harm: a systematic review

abstract:
BackgroundEvidence on the impacts of the pandemic on healthcare presentations for self-harm has accumulated rapidly. However, existing reviews do not include studies published beyond 2020.

AimsTo systematically review evidence on health services utilisation for self-harm during the COVID-19 pandemic.

MethodsA comprehensive search of multiple databases (WHO COVID-19 database; Medline; medRxiv; Scopus; PsyRxiv; SocArXiv; bioRxiv; COVID-19 Open Research Dataset, PubMed) was conducted. Studies reporting presentation frequencies for self-harm published from 1st Jan. 2020 to 7th Sept. 2021 were included. Study quality was assessed using a critical appraisal tool.

ResultsFifty-one studies were included. 59% (30/51) were rated as  low quality, 29% (15/51) as  moderate and 12% (6/51) as  high-moderate. Most evidence (84%, 43/51 studies) was from high-income countries. 47% (24/51) of studies reported reductions in presentation frequency, including all 6 rated as high-moderate quality, which reported reductions of 17- 56%. Settings treating higher lethality self-harm were overrepresented among studies reporting increased demand. Two of the 3 higher quality studies including study observation months from 2021 reported reductions in service utilisation. Evidence from 2021 suggested increased use of health services following self-harm among adolescents, particularly girls.

ConclusionsSustained reductions in service utilisation were seen into the first half of 2021. However, evidence from low- and middle-income countries is lacking. The increased use of health services among adolescents, particularly girls, into 2021 is of concern. Our findings may reflect changes in thresholds for help seeking, use of alternative sources of support and variable effects of the pandemic across different groups.


title: Prevalence mapping of Schistosomiasis among Pre-school aged children in Rwanda

abstract:
Schistosomiasis is endemic in Rwanda and control programs have been implemented with a special focus on school-aged children (SAC) ignoring pre-school aged children (pre-SAC) for which the actual prevalence of the disease is not well established. This study consisted of a cross-sectional quantitative mapping of the distribution of schistosomiasis and identification of associated risk factors among pre-SAC throughout the country. The study covered all the 17 Districts of Rwanda endemic for schistosomiasis with a total sample of 4675 children enrolled from 80 purposively selected villages. The Parasitological assessment of childrens urine and stool samples was conducted using CCA and Kato Katz methods respectively for infection detection. A standard questionnaire was used to collect data on the risk factors and geospatial assessment was performed using tablets and GPS to record geographic coordinates for plotting locations on maps using ArcGIS software.

The overall prevalence of S mansoni infection across the surveyed areas was 24% and 0.8 by CCA and Kato-Katz, respectively. Infection was significantly associated with bathing children in open water bodies. Furthermore, pre-SAC looked after by siblings (sisters) were twice as much likely to be infected compared to those looked after by mothers. Schistosomiasis control interventions are needed for pre-SAC to limit their exposure to open water bodies with expectations of adapted chemotherapy to be availed. Community based deworming campaigns may be the best way to ensure good treatment coverage of pre-SAC in Rwanda.

Author summarySchistosomiasis is one of the Neglected Tropical Diseases (NTD) of public health concern in Rwanda like in many tropical countries. The recently published NTD roadmap by the World Health Organization indicates that schistosomiasis is targeted for elimination as a public health problem worldwide by 2030. For this target to be achieved, all at risk populations should be reached by control programs interventions such as preventive chemotherapy, health education as well as water, sanitation and hygiene (WASH) practices. However, pre-school children (pre-SAC) are among populations at risk for whom infection burden is not fully documented. Implementation of the recent WHO guideline on schistosomiasis control and elimination that recommend inclusion of pre-SAC in control programs will be informed by detailed assessment of the infection burden and distribution in endemic countries. This study is showing for the first time a high burden of schistosomiasis among pre-SAC in high-risk areas of Rwanda. With the imminent availability of the paediatric formulation of Praziquantel (the drug of choice against the disease), the findings should guide the country in implementation strategies that include these children in mass deworming. The findings also highlight a number of risk factors including the passive exposure of these young children by their siblings while bathing them in open waters and the lack of knowledge of parents/guardians on the disease. Additional integrated interventions such as health education, improvement of water supply and sanitation as well as snail surveillance will lead to more sustainable solutions in the march towards schistosomiasis elimination.

category: pediatrics


title: Social connectedness as a determinant of mental health: A scoping review

abstract: Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from research examining social connectedness as a determinant of mental health. The goal of this review was to evaluate recent longitudinal research probing the effects of social connectedness on depression and anxiety symptoms and diagnoses in the general population. A scoping review was performed of PubMed and PsychInfo databases from January 2015 to December 2020 following PRISMA-ScR guidelines using a defined search strategy. The search yielded 56 articles representing 52 unique studies. In research with other than pregnant women, 84% (16 of 19) studies reported that social support benefited symptoms of depression with the remaining 16% (3 of 19) reporting minimal or no evidence that lower levels of social support predict depression at follow-up. In research with pregnant women, 80% (21 of 26 studies) found that low social support increased postpartum depressive symptoms. Among 3 of 4 studies that focused on loneliness, feeling lonely at baseline was related to adverse outcomes at follow-up including higher risks of major depressive disorder, depressive symptom severity, generalized anxiety disorder, and lower levels of physical activity. In 5 of 7 reports, smaller social network size predicted depressive symptoms or disorder at follow-up. In summary, most recent relevant longitudinal studies have demonstrated that social support protects adults in the general population from depressive symptoms and disorders. The results, which were largely consistent across settings, exposure measures, and populations, support efforts to improve clinical detection of high-risk patients, including adults with low social support and elevated loneliness.

category: public and global health


title: Key factors for effective implementation of healthcare workers support interventions in health organisations after patient safety incidents: a protocol for a scoping review

abstract:
IntroductionHealth organisations should support healthcare workers who are physically and psychologically affected by patient safety incidents (second victims). There is a growing body of evidence which focusses on second victim support interventions. However, there is still limited research on the elements necessary to effectively implement and ensure the sustainability of these types of interventions. In this study, we propose to map and frame the key factors which underlie an effective implementation of healthcare worker support interventions in healthcare organisations when healthcare workers are physically and/or emotionally affected by patient safety incidents.

Methods and analysisThis scoping review will be guided by the established methodological Arksey and OMalley framework, Levac and Joanna Briggs Institute (JBI) recommendations. We will follow the JBI three-step process: (1) a preliminary search conducted on two databases; (2) the definition of clear inclusion criteria and the creation of a list of search terms to be used in the subsequent running of the search on a larger number of databases; and (3) additional searches (cross-checking/cross-referencing of reference lists of eligible studies, hand-searching in target journals relevant to the topic, conference proceedings, institutional/organisational websites and networks repositories). We will undertake a comprehensive search strategy in relevant bibliographic databases (Pubmed/Medline, Embase, CINHAL, Web of Science, Scopus, PsycInfo, Epistemonikos, Scielo, Cochrane Library and Open Grey). We will use the Mixed Methods Appraisal Tool (MMAT) 2018 version for quality assessment of the eligible studies. Our scoping review will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR).

Ethics and disseminationThis study will not require ethical approval. Results of the scoping review will be published in a peer-review journal and findings will be presented in scientific conferences as well as in international forums and other relevant dissemination channels.

This protocol is registered on the Open Science Framework (www.osf.io): 10.17605/OSF.IO/WZSE9

Strengths and limitations of this studyO_LITo our knowledge, this is the first scoping review to map and frame the different organisational, operational and contextual factors which underlie the implementation of health worker support programmes after the occurrence of a patient safety incident.
C_LIO_LIThis scoping review uses a rigorous and transparent method for mapping the available evidence.
C_LIO_LIGiven the broad focus of this scoping review, we dont expect that eligible studies will show a direct relation between the key factors and the effectiveness of the implementation of the support interventions.
C_LIO_LIFor better interpretation of the results, we will provide a quality assessment of the included studies, although quality assessment is not mandatory to include in scoping reviews.
C_LIO_LIWe will involve key stakeholders as an additional source of information to complement the literature search.
C_LI


title: Deep Learning Approaches to Identify Patients within the Thrombolytic Treatment Window

abstract: Treatment of acute ischemic stroke is heavily contingent upon time, as there is a strong relationship between time clock and tissue progression. We sought to a develop a deep learning algorithm for classifying time since stroke (TSS) from MR images by comparison to neuroradiologist assessments of imaging signal mismatch and validation on external data. This retrospective study involved patients who underwent MRI from 2011-2019. The models were trained to classify TSS within 4.5 hours; performance metrics with confidence intervals were reported on both internal and external test sets. A total of 772 patients (66 {+/-} 9 years, 319 women) were used for model development and evaluation. Three board-certified neuroradiologists assessments, based on majority vote, yielded a sensitivity of 0.62, a specificity of 0.86, and a Fleiss kappa of 0.46. The deep learning method had higher sensitivity and accuracy than the radiologists and previously reported methods while maintaining the same level of specificity, with the best model achieving an average test accuracy of 0.791, sensitivity of 0.777, and specificity of 0.802. This model achieved higher generalization performance on the validation dataset than the current state of the art for TSS classification. Code in this paper will be available online soon.

category: neurology