bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery of index-linked HIV testing for children: learnings from a qualitative process evaluation of the B-GAP study in Zimbabwe
Authors: Dringus Stefanie , Davis Katherine , Simms Victoria , Bernays Sarah , Redzo Nicol , Bandason Tsitsi , Chikodzore Rudo , Sibanda Edwin , Webb Karen , Ncube Getrude , Kranzer Katharina , Ferrand Rashida A. , Dziva Chikwari Chido
Published: April 2023

Background

Index-linked HIV testing for children, whereby HIV testing is offered to children of individuals living with HIV, has the potential to identify children living with undiagnosed HIV. The “Bridging the Gap in HIV Testing and Care for Children in Zimbabwe” (B-GAP) study implemented and evaluated the provision of index-linked HIV testing for children aged 2–18 years in Zimbabwe. We conducted a process evaluation to understand the considerations for programmatic delivery and scale-up of this strategy.

Methods

We used implementation documentation to explore experiences of the field teams and project manager who delivered the index-linked testing program, and to describe barriers and facilitators to index-linked testing from their perspectives. Qualitative data were drawn from weekly logs maintained by the field teams, monthly project meeting minutes, the project coordinator’s incident reports and WhatsApp group chats between the study team and the coordinator. Data from each of the sources was analysed thematically and synthesised to inform the scale-up of this intervention.

Results

Five main themes were identified related to the implementation of the intervention: (1) there was reduced clinic attendance of potentially eligible indexes due to community-based differentiated HIV care delivery and collection of HIV treatment by proxy individuals; (2) some indexes reported that they did not live in the same household as their children, reflecting the high levels of community mobility; (3) there were also thought to be some instances of ‘soft refusal’; (4) further, delivery of HIV testing was limited by difficulties faced by indexes in attending health facilities with their children for clinic-based testing, stigma around community-based testing, and the lack of familiarity of indexes with caregiver provided oral HIV testing; (5) and finally, test kit stockouts and inadequate staffing also constrained delivery of index-linked HIV testing.

Conclusions

There was attrition along the index-linked HIV testing cascade of children. While challenges remain at all levels of implementation, programmatic adaptations of index-linked HIV testing approaches to suit patterns of clinic attendance and household structures may strengthen implementation of this strategy. Our findings highlight the need to tailor index-linked HIV testing to subpopulations and contexts to maximise its effectiveness.
Viral reactivations and co-infections in COVID-19 patients: a systematic review
Authors: Kim Jenny Yeon Hee , Ragusa Martin , Tortosa Fernando , Torres Ana , Gresh Lionel , Méndez-Rico Jairo Andres , Alvarez-Moreno Carlos Arturo , Lisboa Thiago Costa , Valderrama-Beltrán Sandra Liliana , Aldighieri Sylvain , Reveiz Ludovic
Published: April 2023

Background

Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses.

Methods

Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle–Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables.

Results

In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals.

Conclusion

Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.
Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective analysis
Authors: Yang Yan , You Yannan , Liu Yazun , Geng Lina , Huang Lirong , Zhou Huan , Piao Xiang , Liu Xiao , Wu Mingyun , Wang Yajuan , Zhou Lili , Wang Peng , Shen Shiping , Hu Mingge , Han Zhaopeng , Xue Zheng
Published: April 2023

Objectives

This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during the Omicron variant outbreak.

Methods

This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, and household vaccination rates were collected through electronic health records and telephone interviews.

Results

A total of 603 paediatric patients confirmed to have COVID-19 were included in this study. Both univariate and multivariate analyses were performed to filter independent factors for the duration to viral RNA negative conversion. Data on the redetection of SARS-CoV-2 in the patients after they showed negative results on the RT‒PCR test (intermittent negative status) were also analysed. The median duration of virus shedding was 12 (interquartile range, IQR: 10–14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, and abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patients who had abnormal defecation or with more severe conditions would have delayed virological clearance, while patients who previously had 2 doses of vaccination or had higher household vaccination rates would have accelerated virological clearance. Loss of appetite (odds ratio (OR): 5.343; 95% CI: 3.307–8.632) and abnormal defecation (OR: 2.840; 95% CI: 1.736–4.645) were significantly associated with intermittent negative status.

Conclusion

These findings could provide clues for the early identification of paediatric patients with prolonged viral shedding and could enrich the evidence for the development of prevention and control strategies, especially vaccination policies for children and adolescents.
Risk factors of stillbirths in four district hospitals on Pemba Island, Tanzania: a prospective cohort study
Authors: Skytte Tine Bruhn , Holm-Hansen Charlotte Carina , Ali Said Mouhammed , Ame Shaali , Molenaar Jil , Greisen Gorm , Poulsen Anja , Sorensen Jette Led , Lund Stine
Published: April 2023

Background

More than 2 million third-trimester stillbirths occur yearly, most of them in low- and middle-income countries. Data on stillbirths in these countries are rarely collected systematically. This study investigated the stillbirth rate and risk factors associated with stillbirth in four district hospitals in Pemba Island, Tanzania.

Methods

A prospective cohort study was completed between the 13th of September and the 29th of November 2019. All singleton births were eligible for inclusion. Events and history during pregnancy and indicators for adherence to guidelines were analysed in a logistic regression model that identified odds ratios [OR] with a 95% confidence interval [95% CI].

Results

A stillbirth rate of 22 per 1000 total births in the cohort was identified; 35.5% were intrapartum stillbirths (total number of stillbirths in the cohort, n = 31). Risk factors for stillbirth were breech or cephalic malpresentation (OR 17.67, CI 7.5-41.64), decreased or no foetal movements (OR 2.6, CI 1.13–5.98), caesarean section [CS] (OR 5.19, CI 2.32–11.62), previous CS (OR 2.63, CI 1.05–6.59), preeclampsia (OR 21.54, CI 5.28–87.8), premature rupture of membranes or rupture of membranes 18 h before birth (OR 2.5, CI 1.06–5.94) and meconium stained amniotic fluid (OR 12.03, CI 5.23–27.67). Blood pressure was not routinely measured, and 25% of women with stillbirths with no registered foetal heart rate [FHR] at admission underwent CS.

Conclusions

The stillbirth rate in this cohort was 22 per 1000 total births and did not fulfil the Every Newborn Action Plan’s goal of 12 stillbirths per 1000 total births in 2030. Awareness of risk factors associated with stillbirth, preventive interventions and improved adherence to clinical guidelines during labour, and hence improved quality of care, are needed to decrease the stillbirth rate in resource-limited settings.
Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer
Authors: Wagner Marta , Sobczyński Maciej , Jasek Monika , Pawełczyk Konrad , Porębska Irena , Kuśnierczyk Piotr , Wiśniewski Andrzej
Published: April 2023

Background

ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting machinery – APM, ERAP1 is frequently down-regulated in many cancers. Since ERAP1 expression has not yet been thoroughly investigated in non-small cell lung cancer (NSCLC), we decided to analyze ERAP1 mRNA levels in tissues collected from NSCLC patients.

Methods

Using real-time qPCR, we evaluated ERAP1 mRNA expression in samples of tumor and adjacent non-tumor tissue (serving as control tissue) from 61 NSCLC patients.

Results

We observed a significantly lower level of ERAP1 mRNA expression in tumor tissue (MedTumor = 0.75) in comparison to non-tumor tissue (MedNon-tumor = 1.1), p = 0.008. One of the five tested polymorphisms, namely rs26653, turned out to be significantly associated with ERAP1 expression in non-tumor tissue (difference [d] = 0.59 CI95% (0.14;1.05), p = 0.0086), but not in tumor tissue.

The levels of ERAP1 mRNA expression did not affect the overall survival of NSCLC patients, either in the case of the tumor (p = 0.788) or in non-tumor (p = 0.298) tissue.

We did not detect any association between mRNA ERAP1 expression level in normal tissue and: (i) age at diagnosis (p = 0.8386), (ii) patient’s sex (p = 0.3616), (iii) histological type of cancer (p = 0.7580) and (iv) clinical stage of NSCLC (p = 0.7549). Furthermore, in the case of tumor tissue none of the abovementioned clinical parameters were associated with ERAP1 expression (p = 0.76).

Conclusion

Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy. The rs26653 polymorphism can be considered an expression quantitative trait locus (eQTL) associated with ERAP1 expression in normal lung tissue.
Patients’ and volunteer coaches’ experiences with an informal social network intervention in forensic psychiatric care: a qualitative analysis
Authors: Swinkels Lise T. A. , de Koning Mariken B. , van der Pol Thimo M. , Dekker Jack J. M. , ter Harmsel Janna F. , Popma Arne
Published: April 2023

Background:

Improving supportive social networks in forensic psychiatric patients is deemed important due to the protective effects of such networks on both mental health problems and criminal recidivism. Informal interventions targeted at social network enhancement by community volunteers showed positive effects in various patient and offender populations. However, these interventions have not specifically been studied in forensic psychiatric populations. Therefore, forensic psychiatric outpatients’ and volunteer coaches’ experiences with an informal social network intervention were explored in this study.

Methods:

This qualitative study was based on semi-structured interviews conducted alongside an RCT. Forensic outpatients allocated to the additive informal social network intervention, and volunteer coaches, were interviewed 12 months after baseline assessment. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis was used to identify and report patterns in the data.

Results:

We included 22 patients and 14 coaches in the study. The analysis of interviews revealed five main themes reflecting patients’ and coaches’ experiences: (1) dealing with patient receptivity, (2) developing social bonds, (3) receiving social support, (4) achieving meaningful change, and (5) using a personalized approach. Patient receptivity, including willingness, attitudes, and timing, was a common reported barrier affecting patients’ engagement in the intervention. Both patients’ and coaches’ experiences confirmed that the intervention can be meaningful in developing new social bonds between them, in which patients received social support. Despite, experiences of meaningful and sustainable changes in patients’ social situations were not clearly demonstrated. Coaches’ experiences revealed broadened worldviews and an enhanced sense of fulfillment and purpose. Finally, a personalized, relationship-oriented rather than goal-oriented approach was feasible and preferable.

Conclusion:

This qualitative study showed positive experiences of both forensic psychiatric outpatients and volunteer coaches with an informal social network intervention in addition to forensic psychiatric care. Notwithstanding the limitations, the study suggests that these additive interventions provide an opportunity for forensic outpatients to experience new positive social interactions with individuals in the community, which can initiate personal development. Barriers and facilitators to engagement are discussed to improve further development and implementation of the intervention.

Trial registration:

This study is registered at the Netherlands Trial Register (NTR7163, registration date: 16/04/2018).
Trends in cause of death among patients with renal cell carcinoma in the United States: a SEER-based study
Authors: Zhan Xiangpeng , Chen Tao , Liu Ying , Wan Hao , Liu Xiaoqiang , Deng Xinxi , Fu Bin , Xiong Jing
Published: April 2023

Background

Renal cell carcinoma (RCC) survival has improved due to recent developments in RCC treatment. Therefore, other co-morbid conditions may have a more critical role. This study aims to explore the common causes of death in patients with RCC to improve the management and survival of RCC.

Method

We used the Surveillance, Epidemiology, and End Results (SEER) (1992–2018) database to get patients with RCC. We calculated the percentage of total deaths of six kinds of the cause of death (COD) and the cumulative incidence of death for each selected cause over survival time. The joinpoint regression was utilized to present the trend of mortality rate by COD.

Results

We enrolled 107,683 cases with RCC. RCC was the leading cause of death in patients with RCC [25376(48.3%)], followed by cardiovascular diseases [9023(17.2%)], other cancers [8003 (15.2%)], other non-cancer diseases [4195 (8%)], non-disease cause [4023 (7.7%)], and respiratory diseases [1934 (3.6%)]. The proportion of patients who died of RCC decreased gradually over survival time, and this value decreased from 69.71% in 1992–1996 to 38.96% in 2012–2018. The non-RCC cause mortality rate showed an increasing trend, whereas a slight decrease was observed in RCC specific mortality rate. The distribution of such conditions varied across different patient populations.

Conclusion

RCC was still the primary COD of patients with RCC. However, non-RCC cause death was increasingly important among RCC patients in recent two decades. Cardiovascular disease and other cancers were crucial co-morbidities that required significant attention in the management of RCC patients.
Determinants of motorcycle helmet availability and cost in retail outlets: outcomes of a market survey in northern Ghana
Authors: Adjei Benjamin Noble , Nakua Emmanuel K. , Donkor Peter , Amissah John , Gyaase Daniel , Enuameh Yeetey , Mock Charles
Published: April 2023

Background

Morbidity and mortality from road traffic crashes are steadily increasing globally and they remain a major public health challenge. This burden is disproportionately borne by low-and middle-income countries, especially Sub-Saharan Africa where motorcycle helmet use is low and where there are challenges of affordability and availability of standard helmets. We sought to assess the availability and cost of helmets in retail outlets in northern Ghana.

Methods

A market survey of 408 randomly sampled automobile-related retail outlets in Tamale, northern Ghana was conducted. Multivariable logistic regression was used to identify factors associated with helmet availability and gamma regression was used to identify factors associated with their cost.

Results

Helmets were available in 233 (57.1%) of surveyed retail outlets. On multivariable logistic regression, street vendors were 48% less likely and motorcycle repair shops 86% less likely to sell helmets than automobile/motorcycle shops. Outlets outside the Central Business District were 46% less likely to sell helmets than outlets inside that district. Nigerian retailers were five times more likely to sell helmets than Ghanaian retailers. Median helmet cost was 8.50 USD. Helmet cost decreased by 16% at street vendors, 21% at motorcycle repair shops, and 25% at outlets run by the owner. The cost increased by older age of retailer (1% per year of age), education level of retailer (12% higher for secondary education, 56% higher for tertiary education, compared to basic education), and sex (14% higher for male retailer).

Conclusion

Motorcycle helmets were available in some retail outlets in northern Ghana. Efforts to improve helmet availability should address outlets in which they are less commonly sold, including street vendors, motorcycle repair shops, outlets run by Ghanaians, and outlets outside the Central Business District.
Predictors of hospital-acquired pressure injuries in patients with complete spinal cord injury: a retrospective case–control study
Authors: Balasuberamaniam Phumeena , Wasim Abeer , Shrikumar Mopina , Chen Tan , Anthony Tracey , Phillips Andrea , Nathens Avery , Chapman Martin , Crawford Eric , Schwartz Carolyn E. , Finkelstein Joel
Published: April 2023

Background

Despite current best practices, pressure injuries (PI) remain a devastating and prevalent hospital-acquired complication for patients with acute traumatic spinal cord injuries (SCIs). This study examined associations between risk factors for PI development in patients with complete SCI, such as norepinephrine dose and duration, and other demographic factors or lesion characteristics.

Methods

This case–control study included adults with acute complete SCIs ASIA-A, who were admitted to a level-one trauma center between 2014–18. A retrospective review was implement using data on patient and injury characteristics, including age, gender, level of SCI (cervical vs. thoracic), Injury Severity Score (ISS), length of stay (LOS) and mortality; presence/absence of PI during their acute hospital stay; and treatment factors such as spinal surgery, mean arterial pressure (MAP) targets, and vasopressor treatment. Multivariable logistic regression evaluated associations with PI.

Results

Eighty-two out of 103 eligible patients had complete data, and 30 (37%) developed PIs. Patient and injury characteristics, including age (Mean: 50.6; SD:21.3), location of SCI (48 cervical, 59%) and ISS (Mean 33.1; SD:11.8), did not differ between PI and non-PI groups. Logistic regression analysis revealed that male gender (OR:34.1; CI95:2.3–506.5, p = 0.010) and increased LOS (log-transformed; OR:20.5, CI95:2.8–149.9, p = 0.003) were associated with increased risk of PI. Having an order for a MAP > 80mmg (OR:0.05; CI95:0.01–0.30, p = 0.001) was associated with a reduced risk of PI. There were no significant associations between PI and duration of norepinephrine treatment.

Conclusions

Norepinephrine treatment parameters were not associated with development of PI, suggesting that MAP targets should be a focus for future investigations for SCI management. Increasing LOS should highlight the need for high-risk PI prevention and vigilance.
Palliative care and new technologies. The use of smart sensor technologies and its impact on the Total Care principle
Authors: Ott Tabea , Heckel Maria , Öhl Natalie , Steigleder Tobias , Albrecht Nils C. , Ostgathe Christoph , Dabrock Peter
Published: April 2023

Background

Palliative care is an integral part of health care, which in term has become increasingly technologized in recent decades. Lately, innovative smart sensors combined with artificial intelligence promise better diagnosis and treatment. But to date, it is unclear: how are palliative care concepts and their underlying assumptions about humans challenged by smart sensor technologies (SST) and how can care benefit from SST?

Aims

The paper aims to identify changes and challenges in palliative care due to the use of SST. In addition, normative guiding criteria for the use of SST are developed.

Methods

The principle of Total Care used by the European Association for Palliative Care (EAPC) forms the basis for the ethical analysis. Drawing on this, its underlying conceptions of the human and its socio-ethical aspects are examined with a phenomenological focus. In the second step, the advantages, limitations, and socio-ethical challenges of using SST with respect to the Total Care principle are explored. Finally, ethical-normative requirements for the application of SST are derived.

Results and Conclusion

First, SST are limited in their measurement capabilities. Second, SST have an impact on human agency and autonomy. This concerns both the patient and the caregiver. Third, some aspects of the Total Care principle are likely to be marginalized due to the use of SST. The paper formulates normative requirements for using SST to serve human flourishing. It unfolds three criteria according to which SST must be aligned: (1) evidence and purposefulness, (2) autonomy, and (3) Total Care.
Sexual violence against women remains problematic and highly prevalent around the world
Authors: Li Liqing , Shen Xin , Zeng Guohua , Huang Hongwei , Chen Zhensheng , Yang Jiayi , Wang Xiaofang , Jiang Ming , Yang Sule , Zhang Qi , Li Honglang
Published: April 2023

Background

Sexual violence is far more prevalent in most societies than is usually suspected in daily life. However, no study has systematically summarized the global prevalence rate and the major outcomes of sexual violence against women.

Methods

We directed a wide-raging search in the PubMed, Embase, and Web of Science, catalogs since the beginning to December 2022 for relevant reports about the incidence of sexual fighting touching females. The occurrence frequency was assessed with a random-effects model. The heterogeneity was estimated with I2 values. Differences by research features were assessed over subgroup evaluation and meta-regression.

Results

A total of 32 cross-sectional studies were included (a total of 19,125 participants). The pooled sexual violence rate was 0.29 (95% CI = 0.25–0.34). Subgroup analyses found that there was a higher rate of sexual violence against women in 2010–2019 period (0.33, 95% CI = 0.27–0.37), developing countries (0.32, 95% CI = 0.28–0.37), and interview (0.39, 95% CI = 0.29–0.49). The analysis found that more than half of women (0.56, 95% CI = 0.37–0.75) had post-traumatic stress disorder (PTSD) after experiencing sexual violence, and only a third of women considered seeking support (0.34, 95% CI = 0.13–0.55).

Conclusions

Nearly one out of every three (29%) women around the world has been a victim of sexual violence in their life. This current study investigated the status and characteristics of sexual violence against women, which could provide an important reference for police and emergency health services management.
Associations among socioeconomic status, multimorbidity of non-communicable diseases, and the risk of household catastrophic health expenditure in China: a population-based cohort study
Authors: Wang Yaping , Du Min , Qin Chenyuan , Liu Qiao , Yan Wenxin , Liang Wannian , Liu Min , Liu Jue
Published: April 2023

Background

Multimorbidity of non-communicable diseases (NCDs) is increasingly prevalent among older adults around the world, leading a higher risk of household catastrophic health expenditure (CHE). As current powerful evidence was insufficient, we aimed to estimate the association between multimorbidity of NCDs and the risk of CHE in China.

Methods

We designed a cohort study using data investigated in 2011–2018 from the China Health and Retirement Longitudinal Study, which is a nationally-representative study covering 150 counties of 28 provinces in China. We used mean ± standard deviation (SD) and frequencies and percentages to describe baseline characteristics. Person χ2 test was employed to compare the differences of baseline characteristics between households with and without multimorbidity. Lorenz curve and concentration index were used to measure the socioeconomic inequalities of CHE incidence. Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between multimorbidity and CHE.

Results

Among 17,708 participants, 17,182 individuals were included for the descriptive analysis of the prevalence of multimorbidity in 2011, and 13,299 individuals (8029 households) met inclusion criteria and were included in the final analysis with a median of 83 (interquartile range: 25–84) person-months of follow-up. 45.1% (7752/17,182) individuals and 56.9% (4571/8029) households had multimorbidity at baseline. Participants with higher family economic level (aOR = 0.91, 95% CI: 0.86–0.97) had lower multimorbidity prevalence than those with lowest family economic level. 82.1% of participants with multimorbidity did not make use of outpatient care. The CHE incidence was more concentrated among participants with higher socioeconomic status (SES) with a concentration index of 0.059. The risk of CHE was 19% (aHR = 1.19, 95% CI: 1.16–1.22) higher for each additional NCD.

Conclusions

Approximately half of middle-aged and older adults in China had multimorbidity, causing a 19% higher risk of CHE for each additional NCD. Early interventions for preventing multimorbidity among people with low SES could be intensified to protect older adults from financial hardship. In addition, concerted efforts are needed to increase patients’ rational healthcare utilization and strengthen current medical security for people with high SES to reduce economic disparities in CHE.
The resiliency of noncommunicable diseases services during the public health crisis: a lesson from Bangkok, Thailand
Authors: Pitayarangsarit Siriwan , Bhagaman Nanapas , Yodmai Korravarn , Thangsirikul Nattaya , Tipayamongkholgul Mathuros
Published: April 2023

Background

The healthcare services for non-communicable diseases (NCD) are commonly affected by public health crises like the COVID-19 pandemic. During the pandemic, all healthcare facilities in Bangkok had been overwhelmed by the extreme caseload of COVID-19. Health service resiliency is crucial for the continued service of healthcare facilities post pandemic. This study aims to explore the impacts of COVID-19 on NCD service disruption and addressed the resilience of healthcare services at the operational level.

Methods

Healthcare facility-based surveys and in-depth interviews were conducted among representatives of the facilities in Bangkok from April 2021 to July 2021. The web-based, self-administered questionnaire, was sent to directors or authorities of all healthcare facilities in Bangkok Thailand (n = 169). Two healthcare facilities from three levels of health services were purposively selected. The directors or medical doctors and nurses who are in charge of the NCD service, and working at the six selected health facilities, were invited to participate in the in-depth interviews. Descriptive statistics were used to analyze the survey data, and thematic analysis was used to analyze the data from the in-depth interviews.

Results

The impact of COVID-19 on NCD service disruption in the second wave (2021) was more severe than in the first wave (2020). The main reasons for NCD service disruptions are insufficient staff, and the closure of some services offered by the healthcare facilities. Surprisingly, both the budget and medical supply for healthcare facilities in Bangkok are less affected by the COVID-19 pandemic. Our study revealed resilience capability i.e. absorptive, adaptive, and transformative capabilityamong the healthcare facilities that provide a continuum of care by increasing availability and accessibility to healthcare services for chronic illness as DM. The service disruption in Bangkok may alter from other provinces because of variations in COVID-19 incidence and health services contexts.

Conclusion

During the public health crisis, using affordable and common digital technologies to ensure DM patients can access a continuum of care and providing alternative services such as mobile medical laboratories, medication delivery, and medical refill at drug stores can increase consistent monitoring of glycemic levels and use of prescribed medication.
Therapeutic potential of bacteriophage endolysins for infections caused by Gram-positive bacteria
Authors: Liu He , Hu Zhen , Li Mengyang , Yang Yi , Lu Shuguang , Rao Xiancai
Published: April 2023

Gram-positive (G+) bacterial infection is a great burden to both healthcare and community medical resources. As a result of the increasing prevalence of multidrug-resistant G+ bacteria such as methicillin-resistant Staphylococcusaureus (MRSA), novel antimicrobial agents must urgently be developed for the treatment of infections caused by G+ bacteria. Endolysins are bacteriophage (phage)-encoded enzymes that can specifically hydrolyze the bacterial cell wall and quickly kill bacteria. Bacterial resistance to endolysins is low. Therefore, endolysins are considered promising alternatives for solving the mounting resistance problem. In this review, endolysins derived from phages targeting G+ bacteria were classified based on their structural characteristics. The active mechanisms, efficacy, and advantages of endolysins as antibacterial drug candidates were summarized. Moreover, the remarkable potential of phage endolysins in the treatment of G+ bacterial infections was described. In addition, the safety of endolysins, challenges, and possible solutions were addressed. Notwithstanding the limitations of endolysins, the trends in development indicate that endolysin-based drugs will be approved in the near future. Overall, this review presents crucial information of the current progress involving endolysins as potential therapeutic agents, and it provides a guideline for biomaterial researchers who are devoting themselves to fighting against bacterial infections.
Degradation of neurodegenerative disease-associated TDP-43 aggregates and oligomers via a proteolysis-targeting chimera
Authors: Tseng Yu-Ling , Lu Po-Chao , Lee Chi-Chang , He Ruei-Yu , Huang Yung-An , Tseng Yin-Chen , Cheng Ting-Jen Rachel , Huang Joseph Jen-Tse , Fang Jim-Min
Published: April 2023

Background

Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates and oligomers were neurotoxic and pathologic agents in ALS and frontotemporal lobar degeneration (FTLD). However, misfolding protein has long been considered as an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to degrade these misfolding proteins by designing a series of proteolysis targeting chimeras (PROTACs) against C-TDP-43.

Methods

By applying filter trap assay, western blotting, and microscopy imaging, the degradation efficiency of C-TDP-43 aggregates was studied in Neuro-2a cells overexpressing eGFP-C-TDP-43 or mCherry-C-TDP-43. The cell viability was characterized by alarmarBlue assay. The beneficial and disaggregating effects of TDP-43 PROTAC were examined with the YFP-C-TDP-43 transgenic C. elegans by motility assay and confocal microscopy. The impact of TDP-43 PROTAC on C-TDP-43 oligomeric intermediates was monitored by fluorescence lifetime imaging microscopy and size exclusion chromatography in the Neuro-2a cells co-expressing eGFP-C-TDP-43 and mCherry-C-TDP-43.

Results

Four PROTACs with different linker lengths were synthesized and characterized. Among these chimeras, PROTAC 2 decreased C-TDP-43 aggregates and relieved C-TDP-43-induced cytotoxicity in Neuro-2a cells without affecting endogenous TDP-43. We showed that PROTAC 2 bound to C-TDP-43 aggregates and E3 ligase to initiate ubiquitination and proteolytic degradation. By applying advanced microscopy, it was further shown that PROTAC 2 decreased the compactness and population of C-TDP-43 oligomers. In addition to cellular model, PROTAC 2 also improved the motility of transgenic C. elegans by reducing the C-TDP-43 aggregates in the nervous system.

Conclusions

Our study demonstrated the dual-targeting capacity of the newly-designed PROTAC 2 against both C-TDP-43 aggregates and oligomers to reduce their neurotoxicity, which shed light on the potential drug development for ALS as well as other neurodegenerative diseases.
Acetaldehyde via CGRP receptor and TRPA1 in Schwann cells mediates ethanol-evoked periorbital mechanical allodynia in mice: relevance for migraine
Authors: Landini Lorenzo , Souza Monteiro de Araujo Daniel , Chieca Martina , De Siena Gaetano , Bellantoni Elisa , Geppetti Pierangelo , Nassini Romina , De Logu Francesco
Published: April 2023

Background

Ingestion of alcoholic beverages is a known trigger of migraine attacks. However, whether and how ethanol exerts its pro-migraine action remains poorly known. Ethanol stimulates the transient receptor potential vanilloid 1 (TRPV1) channel, and its dehydrogenized metabolite, acetaldehyde, is a known TRP ankyrin 1 (TRPA1) agonist.

Methods

Periorbital mechanical allodynia following systemic ethanol and acetaldehyde was investigated in mice after TRPA1 and TRPV1 pharmacological antagonism and global genetic deletion. Mice with selective silencing of the receptor activated modifying protein 1 (RAMP1), a component of the calcitonin gene-related peptide (CGRP) receptor, in Schwann cells or TRPA1 in dorsal root ganglion (DRG) neurons or Schwann cells, were used after systemic ethanol and acetaldehyde.

Results

We show in mice that intragastric ethanol administration evokes a sustained periorbital mechanical allodynia that is attenuated by systemic or local alcohol dehydrogenase inhibition, and TRPA1, but not TRPV1, global deletion, thus indicating the implication of acetaldehyde. Systemic (intraperitoneal) acetaldehyde administration also evokes periorbital mechanical allodynia. Importantly, periorbital mechanical allodynia by both ethanol and acetaldehyde is abrogated by pretreatment with the CGRP receptor antagonist, olcegepant, and a selective silencing of RAMP1 in Schwann cells. Periorbital mechanical allodynia by ethanol and acetaldehyde is also attenuated by cyclic AMP, protein kinase A, and nitric oxide inhibition and pretreatment with an antioxidant. Moreover, selective genetic silencing of TRPA1 in Schwann cells or DRG neurons attenuated periorbital mechanical allodynia by ethanol or acetaldehyde.

Conclusions

Results suggest that, in mice, periorbital mechanical allodynia, a response that mimics cutaneous allodynia reported during migraine attacks, is elicited by ethanol via the systemic production of acetaldehyde that, by releasing CGRP, engages the CGRP receptor in Schwann cells. The ensuing cascade of intracellular events results in a Schwann cell TRPA1-dependent oxidative stress generation that eventually targets neuronal TRPA1 to signal allodynia from the periorbital area.
Short-term exposure to ambient fine particulate pollution aggravates ventilator-associated pneumonia in pediatric intensive care patients undergoing cardiovascular surgeries
Authors: Cui Zhaomei , Ma Yingying , Yu Yuanyuan , Li Na , Wang Jun , Wang Anbiao , Tan Qi
Published: April 2023

Background

Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure.

Methods

The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model.

Results

Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 μg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 μg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5–19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 μg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension.

Conclusion

Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations.

Trial registration

The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery. Trial registration number: ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx.
New measures to assess the “Other” three pillars of food security–availability, utilization, and stability
Authors: Calloway Eric E. , Carpenter Leah R. , Gargano Tony , Sharp Julia L. , Yaroch Amy L.
Published: April 2023

Background

In recent reviews of available measures, no existing measures assessed all four pillars of food security and most only assessed one or two pillars–predominantly the access pillar. The purpose of this study was to preliminarily develop novel measures of availability, utilization, and stability that are complementary to the USDA’s household food security survey measure (HFSSM).

Methods

A formative phase included an expert advisory group, literature scans, and interviews with individuals experiencing food insecurity. From April-June 2021, the new measures were piloted in five states (California, Florida, Maryland, North Carolina, and Washington). The cross-sectional pilot survey included the new measures (perceived limited availability, utilization barriers, and food insecurity stability), scales and items for validation (e.g., food security, and self-reported dietary and health outcomes), and demographic questions. Exploratory factor analysis was used to assess dimensionality, internal consistency was assessed using Kuder-Richardson formula 21 (KR21), and convergent and discriminant validity were assessed using Spearman’s correlation coefficients. Also, a brief screener version was created for the utilization barriers measure that may be necessary for certain applications (e.g., clinical intake screening to inform referrals to assistance programs).

Results

The analytic samples (perceived limited availability (n = 334); utilization barriers (n = 428); food insecurity stability (n = 445)) were around 45 years old on average, most households had children, over two-thirds were food insecure, over three-fourths were women, and the samples were racially/ethnically diverse. All items loaded highly and unambiguously to a factor (factor loadings range 0.525–0.903). Food insecurity stability showed a four-factor structure, utilization barriers showed a two-factor structure, and perceived limited availability showed a two-factor structure. KR21 metrics ranged from 0.72 to 0.84. Higher scores for the new measures were generally associated with increased food insecurity (rhos = 0.248–0.497), except for one of the food insecurity stability scores. Also, several of the measures were associated with statistically significantly worse health and dietary outcomes.

Conclusions

The findings support the reliability and construct validity of these new measures within a largely low-income and food insecure sample of households in the United States. Following further testing, such as Confirmatory Factor Analysis in future samples, these measures may be used in various applications to promote a more comprehensive understanding of the food insecurity experience. Such work can help inform novel intervention approaches to address food insecurity more fully.
Changes of improvement in upper limb function predict surgical outcome after laminoplasty in 1 year in patients with cervical spondylotic myelopathy: a retrospective study
Authors: Fudo Takuma , Hashida Ryuki , Yokosuka Kimiaki , Sato Kimiaki , Hiraoka Koji
Published: April 2023

Background

Cervical spondylotic myelopathy preoperative prognostic factors include age, preoperative severity, and disease duration. However, there are no reports on the relationship between changes in physical function during hospitalization and postoperative course, and in recent years, the length of hospital stay has shortened. We aimed to investigate whether changes in physical function during hospitalization can predict the postoperative outcome.

Methods

We recruited 104 patients who underwent laminoplasty for cervical spondylotic myelopathy by the same surgeon. Physical functions, including Simple Test for Evaluating Hand Function (STEF), grip strength, timed up and go test, 10-m walk, and time to stand on one leg, were assessed at admission and discharge. Patients with the Japanese Orthopaedic Association (JOA) score improvement rate of 50% or more were defined as the improved group. Decision tree analysis was investigated factor for identifying improvement in the JOA score. According to this analysis, we divided into two groups using age. Then, we conducted a logistic regression analysis to identify factors that improve the JOA score.

Results

The improved and non-improved groups had 31 and 73 patients, respectively. The improved group was younger (p = 0.003) and had better improved Δgrip strength (p = 0.001) and ΔSTEF (p < .0007). Age was significantly positively correlated with disease duration (r = 0.4881, p =  < .001). Disease duration exhibited a significant negative correlation with the JOA score improvement rate (r = − 0.2127, p = 0.031). Based on the decision tree analysis results, age was the first branching variable, with 15% of patients ≥ 67 years showing JOA score improvement. This was followed by ΔSTEF as the second branching factor. ΔSTEF was selected as the factor associated with JOA improvement in patients ≥67 years (odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01–1.12, p=.0268); in patients <67 years, Δgrip strength was identified (OR 1.30, CI 1.04‒1.62, p=.0049).

Conclusions

In the improved group, upper limb function improved more than lower limb function from the early postoperative period. Upper limb function changes during hospitalization were associated with outcomes one year postoperatively. Improvement factors in upper extremity function differed by age, with changes in grip strength in patients < 67 years and STEF in patients ≥ 67 years, reflecting the outcome at one year postoperatively.
Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial
Authors: Zhang Jialing , Qin Zongshi , So Tsz Him , Chang Tien Yee , Yang Sichang , Chen Haiyong , Yeung Wing Fai , Chung Ka Fai , Chan Pui Yan , Huang Yong , Xu Shifen , Chiang Chun Yuan , Lao Lixing , Zhang Zhang-Jin
Published: April 2023

Background

Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients.

Methods

This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life.

Results

There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: − 0.4, 95% CI − 1.8–1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events.

Conclusion

The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients.

Trial registrationClinicaltrials.gov: NCT04144309. Registered 30 October 2019.