Search

Pneumonia is the second leading cause of hospital admissions and deaths among children <5 years in Uganda. In 2014, Uganda officially rolled out the introduction of the pneumococcal conjugate vaccine (PCV) into routine immunization schedule. However, little is known about the long-term impact of PCV on pneumonia admissions and deaths. In this study, we described the trends and spatial distribution of pneumonia hospital admissions and mortality among children <5 years in Uganda, 2014-2021. We analysed secondary data on pneumonia admissions and deaths from the District Health Information System version 2 during 2014-2021. The proportion of pneumonia cases admitted and case-fatality rates (CFRs) for children <5 years were calculated for children <5 years presenting at the outpatient department. At national, regional, and district levels, pneumonia mortality rates were calculated per 100,000 children <5 years. The Mann-Kendall Test was used to assess trend significance. We found 667,122 pneumonia admissions and 11,692 (2%) deaths during 2014-2021. The overall proportion of pneumonia cases admitted among children <5 years was 22%. The overall CFR was 0.39%, and the overall pneumonia mortality rate among children <5 years was 19 deaths per 100,000. From 2014 to 2021, there were declines in the proportion of pneumonia cases admitted (31% to 15%; p = 0.051), mortality rates (24/100,000 to 14 per 100,000; p = 0.019), and CFR (0.57% to 0.24%; p = 0.019), concomitant with increasing PCV coverage. Kotido District had a persistently high proportion of pneumonia cases that were admitted (>30%) every year while Kasese District had persistently high mortality rates (68-150 deaths per 100,000 children <5 years). Pneumonia admissions, mortality, and case fatality among children <5 years declined during 2013-2021 in Uganda after the introduction of PCV. However, with these trends it is unlikely that Uganda will meet the 2025 GAPPD targets. There is need to review implementation of existing interventions and identify gaps in order to highlight priority actions to further accelerate declines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The integration of robotics into neuroendovascular surgery has the potential to revolutionize the field by enhancing precision, reducing procedure-related risks, and improving patient outcomes. The CorPath GRX system represents a significant advancement in this domain. In this systematically conducted scoping review, we explore the current applications, advances, and challenges associated with robot-assisted neuroendovascular surgery., Methods: A comprehensive literature search was conducted across PubMed, Scopus, Embase, and Web of Science, covering publications from January 2015 to December 2024. Relevant data were extracted from studies involving human subjects and reporting the use of robotic guidance with the CorPath GRX system for neuroendovascular procedures for review and discussion., Results: We identified 14 studies with a total of 336 patients who underwent robot-assisted neuroendovascular procedures, including both diagnostic (48.2%) and therapeutic (51.8%) applications. Among the therapeutic interventions, 140 patients were treated for hemorrhagic pathology, including 128 procedures for unruptured intracranial aneurysms and 12 for ruptured aneurysms. These procedures primarily involved stent-assisted coiling or flow diversion therapy. Additionally, 34 patients were treated for ischemic pathology, primarily carotid artery stenosis, involving balloon angioplasty and stent placement. A tumor was addressed in 1 intervention via coil embolization of tumor feeders, showcasing the versatility of robot-assisted interventions. Technical success rates were high across the studies, with most procedures achieving 100% success. Manual conversions were for device malfunctions or anatomical challenges. Complications reports varied, with some studies detailing specific device malfunctions and others providing less specific accounts., Conclusions: Overall, the CorPath GRX system demonstrated high feasibility and safety for neuroendovascular procedures, indicating significant potential benefits, particularly if integrated into telemedicine practices. The CorPath GRX system shows promise in facilitating precise and safe neuroendovascular procedures. Current evidence highlights a wide range of benefits; however, further research is needed to investigate long-term outcomes and other potential areas of impact., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This includes no affiliations with or involvement in any organization or entity with a financial interest (such as honoraria, educational grants, participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, or other equity interest, and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this paper.

Ebola disease survivors often experience stigma in multiple forms, including felt (perceived) stigma, enacted (action-based) stigma, and institutional stigma. On September 20, 2022, Uganda declared a Sudan Virus Disease (species orthoebolavirus sudanense) outbreak after a patient with confirmed Sudan virus (SUDV) infection was identified in Mubende District. The outbreak led to 142 confirmed and 22 probable cases over the next two months. We examined the types of stigma experienced by survivors and their household members and its effect on their well-being. We conducted a qualitative study during January 2023 in Mubende and Kassanda Districts. We conducted in-depth and key informant interviews with ten SUDV disease survivors, ten household members of SUDV disease survivors, and ten key informants (district officials and health workers in the affected communities). Interviews were recorded, translated, transcribed, and analyzed thematically. Survivors reported experiencing isolation and rejection by community members and loss of work. They reported being denied purchases at shops or having their money collected in a basket and disinfected (enacted stigma), which led to self-isolation (felt stigma). Educational institutions denied admission to some students from affected homes, while parents of children in some affected families stopped sending children to school due to verbal abuse from students and teachers (structural stigma). Prolonged SUDV disease symptoms and additional attention to survivors from responders (including home visits by health workers, public distribution of support items, and conspicuous transport from home to the survivor's clinic) were perceived as aggravating both felt and enacted stigma. Even after the outbreak had been declared over, survivors felt that they were still considered a threat to the community. Survivors experienced mainly enacted stigma which was aggravated by the outbreak response and control activities such as additional attention to survivors from responders. Strengthening community engagement to counteract stigma, rethinking response activities that aggravate stigma, integrated response interventions by partners, private distribution of support items, and increasing awareness and sensitization could reduce stigma among the Ebola disease survivors in future responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The right heart catheterization (RHC) remains an important diagnostic tool for a spectrum of cardiovascular disease processes including pulmonary hypertension (PH), shock, valvular heart disease, and unexplained dyspnea. While it gained widespread utilization after its introduction, the role of the RHC has evolved to provide valuable information for the management of advanced therapies in heart failure (HF) and cardiogenic shock (CS) to name a few. In this review, we provide a comprehensive overview on the indications, utilization, complications, interpretation, and calculations associated with RHC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Background: On September 20, 2022, Uganda declared an Sudan Virus Disease (SVD) outbreak in Mubende District. Another eight districts were infected September-November 2022. We examined how Ugandan community beliefs and practices spread Sudan Ebola Virus (SUDV) in 2022., Methods: A qualitative study was conducted in Mubende, Kassanda, and Kyegegwa districts in February 2023. Nine focus group discussions and six key informant interviews were held. We investigated whether community beliefs and practices contributed to spreading Sudan Ebola Virus (SUDV). Interviews were recorded, translated, transcribed, and thematically analyzed., Results: The community deaths, later found to be due to Sudan Virus Disease(SVD), were often attributed to witchcraft or poisoning. Key informants reported that SVD patients often sought traditional healers or spiritual leaders before or after formal healthcare failed. They also found that traditional healers treated SVD patients without precautions. Religious leaders praying for SVD patients and their symptomatic contacts, SVD patients hiding in friends' homes, and exhuming SVD patients from safe and dignified burials to allow traditional burials were other themes., Conclusion: Diversity in community beliefs and culture likely contributed to spreading the 2022 Ugandan SVD outbreak. Public health systems, traditional healers, and religious leaders can help Uganda control ebolavirus outbreaks by identifying socially acceptable and scientifically supported infection control methods., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The Ministry of Health of Uganda gave the directive and approval to carry out this investigation. Further approval to conduct this study was obtained from Mubende and Kassanda District offices, Mubende Regional Referral Hospital case management team, the National Institute of Public Health and Uganda Ministry of Health. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§. §See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq. “Sarah Paige was employed by USAID when the research for the current paper was conducted. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development." Copyright and Licensing: All materials in the Uganda National Institute of Public Health Quarterly Epidemiological Bulletin is in the public domain and may be used and reprinted without permission; citation as to source; however, is appreciated. Any article can be re-printed or published. It should be referenced in the original form if cited as a reprint. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Total knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-β and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA., Hypothesis: Based on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA., Patients and Methods: In this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities., Results: Losartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79-0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79-0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively., Discussion: In conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA., Level of Evidence: III; an observational cohort study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The frequent population movement across the five East African Countries poses risk of disease spread in the region. A clear understanding of population movement patterns is critical for informing cross-border disease control interventions. We assessed population mobility patterns across the borders of the East African states of Kenya, Uganda, and Rwanda. In November 2022, we conducted Focus Group Discussions (FGDs), Key Informant Interviews (KIIs), and participatory mapping. Participants were selected using purposive sampling and a topic guide used during interviews. Key informants included border districts (Uganda and Rwanda) and county health officials (Kenya). FGD participants were identified from border communities and travellers and these included truck drivers, commercial motorcyclists, and businesspersons. During KIIs and FGDs, we conducted participatory mapping using Population Connectivity Across Borders toolkits. Data were analysed using thematic analysis approach using Atlas ti 7 software. Different age groups travelled across borders for various reasons. Younger age groups travelled across the border for education, trade, social reasons, employment opportunities, agriculture and mining. While older age groups mainly travelled for healthcare and social reasons. Other common reasons for crossing the borders included religious and cultural matters. Respondents reported seasonal variations in the volume of travellers. Respondents reported using both official (4 Kenya-Uganda, 5 Rwanda-Uganda borders) and unofficial Points of Entry (PoEs) (14 Kenya-Uganda, 20 Uganda-Rwanda) for exit and entry movements on borders. Unofficial PoEs were preferred because they had fewer restrictions like the absence of health screening, and immigration and customs checks. Key destination points (points of interest) included: markets, health facilities, places of worship, education institutions, recreational facilities and business towns. Twenty-eight health facilities (10- Lwakhakha, Uganda, 10- Lwakhakha, Kenya, and 8- Cyanika, Uganda) along the borders were the most commonly visited by the travellers and border communities. Complex population movement and connectivity patterns were identified along the borders. These were used to guide cross-border disease surveillance and other border health strategies in the three countries. Findings were used to revise district response and preparedness plans by strengthening community-based surveillance in border communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 King et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To determine the impact of epidural spinal injections (ESIs) on postoperative surgical complications., Methods: This retrospective all-payer database analysis identified 202,181 adult patients undergoing one- to three-level transforaminal lumbar interbody fusion (TLIF) from 2010 to 2020. A 1:1 exact matching on comorbidities and demographics was performed, creating 2 cohorts: 1) patients who received an ESI within 90 days of surgery and 2) patients who did not receive an ESI. The primary outcome was surgical complication rates between groups at 30 days postoperatively. For the secondary outcome, patients were stratified based on injection time before surgery: 1-30, 31-45, 46-60, 61-75, and 76-90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. The P value was set to 0.05 for the primary analysis, and the Bonferroni correction was utilized for the secondary outcome., Results: Exact matching produced 12,491 pairs for analysis. Groups were well-matched on demographics, comorbidities, and fusion levels. The 30-day postoperative rates of surgical complications, hematomas, wound disruptions, or surgical site infections did not differ between groups (P > 0.05). The rate of cerebrospinal fluid (CSF) leak was increased in the ESI group (0.19% vs. 0.09%, P = 0.042). When temporally stratified, patients receiving an ESI within 30 days had significantly higher odds of CSF leak (odds ratio: 4.24, 95% confidence interval: 1.97-9.14)., Conclusions: Patients who receive an ESI within 30 days of transforaminal lumbar interbody fusion are at an increased risk for CSF leak. While the incidence of CSF leak remains small, it may be advisable to avoid ESIs at least 30 days before surgery for certain patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: A retrospective cohort study., Purpose: To examine the effect of cannabis use history on postoperative opioid utilization in patients undergoing one- to three-level lumbar fusion for degenerative spine disease., Overview of Literature: Strategies to minimize dosing and chronic opioid use are needed for spine surgery given their widespread prescription for postsurgical pain management., Methods: In this database study, medical coding was used to identify patients who had undergone one- to three-level lumbar fusions between 2012 and 2021. Propensity score matching was used to create two equal cohorts with respect to cannabis use history. Opioid utilization rates (morphine milligram equivalents [MME]/day) and overuse rates at 6 months post-index procedure were assessed. All pvalues <0.05 were considered statistically significant., Results: Following examination of 153,500 patient records, 1,216 patients were matched into cannabis user and non-cannabis user cohorts. Cannabis users had lower rates of opioid utilization compared to non-cannabis users as early as 2 months after fusion (47.7% vs. 41.1%, p <0.05), a relationship which persisted at 6 months (46.2% vs. 37.7%, p <0.01). Additionally, cannabis users had lower rates of high-dose opioid utilization (≥100 MME per day) during the initial 14-30 days following surgery (6.91% vs. 3.79%, p <0.05)., Conclusions: Patients with a history of cannabis use were less likely to be using opioids as early as 2 months postoperatively and had lower rates of high-dose opioid utilization in the immediate postoperative period. Physicians operating on these patients should consider their cannabis use patterns to provide appropriate titration of pain medication over time.

Background: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics., Methods: For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (R o ) estimates., Findings: Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall R o was 1·25., Interpretation: Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low R o . Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: In February 2022, the Ministry of Health received reports of more than 100 child deaths from a 'strange disease' in Namutumba District over a period of 6 months from politicians through the media. Preliminary investigations by the district rapid response team confirmed the strange disease to be severe malaria. The scope of severe malaria deaths was investigated, associated factors identified, and recommendations made for control measures to inform early malaria treatment strategies in Namutumba District., Methods: A retrospective study was conducted in March 2022 in the most affected subcounty (Ivukula Subcounty) involving cases and controls. A case was defined as a death with a positive malaria test, fever and any of the following: convulsions, difficulty breathing, yellowing of eyes or palms, tea-coloured urine, anaemia (evidenced by pale eyes or palms, or clinically-identified in medical records), loss of consciousness, or reduced urine output (very little or no urine in a day) in a child ≤ 12 years from September 2021 to February 2022 in Ivukula Subcounty, Namutumba District. Controls were survivors with the same signs and symptoms, recruited in a 2:1 ratio with cases. Cases and controls were actively searched using a door-to-door approach with the help of community health workers. Caretakers were interviewed to obtain data on signs and symptoms, socio-demographic information, health-seeking behaviours and health system risk factors. Drugs and bloodstock status information was obtained from health workers using an interview guide. Factors associated with death were identified using multivariate logistic regression and thematic analysis for qualitative data., Results: Among 46 cases, 29 (63%) were < 5 years, and 23 (50%) were female. Death among children with severe malaria was significantly associated with treatment non-completion (aOR = 9.7, 95%CI 1.8-53) and inability to receive blood transfusion for anaemic patients (aOR = 7.1, (95%CI 1.4-36). Healthcare workers reported that inability to reach referral sites due to transport costs, stockouts of anti-malarials and blood products at health facilities, and absence of integrated community case management of childhood illnesses (iCCM) contributed to deaths among children with severe malaria., Conclusion: Lack of access to anti-malarial treatment and to blood transfusions among anaemic patients due to stockouts were associated with severe malaria deaths among children ≤ 12 years in Ivukula Subcounty. Recommendations made were: accurate quantification of anti-malarials for health facilities, offering transport support to severe patients referred to higher-level facilities, and increasing access to blood products. Activation of iCCM could facilitate public health efforts against severe malaria in the district., (© 2024. The Author(s).)

Objective: The study objective was to determine factors associated with obtaining COVID-19 vaccination in people with co-occurring alcohol use disorder (AUD) and serious mental illness (SMI)., Methods: Survey responses were obtained from 135 adults with SMI seeking community-based AUD treatment about their primary series vaccination status, COVID-19 preventative practices, vaccination motivators, reasons for vaccine hesitancy, and strategies to increase vaccination uptake. Vaccinated and unvaccinated groups were compared. Responses to survey items with nominal or Likert scales were analyzed with chi-square tests of association. Logistic regression was employed to determine predictors of vaccine status., Results: Seventy-nine percent (n=107) of participants reported they were vaccinated. A higher proportion of vaccinated participants believed COVID-19 was a serious disease. While both groups adopted preventative hygiene practices at similar rates (e.g., washing hands), vaccinated participants engaged in more interpersonal practices directly involving others (e.g., wearing masks and avoiding crowds). The strongest vaccine motivator was protecting personal health, while the primary reason for hesitancy was potential side effects. Most unvaccinated participants endorsed increased safety information availability (61.1 %) and living with a high-risk-for-severe-infection individual (55.6 %) as reasons to overcome hesitancy., Conclusions: Vaccination rates, motivators, and hesitancy reasons were similar to the general United States population. Strategies to increase vaccination in this high-risk population should include education on vaccine safety and side effects and the impacts of COVID-19 and other respiratory illnesses on others., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael G. McDonell, Ph.D. reports financial support was provided by National Institute on Alcohol Abuse and Alcoholism. Michael G. McDonell, Ph.D. reports financial support was provided by National Institute on Drug Abuse. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda., Methods: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period., Results: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), β-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03)., Conclusion: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve.", (© 2024. The Author(s).)

Identifying tumor-mediated mechanisms that impair immunity is instrumental for the design of new cancer therapies. Regulatory T cells (Tregs) are a key component of cancer-derived immune suppression; however, these lymphocytes are necessary to prevent systemic autoimmunity in mice and humans, and thus, direct targeting of Tregs is not a clinical option for cancer patients. We have previously demonstrated that excising transcription factor Kruppel-like factor 2 ( Klf2 ) within the T cell lineage blocks the generation of peripheral-derived Tregs (pTregs) without impairing production of thymic-derived Tregs. Using this mouse model, we have now demonstrated that eliminating pTregs is sufficient to delay/prevent tumor malignancy without causing autoimmunity. Cancer-bearing mice that expressed KLF2 converted tumor-specific CD4 + T cells into pTregs, which accumulated in secondary lymphoid organs and impaired further T cell effector activity. In contrast, pTreg-deficient mice retained cancer-specific immunity, including improved T cell infiltration into "cold" tumors, reduced T cell exhaustion in tumor beds, restricted generation of tumor-associated myeloid-derived suppressor cells, and the continued production of circulating effector T cells that arose in a cancer-dependent manner. Results indicate that tumor-specific pTregs are critical for early stages of cancer progression and blocking the generation of these inhibitory lymphocytes safely delays/prevents malignancy in preclinical models of melanoma and prostate cancer., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction: Dementia is a common co-morbidity in older people who require urgent or emergency ambulance attendance and influences clinical decisions and care pathways. Following an initial audit of dementia data and consultation with staff, a specific section (tab) to record dementia was introduced on an ambulance service electronic patient record (ePR). This includes a dementia diagnosis button and a free-text section. We aimed to assess whether and how this improved recording., Methods: To re-audit the proportion of ambulance ePRs where dementia is recorded for patients aged ≥65 years, and to describe the frequency of recording in patients aged <65; to analyse discrepancies in the place of recording dementia on the ePR by comparing data from the new dementia tab and other sections of the ePR., Results: We included 112,193 ePRs of patients aged ≥65 with ambulance attendance from a six-month period. The proportion with dementia recorded in patients aged ≥65 was 16.5%, increasing to 19.9% in patients aged ≥75, as compared to 13.5% (≥65) and 16.5% (≥75) in our previous audit. In this audit, of the 16.5% (n = 18,515) of records with dementia recorded, 69.9% (n = 12,939) used the dementia button and 25.4% (n = 4704) recorded text in the dementia tab. Dementia was recorded in ePR free-text fields (but not the dementia tab) in 29.7% of records. Eighteen other free-text fields were used in addition to, or instead of, the dementia tab, including the patient's social history, previous medical history and mental health. Dementia was present on the ePR of 0.4% (n = 461) of patients aged <65., Conclusions: An ePR dementia tab enabled ambulance clinicians to standardise the location of recording dementia and may have facilitated increased recording. We would recommend other ambulance trusts capture this information in a specific section to improve information sharing and to inform care planning for this patient group., Competing Interests: None declared., (© 2024 The Author(s).)

Purpose: To evaluate the seating accuracy of removable partial denture (RPD) frameworks fabricated by two digital workflows involving selective laser melting (SLM) in comparison to the conventional workflow., Materials and Methods: A Kennedy class III modification 1 partially edentulous mandibular arch was used as a master model. Three RPD framework groups were included: (1) a conventional workflow group with conventional impression and casting (CC), (2) a partial digital workflow group with conventional impression and digital fabrication (CD), and (3) a complete digital workflow group with digital impression and digital fabrication (DD). A total of 10 frameworks were produced for each group. The marginal gaps at the occlusal rests, retention arms, and reciprocating arms were measured by a traveling microscope. The data were analyzed with the one-way analysis of variance test., Results: At the framework level, the most superior fit was observed for the CD group (79.5 µm) followed by DD (85.3 µm) and CC (114.2 µm) groups. The CD and DD groups were significantly superior to CC (p < 0.001). This fit pattern was consistent for the retention and reciprocating arms, while the occlusal rest fit was similar among all the groups., Conclusions: The SLM frameworks had a promising seating accuracy in comparison to conventional frameworks. The type of impression, conventional or digital, did not affect the accuracy of SLM frameworks. The differences observed in the present study are likely to be of minimal clinical significance., (© 2024 The Author(s). Journal of Prosthodontics published by Wiley Periodicals LLC on behalf of American College of Prosthodontists.)

Peptide aggregation poses a significant challenge in biopharmaceutical development and neurodegenerative diseases. This study combines computational simulations and experimental validation to uncover the underlying mechanisms and countermeasures for the aggregation of glucagon, a peptide with a high tendency to aggregate. In silico simulations demonstrate that lactose and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) influence glucagon aggregation differently: lactose stabilizes glucagon by increasing the α-helical content, while 2-HPβCD disrupts protein-protein interactions. According to the simulations, 2-HPβCD is particularly effective at preserving the monomeric form of glucagon. Experimental validation with microfluidic modulation spectroscopy (MMS) confirms these findings, showing that glucagon in the presence of 2-HPβCD remains structurally stable, supporting the antiaggregation effect of this excipient. This research provides essential insights into glucagon aggregation obtained through a new powerful tool for monitoring the critical properties of peptide aggregation, suggesting new strategies for addressing this challenge in therapeutic peptide development.

Objectives: Early isolation and care for Ebola disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda., Methods: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ("delays") as short (≤2), moderate (3-5), and long (≥6); the latter two were "delayed isolation." We categorized symptom onset timing as "earlier" or "later," using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews., Results: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation (crude risk ratio = 1.8, 95% confidence interval (1.2-2.8]). Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors., Conclusion: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda., Methods: Using a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data., Results: Forty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection., Conclusion: Both systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future., (© 2024. The Author(s).)

Background: Pneumonia is one of the leading causes of infant mortality globally, particularly in sub-Saharan Africa. In Uganda, pneumonia was the fourth leading cause of death in children <5 years in 2018. Analysis of 2013-2022 data for children <5 years from the District Health Information System indicated a high incidence of severe pneumonia in Kasese District, Uganda. We investigated to identify factors associated with severe pneumonia among children <5 years in Kasese District to inform prevention and control strategies., Methods: We conducted a 1:1 hospital-based case-control study among children aged 2-59 months presenting with pneumonia at five high-volume facilities in Kasese District from January to April 2023. A case was defined as pneumonia with ≥1 of the following danger signs: low oxygen saturation, central cyanosis, severe respiratory distress, feeding difficulties, altered consciousness, and convulsions. Controls were outpatient children aged 2-59 months with a diagnosis of non-severe pneumonia. We reviewed medical records at facilities and used an interviewer-administered questionnaire with caregivers to obtain information on socio-demographic and clinical characteristics. Logistic regression was used to identify factors associated with severe pneumonia., Results: We enrolled 199 cases and 174 controls. The odds of severe pneumonia were higher among children with diarrhoea only (adjusted odds ratio [aOR] = 2.9, 95%CI: 1.7-4.9), or malaria and diarrhoea (aOR = 3.4, 95%CI: 2.0-5.9), than those without a co-existing illness at the time of pneumonia diagnosis. Not being exclusively breastfed for ≥ 6 months (aOR = 2.0, 95%CI: 1.1-3.3) and exposure to indoor air pollution from cooking combustion sources (aOR = 2.9, 95%CI: 1.8-4.7) increased odds of severe pneumonia., Conclusion: The findings highlight the significance of comorbidities, lack of exclusive breastfeeding, and exposure to indoor air pollution in the development of severe pneumonia. Promoting exclusive breastfeeding for ≥ 6 months and advocating for the use of clean energy sources, could mitigate morbidity attributable to severe pneumonia in the region., (© 2024. The Author(s).)

Background: Uganda has a sentinel surveillance system in seven high-risk sites to monitor yellow fever (YF) patterns and detect outbreaks. We evaluated the performance of this system from 2017 to 2022., Methods: We evaluated selected attributes, including timeliness (lags between different critical time points), external completeness (proportion of expected sentinel sites reporting ≥ 1 suspect case in the system annually), and internal completeness (proportion of reports with the minimum required data elements filled), using secondary data in the YF surveillance database from January 2017-July 2022. We conducted key informant interviews with stakeholders at health facility and national level to assess usefulness, flexibility, simplicity, and acceptability of the surveillance system., Results: In total, 3,073 suspected and 15 confirmed YF cases were reported. The median time lag from sample collection to laboratory shipment was 37 days (IQR:21-54). External completeness was 76%; internal completeness was 65%. Stakeholders felt that the surveillance system was simple and acceptable, but were uncertain about flexibility. Most (71%) YF cases in previous outbreaks were detected through the sentinel surveillance system; data were used to inform interventions such as intensified YF vaccination., Conclusion: The YF sentinel surveillance system was useful in detecting outbreaks and informing public health action. Delays in case confirmation and incomplete data compromised its overall effectiveness and efficiency., (© 2024. The Author(s).)

Background: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak., Methods: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases., Results: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data., Conclusion: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events., (© 2024. The Author(s).)

Background and Purpose: To report an improvement with immunotherapy in 34 (85%)/40 patients who required an immunotherapy among 56 patients with sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)., Methods: Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired, chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy that had progressed for >2 months; and 2) definite electrophysiological and/or biopsy evidence of demyelinating neuropathy., Results: Fifty-six patients with sensory CIDP were identified. Evidence of demyelination was obtained from by the routine motor nerve conduction study (NCS) in 39 (70%) patients, from a nerve biopsy in 10, and from a near-nerve needle sensory NCS in 7 patients. The most prominent laboratory abnormality was a high protein level in the cerebrospinal fluid in 21 (49%) of 43 tested patients. Immunotherapy was required in 41 (79%) of the 52 followed-up patients. An improvement with immunotherapy was observed in 36 (88%)/41 patients. In three patients, motor weakness developed in 5-8 years' follow-up period and so, their diagnosis was changed to CIDP., Conclusions: Sensory CIDP is responded to an immunotherapy in 88% of the treated patients. Sensory CIDP was diagnosed by the routine motor NCS in 70% of patients and by a sural nerve biopsy in 18% of patients. Thus, sensory CIDP should be recognized as a treatable CIDP variant among the different types of "idiopathic sensory neuropathy.", Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

Introduction: Rapidly progressive hip osteoarthritis (OA) leading to femoral head collapse (FHC) following intra-articular (IA) corticosteroid injections is a perplexing variant of OA. We explored eight cases of chronic joint pain treated with IA corticosteroid injections. Subsequently, they experienced swift deterioration of the femoral head integrity within as little as 10 weeks. These cases underscore the need for a comprehensive assessment of risk factors versus benefits in this patient population., Case Report: The study reveals a complex interplay between comorbidities, treatments, and outcomes. Patients exhibited various health factors, including obesity, smoking history, cancer treatment, and deficiencies in Vitamin D levels, which have been found to increase the risk of FHC. Furthermore, the study explores the chondrotoxicity of corticosteroids and local anesthetics used in IA injections. In vitro studies show complete loss of chondrocyte viability after a single dose of corticosteroids, potentially leading to cartilage degradation. In addition, local anesthetics may induce cellular demise and structural alterations in the articular cartilage. These factors highlight various influences affecting treatment outcomes in patients with OA., Conclusion: In conclusion, this case series highlights the rare adverse outcome of rapidly progressive hip OA and FHC following IA corticosteroid injections and possible risk factors. While a definitive etiology remains unclear, the study provides valuable conclusions to aid in future treatment decision-making., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Individuals with posttraumatic stress disorder (PTSD) often engage in harmful alcohol use. These co-occurring conditions are associated with negative health consequences and disability. PTSD and harmful drinking are typically experienced as closely related-thus treatments that target both simultaneously are preferred by patients. Many individuals with PTSD and harmful alcohol use receive primary care services but encounter treatment barriers in engaging in specialty mental health and substance use services. A pilot randomized controlled trial of a brief integrated treatment for PTSD and harmful drinking versus primary care treatment as usual (PC-TAU) took place in three U.S. Department of Veterans Affairs (VA) primary care clinics. The intervention (primary care treatment integrating motivation and exposure [PC-TIME]) combines motivational interviewing to reduce alcohol use and brief prolonged exposure for PTSD delivered over five brief sessions. Participants (N = 63) were veterans with PTSD and harmful drinking. Multilevel growth curve modeling examined changes in drinking (average number of drinks per drinking day and percentage of heavy drinking days) and self-reported PTSD severity at baseline, 8, 14, and 20 weeks. Participants reported high satisfaction with PC-TIME and 70% (n = 23) completed treatment. As hypothesized, a significantly steeper decrease in self-reported PTSD severity and heavy drinking was evident for participants randomized to PC-TIME compared with PC-TAU. Contrary to expectations, no significant posttreatment differences in PTSD diagnoses were observed. PC-TIME participants were less likely to exceed National Institute for Alcoholism and Alcohol Abuse (NIAAA) guidelines for harmful alcohol use posttreatment compared with PC-TAU participants. PC-TIME is a promising brief, primary care-based treatment for individuals with co-occurring PTSD and harmful alcohol use. A full-scale randomized clinical trial is needed to fully test its effectiveness., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Gandasari and colleagues [1] open an important opportunity for us to consider how social scientists might contribute to preserving Indigenous cultures in Indonesia. The focus of these authors was on releasing for open use Indigenous data collected from Dayak, Malay, and Chinese communities in Sintang Regency, West Kalimantan, Indonesia. In this commentary, we respond to key issues raised by Gandasari and colleagues [1] to engage in a productive discussion regarding the broader ethical considerations and implications of publishing such Indigenous datasets in academic journals. The main argument of this commentary is that we need to consider the potential ethical dilemmas that come with extracting and releasing such Indigenous knowledge beyond the contexts within which they are located. Central to this commentary is an assertion regarding the need for researchers to consider the perspectives of Indigenous groups in determining what is ethical conduct regarding the use of their knowledge. Also considered are how attempts by researchers to preserve Indigenous cultures by giving their 'data' away reflect broader concerns around the commodification of what we often refer to as data, but which is often understood by Indigenous peoples as their histories, knowledge, and treasured and often sacred insights into the human condition. Working with such knowledge requires us to engage with Indigenous ethics and issues of power between groups in society., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

The light-driven reduction of dinitrogen (N 2 ) to ammonia (NH 3 ) catalyzed by a cadmium sulfide (CdS) nanocrystal‑nitrogenase MoFe protein biohybrid is dependent on a range of different factors, including an appropriate hole-scavenging sacrificial electron donor (SED). Here, the impact of different SEDs on the overall rate of N 2 reduction catalyzed by a CdS quantum dot (QD)-MoFe protein system was determined. The selection of SED was guided by several goals: (i) molecules with standard reduction potentials sufficient to reduce the oxidized CdS QD, (ii) molecules that do not absorb the excitation wavelength of the CdS QD, and (iii) molecules that could be readily reduced by sustainable processes. Earlier studies utilized buffer molecules or ascorbic acid as the SED. The effectiveness of ascorbic acid as SED was compared to dithionite (DT), triethanolamine (TEOA), and hydroquinone (HQ) across a range of concentrations in supporting N 2 reduction to NH 3 in a CdS QD-MoFe protein photocatalytic system. It was found that TEOA supported N 2 reduction rates comparable to those observed for dithionite and ascorbic acid. HQ was found to support significantly higher rates of N 2 reduction compared to the other SEDs at a concentration of 50 mM. A comparison of the rates of N 2 reduction by the biohybrid complex to the standard reduction potential (E o ) of the SEDs reveals that E o is not the only factor impacting the efficiency of hole-scavenging. These findings reveal the importance of the SED properties for improving the efficiency of hole-scavenging in the light-driven N 2 reduction reaction catalyzed by a CdS QD-MoFe protein hybrid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Contact tracing (CT) is critical for ebolavirus outbreak response. Ideally, all new cases after the index case should be previously-known contacts (PKC) before their onset, and spend minimal time ill in the community. We assessed the impact of CT during the 2022 Sudan Virus Disease (SVD) outbreak in Uganda., Methods: We collated anonymized data from the SVD case and contacts database to obtain and analyze data on CT performance indicators, comparing confirmed cases that were PKC and were not PKC (NPKC) before onset. We assessed the effect of being PKC on the number of people infected using Poisson regression., Results: There were 3844 contacts of 142 confirmed cases (mean: 22 contacts/case). Forty-seven (33%) confirmed cases were PKC. PKCs had fewer median days from onset to isolation (4 vs 6; P<0.007) and laboratory confirmation (4 vs 7; P<0.001) than NPKC. Being a PKC vs NPKC reduced risk of transmitting infection by 84% (IRR=0.16, 95% CI 0.08-0.32)., Conclusion: Contact identification was sub-optimal during the outbreak. However, CT reduced the time SVD cases spent in the community before isolation and the number of persons infected in Uganda. Approaches to improve contact tracing, especially contact listing, may improve control in future outbreaks., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mass gatherings frequently include close, prolonged interactions between people, which presents opportunities for infectious disease transmission. Over 20,000 pilgrims gathered at Namugongo Catholic and Protestant shrines to commemorate 2022 Uganda Martyr's Day. We described syndromes suggestive of key priority diseases particularly COVID-19 and viral hemorrhagic fever (VHF) among visiting pilgrims during May 25-June 5, 2022. We conducted a survey among pilgrims at the catholic and protestant shrines based on signs and symptoms for key priority diseases: COVID-19 and VHF. A suspected COVID-19 case was defined as acute respiratory illness (temperature greater 37.5°C and at least one sign/symptom of respiratory infection such as cough or shortness of breath) whereas a suspected VHF case was defined as fever >37.5°C and unexplained bleeding among pilgrims who visited Namugongo Catholic and Protestant shrines from May 25 to June 5, 2022. Pilgrims were sampled systematically at entrances and demarcated zonal areas to participate in the survey. Additionally, we extracted secondary data on pilgrims who sought emergency medical services from Health Management Information System registers. Descriptive analysis was conducted to identify syndromes suggestive of key priority diseases. Among 1,350 pilgrims interviewed, 767 (57%) were female. The mean age was 37.9 (±17.9) years. Nearly all pilgrims 1,331 (98.6%) were Ugandans. A total of 236 (18%) reported ≥1 case definition symptom and 42 (3%) reported ≥2 symptoms. Thirty-nine (2.9%) were suspected COVID-19 cases and three (0.2%) were suspected VHF cases from different regions of Uganda. Among 5,582 pilgrims who sought medical care from tents, 628 (11.3%) had suspected COVID-19 and one had suspected VHF. Almost one in fifty pilgrims at the 2022 Uganda Martyrs' commemoration had at least one symptom of COVID-19 or VHF. Intensified syndromic surveillance and planned laboratory testing capacity at mass gatherings is important for early detection of public health emergencies that could stem from such events., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ninsiima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aberrant skipping of coding exons in CD19 and CD22 compromises the response to immunotherapy in B-cell malignancies. Here, we showed that the MS4A1 gene encoding human CD20 also produces several messenger RNA (mRNA) isoforms with distinct 5' untranslated regions. Four variants (V1-4) were detected using RNA sequencing (RNA-seq) at distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma, only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform contained upstream open reading frames and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, whereas V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly, in vitro CD20-directed chimeric antigen receptor T cells were able to kill both V3- and V1-expressing cells, but the bispecific T-cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on 4 postmosunetuzumab follicular lymphoma relapses and discovered that in 2 of them, the downregulation of CD20 was accompanied by a V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes., Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365., Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180., Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03178864., Competing Interests: Disclosures Dr Boulos reports compensation from Eisai, Jazz Pharmaceuticals, and Paladin Laboratories for consultant services, and a gift from Braebon Medical Corporation. Dr Demchuk reports compensation from Boehringer Ingleheim, HLS Pharmaceuticals, Hoffmann-Laroche, Metronic NovaSignal, and Servier for consultant services, other from AstraZeneca, Data Safety Monitoring Board participation with Philips, and stock and a patent for stroke imaging software with Circle NVI. Dr Dowlatshahi reports compensation from AstraZeneca for consultant services. Dr Field reports compensation from AstraZeneca, HLS Therapeutics, Servier, Bristol Myers Squibb Pfizer, and Roche for consultant services, from the Canadian Medical Protective Association as an Expert Witness, and is on the board of DESTINE Health. M.D. Hill reports compensation for Brainsgate Ltd for consultant services, grants from the Canadian Institutes of Health Research, Medtronic, Microvention Inc, NoNO Inc, and Boehringer Ingleheim, and end point review committee work for Merck. Dr Lanthier reports compensation from Bayer, Bristol Myers Squibb Pfizer, and Servier for consultant services. Dr Lee reports compensation from Bayer and Bristol Myers Squibb for consultant services. Dr Sposato reports compensation from Bayer, Boehringer Ingleheim, Daiichi Sanko Ltd and Pfizer for consultant services. Dr Weitz reports compensation from Alnylam Pharmaceuticals, Anthos, Bayer, Boehringer Ingleheim, Bristol myers Squibb, Daiichi Sankyo Ltd, Ionis Pharmaceuticals, Janssen Global Services LLC, Merck Company Foundation, Novartis, Pfizer, and Portola Pharmaceuticals for consult services. The other authors report no conflicts.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo . Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bazarek, Thaqi, King, Mehta, Patel, Briggs, Reisenbigler, Yousey, Miller, Stutzmann, Marr and Peterson.)

Aberrant skipping of coding exons in CD19 and CD22 compromises responses to immunotherapy for B-cell malignancies. Here, we show that the MS4A1 gene encoding human CD20 also produces several mRNA isoforms with distinct 5' untranslated regions (5'-UTR). Four variants (V1-4) were detectable by RNA-seq in distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant by far. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform was found to contain upstream open reading frames (uORFs) and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching Morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, while V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly, in vitro CD20-directed CAR T cells were able to kill both V3- and V1-expressing cells, but the bispecific T cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on four post-mosunetuzumab follicular lymphoma relapses and discovered that in two of them downregulation of CD20 was accompanied by the V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies., Key Points: In normal & malignant human B cells, CD20 mRNA is alternatively spliced into four 5'-UTR isoforms, some of which are translation-deficient.The balance between translation-deficient and -competent isoforms modulates CD20 protein levels & responses to CD20-directed immunotherapies., Explanation of Novelty: We discovered that in normal and malignant B-cells, CD20 mRNA is alternatively spliced to generate four distinct 5'-UTRs, including the longer translation-deficient V1 variant. Cells predominantly expressing V1 were still sensitive to CD20-targeting chimeric antigen receptor T-cells. However, they were resistant to the bispecific anti-CD3/CD20 antibody mosunetuzumab, and the shift to V1 were observed in CD20-negative post-mosunetuzumab relapses of follicular lymphoma.

Introduction: A novel referral pathway for exhibited breast symptom (EBS) referrals to manage increasing referrals of urgent suspected cancer (USC) was implemented in our trust. We report on the safety and effect on compliance with the 2-week-wait rule (2WW)., Methods: A single-centre longitudinal observational study included all patients referred to a UK breast unit during 13 May 2019 to 27 March 2020 (period 1) and 8 February 2021 to 31 January 2022 (period 2). USC referrals were assessed in a one-stop clinic (red flag clinic [RFC]); EBS referrals were assessed in a new clinic in which clinical evaluation was performed and imaging occurred subsequently (blue flag clinic [BFC]). Patients were followed up to determine the symptomatic interval cancer rate., Results: There were 9,695 referrals; 1,655 referrals (17%) were assessed in the BFC after 63 exclusions. Some 95.9% of patients had a benign clinical examination (P1/P2), 80.1% had imaging (mammogram or ultrasound) and 4% had a tissue biopsy. In total, 16/1,655 (0.97%) BFC patients and 510/7,977 (8.2%) RFC patients were diagnosed with breast cancer (breast cancer detection rate). Some 1,631 patients (with 1,639 referrals) were discharged and followed up for a median of 17 months (interquartile range 12-32) with one subsequent cancer diagnosis (symptomatic interval cancer rate, 0.06%). Implementation of the BFC pathway increased 3-month average trust performance of USC referrals with 2WW standard from 8.5% to 98.7% (period 1) and from 30% to 66% (period 2)., Conclusions: The BFC pathway for EBS patients is safe and implementation led to improvement against the 2WW target for USC referrals, ensuring resources are prioritised to patients with the highest likelihood of breast cancer.

Background: Deep brain stimulation (DBS) can be a life-changing intervention for patients with Parkinson's disease (PD), but its success is largely dependent on precise lead placement. The subthalamic nucleus (STN) is one of the most common surgical targets of DBS, but the close anatomical and physiological resemblance of the STN to the mediocaudal red nucleus renders these landmarks difficult to distinguish., Observations: We present an atypical case in which targeted localization of the STN resulted in symptoms pathognomonic of rubrospinal tract (RST) stimulation. A 79-year-old female with a 12-year history of right-hand resting tremor due to medically refractory PD presented for asleep bilateral STN-DBS surgery. Right STN intraoperative testing revealed left hand and elbow flexion contractures, initially suggestive of corticospinal tract activation, despite imaging studies demonstrating reasonable lead placement in the central dorsolateral STN. The lead was moved anteromedially near the medial border of the STN, but stimulation at this location revealed similar but more robust flexor hand and arm contractures, without any extraocular muscle involvement. Thus, activation of the RST was suspected., Lessons: Isolated activation of the RST is possible during STN-DBS surgery. Its identification can help avoid false localization and suboptimal lead placement.

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic, the All of Us Research Program longitudinal cohort study developed the COVID-19 Participant Experience (COPE) survey to better understand the pandemic experiences and health impacts of COVID-19 on diverse populations within the United States. Six survey versions were deployed between May 2020 and March 2021, covering mental health, loneliness, activity, substance use, and discrimination, as well as COVID-19 symptoms, testing, treatment, and vaccination. A total of 104,910 All of Us Research Program participants, of whom over 73% were from communities traditionally underrepresented in biomedical research, completed 275,201 surveys; 9,693 completed all 6 surveys. Response rates varied widely among demographic groups and were lower among participants from certain racial and ethnic minority populations, participants with low income or educational attainment, and participants with a Spanish language preference. Survey modifications improved participant response rates between the first and last surveys (13.9% to 16.1%, P < 0.001). This paper describes a data set with longitudinal COVID-19 survey data in a large, diverse population that will enable researchers to address important questions related to the pandemic, a data set that is of additional scientific value when combined with the program's other data sources., (© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: Serious mental illnesses (SMI) and alcohol use disorder (AUD) co-occurrence (SMI-AUD) is common, yet little is known about the prevalence and risk factors of cognitive impairment for this population. We used the National Institutes of Health (NIH) Toolbox to identify clinically significant cognitive impairment (CSCI), describe the cognitive profile, and investigate whether psychiatric and AUD severity measures are associated with CSCI in individuals with SMI-AUD., Methods: CSCI was defined as 2 or more fully corrected fluid subtest T scores below a set threshold based on an individual's crystalized composite score. Psychiatric severity measures included the Structured Clinical Interview for DSM-V (SCID-5) for SMI diagnosis and the Positive and Negative Syndrome Scale. AUD severity measures included the SCID-5 for AUD symptom severity score, years of alcohol use, and urine ethyl glucuronide levels. A multivariable logistic regression was used to investigate the adjusted effects of each variable on the probability of CSCI., Results: Forty-one percent (N = 55/135) of our sample had CSCI compared with the base rate of 15% from the NIH Toolbox normative sample. Subtests measuring executive function most frequently contributed to meeting criteria for CSCI (Flanker and Dimensional Change Card Sort). A history of head injury ( P = 0.033), increased AUD symptom severity score ( P = 0.007) and increased negative symptom severity score ( P = 0.027) were associated with CSCI., Conclusions: Cognition should be considered in the treatment of people with SMI-AUD, particularly in those with history of brain injury, higher AUD symptom severity, and/or negative symptom severity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Introduction. Hip replacement is a frequently performed and highly successful treatment for patients with end stage osteoarthritis. Advances in technique and pain management have allowed for rapid mobilization and early discharge after surgery. We hypothesize that pre-incision intra-articular injection of local anesthetic with epinephrine under image guidance combined with post incision peri-articular injection (PAI) may be more effective than PAI alone. Methods. A prospective, randomized, controlled, comparative investigation at a single institution of 41 patients undergoing THA who received standard 30 mL post-arthrotomy, PAI of ropivacaine with epinephrine under direct visualization after prosthesis implantation before closure or an equivalent dose divided into a 10 mL pre-incision, ultrasound guided intra-articular injection and a 20 mL post-arthrotomy PAI. Results. 42 patients were included in this study before its early conclusion with 22 patients in the treatment group and 20 in the control group. There were no significant differences in age, BMI or ASA scores. Additionally, there were no significant differences noted when comparing groups by postoperative outcome measures including OMME, EBL, OR time, PACU minutes, and first and last PACU pain score. Furthermore, there were no significant differences in the PROMs evaluated. Discussion. The addition of ultrasound guided pre-incision intra-articular injection to the standard PAI had no benefit when compared with standard PAI during a THA. Portable mobile phone based ultrasound devices provide a cost effective way to perform musculoskeletal blocks, and further studies on their use and comparative accuracy is warranted. A novel technique for confirmation of injection location is described.

The proton is one of the main building blocks of all visible matter in the Universe 1 . Among its intrinsic properties are its electric charge, mass and spin 2 . These properties emerge from the complex dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics 3-5 . The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering 2 . An example is the highly precise measurement of the electric charge radius of the proton 6 . By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton 7,8  from our measurement. We used a variety of models 9-11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics 12 . This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In the early 2000s, a Scottish Government Oral Health Action Plan identified the need for a national programme to improve child oral health and reduce inequalities. 'Childsmile' aimed to improve child oral health in Scotland, reduce inequalities in outcomes and access to dental services, and to shift the balance of care from treatment to prevention through targeted and universal components in dental practice, community and educational settings. This paper describes how an embedded, theory-based research and evaluation arm with multi-disciplinary input helps determine priorities and provides important strategic direction. Programme theory is articulated in dedicated, dynamic logic models, and evaluation themes are as follows: population-level data linkage; trials and economic evaluations; investigations drawing from behavioural and implementation science; evidence reviews and updates; and applications of systems science. There is also a growing knowledge sharing network internationally. Collaborative working from all stakeholders is necessary to maintain gains and to address areas that may not be working as well, and never more so with the major disruptions to the programme from the COVID-19 pandemic and response. Conclusions are that evaluation and research are synergistic with a complex, dynamic programme like Childsmile. The evidence obtained allows for appraisal of the relative strengths of component interventions and the reach and impact of Childsmile to feed into national policy., (© 2023 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Turbulent filling of molten metal in sand-casting leads to bi-films, porosity and oxide inclusions which results in poor mechanical properties and high scrap rate of sand castings. Hence, it is critical to understand the metal flow in sand-molds, i.e., casting hydrodynamics to eliminate casting defects. While multiple numerical methods have been applied to simulate this phenomenon for decades, harsh foundry environments and expensive x-ray equipment have limited experimental approaches to accurately visualize metal flow in sand molds. In this paper, a novel approach to solve this challenge is proposed using Succinonitrile (SCN) as a more accurate metal analog in place of water. SCN has a long history in solidification research due to its BCC (Body-Centered-Cubic) crystal structure and dendrite-like solidification (melting temperature ~60 °C) like molten aluminum. However, this is the first reported study on applying SCN through novel casting hydrodynamics to accurately visualize melt flow for casting studies. This paper used numerical simulations and experiments using both water and SCN to identify the critical dimensionless numbers to perform accurate metal flow analog testing. Froude's number and wall roughness were identified as critical variables. Experimental results show that SCN flow testing was more accurate in recreating the flow profile of molten aluminum, thus validating its utility as a metal analog for metal flow research. Findings from this study can be used in future metal flow analysis such as: runner, in-gate and integrated filling-feeding-solidification studies.

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team's larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians.

Introduction: Pulmonary rehabilitation is recommended for people with bronchiectasis. Various education topics are included in these programmes, but the content is largely guided by the needs of people with other respiratory conditions., Objectives: With the education topics applicable to people with bronchiectasis unclear, we aimed to explore the perspective of adults with this condition on relevant educational topics in a pulmonary rehabilitation context., Methods: Participants from the Australian Bronchiectasis Registry were invited to undertake a semi-structured interview. Interview transcripts were coded independently, with themes established by consensus (two researchers)., Results: Twenty-one people participated. The major themes were greater clarity on the underlying cause of bronchiectasis and prognosis. Most sought knowledge about self-management strategies and treatments to address extra-pulmonary symptoms. Participants requested more information on physiotherapy options and the role of exercise and physical activity outside of pulmonary rehabilitation. Preferences were mixed for the education delivery model., Conclusions: We have identified unmet educational topics of interest for people with bronchiectasis. Our study provides a framework for education topics desired by adults with bronchiectasis within a pulmonary rehabilitation setting. The topics identified will guide development of an education curriculum for pulmonary rehabilitation that is more fit-for-purpose for people with bronchiectasis., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Dialectical behaviour therapy (DBT) is an effective treatment for borderline personality disorder and other problems underpinned by difficulties with emotional regulation. The main components of DBT are skills training groups and individual therapy. The COVID-19 outbreak forced a rapid adaptation to online delivery, which largely mirrored face-to-face programmes using videoconferencing technology. This study aimed to elicit and describe the experiences and learning of therapists involved in providing high-fidelity DBT programmes via the Australian DBT Institute, which established an online delivery platform called DBT Assist™ prior to the COVID-19 pandemic. The report conforms with the consolidated criteria for reporting qualitative research (COREQ). Seven therapists were interviewed. Data were transcribed and analysed thematically. Delivering skills training online, either exclusively or in hybrid form (with face-to-face individual therapy), was acceptable and even preferable to therapists and clients. It was considered safe, the programme was associated with few non-completers, and it improved the accessibility of DBT to those who might otherwise not be able to engage in a face-to-face programme. Skills training utilized a 'flipped-learning' approach which improved the efficiency of online delivery. Other unique and helpful features of the online programme were described. The best outcomes associated with online DBT are likely to be achieved through careful adaptation to the online environment in accord with the principles of DBT rather than mirroring face-to-face processes. Further research is required to determine the efficacy of online therapy relative to face-to-face, and who might be best suited to different modes of delivery., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation., Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days ., Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol. Trial registration: ISRCTN16327029., Competing Interests: HP reports research funding from National Institute for Health and Care Research. CDD, RL, FM, AC, MAS, PK, AD, DES report no conflicts of interest. GDP reports research funding from National Institute for Health and Care Research, British Heart Foundation and Resuscitation Council UK. He has volunteer roles with Resuscitation Council UK, European Resuscitation Council and the International Liaison Committee on Resuscitation. He is an editor for the journals Resuscitation and Resuscitation Plus., (© 2022 The Author(s).)

Dialectical Behaviour Therapy (DBT) programmes are often the only available treatment for people diagnosed with borderline personality disorder and were rapidly converted to online delivery during the COVID-19 pandemic. Limited research exists surrounding how the major elements of DBT are delivered in an online environment. This scoping review considered the operationalization of online delivery of DBT and its effectiveness. EBSCO host databases were searched using free text. Of 127 papers, 11 studies from 2010 to 2021 investigating online DBT for any clinical population were included in the review. A narrative synthesis of papers selected was undertaken. Seven articles reported results from five clinical trials (n = 437). Most adaptations mirrored face-to-face programmes although there was considerable variation in how therapy was facilitated. Attendance was reported to be greater online with comparable clinical improvements to face-to-face for those who remained in therapy. Additional challenges included managing risk, therapist preparedness and technology difficulties. Online delivery of DBT programmes is feasible and may be more accessible, acceptable and as safe and effective as face-to-face delivery. However, mirroring face to face delivery in an online environment may not be the most effective and efficient way to adapt DBT to online provision. Research is needed to identify areas which require further adaptation., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Glioblastoma, one of the most fatal brain tumors, is associated with a dismal prognosis and an extremely short overall survival. We previously reported that the overexpressed transient receptor potential channel TRPM7 is an essential glioblastoma regulator. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in glioma's initiation and progression. However, the function of lncRNA, HOX transcript antisense intergenic RNA (HOTAIR) mediated by TRPM7 in glioma remains unclear. In this study, HOTAIR expression was found to be positively regulated by TRPM7, significantly upregulated in glioma tissues, and is a poor prognosis factor for glioma patients. Moreover, reduced HOTAIR expression impeded the proliferation and invasion of glioma cells. Mechanistically, HOTAIR directly interacted with miR-301a-3p, and downregulation of miR-301a-3p efficiently reversed FOSL1 suppression induced by siRNA HOTAIR, which implied that HOTAIR positively regulated FOSL1 level through sponging miR-301a-3p and played an oncogenic role in glioma progression. In contrast to HOTAIR's role, miR-301a-3p alone served as a tumor suppressor to decrease glioma cell viability and migration/invasion. In agreement with HOTAIR's role, FOSL1 functioned as a tumorigenic gene in glioma pathogenesis, which was highly expressed in glioma tissues, and was shown to be an unfavorable prognostic factor for glioma patients. Mechanically, FOSL1 inhibition by siRNA FOSL1 efficiently rescued the oncogenic-like phenotypes caused by the miR-301a-3p inhibitor in glioma pathogenesis. SIGNIFICANCE: Our study elucidated the role of TRPM7-mediated HOTAIR as a miRNA sponge to target downstream FOSL1 oncogene and therefore consequently contribute to gliomagenesis, which shed new light on TRPM7/lncRNA-directed diagnostic and therapeutic approach in glioma., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Growing homelessness in Aotearoa New Zealand stems primarily from rising inequalities and poverty. Drawing from scholarship on relational ethics, principled practice and Māori cultural concepts, this paper offers our reflections on nearly two decades of collective work to document and address homelessness. Central to the approach outlined are enduring community partnerships, the cultivation of reciprocal relations, and time spent with homeless people and those trying to work with them. We present exemplars for how we draw on everyday interactions with homeless people and agency staff to enhance local service and broader systemic responses to homelessness., (© 2021 Wiley Periodicals LLC.)

Cardiac amyloidosis (CA) results in symptoms of heart failure, atrial and ventricular arrhythmias, conduction disturbances, and profound autonomic dysfunction. These symptoms present unique management challenges as compared with patients without CA, and can be very debilitating. Thus, management of the cardiovascular symptoms of these patients plays a central role in their care. This review presents an overview of the typical cardiovascular manifestations encountered in patients with CA and highlights the key management considerations for each., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To cocreate an evidence-based resource to enable educators to support students returning to school after concussion; evaluate the usability of and users' satisfaction with the resource; understand the role of the resource in supporting students' return to school; and describe changes in concussion knowledge following a concussion education and training workshop., Design: Survey during a concussion education and training workshop., Setting: Holland Bloorview Kids Rehabilitation Hospital in Toronto, Ont, and York Region District School Board in Richmond Hill, Ont., Participants: Fifty-six educators, of whom 64% were teachers, 11% were school administrators, 23% fulfilled other roles (eg, child and youth worker), and 2% fulfilled unspecified roles., Main Outcome Measures: The survey collected demographic information, usability data via the System Usability Scale, and satisfaction data. Thematic analysis was used for open-ended questions., Results: Participants reported the resource to be easy to use (69.6%), not complex (62.5%), and most felt confident using this resource (83.9%). Participants indicated they were satisfied with the resource (73.2%) and would use it in the future (87.5%). Some found the resource overwhelming and recommended it be summarized in a reference guide. Participants found the links, videos, and classroom accommodations or academic supports to be helpful., Conclusion: SCHOOLFirst is an evidence-based, user-driven resource that was created for educators to support students returning to school following concussion. Educators, health care providers, youth, and families collaborated on developing SCHOOLFirst to improve students' successful return to school following concussion. Educators were satisfied with the resource and saw opportunities to use it to support their students., (Copyright© 2022 the College of Family Physicians of Canada.)