bluuebunny/crossref_metadata_2025 huggingface dataset:
Overweight increases perioperative spinal surgery complications: a single-center retrospective study
Authors: Hirahata Masahiro , Yasui Youichi , Fujita Muneyoshi , Ishii Keisuke , Kawano Hirotaka , Kitagawa Tomoaki
Published: February 2023

Background

The World Health Organization (WHO) defines a person with a body mass index (BMI) greater than or equal to 25 kg/m2 as overweight. Being overweight is a lifestyle-related disease; however, little is known about the impact of overweight on the perioperative complications of orthopedic surgery. This study aimed to define the effect of overweight on the perioperative complications of spinal surgery.

Methods

This retrospective case series study reviewed 269 consecutive patients who underwent spinal surgery. These patients were divided into the overweight (OW) and non-overweight (NOW) groups. Age, BMI, surgical time, blood loss, and perioperative complications were evaluated and compared between the groups.

Results

There were 117 patients (43%) in the OW group and 152 (57%) in the NOW group. Cervical surgery was performed in 72 cases, thoracic surgery in 34, and lumbosacral surgery in 159. The surgical time was significantly longer in the OW group than in the NOW group (204.6 ± 98 min vs. 175 ± 75 min; p = 0.01). Blood loss was greater in the OW group than in the NOW group (446.8 ± 447.9 mL vs. 279 ± 296.5 mL; p = 0.00). Durotomy was more frequent in the OW group than in the NOW group (10 vs. 3 cases; p = 0.02). There was no difference in complications other than durotomy.

Conclusions

OW patients had longer surgical time, more blood loss, and more frequent durotomy than NOW patients. These findings indicate that overweight increases perioperative complications of spinal surgery.
The Danish-American Research Exchange (DARE): a cross-sectional study of a binational research education program
Authors: Mehta Kala M. , Petersen Karin Lottrup , Goodman Steve , Sørensen Henrik Toft , Bøgsted Martin , Olesen Jeppe Dørup , Burks Sylvia , Shaw Richard E. , Hove Jens Dahlgaard , Ousager Jakob , Milla Carlos , Andersen Vibeke , Ejskjær Niels , Brix-Christensen Vibeke , Ghose Shomit , Kjær Andreas , Chin-Hong Peter V.
Published: February 2023

Background

Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the ‘$10 Challenge’.

Methods

We conducted a cross-sectional study of DARE alumni over five consecutive years (2015–2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software.

Results

DARE Medical students were 31.2 years (range 24–35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p < 0.001 for all). Qualitative key themes included: increased confidence, a deepening of research inquiry and linkage to a research network.

Conclusions

Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration.
Factors influencing the implementation of decision support systems for antibiotic prescription in hospitals: a systematic review
Authors: Tokgöz Pinar , Hafner Jessica , Dockweiler Christoph
Published: February 2023

Background

Antibiotic resistance is a major health threat. Inappropriate antibiotic use has been shown to be an important determinant of the emergence of antibiotic resistance. Decision support systems for antimicrobial management can support clinicians to optimize antibiotic prescription.

Objective

The aim of this systematic review is to identify factors influencing the implementation of decision support systems for antibiotic prescription in hospitals.

Methods

A systematic search of factors impeding or facilitating successful implementation of decision support systems for antibiotic prescription was performed in January 2022 in the databases PubMed, Web of Science and The Cochrane Library. Only studies were included which comprised decision support systems in hospitals for prescribing antibiotic therapy, published in English with a qualitative, quantitative or mixed-methods study design and between 2011 and 2021. Factors influencing the implementation were identified through text analysis by two reviewers.

Results

A total of 14 publications were identified matching the inclusion criteria. The majority of factors relate to technological and organizational aspects of decision support system implementation. Some factors include the integration of the decision support systems into existing systems, system design, consideration of potential end-users as well as training and support for end-users. In addition, user-related factors, like user attitude towards the system, computer literacy and prior experience with the system seem to be important for successful implementation of decision support systems for antibiotic prescription in hospitals.

Conclusion

The results indicate a broad spectrum of factors of decision support system implementation for antibiotic prescription and contributes to the literature by identifying important organizational as well as user-related factors. Wider organizational dimensions as well as the interaction between user and technology appear important for supporting implementation.
Being well? A meta-ethnography of older patients and their relatives’ descriptions of suffering and well-being in the transition from hospital to home
Authors: Dragosits Aline , Martinsen Bente , Hemingway Ann , Norlyk Annelise
Published: February 2023

Background

As the average length of hospital stay decreases, more and more older patients will need support during and after the hospital transition, which will mainly be provided by their relatives. Studies highlight the enormous effect such a transition has on the lives of older patients and their relatives. However, research is lacking regarding in-depth understanding of the complexities and the notions of suffering and well-being the older patients and their relatives describe in the transition from hospital to home. Therefore, this study aims to examine the description of suffering and well-being on a deeper, existential level by drawing on existing phenomenological research.

Methods

In order to synthesize and reinterpret primary findings, we used the seven-step method for meta-ethnography. Following specific inclusion criteria and focusing on empirical phenomenological studies about older patients and their relatives experiences of hospital to home transitions, a systematic literature search was conducted. Data from ten studies have been analyzed.

Results

Our analysis identified three intertwined themes: i) ‘Being excluded vs. being included in the transition process’, ii) ‘Being a team: a call for support and a call to support’ and iii) ‘Riding an emotional rollercoaster’. The last theme was unfolded by the two subthemes ‘Taking on the new role as a caregiver: oscillating between struggling and accepting’ and ‘Getting back to normal: oscillating between uncertainty and hope’. Within those themes, older patients and their relatives described rather similar than contradictory aspects.

Conclusions

This study offers insights into the tension between existential suffering and well-being described by the older patients and their relatives during the transition from hospital to home. Especially, the description of well-being in all its nuances which, if achieved, enables older patients and their relatives to identify with the situation and to move forward, this process can then be supported by the health care professionals. However, there is still lack of knowledge with regards to a deeper understanding of existential well-being in this process. Given the increasing tendency towards early hospital discharges, the findings underpin the need to further investigate the experiences of well-being in this process.
Combined pangenomics and transcriptomics reveals core and redundant virulence processes in a rapidly evolving fungal plant pathogen
Authors: Chen Hongxin , King Robert , Smith Dan , Bayon Carlos , Ashfield Tom , Torriani Stefano , Kanyuka Kostya , Hammond-Kosack Kim , Bieri Stephane , Rudd Jason
Published: February 2023

Background

Studying genomic variation in rapidly evolving pathogens potentially enables identification of genes supporting their “core biology”, being present, functional and expressed by all strains or “flexible biology”, varying between strains. Genes supporting flexible biology may be considered to be “accessory”, whilst the “core” gene set is likely to be important for common features of a pathogen species biology, including virulence on all host genotypes. The wheat-pathogenic fungus Zymoseptoria tritici represents one of the most rapidly evolving threats to global food security and was the focus of this study.

Results

We constructed a pangenome of 18 European field isolates, with 12 also subjected to RNAseq transcription profiling during infection. Combining this data, we predicted a “core” gene set comprising 9807 sequences which were (1) present in all isolates, (2) lacking inactivating polymorphisms and (3) expressed by all isolates. A large accessory genome, consisting of 45% of the total genes, was also defined. We classified genetic and genomic polymorphism at both chromosomal and individual gene scales. Proteins required for essential functions including virulence had lower-than average sequence variability amongst core genes. Both core and accessory genomes encoded many small, secreted candidate effector proteins that likely interact with plant immunity. Viral vector-mediated transient in planta overexpression of 88 candidates failed to identify any which induced leaf necrosis characteristic of disease. However, functional complementation of a non-pathogenic deletion mutant lacking five core genes demonstrated that full virulence was restored by re-introduction of the single gene exhibiting least sequence polymorphism and highest expression.

Conclusions

These data support the combined use of pangenomics and transcriptomics for defining genes which represent core, and potentially exploitable, weaknesses in rapidly evolving pathogens.
Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study
Authors: Øyri Linn K. L. , Christensen Jacob J. , Sebert Sylvain , Thoresen Magne , Michelsen Trond M. , Ulven Stine M. , Brekke Hilde K. , Retterstøl Kjetil , Brantsæter Anne Lise , Magnus Per , Bogsrud Martin P. , Holven Kirsten B.
Published: February 2023

Background

Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent.

Methods

This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age).

Results

Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99).

Conclusions

Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.
Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study
Authors: Talisman Shahar , Guedalia Joshua , Farkash Rivka , Avitan Tehila , Srebnik Naama , Kasirer Yair , Schimmel Michael S. , Ghanem Donia , Unger Ron , Granovsky Sorina Grisaru
Published: February 2023

Background

Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality.

Methods

A single-center case–control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks’ gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period.

Results

During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For all term neonates, the mortality rate was 0.16% (n = 311); 47.9% (n = 149) of those had records of a NICU admission. The mortality rate by time points (ratio1:10,0000 births) related to the age at death during the follow-up period was as follows: 29, up to 7 days; 20, 7–28 days; 37, 28 days to 6 months; 21, 6 months to 1 year; 19, 1–2 years; 9, 2–3 years; 10, 3–4 years; and 27, 4 years and more. Following the exclusion of congenital malformations and chromosomal abnormalities, NICU admission remained the most significant risk factor associated with mortality of the study population, HRs, 364.4 [145.3; 913.3] for mortality in the first 7 days of life; 19.6 [12.1; 32.0] for mortality from 28 days through 6 months of life and remained markedly elevated after age 4 years; HR, 7.1 [3.0; 17.0]. The mortality risk related to the NICU admission event, adjusted for admission diagnoses remained significant; HR = 8.21 [5.43; 12.4].

Conclusions

NICU admission for term neonates is a pondering event for the risk of long-term childhood mortality. This group of term neonates may benefit from focused health care.
Association of intellectual disability with overall and type-specific cardiovascular diseases: a population-based cohort study in Denmark
Authors: Wang Hui , Lee Priscilla Ming Yi , Zhang Jun , Svendsen Katrine , Li Fei , Li Jiong
Published: February 2023

Background

Individuals with mental health problems have been shown to have an increased risk of cardiovascular disorder (CVD), but little is known about the risk of early-onset CVD among those with intellectual disability. We aimed to investigate the association between intellectual disability and subsequent CVD, taking into consideration the severity of intellectual disability and neurodevelopmental and neurologic comorbidity.

Methods

This population-based cohort study used individual-level linked data from Danish national health registries. Participants were all live-born singletons born in Denmark during 1978–2016 (n = 2,288,393). Follow-up began from birth and continued until the onset of CVD, death, emigration, or December 31, 2018, whichever came first. Clinical diagnosis of any CVD or type-specific CVDs was identified in the Danish National Patient Register. Time-varying Cox regression analyses were used to estimate the hazard ratio (HR) of intellectual disability associated with overall and type-specific CVDs.

Results

A total of 11,954 individuals received a diagnosis of intellectual disability (7434 males and 4520 females). During a median follow-up time of 18.5 years (interquartile range, 18.1 years), 652 individuals with intellectual disability (5.5%) received a diagnosis of CVD (incidence rate, 2.4 per 1000 person-years), compared with 78,088 (3.4%) CVD cases in individuals without intellectual disability (incidence rate, 1.9 per 1000 person-years), corresponding to a HR of 1.24 (95% CI, 1.15–1.34). Increased risks of CVD were similar in both childhood (HR, 1.24; 95% CI, 1.08–1.43) and early adulthood (HR, 1.25; 95% CI, 1.14–1.38). For type-specific CVDs, intellectual disability was significantly associated with cerebrovascular disease (HR, 2.50; 95% CI, 2.02–3.10), stroke (HR, 2.20; 95% CI, 1.69–2.86), heart failure (HR, 3.56; 95% CI, 2.37–5.35), hypertensive disease (HR, 1.30; 95% CI, 1.22–1.39), and deep vein thrombosis (HR, 2.10; 95% CI, 1.60–2.75). Stratified HRs of overall CVD were 1.14 (95% CI, 1.01–1.30) for borderline/mild intellectual disability, 1.25 (95% CI, 1.01–1.54) for moderate intellectual disability, and 1.91 (95% CI, 1.47–2.48) for severe/profound intellectual disability. After the exclusion of individuals with neurodevelopmental and neurologic comorbidity, intellectual disability remained significantly associated with increased risks of CVD.

Conclusions

Individuals with intellectual disability had increased risks of early-onset CVD, in particular, for cerebrovascular disease, stroke, heart failure, and deep vein thrombosis, and the risks also increased with the severity of intellectual disability. Our findings highlight the awareness of increased risks of CVD in intellectual disability patients.
Aspiration prevention surgeries: a review
Authors: Ueha Rumi , Magdayao Redentor B. , Koyama Misaki , Sato Taku , Goto Takao , Yamasoba Tatsuya
Published: February 2023

Background

Severe dysphagia can cause intractable pneumonia and lead to life-threatening conditions. Intractable aspiration can occur despite medical management for aspiration prevention. Surgical intervention is indicated for intractable aspiration to prevent potentially life-threatening complications. Since the 1970s, several surgical treatments to prevent aspiration have been reported, and various aspiration prevention surgeries have been introduced, but little is known about them or their benefits. This is a review of the types of aspiration prevention surgery, with the aim of increasing aspiration prevention surgery awareness and their clinical outcomes among medical professionals, which will guide the choices of aspiration prevention surgeries for patients with intractable aspiration.

Main body

Aspiration prevention surgeries can be categorized into three according to their approaches: removal of the larynx, altering the structure of the trachea, and closure of the larynx. Aspiration prevention surgeries to remove the larynx include total and central-part laryngectomy. Aspiration prevention surgeries to alter the structure of the trachea include tracheoesophageal diversion, laryngotracheal separation, and the tracheal flap method. Surgeries to close the larynx can be divided into supraglottic laryngeal closure, glottic laryngeal closure, and subglottic laryngeal closure. Aspiration prevention surgeries prevent aspiration and increase oral intake in 50–80% of patients. Most patients lose vocal function after aspiration prevention surgeries; however, some patients who have undergone total laryngectomy or laryngotracheal separation restored their speech function through tracheoesophageal puncture and use of voice prosthesis. Postoperative suture failure is frequent after epiglottic flap closure and total laryngectomy but rare after central-part laryngectomy, laryngotracheal separation, glottic closure, and subglottic closure. Furthermore, aspiration prevention surgeries improve the quality of life of patients and their caregivers by decreasing suctioning frequency.

Conclusions

In this review, we described the history and development of aspiration prevention surgeries. Medical professionals need to continually improve their knowledge and skills to facilitate appropriate aspiration prevention surgeries according to patient condition.
Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial
Authors: Chiarito Mauro , Sanz-Sanchez Jorge , Piccolo Raffaele , Condello Francesco , Liccardo Gaetano , Maurina Matteo , Avvedimento Marisa , Regazzoli Damiano , Pagnotta Paolo , Garcia-Garcia Hector M. , Mehran Roxana , Federici Massimo , Condorelli Gianluigi , Diez Gil Jose Luis , Reimers Bernhard , Ferrante Giuseppe , Stefanini Giulio
Published: February 2023

Background

Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels.

Methods

In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality.

Results

142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes.

Conclusions

In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function.

Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008).

Graphical Abstract
Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo
Authors: Grout Lise , Katuala Givo Yves , Newport Trish , Mahamat Tom Adoum , Gitahi Priscillah , Mandagot Jean Jacques , Quere Michel , Wodon Sophie , Ciglenecki Iza , Bastard Mathieu , Baelongandi Francis , Tshulo Louis , Uluba Herman Jakisa , Sterk Esther , Gignoux Etienne
Published: February 2023

Background

Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not.

Methods

A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively.

Results

Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48–3.16] “before” the MDA to 1.10 [0.5–1.71] deaths/10,000 children under 5 years/day “after”, whereas it remained stable from 2.74 [2.08–3.40] to 2.67 [1.84–3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36–3.49] and 2.60 [1.56–4.33], respectively, for all-cause and malaria-specific mortality among children  < 5 years). Morbidity (all age and  < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11–18] and 25.0% [19–31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27–33] and 49.3% [45–54] in villages and IDP sites with no MDA.

Conclusions

Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.
“It is like an umbrella covering you, yet it does not protect you from the rain”: a mixed methods study of insurance affordability, coverage, and financial protection in rural western Kenya
Authors: Maritim Beryl , Koon Adam D. , Kimaina Allan , Lagat Cornelius , Riungu Elvira , Laktabai Jeremiah , Ruhl Laura J. , Kibiwot Michael , Scanlon Michael L. , Goudge Jane
Published: February 2023

Countries in Sub-Saharan Africa are increasingly adopting mandatory social health insurance programs. In Kenya, mandatory social health insurance is being implemented through the national health insurer, the National Hospital Insurance Fund (NHIF), but the level of coverage, affordability and financial risk protection provided by health insurance, especially for rural informal households, is unclear. This study provides as assessment of affordability of NHIF premiums, the need for financial risk protection, and the extent of financial protection provided by NHIF among rural informal workers in western Kenya.

Methods We conducted a mixed methods study with a cross-sectional household survey (n = 1773), in-depth household interviews (n = 36), and 6 focus group discussions (FGDs) with community stakeholders in rural western Kenya. Health insurance status was self-reported and households were categorized into insured and uninsured. Using survey data, we calculated the affordability of health insurance (unaffordability was defined as the monthly premium being > 5% of total household expenditures), out of pocket expenditures (OOP) on healthcare and its impact on impoverishment, and incidence of catastrophic health expenditures (CHE). Logistic regression was used to assess household characteristics associated with CHE.

Results Only 12% of households reported having health insurance and was unaffordable for the majority of households, both insured (60%) and uninsured (80%). Rural households spent an average of 12% of their household budget on OOP, with both insured and uninsured households reporting high OOP spending and similar levels of impoverishment due to OOP. Overall, 12% of households experienced CHE, with uninsured households more likely to experience CHE. Participants expressed concerns about value of health insurance given its cost, availability and quality of services, and financial protection relative to other social and economic household needs. Households resulted to borrowing, fundraising, taking short term loans and selling family assets to meet healthcare costs.

Conclusion Health insurance coverage was low among rural informal sector households in western Kenya, with health insurance premiums being unaffordable to most households. Even among insured households, we found high levels of OOP and CHE. Our results suggest that significant reforms of NHIF and health system are required to provide adequate health services and financial risk protection for rural informal households in Kenya.
Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art
Authors: Wu Sitong , Fan Kevin , Yang Qi , Chen Zhao , Hou Yi , Zou Yinghua , Cai Weibo , Kang Lei
Published: February 2023

The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.
Visualization of SARS-CoV-2 particles in naso/oropharyngeal swabs by thin section electron microscopy
Authors: Laue Michael , Hoffmann Tobias , Michel Janine , Nitsche Andreas
Published: February 2023

Background

SARS-CoV-2 replicates efficiently in the upper airways of humans and produces high loads of virus RNA and, at least in the initial phase after infection, many infectious virus particles. Studying virus ultrastructure, such as particle integrity or presence of spike proteins, and effects on their host cells in patient samples is important to understand the pathogenicity of SARS-CoV-2.

Methods

Suspensions from swab samples with a high load of virus RNA (Ct < 20) were sedimented by desktop ultracentrifugation and prepared for thin section electron microscopy using a novel method which is described in detail. Embedding was performed in Epon or in LR White resin using standard or rapid protocols. Thin sections were examined using transmission electron microscopy.

Results

Virus particles could be regularly detected in the extracellular space, embedded in a background of heterogenous material (e.g. vesicles and needle-like crystals), and within ciliated cells. Morphology (i.e. shape, size, spike density) of virus particles in the swab samples was very similar to particle morphology in cell culture. However, in some of the samples the virus particles hardly revealed spikes. Infected ciliated cells occasionally showed replication organelles, such as double-membrane vesicles. The most common cells in all samples were keratinocytes from the mucosa and bacteria.

Conclusions

The new method allows the ultrastructural visualization and analysis of coronavirus particles and of infected host cells from easy to collect naso/oropharyngeal patient swab samples.
Efficacy and safety of acupuncture for hand osteoarthritis: study protocol for a multi-center, randomized, sham-controlled clinical trial
Authors: Wang Weiming , Shi Hangyu , Liu Yan , Sun Yuanjie , Chen Yu , Liu Zhishun
Published: February 2023

Background

Hand osteoarthritis (OA) is a prevalent disorder in the general population. Patients with hand OA often report symptoms of pain, stiffness, and functional limitations, which cause clinical burden and impact on quality of daily life. However, the efficacy of current therapies for hand OA is limited. Other therapies with better effects and less adverse events are in urgent need. Acupuncture is well known for analgesia and has been proved effective in treating basal thumb joint arthritis. This study aims to clarify the efficacy and safety of acupuncture treatment for clinical symptomatic improvement of hand OA.

Methods

This will be a sham-controlled, randomized, multi-center clinical trial. A total of 340 participants will be recruited and randomly allocated to either traditional acupuncture group or sham acupuncture group. All participants will receive 12 treatment sessions over 4 weeks and 2 follow-up assessments in the following 3 months at week 8 and week 16. The primary outcome will be the proportion of responders at week 5. Secondary outcomes will include visual analog scale, Australian Canadian Osteoarthritis Hand Index, Functional Index for hand OA, the number of symptomatic joints, hand grip strength and pinch strength, global assessment, the World Health Organization Quality of Life abbreviated version and expectations. Safety will be evaluated during the whole process of the trial. All outcomes will be analyzed following the intention-to-treat principle.

Discussion

This prospective trial will provide high-quality evidence on evaluating the efficacy and safety of acupuncture treatment for hand OA. Results of this trial might contribute in offering a new option to clinical recommendations.

Trial registration ClinicalTrials.gov Identifier: NCT05267093. Registered 23 February 2022.
Combined with UPLC-Triple-TOF/MS-based plasma lipidomics and molecular pharmacology reveals the mechanisms of schisandrin against Alzheimer’s disease
Authors: Zhao Tian-tian , Zhang Ying , Zhang Cheng-qin , Chang Ya-fei , Cui Mei-rong , Sun Yue , Hao Wen-qian , Yan Yu-meng , Gu Shuo , Xie Yao , Wei Bin-bin
Published: February 2023

Background

Alzheimer’s disease (AD), a type of neurodegeneration disease, is characterized by Aβ deposition and tangles of nerve fibers. Schisandrin is one of the main components of Fructus Schisandrae Chinensis. Researches showed that schisandrin can improve the cognitive impairment and memory of AD mice, but the specific mechanism has not been fully elucidated.

Purpose

The purpose of this study is to investigate the possible mechanism of schisandrin in improving AD pathology.

Methods

The Morris water maze test was executed to detect spatial learning and memory. Ultra performance liquid chromatography-Triple time of flight mass spectrometry (UPLC-Triple-TOF/MS)-based plasma lipidomics was used to study the changes of plasma lipids. Moreover, we measured the levels of protein and mRNA expression of APOE and ABCA1 in the rat brains and in BV2 microglia.

Results

Our study found that schisandrin could improve learning and memory, and reduce Aβ deposition in AD rats. Furthermore, we found that schisandrin can improve plasma lipid metabolism disorders. Therefore, we hypothesized schisandrin might act via LXR and the docking results showed that schisandrin interacts with LXRβ. Further, we found schisandrin increased the protein and mRNA expression of LXR target genes APOE and ABCA1 in the brain of AD rats and in BV2 microglia.

Conclusion

Our study reveals the neuroprotective effect and mechanism of schisandrin improves AD pathology by activating LXR to produce APOE and ABCA1.
The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain
Authors: Toya Akie , Fukada Masahide , Aoki Eiko , Matsuki Tohru , Ueda Masashi , Eda Shima , Hashizume Yoshio , Iio Akio , Masaki Shigeo , Nakayama Atsuo
Published: February 2023

NLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rodents. It has been confirmed only recently that human NLGN4 is abundantly expressed in the cerebral cortex and is localized mainly to excitatory synapses. However, the detailed histological distribution of NLGN4, which may have important implications regarding the relationships between NLGN4 and autistic phenotypes, has not been clarified. In this study, we raised specific monoclonal and polyclonal antibodies against NLGN4 and examined the distribution of NLGN4 in developing and developed human brains by immunohistochemistry. We found that, in the brain, NLGN4 is expressed almost exclusively in neurons, in which it has a widespread cytoplasmic pattern of distribution. Among various types of neurons with NLGN4 expression, we identified consistently high expression of NLGN4 in hypothalamic oxytocin (OXT)/vasopressin (AVP)-producing cells. Quantitative analyses revealed that the majority of OXT/AVP-producing neurons expressed NLGN4. NLGN4 signals in other large neurons, such as pyramidal cells in the cerebral cortex and hippocampus as well as neurons in the locus coeruleus and the raphe nucleus, were also remarkable, clearly contrasting with no or scarce signals in Purkinje cells. These data suggest that NLGN4 functions in systems involved in intellectual abilities, social abilities, and sleep and wakefulness, impairments of which are commonly seen in autism.
Effectiveness of an evidence-based care pathway to improve mobility and participation in older patients with vertigo and balance disorders in primary care (MobilE-PHY2): study protocol for a multicentre cluster-randomised controlled trial
Authors: Horstmannshoff Caren , Skudlik Stefanie , Petermann Jenny , Kiesel Theresia , Döringer Tobias , Crispin Alexander , Hermsdörfer Joachim , Köberlein-Neu Juliane , Jahn Klaus , Schädler Stefan , Bauer Petra , Voigt Karen , Müller Martin
Published: February 2023

Background

Vertigo, dizziness or balance disorders (VDB) are common leading symptoms in older people, which can have a negative impact on their mobility and participation in daily live, yet, diagnosis is challenging and specific treatment is often insufficient. An evidence-based, multidisciplinary care pathway (CPW) in primary care was developed and pilot tested in a previous study. The aim of the present study is to evaluate the effectiveness and safety of the CPW in terms of improving mobility and participation in community-dwelling older people with VDB in primary care.

Methods

For this multicentre cluster randomised controlled clinic trial, general practitioners (GP) will be recruited in two regions of Germany. A total of 120 patients over 60 years old with VDB will be included. The intervention is an algorithmized CPW. GPs receive a checklist for standardise clinical decision making regarding diagnostic screening and treatment of VDB. Physiotherapists (PT) receive a decision tree for evidence-based physiotherapeutic clinical reasoning and treatment of VDB. Implementation strategies comprises educational trainings as well as a workshop to give a platform for exchange for the GPs and PTs, an information meeting and a pocket card for home care nurses and informal caregivers and telephone peer counselling to give all participants the capability, opportunity and the motivation to apply the intervention. In order to ensure an optimised usual care in the control group, GPs get an information meeting addressing the national guideline. The primary outcome is the impact of VDB on participation and mobility of patients after 6 month follow-up, assessed using the Dizziness Handicap Inventory (DHI) questionnaire. Secondary outcomes are physical activity, static and dynamic balance, falls and fear of falling as well as quality of life. We will also evaluate safety and health economic aspects of the intervention. Behavioural changes of the participants as well as barriers, facilitating factors and mechanisms of impact of the implementation will be investigated with a comprehensive process evaluation in a mixed-methods design.

Discussion

With our results, we aim to improve evidence-based health care of community-dwelling older people with VDB in primary care.

Trial registration

DRKS, DRKS00028524 retrospectively registered on March 24, 2022.
The COMFORT trial: a randomised control trial comparing group-based COMpassion-FOcussed therapy and breathing pattern ReTraining with treatment as usual on the psychological functioning of patients diagnosed with cancer recurrence during COVID
Authors: Lynch Sinead , Lowry Damien , Finnerty Clodagh , O’Meara Yvonne , Brennan Donal
Published: February 2023

Background

A cancer diagnosis is a known precipitant of psychological distress, with fear of recurrence being a well-documented distressing consequence of cancer. Cancer recurrence often results in an additional psychological burden, which may exacerbate as a result of the COVID-19 pandemic.

Methods

This is a single-centre, prospective, randomised controlled trial. Patients identified as having experienced cancer recurrence since March 2020 (the onset of the COVID-19 pandemic in Ireland) will be screened for participation. Eligible, consenting candidates who score 4 or higher on the Distress Thermometer will be enrolled in the study. Participants will be randomly allocated to receive either a 6-week, group-based, online, compassion-focussed therapy and breathing pattern retraining intervention or the control arm. Those in the control arm will all be offered the group intervention after the 18-week study period. The primary outcome is the Distress Thermometer score at 18 weeks post-baseline though secondary outcomes will include measures of mood, traumatic distress and mental adjustment to cancer.

Discussion

To our knowledge, this protocol describes the first RCT which directly examines the effect of a group-based psychological intervention on Irish patients experiencing cancer recurrence in the context of COVID-19. The outcome of this trial is likely to be twofold: It will determine if the psychological intervention achieves its primary objective of distress amelioration 3 months post-intervention and to establish the feasibility of delivering this intervention in a virtual format.

Trial registration

ClinicalTrials.gov NCT05518591. Registered on 25 August 2022. All items from the World Health Organization Trial Registration Data set have been included.
Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial
Authors: Hegelund Maria H. , Ritz Christian , Nielsen Thyge L. , Olsen Mette F. , Søborg Christian , Braagaard Lone , Mølgaard Christian , Krogh-Madsen Rikke , Lindegaard Birgitte , Faurholt-Jepsen Daniel
Published: February 2023

Background

Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD.

Methods

An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline.

Discussion

Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD.

Trial registration

ClinicalTrials.gov NCT04873856
. Registered on May 3, 2021.