bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of enhanced recovery after surgery among patients undergoing percutaneous nephrolithotomy: a systematic review and meta-analysis
Authors: Liu Liang , Xiao Yu , Yue Xiao , Wang Qiang
Published: February 2024

Background:

The enhanced recovery after surgery (ERAS) method has been widely used in surgery and anesthesia worldwide and has been applied to a wide range of surgical specialties, including colorectal surgery, gynecology, liver surgery, breast surgery, urology, and spinal surgery. An increasing number of studies have demonstrated its safety and efficacy in various fields. The safety and effectiveness of ERAS for percutaneous nephrolithotomy (PCNL) remain controversial. This study aimed to review the safety and effectiveness of ERAS for PCNL.

Methods:

The Chinese National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Biomedical Literature Service System (SinoMed), Chinese Science and Technology Journal Full Text Database (VIP), Cochrane Library, PubMed, Web of Science, and Embase databases were searched for eligible studies published until 19 September 2022. Outcome measures included postoperative hospital stay, total hospital stay, incidence of postoperative complications, stone-free rate (SFR), operative time, postoperative indwelling nephrostomy tube time, catheter encumbrance time, and nursing satisfaction. All analyses were performed using random-effects or fixed-effects models. Clinical heterogeneity was treated with subgroup, sensitivity, or descriptive analyses only when clinical heterogeneity was not excluded. Publication bias was assessed using funnel plots. Twenty-five studies (1545 observational patients and 1562 controls) were included.

Results:

The ERAS group had a shorter postoperative hospital stay [WMD=−2.59, 95% CI=(−3.04, −2.14), P<0.001], total hospital stay [WMD=−2.59, 95% CI=(−3.04, −2.14), P<0.001], and lower complication rate [RR=0.36, 95% CI=(0.29–0.43), P<0.001] than the control group. The ERAS group had a shorter surgery time [WMD=−3.57, 95% CI=(−5.88, −1.26), P=0.003], postoperative indwelling nephrostomy tube time [WMD=−1.94, 95% CI=(−2.69, −1.19), P<0.001], catheter encumbrance time [WMD=−2.65, 95% CI=(−4.83, −0.46), P=0.02], and higher satisfaction [RR=1.15, 95% CI=(1.05–1.25), P=0.001] than the control group. The difference in the stone-free rate between the two groups was not statistically significant [RR=1.03, 95% CI=(0.97–1.09), P=0.38], but the stone-free rate of the observation group (ERAS group) in each study was higher than that of the control group.

Conclusion:

ERAS not only ensures the safety of PCNL but also promotes postoperative rehabilitation of patients (shorter surgery time, postoperative indwelling nephrostomy tube time, postoperative hospital time, and lower complication rate). At the same time, differences in the stone-free rate were not statistically significant, but the stone-free rate of ERAS in each study was higher than that of the usual care for PCNL patients.
Topical Corticosteroid Phobia Among Women Affected With Vulvar Lichen Sclerosus: Results From a Cross-sectional Survey
Authors: Borghi Alessandro , Flacco Maria Elena , Pacetti Lucrezia , Toni Giulia , Corazza Monica
Published: February 2024

Objective

Topical corticosteroid (TC) phobia (TCP) is common in subjects affected with chronic inflammatory skin diseases who need prolonged corticosteroid treatments. The aim of this study was to assess TCP in women affected with vulvar lichen sclerosus (VLS).

Materials and Methods

This observational, cross-sectional study included adult patients with VLS who either started or were undergoing a TC treatment at our vulva unit between May 2022 and May 2023. All patients completed the self-administered TOPICOP questionnaire, which is validated for measuring concerns, worries, and beliefs about TC use. The scores obtained were analyzed in relation to demographic, history, and clinical data.

Results

The majority of the 165 (92.1%, 66.5 ± 11.9 years) included patients who had previously undergone TC treatments, mostly for VLS; 81.8% of them had received information about TCs, mainly from dermatologists (86.7%). The median global TOPICOP score was 16.7% (interquartile range. 8.3–30.6), corresponding to a raw median value of 6.0 (interquartile range, 3.0–11.0). The median subscores for the 2 TOPICOP domains, namely, mistaken beliefs and worries about TCs, were equal to each other. At multivariate analysis, none of the collected variables showed a significant association with the degree of TCP.

Conclusions

In our VLS patients, TCP resulted rather low, probably because of the small skin area being treated and the high percentage of women who had already used TCs and who had received information about them from a dermatologist. This latter point suggests that adequate counseling could be a strong basis for greater awareness and serenity in the long-term use of TCs.
Nurses' Perceptions of Caring at Work
Authors: Drake Jennifer , Davis Theresa M. , O'Brien Anne-Marie , Parker Carla , Swamidoss Douglas Carol , Thomas Donna , Rickard Sarah , Sintich Maureen E. , Gollenberg Audra , Mowery Bernice D.
Published: February 2024

OBJECTIVES

Study objectives were to explore nurses' perceptions of self-care, co-worker, and leader caring within healthcare work environments and assess reliability of 3 Watson Caritas Scores.

BACKGROUND

Assessing caring in an organization where Watson's Theory of Human Caring guides nursing practice offers insight into the professional practice environment.

METHOD

This study reports quantitative data from mixed-methods descriptive, cross-sectional survey of 1307 RNs at a large healthcare system.

RESULTS

Mean scores were self = 5.46, co-worker = 5.39, and leader score = 5.53, and median scores were >5.6 (range, 1-7). All scales had a positive and significant correlation to likelihood to recommend the organization, with the largest being feeling cared for by leaders. Internal reliability of the 3 scales was ≥0.9.

Conclusion

Nurse perceptions of caring may influence the organization's reputation. Assessing the perception of caring among nursing staff after the introduction and enculturation of this framework is needed. Results support psychometric value for 3 Watson Caritas Scores.
Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013–2016
Authors: Zhang Shuangxia , Gao Xiang , Ma Xiaopeng , Wang Jinghua , Zhu Yunxia
Published: February 2024

According to this cross-sectional study, individuals in the United States between the ages of 20 and 59 years who have low vitamin D levels are more likely to have a prevalent infection of Trichomonas vaginalis.

Background

Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored.

Methods

Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results.

Results

The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69–0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30–0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09–0.61; P < 0.001] for T3).

Conclusions

Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.
Optometrists need to incorporate their understanding of the impact of dry eye disease in their patient management
Authors: Mathan Zoë M. J. , van Tilborg Mirjam M. A.
Published: February 2024

SIGNIFICANCE

The impact of dry eye disease on patients' daily lives is understood by optometrists, but they seldom use this understanding in their patient management.

PURPOSE

Dry eye disease can significantly impact a person's daily life and is known to cause psychological symptoms. Treating and managing patients with dry eye disease can be challenging, as an approach based solely on signs is unlikely to reflect patients' true burden. Because optometrists play a crucial role in the care of dry eye disease patients, it is necessary to examine their awareness of the negative impact of dry eye disease on patients' daily lives and how they manage this during their consultation time, including diagnosis and management.

METHODS

This study has an exploratory, qualitative research design. Twelve semistructured online interviews were conducted with optometrists in second-line eye care through a convenience sample. The interviews were recorded, transcribed verbatim, and analyzed after a thematic analysis.

RESULTS

The main findings were that few optometrists actively asked about patients' perceived burden, many optometrists did not mention all the possible treatment options or practical advice that could benefit dry eye disease patients, and few were aware of the possible help that other health care providers could provide, besides the optometrist.

CONCLUSIONS

Dutch optometrists are aware of the impact that dry eye disease can have on their patients' daily lives, but seldom use this information as part of their management plan.
Objective and subjective assessment of accommodative insufficiency
Authors: León Alejandro , Rosenfield Mark , Medrano Sandra Milena , Durán Sandra Carolina , Pinzón Carol Violet
Published: February 2024

SIGNIFICANCE

A variety of subjective and objective procedures are available to measure the amplitude of accommodation. However, it is unclear whether the standard criterion of Hofstetter's minimum minus 2 D can be used to diagnose accommodative insufficiency with each of these techniques.

PURPOSE

The use of objective dynamic retinoscopy and three subjective techniques to diagnosis accommodative insufficiency was examined.

METHODS

A total of 632 subjects between 8 and 19 years of age were enrolled. Accommodative lag, monocular accommodative facility, and subjective (push-up, modified push-down, and minus lens) and objective (dynamic retinoscopy) amplitude of accommodation were quantified. Accommodative insufficiency was diagnosed based on Hofstetter's minimum minus 2 D for each subjective method, as well as adding an additional subjective criterion (either accommodative lag exceeding 0.75 D or monocular accommodative facility falling below the age-expected norms).

RESULTS

The prevalence of accommodative insufficiency was lowest and highest with the push-up (7.9 and 1%) and dynamic retinoscopy (94 and 12%) procedures when measured without and with the additional subjective criteria, respectively. Comparing the validity of dynamic retinoscopy against the traditional criterion, moderate to low sensitivity and high specificity were found. However, adding the additional subjective criteria improved the findings with moderate to high sensitivity and high specificity. Using a cutoff for dynamic retinoscopy of 7.50 D showed moderate diagnostic accuracy based on likelihood ratios.

CONCLUSIONS

It is clear that a revised definition of accommodative insufficiency is required, which must include the method of assessing accommodation. The various objective and subjective methods for quantifying the amplitude of accommodation are not interchangeable, and subjective assessment does not provide a valid measure of the accommodative response.
2022 Glenn A. Fry Award lecture: Enhancing clinical assessment for improved ophthalmic management
Authors: Wolffsohn James S.
Published: February 2024

Detailed clinical assessment is critical to allow sensitive evaluation of the eye and its management. As technology advances, these assessment techniques can be adapted and refined to improve the detection of pathological changes of ocular tissue and their impact on visual function. Enhancements in optical medical devices including spectacle, contact, and intraocular lenses have allowed for a better understanding of the mechanism and amelioration of presbyopia and myopia control. Advancements in imaging technology have enabled improved quantification of the tear film and ocular surface, informing diagnosis and treatment strategies. Miniaturized electronics, large processing power, and in-built sensors in smartphones and tablets capacitate more portable assessment tools for clinicians, facilitate self-monitoring and treatment compliance, and aid communication with patients. This article gives an overview of how technology has been used in many areas of eye care to improve assessments and treatment and provides a snapshot of some of my studies validating and using technology to inform better evidence-based patient management.
Normative framework and occupational mental health hotlines in Colombia: an analysis of their results and challenges
Authors: Galeano Buenaventura Judith Vanessa , Vargas Betancourt Mónica Lorena , Cuervo Díaz Diana Elizabeth
Published: February 2024

This article discusses the interaction between regulations and the implementation of mental health hotlines for the working population in Colombia, as well as the results obtained from this initiative. Two elements were analyzed here: the role of hotlines in workers’ mental health and the role of regulations in their functioning. During the COVID-19 pandemic, concerns about mental health increased, highlighting the effectiveness of hotlines. The document review presents findings from existing literature on mental health hotlines and the regulatory framework related to this issue in Colombia. Such findings reveal that these lines remain relevant beyond the pandemic and emphasize regulations as a critical factor in promoting mental health in the workplace. Additionally, from a clinical perspective, the focus of hotlines is on improving access to mental health services, which can provide personalized support to workers under emotional pressure. From a research perspective, there is a need to assess the effectiveness of tele-orientation in the workplace and devise strategies to optimize its integration with other mental health services.
Durable Efficacy of Switching From a 3- or 4-Drug Tenofovir Alafenamide–Based Regimen to the 2-Drug Regimen Dolutegravir/Lamivudine in the TANGO Study Through Week 196
Authors: De Wit Stéphane , Bonnet Fabrice , Osiyemi Olayemi , Bisshop Fiona , Olalla Julian , Routy Jean-Pierre , Wyen Christoph , Moodley Riya , Pappa Keith , Wang Ruolan , Oyee James , Saggu Parminder , Letang Emilio , Wynne Brian , Jones Bryn , Smith Kimberly Y. , Ait-Khaled Mounir
Published: February 2024

Background:

Switching to the 2-drug regimen dolutegravir (DTG)/lamivudine (3TC) demonstrated durable noninferior efficacy vs continuing 3- or 4-drug tenofovir alafenamide–based regimens for maintaining virologic suppression in people with HIV-1 through week 144 in TANGO.

Setting:

One hundred thirty-four centers, 10 countries.

Methods:

Adults with HIV-1 RNA <50 copies/mL for >6 months and no history of virologic failure were randomized to switch from stable tenofovir alafenamide–based regimens to DTG/3TC on day 1 [early-switch (ES) group] for 196 weeks. Those randomized to continue tenofovir alafenamide–based regimens on day 1 who maintained virologic suppression at week 144 switched to DTG/3TC at week 148 [late-switch (LS) group]. Efficacy, safety, and tolerability (including weight and biomarker changes) of DTG/3TC in ES and LS groups were assessed through week 196.

Results:

Overall, 369 participants switched to DTG/3TC on day 1 (ES) and 298 switched at week 148 (LS). In the ES group, 83% (306/369) maintained virologic suppression through year 4, and 3% (11/369) reported new adverse events between weeks 144 and 196. The LS group at week 196 and the ES group at week 48 had comparable proportions with virologic suppression (93% each) and similar safety profiles. No LS participants and 1 ES participant met confirmed virologic withdrawal criteria through week 196, with no resistance-associated mutations observed. Treatment continued to be well tolerated long term.

Conclusions:

Switching from tenofovir alafenamide–based regimens to DTG/3TC showed durable efficacy, high barrier to resistance, and good tolerability through 4 years. These results support DTG/3TC as a robust treatment for maintaining virologic suppression.
Virtual Monoenergetic Images Facilitate Better Identification of the Arc of Riolan During Splenic Flexure Takedown
Authors: Li Qian , Zhang Pengfei , Zhang Ranxu , Zhang Jianfeng , Tian Ruoxi , Gao Tianyi , Huang Yu , Zhang Ping , Wei Wei , Hong Rui , Wang Guiying , Zhao Jian
Published: February 2024

Objective

This study aimed to investigate whether virtual monoenergetic images (VMIs) can aid radiologists and surgeons in better identifying the arc of Riolan (AOR) and to determine the optimal kilo electron volt (keV) level.

Methods

Thirty-three patients were included. Conventional images (CIs) and VMI (40–100 keV) were reconstructed using arterial phase spectral-based images. The computed tomography (CT) attenuation and noise of the AOR, the CT attenuation of the erector spinal muscle, and the background noise on VMI and CI were measured, respectively. The signal-to-noise ratio, contrast-to-noise ratio (CNR), and signal intensity ratio were calculated. The image quality of the AOR was evaluated according to a 4-point Likert grade.

Results

The CT attenuation, noise, CNR, and signal intensity ratio of the AOR were significantly higher in VMI at 40 and 50 keV compared with CI (P < 0.001); VMI at 40 keV was significantly higher than 50 keV (P < 0.05). No significant difference in signal-to-noise ratio, background noise, and CT attenuation of the spinal erector muscle was observed between VMI and CI (P > 0.05). virtual monoenergetic image at 40 keV produced the best subjective scores.

Conclusions

Virtual monoenergetic image at 40 keV makes it easier to observe the AOR with optimized subjective and objective image quality. This may prompt radiologists and surgeons to actively search for it and encourage surgeons to preserve it during splenic flexure takedown.
Evaluation of the Usefulness of Contrast-Enhanced Computed Tomography for the Early Detection of Anastomotic Leakage After Esophagectomy
Authors: Morikawa Kazuhiko , Tanishima Yuichiro , Igarashi Takao , Ohki Yohei , Takahashi Keita , Kurogochi Takanori , Yano Fumiaki , Ojiri Hiroya
Published: February 2024

Objective

Anastomotic leakage is one of the most severe complications after esophagectomy. However, a diagnostic gold standard for anastomotic leakage has not been established yet. This retrospective cohort study aimed to evaluate the potential use of routine postoperative contrast-enhanced computed tomography findings as an early predictor of anastomotic leakage in patients who underwent esophagectomy for esophageal cancer.

Methods

This study included 75 patients who underwent Mckeown esophagectomy, of whom 22 developed anastomotic leakage after surgery. The computed tomography findings for this patient cohort were categorized into 3 grades based on mural enhancement patterns observed at the anastomotic site. Both semiquantitative and quantitative analyses were performed, and the interobserver agreement between the 2 experienced radiologists was assessed.

Results

It was found that poor enhancement in both the early and portal venous phases (grade 2) had a robust association with the occurrence of anastomotic leakage. The computed tomography enhancement ratio that is used to estimate wall degeneration and ischemia was significantly higher in patients with anastomotic leakage.

Conclusions

Routine postoperative contrast-enhanced computed tomography could be beneficial for the early detection of anastomotic leakage, even in asymptomatic patients, after esophagectomy.
Surgical Correction of Depressed Scars After Upper Blepharoplasty: A Turnover Orbicularis-Septum Composite Flap Technique
Authors: Liu Zhigang , Liu Miaoqing , Huang Wen , Wang Zhijun , Shi Heng
Published: February 2024

Objective:

Depressed scarring is a common complication after incisional upper blepharoplasty and frequently contributes to patient dissatisfaction. Correcting this deformity presents a significant challenge for oculoplastic surgeons. This study aims to investigate the clinical effectiveness of employing the turnover orbicularis-septum composite flap technique in correcting depressed scars after double eyelid surgery.

Methods:

This is a retrospective study of 118 patients who underwent revision blepharoplasty with depressed scar from November 2020 to February 2023. During the revision procedure, the adhesions of the original scar were meticulously dissected, and the residual orbital fat was thoroughly released. The orbicularis-septum composite flap was then inverted downward and smoothly laid over the depressed scar area to address the tissue deficit. After surgery, patient satisfaction was evaluated by assessing the improvement of the depressed scars and the shape of the double eyelid folds.

Results:

Follow-up assessments were conducted over a period of 6 to 24 months postoperatively. The results were judged as fully satisfied in 78 cases (66.1%), basically satisfied in 32 cases (27.1%), and unsatisfied in 8 cases (6.8%). Among the unsatisfied patients, 5 patients complained of eyelid fold shallow or disappear, and 3 patients complained of asymmetry. All patients exhibited varying degrees of improvement in the depressed scars.

Conclusions:

The turnover orbicularis-septum composite flap technique provides an effective approach for the treatment of depressed scars with a high satisfaction rate.
Phenotypic antibiotics susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna State, North-west Nigeria
Authors: Ezeh Peace Amarachukwu , Olayinka Busayo Olalekan , Bolaji Rebecca Olajumoke , Suleiman Babangida Ahmed , Olowookere Ahmed
Published: February 2024

Background: The increasing resistance of clinical Enterobacteriaceae infection to commonly prescribed antibiotics have been reported around the world. Data is generally lacking on the prevalence and antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna, northwest Nigeria. This study thus aimed to determine the diversity of clinical Enterobacteriaceae isolates recovered from clinical specimens of patients admitted into two selected healthcare institutions in Kaduna, Nigeria.
Methods: Non-duplicate clinical bacteria isolates recovered from various specimens were collected and identified using rapid biochemical identification kits. The susceptibility of identified Enterobacteriaceae to various antibiotics and phenotypic detection of carbapenemase enzymes were thereafter determined.
Results:  Of the 500 collected bacterial isolates, 108 (21.6 %) were identified as Enterobacteriaceae, with Pantoea agglomerans (52, 48.1%), Klebsiella oxytoca (19, 17.6%) as the most prevalent. The isolates exhibited high resistance to azithromycin (69%) and ceftazidime (42%), while exhibiting low resistance to amikacin (7%) and imipenem (10%). Among the carbapenem-resistant Enterobacteriaceae (CRE) isolates, a significant proportion (66.6 %) tested positive for carbapenemase activity.
Conclusion: This study reports a high prevalence of multi-drug resistant Enterobacteriaceae in Kaduna, northwest Nigeria. The emergence of pathogenic P. agglomerans and an alarmingly high prevalence of carbapenemase-producing CRE are also observed. The presence of carbapenemase producers in an area with low carbapenem usage and resistance rates raises significant concerns. Continuous surveillance and robust antibiotic stewardship policies are imperative to preserve the efficacy of carbapenems in this region.
Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses
Authors: Asamoah-Boaheng Michael , Goldfarb David M. , Kayda Iryna , Yap Justin , Kirkham Tracy , Karim Mohammad Ehsanul , Demers Paul , Copp Jeffrey M. , Grunau Brian
Published: February 2024

Introduction Comparative immunogenicity from different mRNA booster vaccines (directed at wild-type [WT], BA.1, or BA.4/5 antigens) remains unclear. Methods We included blood samples from adult paramedics who received three mRNA WT-directed vaccines plus a fourth dose of: (1) WT monovalent; (2) Moderna BA.1-WT bivalent; or (3) Pfizer BA.4/5-WT bivalent vaccine. The primary outcome was angiotensin-converting enzyme 2 (ACE-2) inhibition to BA.4/5 antigen. We used optimal pair matching (using age, sex-at-birth, preceding SARS-CoV-2 infection, and fourth vaccine-to-blood collection interval) to create balanced groups to individually compare each vaccine type to each other vaccine (overall, within subgroups defined by SARS-CoV-2 infection, and after combining BA.1 and BA.4/5 cases). We compared outcomes with Wilcoxon matched pairs signed rank test. Results Overall, 158 paramedics (mean age 45 years) were included. ACE-2 inhibition was higher for BA.1 compared to WT (p=0.002); however, no difference was detected between BA.4/5 vs. WT, or BA.1 vs BA.4/5. Among cases with preceding SARS-CoV-2, there were no between-group differences. Among cases without preceding SARS-CoV-2, the only difference was BA.1 > WT (p=0.003). BA.1 and BA.4/5 cases combined had higher ACE2 inhibition than WT (p = 0.003). Conclusion Omicron-directed vaccines appear to improve Omicron-specific immunogenicity; however, this appears limited to SARS-CoV-2-naïve individuals.
The rasterdiv package for measuring diversity from space
Authors: Marcantonio Matteo , Thouverau Elisa , Rocchini Duccio
Published: February 2024

This book chapter provides an extensive overview of therasterdivpackage which provides a comprehensive suite of functions designed to calculate diversity indices from numerical matrices, including those derived from optical remote sensing imagery. It facilitates a deeper analysis of spatial heterogeneity and ecosystem complexity by translating pixel values into ecological indicators. This package serves as a valuable tool for researchers and practitioners in the fields of landscape ecology, biodiversity monitoring, and environmental management, allowing for an enhanced understanding of landscape patterns and their ecological implications through advanced quantitative measures.
Understanding staff needs for Improving End-of-life Care in Critical Care Units
Authors: Tavabie S , Pearson S , Balabanovic J , Batho A , Juj M , Kastande P , Bennetts J , Collis E , Bonnici T.
Published: February 2024

Objectives

Critical care is a place of frequent death, up to a quarter of those admitted die during admission. Caring for dying people provides many challenges, practically, professionally and personally. The aim of this study was to better understand the perspectives of staff caring for dying people in critical care and identify their priorities for improvement.

Method

Three multidisciplinary focus groups of critical care staff at a large central London hospitals trust were facilitated with a semi structured format and digitally transcribed. Inductive thematic analysis was conducted to extract themes.

Results

N=34 (18 nursing, 7 allied health professionals, 6 medical, 3 clerical/administrative) The five themes were structured as priority statements: “We need to recognise” included the subthemes of being “sick enough to die” and potential rapid deteriorations in this setting; “We need to understand” with subthemes of perspectives on dying and prioritising time for conversations; “We need to connect” with subthemes of therapeutic relationship and physical presence; “We need to collaborate” with subthemes of critical care working and empowerment, and cross teams working; “We need support” with themes of experiencing support and making time to support others.

Conclusion

We present an approach to identifying critical care departmental priorities for an end-of-life care improvement programme. The themes extracted will be used to evaluate systems for dying in critical care, aiming to empower staff to provide excellent care every time they look after a dying person.
Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19
Authors: Boon Adrianus C.M. , L. Bricker Traci , Fritch Ethan J. , Leist Sarah R. , Gully Kendra , Baric Ralph S. , Graham Rachel L. , Troan Brigid V. , Mahoney Matthew , Janetka James W.
Published: February 2024

We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited sub nanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.

IMPORTANCE

SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host-cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and therapeutic drug for the treatment of COVID-19 in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.
Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua
Authors: Narvaez Federico , Montenegro Carlos , Juarez Jose Guillermo , Zambrana José Victor , Gonzalez Karla , Videa Elsa , Arguello Sonia , Barrios Fanny , Ojeda Sergio , Plazaola Miguel , Sanchez Nery , Camprubí-Ferrer Daniel , Kuan Guillermina , Bailey Gabriela Paz , Harris Eva , Balmaseda Angel
Published: February 2024

Dengue, a major public health threat, is a viral infection spread by mosquitoes that can cause a range of symptoms from mild to life-threatening. Our study analyzed 19 years of data from two pediatric studies in children 2 to 17 years of age in Managua, Nicaragua. We aimed to understand how dengue severity varies with different serotypes of dengue virus (DENV1-4) and whether the child had a previous dengue infection. We found that DENV2 and DENV3 caused the most sever disease in children. DENV3 lead to sever outcomes in both primary (first-time) and secondary (repeat) infections, while DENV2 is particularly severe in secondary infections. These findings highlight the importance of a balanced dengue vaccine that can protect against all four virus strains, as current vaccines show varying effectiveness. Our research emphasizes the need for effective prevention and treatment strategies to manage dengue, particularly in regions where the virus is widespread.

Background

Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.

Methods

This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients.

Results

We enrolled a total of 15,266 participants, of whom 3,227 (21%) were positive for DENV infection. Of 2,630 cases with serotype result by RT-PCR, 557 corresponded to DENV1, 992 to DENV2, 759 to DENV3 and 322 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock.

Conclusions

These findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.
SARS-CoV-2 virus in Raw Wastewater from Student Residence Halls with concomitant 16S rRNA Bacterial Community Structure changes
Authors: Li Y. , Ash K. T. , Joyner D. C. , Williams D. E. , Hazen T. C.
Published: February 2024

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in sewage is well-established, but the concomitant changes in microbial compositions during the pandemic remain insufficiently explored. This study investigates the impact of the SARS-CoV-2 virus on microbial compositions in raw sewage, utilizing 16S rRNA sequencing to analyze wastewater samples collected from six dormitories over a one-year field trial at the University of Tennessee, Knoxville. The concentration of SARS-CoV-2 RNA was assessed using a reverse transcription-quantitative polymerase chain reaction. Significant variations in bacterial composition were evident across the six dormitories, highlighting the importance of independently considering spatial differences when evaluating the raw wastewater microbiome. Positive samples for SARS-CoV-2 exhibited a prominent representation of exclusive species across all dormitories, coupled with significantly reduced bacterial diversity compared to negative samples. The correlation observed between the relative abundance of enteric pathogens and potential pathogens at sampling sites introduces a significant dimension to our understanding of COVID-19, especially the notable correlation observed in positive SARS-CoV-2 samples. Furthermore, the significant correlation in the relative abundance of potential pathogens between positive and negative SARS-CoV-2 raw sewage samples may be linked to the enduring effects of microbial dysbiosis observed during COVID-19 recovery. These findings provide valuable insights into the microbial dynamics in raw sewage during the COVID-19 pandemic.
Restrained memory CD8+T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID
Authors: Rodriguez Lucie , Tan Ziyang , Lakshmikanth Tadepally , Wang Jun , Barcenilla Hugo , Swank Zoe , Zuo Fanglei , Abolhassani Hassan , Pavlovitch-Bedzyk Ana Jimena , Wang Chunlin , Gonzalez Laura , Mugabo Constantin Habimana , Johnsson Anette , Chen Yang , James Anna , Mikes Jaromir , Kleberg Linn , Sundling Christopher , Björnson Mikael , Bonnier Malin Nygren , Ståhlberg Marcus , Runold Michael , Björkander Sophia , Melén Erik , Meyts Isabelle , Weyenbergh Johan Van , Hammarström Qian-Pan , Davis Mark M , Walt David R. , Landegren Nils ,   COVID Human Genetic Effort, Aiuti Alessandro , Casari Giorgio , Casanova Jean-Laurent , Jamoulle Marc , Bruchfeld Judith , Brodin Petter
Published: February 2024

During the COVID-19 pandemic it was widely described that certain individuals infected by SARS-CoV-2 experience persistent disease signs and symptoms, Long COVID, which in some cases is very severe with life changing consequences. To maximize our chances of identifying the underpinnings of this illness, we have focused on 121 of the most severe cases from >1000 patients screened in specialized clinics in Sweden and Belgium. We restricted this study to subjects with objective measures of organ damage or dysfunction, >3 months following a verified, but mild-to-moderate SARS-CoV-2 infection. By performing systems-level immunological testing and comparisons to controls fully convalescent following a similar mild/moderate COVID-19 episode, we identify elevated serological responses to SARS-CoV-2 in severe Long COVID suggestive of chronic antigen stimulation. Persistent viral reservoirs have been proposed in Long COVID and using multiple orthogonal methods for detection of SARS-CoV-2 RNA and protein in plasma we identify a subset of patients with detectable antigens, but with minimal overlap across assays, and no correlation to symptoms or immune measurements. Elevated serologic responses to SARS-CoV-2 on the other hand were inversely correlated with clonally expanded memory CD8+T cells, indicating that restrained clonal expansion enables viral persistence, chronic antigen exposure and elevated IgG responses, even if antigen-detection in blood is not universally possible.
Thalamocortical network neuromodulation for epilepsy
Authors: Agashe Shruti , Alcala-Zermeno Juan Luis , Osman Gamaleldin M. , Starnes Keith , Brinkmann Benjamin H. , Sheffield Doug , Leyde Kent , Stead Matt , Miller Kai J. , Van Gompel Jamie J. , Worrell Gregory A. , Lundstrom Brian N. , Gregg Nicholas M.
Published: February 2024

Objectives

Despite the growing interest in network-guided neuromodulation for epilepsy, uncertainty about the safety and long-term efficacy of thalamocortical stimulation persist. Our evaluation focused on the use of a 4-lead open-loop implantable pulse generator (IPG) for thalamocortical network neuromodulation.

Methods

We retrospectively reviewed seven subjects with diverse seizure networks (SNs)—poorly localized, regional, or multifocal—undergoing thalamocortical neuromodulation. Employing a 4-lead system, electrodes targeted both thalamic and cortical SN nodes. We assessed seizure severity, life satisfaction, and sleep quality on a 10-point scale, and seizure frequency via telephone interviews and chart review. Six subjects underwent open-loop stimulation trials during intracranial EEG (iEEG) to confirm SN engagement and optimize settings, targeting the suppression of interictal epileptiform discharges (IEDs) and seizures. Outcomes were assessed by Wilcoxon sign-rank test, 0.05 significance level.

Results

After a median of 17 months post-implantation (range 13–60), subjects had a median disabling seizure reduction of 93% (range 50-100%, p=0.0156), with 100% responder rate (≥50% reduction in seizure frequency). The median improvement in seizure severity was 3.5 out of 10 points (p=0.0312), life satisfaction 4.5 points (p= 0.0312), and quality of sleep 3 points (p=0.062). No perioperative complications occurred. Rare transient seizure exacerbations and stimulation-related sensory/motor side effects resolved with parameter adjustments. One subject required surgical revision due to delayed infection. Six subjects had permanent electrode placement refined by iEEG trial stimulation; five subjects had >90% reduction in seizure frequency during iEEG stimulation.

Significance

Thalamocortical network neuromodulation using a 4-lead open-loop system is safe, and is associated with significant improvements in seizure control and patient quality of life. Trial stimulation during iEEG shows promise for enhancing SN engagement and parameter optimization, but requires further study. Prospective controlled trials are needed to establish the validity of thalamocortical network neuromodulation for epilepsy.

Key Points

Thalamocortical neuromodulation with a 4-lead open-loop stimulation system is feasible and safe, and is associated with significant improvements in seizure control and life satisfaction.

Trials of therapeutic stimulation during phase 2 iEEG monitoring has the potential to refine seizure network engagement and optimize stimulation parameters, for more effective chronic neuromodulation.

Prospective controlled trials are needed to validate the efficacy of thalamocortical network neuromodulation.
Individual patterns of activity predict the response to physical exercise as an intervention in mild to moderate depression
Authors: Spulber Stefan , Ceccatelli Sandra , Forsell Yvonne
Published: February 2024

Physical exercise (PE) as antidepressive intervention is a promising alternative, as shown by multiple meta-analyses. However, there is no consensus regarding optimal intensity and duration of exercise, and there are no objective criteria available for personalized indication of treatment. The aims of this study were (1) to evaluate whether individual activity patterns before intervention can predict the response to treatment; and (2) to evaluate whether the patient outcome can be improved by using prior information on treatment efficacy at individual level. The study included subjects with mild to moderate depression randomized to three levels of exercise intensity in the Regassa study. Using a previously developed pipeline for data analysis, we have generated linear regression ensembles to predict the response to treatment using features extracted from actigraphy recordings. To understand the contribution of individual features, we performed a Bayesian analysis of coefficients, and found that different levels of PE intensity yield distinct signatures in enriched feature subsets. Next, we used the trained ensembles for a counterfactual analysis of response and remission rate provided prior knowledge of response to treatment outcome. The response to either PE regime was estimated for all patients, irrespective of original treatment assignment. Each patient was then virtually allocated to the PE regime predicted to yield best outcome, and the response and remission rates were compared against simulated random assignment to treatment. The counterfactual analysis showed that assignment to best individual PE regime yields significantly higher (increase by 28%) remission rates as compared to random assignment to treatment, which is accounted for by improved response in about 32% of the patients as compared to observed treatment outcome. While it is not possible to claim individual protocol optimization, our data suggest it may be possible to identify a PE regime to yield the best results for a patient based on individual circadian patterns of activity.
Association between altitude and death from COVID-19 in subjects with diabetes mellitus during the first wave: cross sectional study of the National Death Index
Authors: Ambrosio-Ojose Raúl Manuel , Casquero-Zambrano Cesar Josué , Vasquez-Hassinger Tery , Yovera-Aldana Marlon
Published: February 2024

Background

In high Andean areas, there is greater insulin sensitivity which may be a protective factor against complications in subjects with diabetes mellitus.

Objective

Determine the association between altitude of residence and death from COVID-19 in deaths with diabetes mellitus in Peru during the first wave..

Methods

We carried out a cross-sectional analysis of deaths registered in the National Death System of Peru (SINADEF in Spanish). We selected Peruvians with diabetes mellitus identified by presenting the diagnosis in any of the six boxes on the certificate. The dependent variable was death from COVID-19 as the basic cause of death, located in last place among causes A, B, C and D according to the Pan American Health Organization. The independent variable was the altitude of residence, categorized as less than 1 500 m a.s.l, 1 500 to 2 499 m a.s.l. and greater than 2 500 m a.sl. Through a multilevel analysis by geographic region and using a Poisson regression, we obtained the risk ratios of death from COVID-19 according to the altitude of residence. We adjusted by individual and contextual variables.

Results

We included 16 406 deaths with diabetes mellitus between March-December 2020. 34.3% died from Covid19 and 9.7% came from areas above 2 500 m. The proportion of deaths from COVID-19 of those with residence altitude above 2 500 m was 20% lower compared to residents below 1 500 m (RR: 0.80; 95% CI: 0.70 – 0.91; p<0.001), adjusted for individual and socioeconomic factors. Its influence is also shown as the altitude changes every 100, 250, 500 and 1000 m a.s.l., through multilevel analysis.

Conclusion

A higher altitude of residence is associated with a lower proportion of deaths from COVID-19 in people with diabetes mellitus during the first wave in Peru. The study contribute to expanding knowledge of the effects of altitude with respect to mortality in people with diabetes mellitus in a context of a highly contagious and virulent infectious disease.
Identification of Mitosis Stages Using Artificial Neural Networks for 3D Time Lapse Cell Sequences
Authors: Dincer Tolga , Stegmaier Johannes , Jose Abin
Published: February 2024

Cells, the fundamental units of life, are central to medical research, particularly in cancer studies due to their rapid, uncontrolled division. Understanding cell behavior is crucial, with a focus on mitosis, which has distinct cell division stages. However, precise detection of these phases, especially mitosis initiation in 3D, remains an underexplored research area. Our work explores 3D cell behavior, leveraging the increasing computational capabilities and prevalence of 3D imaging techniques. We introduce diverse 3D Convolutional Neural Network (CNN) architectures such as a base 3D CNN model, 3D CNN binary model, and 3D CNN pairwise model. An ensemble model based on the 3D CNN architectures shows higher classification accuracy on two time-series datasets. This research gives better insights into understanding cell behaviour in a multidimensional manner, contributing to medical research. To the best of our understanding, we are the first to delve into the utilization of Convolutional Neural Network architectures for the 3D classification of mitosis stages.