bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of COVID-19 on the surgical volume of general surgery residents as main surgeons in a National Training Program in Costa Rica
Authors: Rivera-Chavarría Jose Pablo , Gutierrez-Lopez Carlos , Castro-Cordero Jose Antonio , Jimenez-Ramirez Gustavo
Published: August 2021

To quantify the impact of coronavirus disease 19 (COVID-19) on the surgical volume of residents’ medical practice in Costa Rica's General Surgery Residency Program.

The COVID-19 pandemic has caused a significant disruption in people's lives. Health systems worldwide have been forced to adapt to the new normal, which has posed a challenge for medical residency programs, especially in the surgical field.

This transversal study includes the surgical records of all residents of the General Surgery program who worked as main surgeons at the Mexico Hospital of the Costa Rican Social Security between December 23, 2019, and June 25, 2020.

As main surgeons, a total of 10 residents performed 291 pre-pandemic surgeries and 241 pandemic surgeries.

When comparing the distribution of procedures performed by residency levels, it is observed that the postgraduate year -2 increased the number of procedures performed during the pandemic period (pre-pandemic 19% vs pandemic 27%, P = .028). There was no statistically significant difference between the pre-pandemic and pandemic periods in the remaining levels.

When comparing the procedures by unit, a statistically significant decrease was observed in the Endocrine-Abdominal Wall Unit (pre-pandemic 18.3% vs pandemic 5.4%, P < .001). Conversely, a statistically significant increase was identified in Surgical Emergencies Unit procedures (40.0% vs post 51.7%, P = .007). No statistically significant differences were observed in the remaining the Units.

The COVID-19 pandemic had no statistically significant effect on surgeries performed by residents of the General Surgery Residency Program as main surgeons in a national training center in Costa Rica. The Department's timely measures and pro-resident attitude were the key reasons for the above results.
Non-resuscitative first aid training and assessment for junior secondary school students
Authors: Cheng Yee Han , Yeung Chi Yeung , Sharma Amar , So Kit Ying , Ko Hiu Fai , Wong Kevin , Lam Paul , Lee Anna
Published: August 2021

School-based first aid interventions can contribute to the number of adults trained in first aid in the community over time but few studies have examined the effectiveness of teaching non-resuscitative first aid on knowledge, attitudes and skills. Currently, there is no consensus on the optimal content and duration of first aid training for junior secondary students. The aim of this study was to evaluated the effectiveness of a 2.5 hour introductory non-resuscitative first aid course for junior secondary students.

This prospective, single-centre, pre-post study included 140 students (11–13 years old). Students completed a questionnaire on first aid knowledge, attitude towards first aid and self-confidence to perform first aid before and after a training session. Six emergency medicine physicians taught practical first aid skills training. A game-based formative assessment was undertaken where the instructors assessed small teams of students’ role-playing injured classmates and first aid responders (and vice-versa) treating abrasions, ankle sprain, choking and a scald injury.

Few students had prior first aid training (14%). After adjusting for student's age, sex, prior first aid training and format delivery, the course was associated with increased mean knowledge score (pre-training 53%, post-training 88%; mean difference [MD] 35%, 95% CI: 32% to 38%), positive attitudes and more confidence in performing first aid after training (all P < .001). All teams showed a good level of competency in treating simulated injuries with first aid kits.

This brief non-resuscitative first aid course was associated with noticeable and valuable changes in knowledge score and self-confidence level in performing first aid. The game-based formative assessment facilitated a positive learning environment for skill competency evaluation.
Palliation of malignant dysphagia with a segmented self-expanding metal stent
Authors: Wiese Marie-Sophie , Dratsch Thomas , Plum Patrick Sven , Lorenz Florian , Rieck Isabel , Pinto dos Santos Daniel , Alakus Hakan , Bludau Marc , Kleinert Robert , Goeser Tobias , Bruns Christiane Josephine , Chon Seung-Hun
Published: August 2021

Self-expanding metal stents (SEMSs) in different geometric shapes are an established palliative treatment for malignant tumors of the esophagus. Mechanical properties and stent design have an impact on patient comfort, migration rate, and removability. SEMS with a segmented design (segSEMS) have recently become available on the market, promising new biomechanical properties for stent placement in benign and malignant esophageal diseases. In this study, we evaluated recurrent dysphagia, quality of life as well as technical success and complications for segmented SEMS-implantation in a retrospective study in palliative patients with dysphagia caused by malignant tumors of the esophagus.

Between May 2017 and December 2018, patients presented to the interdisciplinary department of endoscopy of the University Hospital Cologne underwent segmented SEMS placement for malignant dysphagia. Patient follow-up was evaluated, and complications were monitored. Quality of life and functional improvement were monitored using the EORTC QLQ-C30 and QLQ-OE18.

A total of 20 consecutive patients (16 men, 4 women; mean age: 65.5, range: 46–82) participated in the study and were treated with 20 segSEMS in total. The success rate of stent placement was 100%. Stent migration occurred in 3 patients (15.0%). Insertion of segSEMS immediately lead to a 48.0% reduction of dysphagia in the first 2 months (P < .001). Pain while eating (odynophagia) could also be significantly reduced by 39.6% over the first 2 months (P < .001).

Implantation of segSEMS is a feasible and effective treatment for dysphagia in palliative patients with malignant tumors of the esophagus, offering immediate relief of symptoms and gain of physical functions.
Endoscopy within 7 days after detecting high calprotectin levels can be useful for therapeutic decision-making in ulcerative colitis
Authors: Yong Ho Min , Park Sung-Jo , Jeon Seong Ran , Park Heesu , Kim Hyun Gun , Lee Tae Hee , Park Junseok , Kim Jin-Oh , Lee Joon Seong , Ko Bong Min , Goong Hyeon Jeong , Park Suyeon
Published: August 2021

The aim of this study was to assess the appropriate time interval to identify the association between the fecal calprotectin (FC) test and endoscopic activity, and to evaluate whether the time interval affects the therapeutic plan adjustment in patients with ulcerative colitis (UC).

This study included 103 patients who underwent FC tests and endoscopic examinations within the past three months. The FC test results classified cases into three groups as follows: moderate to severe (>200, >250, or >300 μg/g), mild (100–200, 100–250, or 100–300 μg/g), and inactive (<100 μg/g) activity. The Mayo endoscopic subscore was used to determine endoscopic activity. Therapeutic plan adjustment included the addition or increased dosage of anti-inflammatory drugs, steroids, immunomodulators, and biologics.

Using the cutoff value for FC of 200 μg/g, the appropriate time interval for dividing the association and non-association between Mayo endoscopic subscore and FC was 7 days (sensitivity, 74.4%; specificity, 50.0%; area under the curve [AUC], 0.6032). When using FC 250 or 300 μg/g, the appropriate time interval was 5.5 days, with a sensitivity of 71.7% and specificity of 49.1 (AUC 0.5862) in FC 250 μg/g, a sensitivity of 69.6%, and a specificity of 47.4 (AUC 0.5549) for FC 300 μg/g. Therapeutic plans changed in 29.1% of patients. In patients with shorter intervals (≤7 days) between the FC test and endoscopy, significant therapeutic plan adjustments were observed in patients with UC (36.5% vs. 17.5%, P = .047).

Although the need for endoscopy within 7 days after detecting high FC (≥ 200 μg/g) was not statistically supported, endoscopy within a shorter interval (≤7 days) in UC patients with high FC can help determine the therapeutic plan.
Critical Success Factors for Addressing Discharge Inefficiency at a Large Academic Medical Center
Authors: Feldman Sue S. , Kennedy Kierstin Cates , Nafziger Sarah M. , Orewa Gregory N. , Kpomblekou-Ademawou Enyonam , Hearld Kristine Ria , Hall Allyson G.
Published: August 2021

Background:

Delayed discharges can be a systemic issue. Understanding the systemic factors that contribute to discharge inefficiencies is essential to addressing discharge inefficiencies.

Purpose:

This article reports on a Lean Six Sigma approach and the process to identifying inefficiencies and systemic barriers to early discharge in a large US academic medical center.

Methods:

A qualitative methodology guided this project. In particular, direct observation methods were used to help the project team identify factors contributing to discharge inefficiencies.

Results:

Overall, findings suggest that establishing consistent multidisciplinary team communication processes was a contributing factor to reducing the inefficiencies around discharges. On a more granular level, key barriers included disparate communication systems, disruptors (specifically Kaizen bursts), and unique role challenges.

Conclusions:

This article provides a framework for addressing discharge inefficiencies. Because the output of the process, a critical contributor to the overall outcome, is often not analyzed, this analysis provides value to others contemplating the same or similar process toward discharge efficiency.
Where Did the Blood Go?: A Meckel’s Diverticulum Bleed Without Hematochezia or Melena
Authors: Tracy Michaela , Weil Brent R. , Verhave Menno
Published: August 2021

A 2-year-old patient with chronic abdominal pain presented with acutely worsening abdominal pain and acute anemia. The patient had no stigmata of bleeding including no hematemesis, melena or hematochezia, but had falling hemoglobin and hematocrit over the course of 24 hours. Abdominal ultrasound and computerized tomography showed a large cystic, fluid filled mass in the right midabdomen. The patient was taken to the operating room and a blood-filled mass arising from the ileum was identified and resected by the surgical team. Pathology was consistent with Meckel’s diverticulum with heterotopic gastric mucosa. This is an atypical presentation of Meckel’s diverticulum with bleeding contained within the diverticulum rather than bleeding in the intestinal lumen. Gastroenterologists must consider this unusual presentation when encountering progressive, acute anemia even in the absence of overt gastrointestinal blood loss.
Child With Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Authors: Alghamdi Khalid A. , Bokhari Alaa M. , El Hag Imad A.
Published: August 2021

Many patients present to our clinic with Helicobacter pylori (H. pylori) infection. Most have nonspecific symptoms that cannot be immediately attributed to H. pylori. The joint European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)/North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines recommend upper gastroscopy to detect the cause of such symptoms. Herein, we present the case of a 9-year-old girl diagnosed with gastric mucosa-associated lymphoid tissue lymphoma associated with H. pylori infection using upper gastroscopy. We believe that a patient of such a young age with this serious condition secondary to H. pylori will highlight the importance of upper gastrointestinal endoscopy in such cases.
A Governance Framework to Integrate Longitudinal Clinical and Community Data in a Distributed Data Network: The Childhood Obesity Data Initiative
Authors: Kraus Emily M. , Scott Kenneth A. , Zucker Rachel , Heisey-Grove Dawn , King Raymond J. , Carton Thomas W. , Daley Matthew F. , Deakyne Davies Sara J. , Block Jason P. , Haemer Matthew , Goodman Alyson B. , Garrett Nedra , Davidson Arthur J.
Published: August 2021

Context:

Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research.

Objective:

A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems.

Participants and Setting:

Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research.

Design:

A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement.

Results:

A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications.

Conclusion:

CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts.
The Childhood Obesity Data Initiative: A Case Study in Implementing Clinical-Community Infrastructure Enhancements to Support Health Services Research and Public Health
Authors: King Raymond J. , Heisey-Grove Dawn M. , Garrett Nedra , Scott Kenneth A. , Daley Matthew F. , Haemer Matthew A. , Podila Pradeep , Block Jason P. , Carton Tom , Gregorowicz Andrew J. , Mork K. Peter , Porter Renee M. , Chudnov Daniel L. , Jellison Jim , Kraus Emily M. , Harrison Megan R. , Sucosky Marissa Scalia , Armstrong Sarah , Goodman Alyson B.
Published: August 2021

Context:

We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process.

Program:

The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners.

Implementation:

CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020.

Evaluation:

We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes.

Discussion:

We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs.
Sociodemographic Correlates of Self-reported Discrimination in HIV Health Care Settings Among Persons With Diagnosed HIV in the United States, Medical Monitoring Project, 2018–2019
Authors: McCree Donna Hubbard , Beer Linda , Jeffries William L. , Tie Yunfeng , Fagan Jennifer , Crim Stacy M.
Published: August 2021

Background:

HIV-related discrimination in health care settings is associated with negative health outcomes among persons with HIV (PWH). This article describes and compares differences in the prevalence of self-reported experiences with discrimination in health care settings by sociodemographic and clinical care factors among persons with diagnosed HIV in the United States.

Methods:

We analyzed interview and medical record data collected during June 2018–May 2019 from 3850 PWH who had received HIV care in the past 12 months. We calculated weighted percentages and associated 95% confidence intervals and assessed the association between any experience of discrimination and selected sociodemographic and clinical characteristics using prevalence ratios with predicted marginal means.

Results:

Approximately 25% of PWH who had an HIV care visit in the past 12 months reported experiencing any discrimination. Experiences with discrimination were significantly more prevalent among persons aged 18–29 years (34%); transgender persons (41%); persons of gay (25%), bisexual (31%), or other (40%) sexual orientations; and persons who did not have a regular provider (39%), lived at/below poverty level (28%), were homeless (39%) or incarcerated (37%) in the past 12 months. PWH who experienced discrimination were more likely to have missed at least one HIV care visit, not be taking antiretroviral therapy, and have missed antiretroviral therapy doses. Recent and sustained viral suppression were not significantly associated with experiencing any discrimination.

Conclusions:

Interventions that address the sociocultural and structural factors associated with discrimination in all health care settings are needed to improve health outcomes among PWH and end the HIV epidemic in the United States.
General surgeon involvement in the care of patients designated with an American Association for the Surgery of Trauma–endorsed ICD-10-CM emergency general surgery diagnosis code in Wisconsin
Authors: Ingraham Angela , Schumacher Jessica , Fernandes-Taylor Sara , Yang Dou-Yan , Godat Laura , Smith Alan , Barbosa Ronald , Cribari Chris , Salim Ali , Schroeppel Thomas , Staudenmayer Kristan , Crandall Marie , Utter Garth ,   on behalf of the AAST Committee on Patient Assessment
Published: August 2021

BACKGROUND

The current national burden of emergency general surgery (EGS) illnesses and the extent of surgeon involvement in the care of these patients remain largely unknown. To inform needs assessments, research, and education, we sought to: (1) translate previously developed International Classification of Diseases (ICD), 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes representing EGS conditions to ICD 10th Revision, CM (ICD-10-CM) codes and (2) determine the national burden of and assess surgeon involvement across EGS conditions.

METHODS

We converted ICD-9-CM codes to candidate ICD-10-CM codes using General Equivalence Mappings then iteratively refined the code list. We used National Inpatient Sample 2016 to 2017 data to develop a national estimate of the burden of EGS disease. To evaluate surgeon involvement, using Wisconsin Hospital Association discharge data (January 1, 2016 to June 30, 2018), we selected adult urgent/emergent encounters with an EGS condition as the principal diagnosis. Surgeon involvement was defined as a surgeon being either the attending provider or procedural physician.

RESULTS

Four hundred and eighty-five ICD-9-CM codes mapped to 1,696 ICD-10-CM codes. The final list contained 985 ICD-10-CM codes. Nationally, there were 2,977,843 adult patient encounters with an ICD-10-CM EGS diagnosis. Of 94,903 EGS patients in the Wisconsin Hospital Association data set, most encounters were inpatient as compared with observation (75,878 [80.0%] vs. 19,025 [20.0%]). There were 57,780 patients (60.9%) that underwent any procedure. Among all Wisconsin EGS patients, most had no surgeon involvement (64.9% [n = 61,616]). Of the seven most common EGS diagnoses, surgeon involvement was highest for appendicitis (96.0%) and biliary tract disease (77.1%). For the other five most common conditions (skin/soft tissue infections, gastrointestinal hemorrhage, intestinal obstruction/ileus, pancreatitis, diverticular disease), surgeons were involved in roughly 20% of patient care episodes.

CONCLUSION

Surgeon involvement for EGS conditions ranges from highly likely (appendicitis) to relatively unlikely (skin/soft tissue infections). The wide range in surgeon involvement underscores the importance of multidisciplinary collaboration in the care of EGS patients.

LEVEL OF EVIDENCE

Prognostic/epidemiological, Level III.
Rib Fracture Frailty Index: A risk stratification tool for geriatric patients with multiple rib fractures
Authors: Choi Jeff , Marafino Ben J. , Vendrow Edward B. , Tennakoon Lakshika , Baiocchi Michael , Spain David A. , Forrester Joseph D.
Published: August 2021

BACKGROUND

Rib fractures are consequential injuries for geriatric patients (age, ≥65 years). Although age and injury patterns drive many rib fracture management decisions, the impact of frailty—which baseline conditions affect rib fracture-specific outcomes—remains unclear for geriatric patients. We aimed to develop and validate the Rib Fracture Frailty (RFF) Index, a practical risk stratification tool specific for geriatric patients with rib fractures. We hypothesized that a compact list of frailty markers can accurately risk stratify clinical outcomes after rib fractures.

METHODS

We queried nationwide US admission encounters of geriatric patients admitted with multiple rib fractures from 2016 to 2017. Partitioning around medoids clustering identified a development subcohort with previously validated frailty characteristics. Ridge regression with penalty for multicollinearity aggregated baseline conditions most prevalent in this frail subcohort into RFF scores. Regression models with adjustment for injury severity, sex, and age assessed associations between frailty risk categories (low, medium, and high) and inpatient outcomes among validation cohorts (odds ratio [95% confidence interval]). We report results according to Transparent Reporting of Multivariable Prediction Model for Individual Prognosis guidelines.

RESULTS

Development cohort (n = 55,540) cluster analysis delineated 13 baseline conditions constituting the RFF Index. Among external validation cohort (n = 77,710), increasing frailty risk (low [reference group], moderate, high) was associated with stepwise worsening adjusted odds of mortality (1.5 [1.2–1.7], 3.5 [3.0–4.0]), intubation (2.4 [1.5–3.9], 4.7 [3.1–7.5]), hospitalization ≥5 days (1.4 [1.3–1.5], 1.8 [1.7–2.0]), and disposition to home (0.6 [0.5–0.6], 0.4 [0.3–0.4]). Locally weighted scatterplot smoothing showed correlations between increasing RFF scores and worse outcomes.

CONCLUSION

The RFF Index is a practical frailty risk stratification tool for geriatric patients with multiple rib fractures. The mobile app we developed may facilitate rapid implementation and further validation of RFF Index at the bedside.

LEVEL OF EVIDENCE

Prognostic study, level III.
The Challenging Management of an Intracardiac Thrombus in a Liver Transplant Patient at the Reperfusion Phase: A Case Report and Brief Literature Review
Authors: Vetrugno Luigi , Cherchi Vittorio , Lorenzin Dario , De Lorenzo Francesco , Ventin Marco , Zanini Victor , Terrosu Giovanni , Risaliti Andrea , Baccarani Umberto , Bove Tiziana
Published: August 2021

The exact origin of intracardiac thrombi formation during orthotopic liver transplant remains unknown. The altered balance between hypercoagulability, hypocoagulation, and endothelial dysfunction associated with end-stage liver disease is thought to play a pivotal role. Venous stasis, vascular clamping, and reperfusion could also contribute to clot formation. The incidence of intracardiac thrombi formation stands at 4.2%, associated with a mortality rate of 45.5%, and to date, no consensus exists regarding the best way to treat this complication. Intraoperative transesophageal echocardiography is the only effective method for diagnosing intracardiac thrombi formation early, while point-of-care coagulation testing could guide the coagulation management potentially improving patient outcomes.
Survivors of SARS-CoV-2 Infection Show Neuropsychiatric Sequelae Measured by Surveys, Neurocognitive Testing, and Magnetic Resonance Imaging: Preliminary Results
Authors: Hack Laura M. , Brawer Jacob , Chesnut Megan , Zhang Xue , Wintermark Max , Jiang Bin , Grant Philip , Bonilla Hector , Stetz Patrick , Yesavage Jerome A. , Subramanian Aruna , Williams Leanne M.
Published: August 2021

A significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with ‘brain-fog’. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.
Unexplained longitudinal variability in COVID-19 antibody status by Lateral Flow Immuno-Antibody testing
Authors: Davis Katrina , Oetzmann Carolin , Carr Ewan , Lavelle Grace , Leightley Daniel , Malim Michael , Vitiello Valentina , Wickersham Alice ,   KCL-CHECK team, Razavi Reza , Hotopf Matthew
Published: August 2021

Background

COVID-19 antibody testing allows population studies to classify participants by previous SARS-CoV-2 infection status. Home lateral flow immune-antibody testing devices offer a very convenient way of doing this, but relatively little is known about how measurement and antibody variability will affect consistency in results over time. We examined consistency by looking at the outcome of two tests three months apart while COVID-19 infection rates were low (summer 2020 in the UK).

Methods

The KCL-Coronavirus Health and Experiences in Colleagues at King’s is an occupational cohort of staff and postgraduate research students. Lateral flow immune-antibody testing kits were sent to participant’s homes in late June 2020 and late September 2020. Participants also completed regular surveys that included asking about COVID-19 symptoms and whether they thought they had been infected.

Results

We studied 1489 participants returned valid results in both June and September (59% of those sent kits). Lateral flow immune-antibody test was positive for 7.2% in June and 5.9% in September, with 3.9% positive in both. Being more symptomatic or suspecting infection increased the probability of ever being positive. Of those positive in June, 46% (49/107) were negative in September (seroreversion), and this was similar regardless of symptom characteristics, suspicion, and timing of possible infection. A possible outlier was those aged over 55 years, where only 3 of 13 (23%) had seroreversion.

Discussion

These results do not follow the pattern reported from studies specifically designed to monitor seropositivity, which have found greater consistency over time and the influence of presence, timing and severity of symptoms on seroreversion. We suggest several factors that may have contributed to this difference: our low bar in defining initial seropositivity (single test); a non-quantitative test known to have relatively low sensitivity; participants carrying out testing. We would encourage other studies to use these real-world performance characteristics alongside those from laboratory studies to plan and analyse any antibody testing.
The impact of studies with no events in both arms on meta-analysis of rare events: a simulation study using generalized linear mixed model
Authors: Xu Chang , Lin Lifeng
Published: August 2021

Objective

The common approach to meta-analysis with double-zero studies is to remove such studies. Our previous work has confirmed that exclusion of these studies may impact the results. In this study, we undertook extensive simulations to investigate how the results of meta-analyses would be impacted in relation to the proportion of such studies.

Methods

Two standard generalized linear mixed models (GLMMs) were employed for the meta-analysis. The statistical properties of the two GLMMs were first examined in terms of percentage bias, mean squared error, and coverage. We then repeated all the meta-analyses after excluding double-zero studies. Direction of estimated effects and p-values for including against excluding double-zero studies were compared in nine ascending groups classified by the proportion of double-zero studies within a meta-analysis.

Results

Based on 50,000 simulated meta-analyses, the two GLMMs almost achieved unbiased estimation and reasonable coverage in most of the situations. When excluding double-zero studies, 0.00% to 4.47% of the meta-analyses changed the direction of effect size, and 0.61% to 8.78% changed direction of the significance of p-value. When the proportion of double-zero studies increased in a meta-analysis, the probability of the effect size changed the direction increased; when the proportion was about 40% to 60%, it has the largest impact on the change of p-values.

Conclusion

Double-zero studies can impact the results of meta-analysis and excluding them may be problematic. The impact of such studies on meta-analysis varies by the proportion of such studies within a meta-analysis.
Comparative Analysis of the Chemotherapy-related Cognitive Impairments in Patients with Breast Cancer: a Community-based Research
Authors: Owrangi Maryam , Gholamzadeh Mohammad Javad , Gharamaleki Maryam Vasaghi , Mousavi Seyedeh Zahra , Kamali Ali-Mohammad , Dehghani Mehdi , Chakrabarti Prasun , Nami Mohammad
Published: August 2021

Purpose

With increasing breast cancer (BC) survival rates, the survivors’ quality of life (QoL) has become an important issue. Chemotherapy-induced cognitive impairment, known as “chemobrain” has been addressed recently. Therefore, cognitive function as one of the determinants of QoL should be considered while prescribing chemotherapeutics. In this study, we aimed to evaluate the effects of two common chemotherapy regimens on BC survivors’ cognition.

Methods

The participants comprised 35 BC patients who underwent two common chemotherapy regimens, AC-T and TAC, and 24 matched healthy volunteers. The participants were assessed regarding anxiety, depression, general health status, and cognitive function including aspects of concentration, verbal ability, reasoning, memory, and visuospatial skill through Addenbrooke’s Cognitive Examination (ACE-P) and Cambridge Brain Science (CBS) tests.

Results

Regarding depression and anxiety, there were no significant differences between the three groups. However, BC patients significantly complained of chronic fatigue compared to healthy volunteers (P-value = 0.027). Besides, ACE-P revealed the language domain to be affected in the AC-T group in comparison with the TAC-treated cases (P-value = 0.036). Moreover, the patients receiving the AC-T regimen had worse performance in visuospatial working memory and attention domains compared to the TAC group considering CBS tests (P-value = 0.031 and 0.008, respectively).

Conclusion

The results represent the AC-T regimen to be more toxic than the TAC in domains of language, concentration, and visuospatial working memory.

Implications for cancer survivors

The AC-T regimen should be prescribed with caution in BC patients suffering from baseline cognitive impairments to improve post-chemotherapy QoL.

Graphical Abstract
Disruption of spatiotemporal clustering in dengue cases bywMelWolbachiain Yogyakarta, Indonesia
Authors: Dufault Suzanne M. , Tanamas Stephanie K. , Indriani Citra , Utarini Adi , Ahmad Riris Andono , Jewell Nicholas P. , Simmons Cameron P. , Anders Katherine L.
Published: August 2021

Abstract

Dengue exhibits focal clustering in households and neighborhoods, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacteriumWolbachia(wMel-strain) into theAedes aegyptimosquito population. We analysed 318 serotyped and geolocated dengue cases (and 5,921 test-negative controls) from a randomized controlled trial in Yogyakarta, Indonesia ofwMel deployments. We find evidence of spatial clustering up to 300m among the 265 dengue cases (3,083 controls) in the untreated trial arm. Participant pairs enrolled within 30 days and 50m had a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds of being homotypic (i.e. potentially transmission-related) as compared to pairs occurring at any distance. In contrast, we find no evidence of spatiotemporal clustering among the 53 dengue cases (2,838 controls) resident in thewMel-treated arm. Introgression ofwMelWolbachiaintoAedes aegyptimosquito populations interrupts focal dengue virus transmission leading to reduced case incidence; the true intervention effect may be greater than the 77% efficacy measured in the primary analysis of the Yogyakarta trial.
COVID-19 in Scottish care homes: A metapopulation model of spread among residents and staff
Authors: Baister Matthew , McTaggart Ewan , McMenemy Paul , Megiddo Itamar , Kleczkowski Adam
Published: August 2021

Care homes in the UK were disproportionately affected by the first wave of the COVID-19 pandemic, accounting for almost half of COVID-19 deaths over the course of the period from 6th March – 15th June 2020. Understanding how infectious diseases establish themselves throughout vulnerable communities is crucial for minimising deaths and lowering the total stress on the National Health Service (NHS Scotland). We model the spread of COVID-19 in the health-board of NHS Lothian, Scotland over the course of the first wave of the pandemic with a compartmental Susceptible - Exposed - Infected reported - Infected unreported - Recovered - Dead (SEIARD), metapopulation model. Care home residents, care home workers and the rest of the population are modelled as subpopulations, interacting on a network describing their mixing habits. We explicitly model the outbreak’s reproduction rate and care home visitation level over time for each subpopulation, and execute a data fit and sensitivity analysis, focusing on parameters responsible for intra-subpopulation mixing: staff sharing, staff shift patterns and visitation. The results suggest that hospital discharges were not predominantly responsible for the early outbreak in care homes, and that only a few such cases led to infection seeding in care homes by the 6th of March Sensitivity analysis show the main mode of entry into care homes are infections by staff interacting with the general population. Visitation (before cancellation) and staff sharing were less significant in affecting outbreak size. Our model suggests that focusing on the protection and monitoring of staff, followed by reductions in staff sharing and quick cancellations of visitation can significantly reduce future infection attack rates of COVID-19 in care homes.
Nomogram-Based Prognostic Model to predict the High blood pressure in Children and Adolescents —— Finding from 342,736 individual in China
Authors: Liang Jing-hong , Zhao Yu , Chen Yi-can , Huang Shan , Zhang Shu-xin , Jiang Nan , Kakaer Aerziguli , Chen Ya-jun
Published: August 2021

Background

Predicting the potential risk factors of High blood pressure(HBP) among children and adolescents is still a knowledge gap. Our study aimed to establish and validate a nomogram-based model for identifying children and adolescents at risk of developing HBP based on a population-based prospective study.

Methods

Hypertension was defined as systolic blood pressure or diastolic blood pressure above 95th percentile, using age, gender and height-specific cut-points. Penalized regression with Lasso was used to identify the strongest predictors of hypertension. Internal validation was conducted by 5-fold cross-validation and bootstrapping approach. The predictive variables were identified along with the advanced nomogram plot by conducting univariate and multivariate logistic regression analyses. A nomogram was constructed by training group comprised of 239,546(69.89%)participants and subsequently validated by externally group with 103,190(30.11%)participants.

Results

Of 342,736 children and adolescents, a total of 55,480(16.19%) youths were identified with HBP with mean age 11.51±1.45 year and 183,487 were boys(53.5%). Nine significant relevant predictors were identified including: age, gender, weight status, birthweight, breastfeeding, gestational hypertension, family history of obesity, family history of hypertension and physical activity. An acceptable discrimination[Area under the receiver operating characteristic curve(AUC):0.742(Development group), 0.740(Validation group)] and good calibration(Hosmer and Lemeshow statistics, P > 0.05) were observed in our models. An available web-based nomogram was built online.

Conclusions

This model composed of age, gender, early life factors, family history of disease, and lifestyle factors may predict the risk of HBP among children and adolescents, which has developed a promising nomogram that may aid in more accurately for identifying the HBP among youths in primary care.

Funding Sources

The work was supported by the National Natural Science Foundation of China (No. 81673193).
A community based case-control study to determine the risk factors of dengue fever in Bangladesh
Authors: Rahman Md. Sahidur , Mehejabin Fatema , Rashid Rumana
Published: August 2021

In a tropical country like Bangladesh where the climatic condition favors the growth of Aedes mosquito vectors, the success of dengue prevention depends largely on the proper identification and controlling of the socio-demographic and lifestyle-related risk factors. A case-control study including 150 cases and 150 controls were conducted aimed to explore the potential risk and protective factors and their association with dengue virus infection in the Chattogram district of Bangladesh. Cases were confirmed for dengue patients admitted in Chattogram medical college hospital and Bangladesh institute of tropical and infectious diseases during August and September 2019. Whereas, controls were non-dengue patients admitted in other departments of the same hospitals through gender age and location matching. The questionnaire data were collected through telephone-based interviews which included information regarding general demography, daily life activities, housing with its surroundings status. Chi-square and binary logistic regression were performed for identifying potential risk factors and their association with the occurrences of dengue fever.

The study found that travel history to the high incidence area, the place of staying most of the time, living in 21 to 40 years old houses, and the temporary residence of the city were statistically significant risk factors for getting the dengue infection. On contrary, Quality of indoor daylight, ventilation, bus stand/garage, stagnant water, and any construction site around 250 meters of the house did not show significant association with dengue fever.
Single-Cell Multiome Sequencing Clarifies Enteric Glial Cell Diversity and Identifies an Intraganglionic Population Poised for Neurogenesis
Authors: Guyer Richard A. , Stavely Rhian S. , Robertson Keiramarie , Bhave Sukhada , Hotta Ryo , Kaltschmidt Julia A. , Goldstein Allan M.
Published: August 2021

The enteric nervous system (ENS) consists of glial cells (EGCs) and neurons derived from neural crest precursors. EGCs retain capacity for large-scale neurogenesis in culture, and in vivo lineage tracing has identified neurons derived from glial cells in response to inflammation. We thus hypothesize that EGCs possess a chromatin structure poised for neurogenesis. We use single-cell multiome sequencing to assess EGCs undergoing spontaneous neurogenesis in culture, as well as freshly isolated small intestine myenteric plexus EGCs. Cultured EGCs maintain open chromatin at genomic loci accessible in neurons, and neurogenesis from EGCs involves dynamic chromatin rearrangements with a net decrease in accessible chromatin. Multiome analysis of freshly isolated EGCs reveals transcriptional diversity, with open chromatin at neuron-associated genomic elements. A subset of EGCs, highly enriched within the myenteric ganglia, has a gene expression program and chromatin state consistent with neurogenic potential.
Repeated introduction of micropollutants enhances microbial succession despite stable degradation patterns
Authors: Izabel-Shen Dandan , Li Shuang , Luo Tingwei , Wang Jianjun , Li Yan , Sun Qian , Yu Chang-Ping , Hu Anyi
Published: August 2021

The increasing-volume release of micropollutants into natural surface waters has raised great concern due to their environmental accumulation. Persisting micropollutants can impact multiple generations of organisms, but their microbially-mediated degradation and their influence on community assembly remain understudied. Here, freshwater microbes were treated with several common micropollutants, alone or in combination, and then transferred every 5 days to fresh medium containing the same micropollutants to mimic the repeated exposure of microbes. Metabarcoding of 16S rRNA gene makers was chosen to study the succession of bacterial assemblages following micropollutant exposure. The removal rates of micropollutants were then measured to assess degradation capacity of the associated communities. The degradation of micropollutants did not accelerate over time but altered the microbial community composition. Community assembly was dominated by stochastic processes during early exposure, via random community changes and emergence of seedbanks, and deterministic processes later in the exposure, via advanced community succession. Early exposure stages were characterized by the presence of sensitive microorganisms such as Actinobacteria and Planctomycetes, which were then replaced by more tolerant bacteria such as Bacteroidetes and Gammaproteobacteria. Our findings have important implication for ecological feedback between microbe-micropollutants under anthropogenic climate change scenarios.
Bi-reporter vaccinia virus for tracking viral infections in vitro and in vivo
Authors: Chiem Kevin , Lorenzo Maria , Rangel-Moreno Javier , De La Luz Garcia-Hernandez Maria , Park Jun-Gyu , Nogales Aitor , Blasco Rafael , Martínez-Sobrido Luis
Published: August 2021

Recombinant viruses expressing reporter genes allow visualization and quantification of viral infections and can be used as valid surrogates to identify the presence of the virus in infected cells and animal models. However, one of the limitations of recombinant viruses expressing reporter genes is the use of either fluorescent or luciferase proteins that are used alternatively for different purposes. Vaccinia virus (VV) is widely used as a viral vector, including recombinant (r)VV singly expressing either fluorescent or luciferase reporter genes that are useful for specific purposes. In this report, we engineered two novel rVV stably expressing both fluorescent (Scarlet or GFP) and luciferase (Nluc) reporter genes from different loci in the viral genome. In vitro, these bi-reporter expressing rVV have similar growth kinetics and plaque phenotype than those of the parental WR VV isolate. In vivo, rVV Nluc/Scarlet and rVV Nluc/GFP effectively infected mice and were easily detected using in vivo imaging systems (IVIS) and ex vivo in the lungs from infected mice. We used these bi-reporter expressing rVV to assess viral pathogenesis, infiltration of immune cells in the lungs, and to directly identify the different subsets of cells infected by VV in the absence of antibody staining. Collectively, these rVV expressing two reporter genes open the feasibility to study the biology of viral infections in vitro and in vivo, including host-pathogen interactions and dynamics or tropism of viral infections. Moreover, they represent an excellent approach for the discovery of new prophylactics and/or therapeutics for the treatment of poxvirus infections.

IMPORTANCE

Despite the eradication of variola virus (VARV), the causative agent of smallpox, poxviruses still represent an important threat to human health due to their possible use as bioterrorism agents and the emergence of zoonotic poxvirus diseases. Recombinant vaccinia viruses (rVV) expressing easily traceable fluorescent or luciferase reporter genes have significantly contributed to the progress of poxvirus research. However, rVV expressing one marker gene have several constraints for in vitro and in vivo studies, since both fluorescent and luciferase proteins impose certain limitations for specific applications. To overcome these limitations, we generated optimized rVV stably expressing both fluorescent (Scarlet or GFP) and luciferase (Nluc) reporter genes to easily track viral infection in vitro and in vivo. This new generation of double reporter-expressing rVV represent an excellent option to study viral infection dynamics in cultured cells and validated animal models of infection, and for the discovery of new poxvirus antiviral treatments.