bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-tailored Contrast Delivery Protocols for Computed Tomography Coronary Angiography
Authors: van den Boogert Thomas P.W. , Lopes Ricardo R. , Lobe Nick H.J. , Verwest Tim A. , Stoker Jaap , Henriques José P. , Marquering Henk A. , Planken R. Nils
Published: July 2021

Purpose:

The first objective of this study was to evaluate the efficacy of a patient-tailored contrast delivery protocol for coronary computed tomography angiography (CTCA), in terms of diagnostic coronary attenuation and total iodine load (TIL), by adjusting the iodine delivery rate (IDR) via dilution for body weight and tube voltage (kV), as compared with a protocol with a fixed bolus of contrast in a clinical setting. The secondary objective was to assess the association between the test-bolus data and luminal attenuation in CTCA.

Materials and Methods:

Patients who underwent CTCA with fixed IDR contrast delivery (cohort 1) or with IDR adjusted for body weight and kV settings (70 to 120 kV) (cohort 2) were included, and compared for intravascular luminal attenuation and TIL. The association between intravascular luminal attenuation and test-bolus scan data was investigated with linear regression.

Results:

In cohort 1 (176 patients), the mean luminal attenuation differed markedly between kV categories, whereas in cohort 2 (154 patients), there were no marked differences. The mean TIL reduced significantly (20.1±1.2 g in cohort 1, 17.7±3.0 g in cohort 2, P<0.001). The peak height of the test-bolus scan was independently associated with luminal attenuation in the ascending aorta, with a 0.58 HU increase per HU peak-height increase (SE=0.18, P<0.001).

Conclusion:

Clinical implementation of a patient-tailored contrast delivery protocol for CTCA, adjusted for body weight and kV, improves luminal attenuation and significantly reduces the TIL. The peak height of the test-bolus scan is associated with luminal attenuation in the ascending aorta in the CTCA scan.
Heterotopic Ossification in Burn Patients
Authors: Sun Yi , Lin Yuzhe , Chen Zenggan , Breland Andrew , Lineaweaver William C. , Zhang Feng
Published: July 2021

Heterotopic ossification (HO) is a known complication of burns. The incidence of this complication is low. The etiology is unclear, but experiment conducted about HO can be significant. Currently, there are still no targeted, effective preventive and therapeutic measures against it. In this study, the relevant literature is summarized to demonstrate the potential pathogenic mechanisms, diagnosis, prophylaxis, and treatment measures of HO in burn patients. Early diagnosis and treatment can be effective in improving the prognosis of patients.
Risk Factors of Carpal Tunnel Syndrome in Taiwan
Authors: Yang Cristhiam , Chen Hsin-Hung , Lee Min-Chao , Kao Huang-Kai , Lin Yu-Te , Chen Chien-Tzung , Chang Chee-Jen , Tsai Chia-Hsuan
Published: July 2021

Background

Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics.

Methods

A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS.

Results

Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50–59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly.

Conclusions

Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities.
Transconjunctival Surgical Access With Modified Aesthetic Lateral Canthotomy
Authors: Shinohara Elio Hitoshi , Gaujac Cristiano , Pedron Irineu Gregnanin , Salles Marcos Barbosa , Horikawa Fernando Kendi
Published: July 2021

Displaced fractures of the zygomatic bone that require surgical treatment are accessed transcutaneously but these accesses to the skin can cause a hypertrophy scar in patients with this predisposition. This paper indicates a modification in the lateral canthotomy that aim to minimize the hypertrophic scar in the treatment of zygomatic fracture.
The Impact of the Informed Consent Process on the Anxiety Levels of Patients Undergoing Rhinoplasty
Authors: Aysel Abdulhalim , Uz Uzdan , Karatan Berrak , Aydin Enes , Erdoğan Esin , Yilmaz Fatih , Müderris Togay
Published: July 2021

Septorhinoplasty is one of the most common elective surgical procedures in otolaryngology. The present study aimed to evaluate the anxiety levels of patients who underwent septorhinoplasty at different times, compare the information methods, and determine the understanding of the informed consent through recall rates of the complications explained in the informed consent process. The patients were divided into the following 2 groups: Group 1 (giving information 14 days before the surgery) and Group 2 (giving information 3 days before the surgery). For the preoperative anxiety measurement, the State anxiety scale of the State-Trait Anxiety Inventory (STAI) was used. All patients were asked to recall the complications they remembered from the consent form on the day before the surgery. Each group has consisted of 25 patients. No significant difference was found between the STAI-1 and STAI-2a anxiety scores between groups. In Group 1, the STAI-2b anxiety score was significantly lower than the STAI-1 and STAI-2a scores (P < 0.05). In Group 2, the mean score of STAI-2b was not significantly higher than the STAI-1 and STAI-2 scores (P > 0.05). When the STAI-2b scores of the two groups were compared, the scores of Group 2 were significantly higher (P < 0.05). The most commonly remembered complications were bruising and swelling in both of the groups. In conclusion, the authors believe that long-term cooperation between the surgical team and the patient will reduce the anxiety levels of the patients and increase patients’ satisfaction, resulting in a significant reduction in the amount of potential legal processes.

Level of Evidence: 2
Huge Fenestration of the Vertebral Artery and Fenestrated Basilar Artery
Authors: Rădoi Petrinel Mugurel , Rusu Mugurel Constantin , Mincă Dragoş-Ionuţ , Toader Corneliu
Published: July 2021

Background:

Fenestrations, such as those of the vertebral artery (VA), are generally regarded as arterial slits. To the authors’ knowledge, large fenestrations of the VA were reported twice previously, those morphological patterns being different. We hereby report a third pattern of such large fenestration of the VA.

Methods:

It was found serendipitously on the computed tomography angiograms of a 63 year-old male which were documented retrospectively.

Results:

The findings were as follows:

Conclusions:

Large fenestrations of the VA could result if, during embryogenesis, the proximal segment of the lateral basivertebral anastomosis and the distal segment of the proatlantal artery persist. Large fenestrations of the VA bring into a narrow neurosurgical field an additional arterial trunk that should be carefully documented preoperatively in order to avoid hemorrhagic events.
A Novel Surgical Approach for Rhinophyma: Experience From a Cohort of Thirty Patients
Authors: Li Wen , He Xufeng , Chen Wenjun , Ding Peijun , He Xiang , Zhang Huimin
Published: July 2021

Background:

Rhinophyma is the severe rosacea whit hypertrophy of sebaceous glands in nasal tissue, which severely influences the patient's appearance. Surgical therapy is the best method for treating moderate-to-severe rhinophyma. In this study, we used a new ameliorated scarification for 30 patients with moderate-to-severe rhinophyma.

Objective:

To observe the effect of five-blades scratcher surgery on moderate-to severe rhinophyma between 2016 and 2019 in our center.

Materials and Methods:

A total of 30 patients were treated with five-blades scratcher under tumescent anesthesia. Outcomes were determined by a patient questionnaire.

Results:

Of 30 patients, all of them answered the questionnaire and were included in this study with a follow-up time of 12 months. Cosmetic results were evaluated as very good or good in 90% of patients. The majority of patients (87%) were very satisfied or satisfied with the postoperative result. Surgical treatment of rhinophyma improved patients’ quality of life in 67% of patients. Recurrence of rhinophyma was detected in 7% of patients. In all, 100% of the patients stated that they would recommend this treatment to others.

Conclusions:

Five-blades scratcher is an effective therapy for rhinophyma with excellent outcome.
The Risk of Osseointegration in the Coronavirus Disease 19 Pandemic
Authors: Mulinari-Santos Gabriel , Paino-Sant’Ana Amanda , Okamoto Roberta , Coléte Juliana Zorzi , Neto João Lopes Toledo
Published: July 2021

Coronavirus disease 19 (COVID-19) is associated with respiratory complications but also with alterations on bone metabolism. Coronavirus disease 19, therefore, might be a risk factor for osseointegration. Recent studies suggest that severe acute respiratory syndrome coronavirus 2 is related with bone abnormalities mainly for act via renin-angiotensin system. This report aims to list the bone alterations caused by coronavirus disease 19 and the possible consequences on the peri-implant bone healing. The current data add to the accumulating knowledge that coronavirus disease 19 may negatively impact the osseointegration and it requires further research.
How Do We Start Palliative Care for Patients With End-Stage Liver Disease?
Authors: Kim Sookyung , Lee Kyunghwa , Kim Changhwan , Choi Jahyun , Kim Sanghee
Published: July 2021

Patients with end-stage liver disease undergo repetitive patterns of recovery and deterioration and are burdened with uncertainty. Although quality of life is low in patients with end-stage liver disease and their family members, few studies have been conducted to identify what palliative care should be provided for them. This integrative review aimed to explore palliative care for patients with end-stage liver disease, focusing on the components and outcome measurements for further research. After searching for studies on palliative care for end-stage liver disease published between 1995 and 2017, 12 studies that met the inclusion criteria were analyzed. The common components of palliative care for patients with liver disease were: (a) an interdisciplinary approach, (b) early palliative care, (c) discussion goals of care with patient and family members, (d) symptom management, and (e) psychosocial support. It was reported that patients who were provided palliative care had improved itching, well-being, appetite, anxiety, fatigue, and depression, increased the number of do-not-resuscitate orders, palliative care consultations, and decreased length of stay. These findings could guide the development of palliative care for end-stage liver disease patients.
Kidney Transplants in Controlled Donation Following Circulatory Death, or Maastricht Type III Donors, With Abdominal Normothermic Regional Perfusion, Optimizing Functional Outcomes
Authors: Ramirez Patricia , Vázquez David , Rodríguez Gabriel , Rubio Juan José , Pérez Marina , Portolés Jose Maria , Carballido Joaquín
Published: July 2021

Background.

Warm ischemia time and ischemia-reperfusion damage result in higher rates of delayed graft function and primary nonfunction in kidney transplants (KTs) from controlled donation after circulatory death (cDCD). This study aimed to assess early and late kidney function and patient and graft survival of KT from cDCD preserved with normothermic regional perfusion (NRP) and to compare with KT from brain death donors (DBDs) and cDCD preserved with rapid recovery (RR).

Methods.

Patients who received a KT at our institution from 2012 to 2018 were included, with a minimum follow-up period of 1 y. They were categorized by donor type and conditioning methods: DBD, cDCD with NRP, and cDCD with RR. Early and late graft function, along with patient and graft survival were analyzed in all groups.

Results.

A total of 182 KT recipients were included in the study (98 DBD and 84 cDCD). Out of the cDCDs, 24 kidneys were recovered with the use of NRP and 62 with RR; 22 of the 24 kidneys were ultimately transplanted. The cDCD using NRP group showed lower rates of delayed graft function compared with the cDCD with RR group (36.3% versus 46.7%, P = 0.01). Also, primary nonfunction rates were lower in the cDCD using NRP group (4.5% versus 6.4% cDCD-RR and 10.2% DBD). Patient survival rates were >90% in all groups. No differences were found in graft survival rates at 1 y.

Conclusions.

The use of abdominal NRP improves early function recovery of KT from cDCD, making their outcomes comparable with those of DBD.
Early Allograft Dysfunction After Liver Transplantation With Donation After Circulatory Death and Brain Death Grafts: Does the Donor Type Matter?
Authors: Mazilescu Laura Ioana , Kotha Sreelakshmi , Ghanekar Anand , Lilly Leslie , Reichman Trevor W. , Galvin Zita , Cattral Mark S. , Bhat Mamatha , McGilvray Ian D. , Sapisochin Gonzalo , Sayed Blayne , Selzner Markus , Selzner Nazia
Published: July 2021

Background.

Early allograft dysfunction (EAD) after liver transplantation has been associated with long-term reduced graft and patient survival.

Methods.

In this single-center cohort study, we aimed to compare incidence, risk factors, and outcomes in liver transplant recipients who developed EAD. Patients who received donation after circulatory death (DCD) or donation after brain death (DBD) grafts between January 2007 and December 2017 were included. EAD was defined as bilirubin of ≥10 mg/dL (171 μmol/L) or an international normalized ratio of ≥1.6 on postoperative day 7 or transaminases >2000 U\L in the first-week posttransplantation as previously described.

Results.

In our cohort of 1068 patients, incidence of EAD was 44%. EAD occurred more frequently in the DCD versus DBD group (71% versus 41%, P < 0.01). Overall, recipients who developed EAD showed a significantly lower graft and patient survival at 1, 3, and 5 y after transplantation (all P < 0.05). This was also the case for recipients of DBD grafts. However, for recipients of DCD grafts, patient and graft survival were not affected by the presence of EAD. For recipients of DBD grafts, donor age, body mass index (BMI) and gender, recipient BMI and model for end-stage liver disease score and warm and cold ischemia time were associated with EAD. For DCD recipients, donor BMI and cold ischemia time were associated with EAD.

Conclusions.

In our cohort study, EAD resulted in reduced long-term patient and graft survival only for DBD recipients but not for DCD recipients. Predictive markers for EAD were dependent on the donor type.
Impact of the Mayo Adhesive Probability Score on Donor and Recipient Outcomes After Living-donor Kidney Transplantation: A Retrospective, Single-center Study of 782 Transplants
Authors: Sato Yu , Noguchi Hiroshi , Mei Takanori , Kaku Keizo , Okabe Yasuhiro , Nakamura Masafumi
Published: July 2021

Background.

This study was performed to assess the impact of the Mayo Adhesive Probability (MAP) score on donor and recipient outcomes after living-donor kidney transplantation (LDKT).

Methods.

We retrospectively analyzed 782 transplants involving LDKT between February 2008 and October 2019 to assess the correlation between the MAP score and outcome after LDKT. We divided the transplants into 2 groups according to the donor MAP score: 0 (MAP0) and 1–5 (MAP1–5).

Results.

Compared with the MAP0 group, donors in the MAP1–5 group were significantly older, had higher body mass index, and were more likely to be men. The prevalences of hypertension, hyperlipidemia, and diabetes were also higher among donors in the MAP1–5 group than among donors in the MAP0 group. Operative time, estimated blood loss during donor nephrectomy, and percentage of glomerular sclerosis were significantly greater in the MAP1–5 group than in the MAP0 group. Donor and recipient perioperative complications were comparable between the 2 groups; death-censored graft survival rates also did not significantly differ between groups. Although the recipient mean estimated glomerular filtration rate (eGFR) from postoperative d 1 to 7 was significantly higher in the MAP0 group than in the MAP1–5 group (P = 0.007), eGFR reductions within 5 y after transplantation were similar between groups. There were no significant differences between groups in recipient mortality and biopsy-proven acute rejection episodes within 1 y after transplantation. Additionally, multivariate analysis showed that the only factors affecting recipient eGFR at postoperative d 7 were donor age, recipient age, and female sex (P < 0.001, <0.001, and =0.004, respectively).

Conclusions.

The MAP score did not influence surgical complications or graft survival; therefore, it should not affect donor selection.
Salipiger mangrovisoli sp. nov., isolated from mangrove soil and the proposal for the reclassification of Paraphaeobacter pallidus as Salipiger pallidus comb. nov.
Authors: Du Juan , Liu Yang , Pei Tao , Deng Ming-Rong , Zhu Honghui
Published: July 2021

A novel Gram-stain-negative, aerobic and rod-shaped bacterial strain designated as 6D45AT was isolated from mangrove soil and characterized using a polyphasic taxonomic approach. Strain 6D45AT was found to grow at 10–37 °C (optimum, 28 °C), at pH 6.0–9.0 (optimum, 7.0) and in 0–5 % (w/v) NaCl (optimum, 2%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 6D45AT fell into the genus

Salipiger

and shared 99.1 % identity with the closest type strain

Salipiger pacificus

CGMCC 1.3455T and less than 97.2 % identity with other type strains of this genus. The 34.8 % digital DNA–DNA hybridization (dDDH) and 88.3 % average nucleotide identity (ANI) values between strain 6D45AT and the closest relative above were well below recognized thresholds of 70 % DDH and 95–96 % ANI for species definition, implying that strain 6D45AT should represent a novel genospecies. The phylogenomic analysis indicated that strain 6D45AT formed an independent branch distinct from reference strains. The predominant cellular fatty acid of strain 6D45AT was summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c, 66.9 %); the polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, two unidentified glycolipids and an unknown lipid; the respiratory quinone was Q-10. The genomic DNA G+C content was 66.5 mol %. Based on the phenotypic and genotypic characteristics, strain 6D45AT is concluded to represent a novel species of the genus

Salipiger

, for which the name Salipiger mangrovisoli sp. nov., is proposed. The type strain of the species is 6D45AT (=GDMCC 1.1960T=KCTC 82334T). We also propose the reclassification of

Paraphaeobacter pallidus

as Salipiger pallidus comb. nov. and ‘

Pelagibaca abyssi

’ as a species of the genus

Salipiger

.
Hospital transmission of borderline oxacillin-resistant Staphylococcus aureus evaluated by whole-genome sequencing
Authors: Konstantinovski Maria M. , Veldkamp Karin Ellen , Lavrijsen Adriana P. M. , Bosch Thijs , Kraakman Margriet E. M. , Nooij Sam , Claas Eric C. J. , Gooskens Jairo
Published: July 2021

Introduction.

Staphylococcus aureus

is a major cause of hospital infections worldwide. Awareness towards methicillin-resistant

S. aureus

(MRSA) infections is high but attention towards borderline oxacillin-resistant

S. aureus

(BORSA) is limited, possibly due to an underestimated clinical relevance, presumption of low incidence and diagnostic limitations.

Gap statement. BORSA surveillance has not been routinely implemented, and thus consensus with regard to a definition and infection control measures is lacking.

Aim. Our goals were to investigate the occurrence, molecular characteristics and clinical manifestations of BORSA infections in the hospital setting.

Methodology. Following an increased incidence in 2016, BORSA cases in 2014/2016 (in our institution) were more specifically evaluated. Medical records were reviewed to investigate epidemiological links, clinical characteristics and outcomes. Resistance and virulence markers were assessed by whole genome sequencing (WGS). Conventional methods: amplified fragment length polymorphism (AFLP) ; multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were compared with core genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analysis to confirm genetic clusters.

Results. From 2009 to 2013, BORSA comprised 0.1 % of all clinical

S. aureus

strains. In 2016, the incidence was six-fold higher in comparison to the baseline. Whole-genome SNP and cgMLST confirmed two BORSA clusters among patients with dermatological conditions. Patients with BORSA presented with skin infections, and one case developed a severe invasive infection with a fatal outcome. Infection control measures successfully prevented further transmission in both clusters. WGS findings showed that BORSA strains carried multiple resistance and virulence genes with increased pathogenic potential.

Conclusion. WGS and cgMLST effectively characterized and confirmed BORSA clusters among at-risk patients with clinical manifestations ranging from mild skin infections to life-threatening bacteraemia. Clinical awareness and active monitoring are therefore warranted for the timely implementation of infection control measures to prevent BORSA transmission in high-risk patients.
CAUSES AND CONSEQUENCES OF STIGMA LEADING TO MENTAL DISORDERS AMONG LEPROSY AFFECTED: KEY ELEMENTS IN THE PROCESS OF COUNSELLING TO IMPROVE MENTAL HEALTH CARE
Authors: Raju Moturu S.
Published: July 2021

Despite counselling has been in practice for quite a long time not yet an essential ingredient in leprosy control programmes especially in India nor a standardised system is available for prevention of mental disorders. With the broad objective to fulfil this need an action research was carried out to explore the unfulfilled needs of leprosy affected that are creating crisis situations lead to mental health issues while experimenting a practicably affective process of counselling system and document the essential stages to be involved in carrying out inter-personal counselling on each one’s unique problems. The study was conducted by the Psych-social counselling and Guidance Centre of Gandhi Memorial Leprosy Foundation on 146 leprosy affected. Counselling provided by trained counsellors in every monthly visit for MDT till declared RFT or afterwards.

Results

Systematic process of counselling needs to be caried out in the following five essential stages viz Rapport Establishment, Identification of Crisis Situation, Psycho-Social Diagnosis, Prescription of Counselling Elements and Fulfilment of counselling elements

Majority or psychological problems initially develop due to cognitive issues of affected individuals, their family members, society members, work place, institutions and treatment centres etc. If not attended at initial stage result to treatment compliance issues leading to deformity which accelerates adjustment problems in the family, society, workplace, educational and other institutions thus in turn lead in to unemployment, stigmatization of the patient from family and all sorts of mental disorders.. prior to reaching the stage of needing treatment.

The study concludes that a systematic counselling addressing the issues at the cognitive level also including decision makers in the family, along with leprosy treatment can be a successful method to prevent the mental health problems and throw light towards zero stigma
Intravenous Iron Decreases Rehospitalizations but Doesn’t Change mortality in Patients Admitted with Acute Heart Failure and Iron Deficiency: A Systematic review and Meta-analysis
Authors: Baral Nischit , Karki Nabin R. , Akram Imran , Khan Ashiya , Adhikari Govinda , Rauniyar Rohit , Abdelazeem Basel , Dhungana Santosh K. , Ranabhat Bandana , Kunadi Arvind
Published: July 2021

Introduction

The role of intravenous (IV) iron in chronic heart failure has been well studied, however, its role in acute heart failure (AHF) is less well-known. Including the recent AFFIRM-HF trial, we performed a systematic review and meta-analysis to highlight the role of IV iron in AHF with iron deficiency.

Hypothesis

We hypothesized that IV iron doesn’t change mortality or heart failure re-hospitalization rates in patients with AHF with iron deficiency.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies published from inception till June 30, 2021. We searched PubMed, MEDLINE, EMBASE (embase.com), and Cochrane database including only RCTs and Cohort studies. We also included one prospective and one retrospective Cohort studies and two RCTs in our meta-analysis. Eligible studies included adults with AHF, left ventricular ejection fraction less than 40%-50%, and able to receive IV iron therapy. Outcomes included re-hospitalization rates and overall mortality from 30 days to 52 weeks post randomization (in one RCT). We used random-effects model calculating Risk Ratio (RR) with 95% confidence interval (95% CI) using Review Manger 5.4 software. I2statistics was used to assess heterogeneity.

Results

There were total 1561 participants in both groups (IV iron and placebo/control) of four studies. The controls were comparable in both cohort studies and both the RCTs were well matched. Our results showed re-hospitalization in 278 of 833 (33.37%) patients in the IV iron/exposure group and 337 of 728 (0.46%) patients in the placebo/control group. The pooled result showed that the risk of rehospitalization was comparable across both groups (RR 0.85, 95%CI 0.62-1.17; I2=45%, P=0.14). However, subgroup analysis, including RCTs only showed that IV iron decreases re-hospitalization rate by 28% compared to placebo (RR 0.72, 95% CI: 0.64, 0.82, I2=0%, P<0.00001) but didn’t improve mortality when compared to placebo (RR 0.97, 95% CI: 0.73, 1.30, I2 =0%).

Conclusions

IV iron showed significant improvement in re-hospitalization rate for AHF hospitalizations in iron deficient patients but didn’t improve overall mortality. We need larger RCTs to further validate its effect on mortality.
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
Authors: Minervina Anastasia A. , Pogorelyy Mikhail V. , Kirk Allison M. , Crawford Jeremy Chase , Allen E. Kaitlynn , Chou Ching-Heng , Mettelman Robert C. , Allison Kim J. , Lin Chun-Yang , Brice David C. , Zhu Xun , Vegesana Kasi , Wu Gang , Trivedi Sanchit , Kottapalli Pratibha , Darnell Daniel , McNeely Suzanne , Olsen Scott R. , Schultz-Cherry Stacey , Estepp Jeremie H. ,   the SJTRC Study Team, McGargill Maureen A. , Wolf Joshua , Thomas Paul G.
Published: July 2021

Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the ex vivo profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection. We found that the order of exposure determined the relative distribution between spike- and non-spike-specific responses, with vaccination after infection leading to further expansion of spike-specific T cells and differentiation to a CCR7-CD45RA+ effector phenotype. In contrast, individuals experiencing a breakthrough infection mount vigorous non-spike-specific responses. In-depth analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all types of exposures elicit diverse repertoires characterized by shared, dominant TCR motifs, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and that current vaccination protocols continue to expand and differentiate spike-specific memory responses.
Significant Structural Breaks in the International Incidence of Hepatitis Delta Virus
Authors: Fallon Braden S. , Cooke Elaine M. , Hesterman Matthew C. , Norseth Jared S. , Akhundjanov Sherzod B. , Weller Melodie L.
Published: July 2021

Background & Aims

The international incidence of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to limited testing and lack of active surveillance for this rare infectious disease. These limitations prevent the detection of low-level and/or geographically dispersed changes in the incidence of HDV diagnoses. A study was designed to enable international active tracking and analyses of HDV epidemiology by aggregating international HDV and Hepatitis B Virus (HBV) diagnoses datasets.

Methods

Publicly accessible datasets containing yearly incidence for HDV and HBV diagnoses were mined from government publications for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. The Bayesian Information Criterion (BIC) was used to determine the best-fitting breakpoint model for the number of breakpoints and the break dates identified using the determined model.

Results

Aggregated analysis of these HDV and HBV datasets spanning 1999-2020 identified structural breaks in the timeline of HDV incidence in 2002, 2012, and 2017. A significant increase in the international HDV incidence, relative to reported HBV diagnoses, occurred in 2013-2017. Secondary analysis identified four distinct temporal clusters of HDV incidence, including Cluster I (Macao, Taiwan), Cluster II (Argentina, Brazil, Germany, Thailand), Cluster III (Bulgaria, Netherlands, New Zealand, United Kingdom, United States), and Cluster IV (Australia, Austria, Canada, Finland, Norway, Sweden).

Conclusion

Re-evaluation of the testing paradigm for HDV in HBV-positive patients and an active surveillance status of HDV are warranted to define the etiology of the structural breaks in HDV incidence timelines.
The cost of building an environmental surveillance system for typhoid
Authors: Hagedorn Brittany L. , Zhou Nicolette A. , Fagnant-Sperati Christine S. , Shirai Jeffry H. , Gauld Jillian , Wang Yuke , Boyle David S. , Meschke John Scott
Published: July 2021

Introduction

The typhoid conjugate vaccine is a safe and effective method for preventing Salmonella enterica serovar Typhi (typhoid) and the WHO’s guidance supports its use in locations with ongoing transmission. However, many countries lack a robust clinical surveillance system, making it challenging to determine where to use the vaccine. Environmental surveillance is an alternative approach to identify ongoing transmission, but the cost to implement such a strategy is previously unknown.

Methods

We estimated the cost of an environmental surveillance program for thirteen potential protocols. Unit costs were obtained from research labs involved in protocol development and equipment information was obtained from manufacturers and expert opinion. The cost model includes thirteen components and twenty-seven pieces of equipment. We used Monte Carlo simulations to project total costs.

Results

Total costs per sample including setup, overhead, and operational costs, range from $357–794 at a scale of 25 sites to $116–532 at 125 sites. Operational costs (ongoing expenditures) range from $218–584 per sample (25 sites) to $74–421 (125 sites). Eleven of the thirteen protocols have operational costs below $200 at this higher scale. Protocols with high up-front equipment costs benefit more from scale efficiencies. Sensitivity analyses show that laboratory labor, process efficiency, and the cost of consumables are the primary drivers of cost.

Conclusion

At scale, environmental surveillance may be affordable, depending on the protocol chosen and the geographic context. Costs will need to be considered along with protocol sensitivity. Opportunities to leverage existing infrastructure and multi-disease platforms may be necessary to further reduce costs.

Summary Box

What is already known?

Environmental surveillance has been used for polio transmission surveillance to target vaccination campaigns to prevent outbreaks. Similarly, methods for typhoid environmental surveillance are being developed, and could be used to support vaccine introduction decisions, if they are accurate and affordable.

What are the new findings?

Across the scenarios examined, operational costs are between $74–584 per sample depending on the scale and protocol selected. Operational costs are 67–79% of total annualized costs across the same permutations.

What do the new findings imply?

Policymakers can use these estimates and understanding of the efficiency of scale benefits in order to design a surveillance system that balances total cost with surveillance sensitivity and geographic coverage.
Understanding genetic risk factors for common side effects of antidepressant medications
Authors: Campos Adrian I. , Mulcahy Aoibhe , Thorp Jackson G. , Wray Naomi R. , Byrne Enda M. , Lind Penelope A. , Medland Sarah E. , Martin Nicholas G. , Hickie Ian B. , Rentería Miguel E.
Published: July 2021

Major depression is one of the most disabling health conditions internationally. In recent years, new generation antidepressant medicines have become very widely prescribed. While these medicines are efficacious, side effects are common and frequently result in discontinuation of treatment. Compared with specific pharmacological properties of the different medications, the relevance of individual vulnerability is understudied. We used data from the Australian Genetics of Depression Study to gain insights into the aetiology and genetic risk factors to antidepressant side effects. As expected, the most commonly reported longer-term side effects were reduced sexual function and weight gain. Importantly, participants reporting a specific side effect for one antidepressant were more likely to report the same side effect for other antidepressants, suggesting the presence of shared individual or pharmacological factors. Depression Polygenic Risk Scores (PRS) were associated with side effects that overlapped with depressive symptoms, including suicidality and anxiety. Body Mass Index PRS were strongly associated with weight gain from all medications. PRS for headaches were associated with headaches from sertraline. Insomnia PRS showed some evidence of predicting insomnia from amitriptyline and escitalopram. Our results suggest a set of common factors underlying the risk for antidepressant side effects. These factors seem to be, at least in part, explained by genetic liability related to depression severity and the nature of the side effect. Future studies on the genetic aetiology of side effects will enable insights into their underlying mechanisms and the possibility of risk stratification and prophylaxis strategies.
Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus-19 – The IONIC Trial Protocol
Authors: Sharma Kavi , Berry Lisa , Vryonis Evangelos , Ali Asad , Lara Beatriz , Noufaily Angela , Parsons Nick , Bradley Christopher James , Haley Becky , Maria Tabuso , Arasaradnam Ramesh
Published: July 2021

Background

Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone.

Methods

IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc.

Discussion

The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.

Trial Registration

The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 (ISRCTN53038326) and Clinicaltrials.gov on 17.08.2020 (NCT04516915)

Strengths and Limitations

This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.
Gut bacterial tyrosine decarboxylase gene abundance associates with disease duration, medication exposure, and gastrointestinal symptoms in a longitudinal cohort of Parkinson’s disease patients
Authors: van Kessel Sebastiaan P. , Auvinen Petri , Scheperjans Filip , Aidy Sahar El
Published: July 2021

Gut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms by which drug-microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching the circulation in patients with Parkinson’s disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a time period of two years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, anti-PD medication, and gastrointestinal symptoms and warrants further research on the effect of anti-PD medication on microbial changes and gastrointestinal-function.
Inequalities in access to healthcare by local policy model among newly arrived refugees: evidence from population-based studies in two German states
Authors: Wenner Judith , Biddle Louise , Gottlieb Nora , Bozorgmehr Kayvan
Published: July 2021

Background

Access to healthcare is restricted for newly arriving asylum seekers and refugees (ASR) in many receiving countries, which may lead to inequalities in health. In Germany, regular access and full entitlement to healthcare (equivalent to statutory health insurance, SHI) is only granted after a waiting time of 18 months. During this time of restricted entitlements, local authorities implement different access models to regulate asylum seekers’ access to healthcare: the electronic health card (EHC) or the healthcare voucher (HV). This paper examines inequalities in access to healthcare by comparing healthcare utilization by ASR under the terms of different local models (i.e., regular access equivalent to SHI, EHC, and HV).

Methods

We used data from three population-based, cross-sectional surveys among newly arrived ASR (N=863) and analyzed six outcome measures: specialist and general practitioner (GP) utilization, unmet needs for specialist and GP services, emergency department use and avoidable hospitalization. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals for all outcome measures, while considering need by adjusting for socio-demographic characteristics and health-related covariates.

Results

Compared to ASR with regular access, ASR under the HV model showed lower needs-adjusted odds of specialist utilization (OR=0.41 [0.24-0.66]) and a tendency towards lower GP (OR=0.61 [0.33-1.16]) and emergency department utilization (OR=0.74 [0.48-1.14]). ASR under the EHC model showed a tendency toward higher specialist unmet needs (OR= 1.89 [0.98-3.64]) and avoidable hospitalizations (OR=1.69 [0.87-3.30]) compared to ASR with regular access. A comparison between EHC and HV showed higher odds for specialist utilization under the EHC model as compared to the HV model (OR=2.39 [1.03-5.52]).

Conclusion

ASR using the HV are disadvantaged in their access to healthcare compared to ASR having either an EHC or regular access. Given equal need, they use specialist (and partly also GP) services less. The identified inequalities constitute inequities in access to healthcare that could be reduced by policy change from HV to the EHC model during the initial 18 months waiting time, or by granting ASR regular healthcare access upon arrival. Minor differences in unmet needs, emergency department use and avoidable hospitalization between the models deserve further exploration in future studies.
Child Suicide Rates During the COVID-19 pandemic in England
Authors: Odd David , Williams Tom , Appleby Louis , Gunnell David , Luyt Karen
Published: July 2021

Background

There is concern about the impact of COVID-19, and the control measures to prevent the spread, on children’s mental health. The aim of this work was to identify if there had been a rise of childhood suicide during the COVID pandemic; using data from England’s National Child Mortality Database (NCMD).

Method

Child suicide rates between April to December 2020 were compared with those in 2019 using negative binomial regression models, and characteristics compared. In a subset (1st January to 17th May 2020) further characteristics and possible contributing factors were obtained.

Results

A total of 193 likely childhood deaths by suicide were reported. There was no evidence overall suicide deaths were higher in 2020 than 2019 (RR 1.09 (0.80-1.48), p=0.584) but weak evidence that the rate in the first lockdown period (April to May 2020) was higher than the corresponding period in 2019 (RR 1.56 (0.86-2.81), p=0.144). Characteristics of individuals were similar between periods. Restriction to education and other activities, disruption to care and support services, tensions at home and isolation appeared to be contributing factors.

Limitations

As child suicides are fortunately rare, the analysis is based on small numbers of deaths with limited statistical power to detect anything but major increases in incidence.

Conclusion

We found no consistent evidence that child suicide deaths increased during the COVID-19 pandemic although there was a concerning signal they may have increased during the first UK lockdown. A similar peak was not seen during the following months, or the second lockdown.
Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel
Authors: Prunas Ottavia , Warren Joshua L. , Crawford Forrest W. , Gazit Sivan , Patalon Tal , Weinberger Daniel M. , Pitzer Virginia E.
Published: July 2021

The individual-level effectiveness of vaccines against clinical disease caused by SARS-CoV-2 is well-established. However, few studies have directly examined the effect of COVID-19 vaccines on transmission. We quantified the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech mRNA-based vaccine) against household transmission of SARS-CoV-2 in Israel. We fit two time-to-event models – a mechanistic transmission model and a regression model – to estimate vaccine effectiveness against susceptibility to infection and infectiousness given infection in household settings. Vaccine effectiveness against susceptibility to infection was 80-88%. For breakthrough infections among vaccinated individuals, the vaccine effectiveness against infectiousness was 41-79%. The overall vaccine effectiveness against transmission was 88.5%. Vaccination provides substantial protection against susceptibility to infection and slightly lower protection against infectiousness given infection, thereby reducing transmission of SARS-CoV-2 to household contacts.

One-Sentence Summary

Vaccination reduced both the rate of infection with SARS-CoV-2 and transmission to household contacts in Israel.
Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia
Authors: Alhamlan Fatimah S. , Almaghrabi Reem S. , Devol Edward B. , Alotaibi Anwar B. , Alageel Saleh M. , Obeid Dalia A. , Alraddadi Basem M. , Althawadi Sahar I. , Mutabagani Maysoon S. , Al-Qahtani Ahmed A.
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the catastrophic coronavirus disease 2019 (COVID-19) global pandemic. This study aimed to provide epidemiologic and clinical characteristics of patients with confirmed COVID-19 in Saudi Arabia and to determine whether characteristic profiles differ between patients who are symptomatic vs. asymptomatic for the disease. The first 492 consecutive patients diagnosed with SARS-CoV-2 infection at King Faisal Specialist Hospital and Research Centre in Saudi Arabia between March and September 2020 were included in this study. An electronic case report form developed using REDCap was used to collect data for each patient, including demographic characteristics, virus exposure (travel history, and human and animal contact), vaccination history, comorbidities, signs and symptoms, laboratory and radiographic reports, cardiac workup, medications, treatment regimens, and patient outcome. This patient cohort was 54% male, with 20.4% aged more than 60 years, 19.9% aged 31 to 40 years, and 17% aged 41 to 50 years. Most patients (79.2%) were symptomatic. Variables that significantly differed between symptomatic and asymptomatic patients were age, blood oxygen saturation percentage, hemoglobin level, lymphocyte count, neutrophil to lymphocyte (NTL) ratio, alanine aminotransferase (ALT) level, and aspartate aminotransferase (AST) level. Asymptomatic patients were mostly younger, with lower body mass index and ALT and AST levels but higher lymphocyte counts, NTL ratio, and CD4, CD8, natural killer cell, IgG, and IgM levels. The median incubation period reported for this cohort was 16 day, with upper and lower 95% quartiles of 27 and 10 days, respectively. Factors associated with increased risk of mortality were age (older than 42 years) and comorbidities, including specifically diabetes mellitus and hypertension. Patients who were not given an antiviral regimen were associated with better prognosis than patients who received an antiviral regimen (HR, 0.07; 95% CI, 0.011-0.25). Similar to countries worldwide, Saudi Arabia has explored treatment options to save the lives of patients during the COVID-19 pandemic. Our analyses will inform clinicians as well as policy makers to adopt the best strategies for SARS-CoV-2 infection management and treatment options.