bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of preoperative simulation on the reduction quality and clinical outcomes of open reduction and internal fixation for complex proximal humerus fractures
Authors: Wu Rui-Ji , Zhang Wei , Lin Yan-Ze , Fang Zhang-Lu , Wang Kang-Nan , Wang Chang-Xing , Yu Dong-Sheng
Published: March 2023

Purpose

Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures.

Method

A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed.

Results

This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2–5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8–18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5–7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1–0.6).

Conclusions

This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs.
Comparison of cardiovascular disease risk factors among FiLWHEL (2014–2016), NNS (2013) and KNHANES (2013–2015) women
Authors: Provido Sherlyn Mae P. , Abris Grace P. , Lee Heejin , Okekunle Akinkunmi Paul , Gironella Glen Melvin , Capanzana Mario V. , Chung Grace H. , Hong Sangmo , Yu Sung Hoon , Lee Chang Beom , Lee Jung Eun
Published: March 2023

Objectives

This study assessed the CVD risk factors among Filipino women (FW) in Korea and compared them with FW in the Philippines and women in Korea (KW).

Methods

A cohort of 504 women from the Filipino Women's Health and Diet Study (FiLWHEL) aged 20–57 years old were age-matched (1:1 ratio) with women from the 2013 National Nutrition Survey in the Philippines and the 2013–2015 Korean National Health and Nutrition Examination Survey. Anthropometric data, blood pressure (BP), lipid and glucose levels were compared across the four populations by calculating the odds ratio (OR)s and 95% confidence interval (CI)s using conditional logistic regression models.

Results

Compared to KW, FW in Korea and FW in the Philippines were more than 2 and 3 times higher odds of having obesity for BMI ≥ 30 kg/m2 and waist circumference ≥ 88 cm, respectively. However, FW in Korea had the highest odds (OR 5.51, 95% CI 3.18–9.56) of having hypertension compared to KW. FW in the Philippines had the highest odds of having dyslipidemia (compared to KW, total cholesterol ≥ 200 mg/dL: OR 8.83, 95% CI 5.30–14.71; LDL-C ≥ 130 mg/dL: OR 3.25, 95% CI 2.13–4.98; and triglyceride ≥ 150 mg/dL: OR 2.59, 95% CI 1.59–4.22), but FW in Korea and KW had similar prevalence of dyslipidemia.

Conclusions

FW in Korea had higher prevalence of obesity and hypertension, with similar prevalence of dyslipidemia compared to KW in this sample. FW in the Philippines had higher prevalence of dyslipidemia compared to FW in Korea. Further prospective studies are warranted to examine the CVD risk factors among continental and native-born Filipino women.
Cost-effectiveness of improvement strategies for reperfusion treatments in acute ischemic stroke: a systematic review
Authors: Nguyen Chi Phuong , Maas Willemijn J. , van der Zee Durk-Jouke , Uyttenboogaart Maarten , Buskens Erik , Lahr Maarten M. H. ,   on behalf of the CONTRAST consortium
Published: March 2023

Background

Reducing delays along the acute stroke pathway significantly improves clinical outcomes for acute ischemic stroke patients eligible for reperfusion treatments. The economic impact of different strategies reducing onset to treatment (OTT) is crucial information for stakeholders in acute stroke management. This systematic review aimed to provide an overview on the cost-effectiveness of several strategies to reduce OTT.

Methods

A comprehensive literature search was conducted in EMBASE, PubMed, and Web of Science until January 2022. Studies were included if they reported 1/ stroke patients treated with intravenous thrombolysis and/or endovascular thrombectomy, 2/ full economic evaluation, and 3/ strategies to reduce OTT. The Consolidated Health Economic Evaluation Reporting Standards statement was applied to assess the reporting quality.

Results

Twenty studies met the inclusion criteria, of which thirteen were based on cost-utility analysis with the incremental cost-effectiveness ratio per quality-adjusted life year gained as the primary outcome. Studies were performed in twelve countries focusing on four main strategies: educational interventions, organizational models, healthcare delivery infrastructure, and workflow improvements. Sixteen studies showed that the strategies concerning educational interventions, telemedicine between hospitals, mobile stroke units, and workflow improvements, were cost-effective in different settings. The healthcare perspective was predominantly used, and the most common types of models were decision trees, Markov models and simulation models. Overall, fourteen studies were rated as having high reporting quality (79%-94%).

Conclusions

A wide range of strategies aimed at reducing OTT is cost-effective in acute stroke care treatment. Existing pathways and local characteristics need to be taken along in assessing proposed improvements.
The CARAMAL study could not assess the effectiveness of rectal artesunate in treating suspected severe malaria
Authors: Watson James A. , Peto Thomas J. , White Nicholas J.
Published: March 2023

CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that “pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival”. We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.
The prognostic value of gastroesophageal reflux disorder in interstitial lung disease related hospitalizations
Authors: Alqalyoobi Shehabaldin , Little Bertis Brit , Oldham Justin M. , Obi Ogugua Ndili
Published: March 2023

Background

Gastroesophageal reflux disease (GERD) is a common comorbidity in patients with interstitial lung disease (ILD). We built and validated a model using the national inpatient sample (NIS) database to assess the contributory role of GERD in ILD-related hospitalizations mortality.

Methods

In this retrospective analysis, we extracted ILD-related hospitalizations data between 2007 and 2019 from the NIS database. Univariable logistic regression was used for predictor selection. Data were split into the training and validation cohorts (0.6 and 0.4, respectively). We used decision tree analysis (classification and regression tree, CART) to create a predictive model to explore the role of GERD in ILD-related hospitalizations mortality. Different metrics were used to evaluate our model. A bootstrap-based technique was implemented to balance our training data outcome to improve our model metrics in the validation cohort. We conducted a variance-based sensitivity analysis to evaluate GERD's importance in our model.

Findings

The model had a sensitivity of 73.43%, specificity of 66.15%, precision of 0.27, negative predictive value (NPV) of 93.62%, accuracy of 67.2%, Matthews Correlation Coefficient (MCC) of 0.3, F1 score of 0.4, and area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.76. GERD did not predict survival in our cohort. GERD contribution to the model was ranked the eleventh among twenty-nine variables included in this analysis (importance of 0.003, normalized importance of 5%). GERD was the best predictor in ILD-related hospitalizations who didn’t receive mechanical ventilation.

Interpretations

GERD is associated with mild ILD-related hospitalization. Our model-performance measures suggest overall an acceptable discrimination. Our model showed that GERD does not have a prognostic value in ILD-related hospitalization, indicating that GERD per se might not have any impact on mortality in hospitalized ILD patients.
Unmet healthcare needs and health inequalities in people with spinal cord injury: a direct regression inequality decomposition
Authors: Oña Ana , Athanasios Kyriakides , Tederko Piotr , Escorpizo Reuben , Arora Mohit , Sturm Christian , Yang Shujuan , Barzallo Diana Pacheco
Published: March 2023

Background

Inequality in health is a prevalent and growing concern among countries where people with disabilities are disproportionately affected. Unmet healthcare needs explain a large part of the observed inequalities between and within countries; however, there are other causes, many non-modifiable, that also play a role.

Aim

This article explores the difference in health across income levels in populations with spinal cord injury (SCI). SCI is of special interest in the study of health systems, as it is an irreversible, long-term health condition that combines a high level of impairment with subsequent comorbidities.

Methods

We estimated the importance of modifiable and non-modifiable factors that explain health inequalities through a direct regression approach. We used two health outcomes: years living with the injury and a comorbidity index. Data come from the International Spinal Cord Injury Survey (InSCI), which has individual data on people with SCI in 22 countries around the world. Due to the heterogeneity of the data, the results were estimated country by country.

Results

On average, the results exhibit a prevalence of pro-rich inequalities, i.e., better health outcomes are more likely observed among high-income groups. For the years living with the injury, the inequality is mostly explained by non-modifiable factors, like the age at the time of the injury. In contrast, for the comorbidity index, inequality is mostly explained by unmet healthcare needs and the cause of the injury, which are modifiable factors.

Conclusions

A significant portion of health inequalities is explained by modifiable factors like unmet healthcare needs or the type of accident. This result is prevalent in low, middle, and high-income countries, with pervasive effects for vulnerable populations like people with SCI, who, at the same time are highly dependent on the health system. To reduce inequity, it is important not only to address problems from public health but from inequalities of opportunities, risks, and income in the population.

Highlights

• Better health status is evident among high-income groups, which is reflected in pro-rich inequalities.

• Age at the time of the injury is the most important factor to explain inequalities in years living with the injury.

• Unmet health care needs are the most important factor to explain inequalities in comorbidities.

• The inequality in health varies by country dependent upon socioeconomic factors.
Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis
Authors: Luo Haotian , Chen Danying , Li Ruoyu , Li Runze , Teng Yungshan , Cao Yang , Zou Xuenong , Wang Weicai , Zhou Chen
Published: March 2023

Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases.
Associations of alcohol consumption with breast tissue composition
Authors: Yaghjyan Lusine , Heng Yujing J. , Baker Gabrielle M. , Rosner Bernard A. , Tamimi Rulla M.
Published: March 2023

Background

We investigated the associations of alcohol with percentage of epithelium, stroma, fibroglandular tissue (epithelium + stroma), and fat in benign breast biopsy samples.

Methods

We included 857 cancer-free women with biopsy-confirmed benign breast disease within the Nurses’ Health Study (NHS) and NHSII cohorts. Percentage of each tissue was measured on whole slide images using a deep-learning algorithm and then log-transformed. Alcohol consumption (recent and cumulative average) was assessed with semi-quantitative food frequency questionnaires. Regression estimates were adjusted for known breast cancer risk factors. All tests were 2-sided.

Results

Alcohol was inversely associated with % of stroma and fibroglandular tissue (recent ≥ 22 g/day vs. none: stroma: β = − 0.08, 95% Confidence Interval [CI] − 0.13; − 0.03; fibroglandular: β = − 0.08, 95% CI − 0.13; − 0.04; cumulative ≥ 22 g/day vs. none: stroma: β = − 0.08, 95% CI − 0.13; − 0.02; fibroglandular: β = − 0.09, 95% CI − 0.14; − 0.04) and positively associated with fat % (recent ≥ 22 g/day vs. none: β = 0.30, 95% CI 0.03; 0.57; cumulative ≥ 22 g/day vs. none: β = 0.32, 95% CI 0.04; 0.61). In stratified analysis, alcohol consumption was not associated with tissue measures in premenopausal women. In postmenopausal women, cumulative alcohol use was inversely associated with % of stroma and fibroglandular tissue and positively associated with fat % (≥ 22 g/day vs. none: stroma: β = − 0.16, 95% CI − 0.28; − 0.07; fibroglandular: β = − 0.18, 95% CI − 0.28; − 0.07; fat: β = 0.61, 95% CI 0.01; 1.22), with similar results for recent alcohol use.

Conclusion

Our findings suggest that alcohol consumption is associated with smaller % of stroma and fibroglandular tissue and a greater % of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.
Tick-borne pathogens and body condition of cattle in smallholder rural livestock production systems in East and West Africa
Authors: Heylen Dieter J. A. , Kumsa Bersissa , Kimbita Elikira , Frank Mwiine Nobert , Muhanguzi Dennis , Jongejan Frans , Adehan Safiou Bienvenu , Toure Alassane , Aboagye-Antwi Fred , Ogo Ndudim Isaac , Juleff Nick , Crafford Dionne , Fourie Josephus , Labuchange Michel , Madder Maxime
Published: March 2023

Background

The majority of the African population lives in rural areas where they heavily depend on crop and livestock production for their livelihoods. Given their socio-economic importance, we initiated a standardized multi-country (Benin, Burkina Faso, Ghana, Nigeria, Ethiopia Tanzania and Uganda) surveillance study to assess the current status of important tick-borne haemoparasites (TBHPs) of cattle.

Methods

We assessed pathogen prevalences (Anaplasma marginale, Anaplasma centrale, Babesia bigemina, Babesia bovis, Ehrlichia ruminantium, andTheileria parva) in the blood of 6447 animals spread over fourteen districts (two districts per country). In addition, we screened for intrinsic (sex, weight, body condition) and extrinsic (husbandry, tick exposure) risk factors as predictors of infections with TBHPs.

Results

There was a large macro-geographic variation observed inA. marginale, B. bigemina, B. bovisandE. ruminantiumprevalences. Most correlated with the co-occurrence of their specific sets of vector-competent ticks. Highest numbers of infected cattle were found in Ghana and Benin, and lowest in Burkina Faso. WhileT. parvawas seldomly found (Uganda only: 3.0%),A. marginalewas found in each country with a prevalence of at least 40%.Babesia bovisinfected individuals had lower body condition scores. Age (as estimated via body weight) was higher inA. marginaleinfected cattle, but was negatively correlated withB. bigeminaandE. ruminantiumprevalences.Ehrlichia ruminantiuminfection was more often found in males, andA. marginalemore often in transhumance farming. High levels of co-infection, especially the combinationA. marginale × B. bigemina, were observed in all countries, except for Uganda and Burkina Faso.Babesia bigeminawas more or less often observed than expected by chance, when cattle were also co-infected withE. ruminantiumorA. marginale, respectively.

Conclusions

Tick-borne pathogens of cattle are ubiquitous in African’s smallholder cattle production systems. Our standardized study will help a wide range of stakeholders to provide recommendations for TBHP surveillance and prevention in cattle, especially forB. boviswhich heavily impacts production and continues its spread over the African continent via the invasiveRhipicephalus microplustick.

Graphical Abstract
Detection of Virulence and β-lactamase resistance genes of non-typhoidal Salmonella isolates from human and animal origin in Egypt "one health concern"
Authors: Diab Mohamed S. , Thabet Asmaa S. , Elsalam Mohamed Abd , Ewida Rania M. , Sotohy Sotohy A.
Published: March 2023

Background

Non-typhoidal Salmonella (NTS) is a major foodborne zoonotic pathogen worldwide. In the current study, Various NTS strains were isolated from (cows, milk and dairy products in addition to humans) in New Valley and Assiut Governorate, Egypt. NTS were firstly serotyped and tested by antibiotic sensitivity test. Secondly, some virulence genes and Antibiotic resistance genes have been identified by using PCR. Finally, Phylogenesis was performed depending on the invA gene, for two S. typhimurium isolates (one of animal origin and the other of human origin for evaluating zoonotic potential).

Results

Out of 800 examined samples, the total number of isolates was 87 (10.88%), which were classified into 13 serotypes, with the most prevalent being S. Typhimurium and S. enteritidis. Both bovine and human isolates showed the highest resistance to clindamycin and streptomycin, with 90.80% of the tested isolates exhibiting MDR. The occurrence of the invA gene was 100%, while 72.22%, 30.56%, and 94.44% of the examined strains were positive for stn, spvC, and hilA genes, respectively. Additionally, blaOXA-2 was detected in 16.67% (6/ 36) of the tested isolates, while blaCMY-1 was detected in 30.56% (11of 36) of the tested isolates. Phylogenesis revealed a high degree of similarity between the two isolates.

Conclusions

The high occurrence of MDR strains of NTS in both human and animal samples with high degree of genetic similarity, shows that cows, milk and milk product may be a valuable source of human infection with NTS and interfere with treatment procedures.
Isolation and multilocus sequence typing of Borrelia burgdorferi from Ixodes scapularis collected from dogs in Ontario, Canada
Authors: Nichol Grace K. , Weese J. Scott , Clow Katie M.
Published: March 2023

Objective

To identify the multilocus sequence typing (MLST) sequence types of Borrelia burgdorferi from Ixodes scapularis in Ontario, Canada.

Results

One hundred and eighty-five I. scapularis ticks were submitted from 134 dogs via participating clinics from April 1, 2019, to March 31, 2020. Seventeen MLST sequence types of B. burgdorferi were detected from fifty-eight cultured isolates from 21 ticks. The most common MLST sequence types were 12 and 16. Mixed infections of two MLST sequence types were detected in four ticks. Three sequence types (48, 317, 639) were new detections in Ontario.
Clinical outcomes of dupilumab therapy in chronic rhinosinusitis with nasal polyps in a Canadian tertiary care rhinology practice
Authors: Grose Elysia , Li Alyssa Y. , Lee John M.
Published: March 2023

Background

In 2020, dupilumab became the first monoclonal antibody therapy to be approved by Health Canada for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). The primary aim of this study was to characterize the outcomes in an initial cohort of patients with CRSwNP who have undergone dupilumab therapy.

Methods

A retrospective study was conducted of patients with CRSwNP who were treated with dupilumab. Demographic information, comorbidities, number of previous surgeries, and insurance information were collected. The primary outcome were changes in the sinonasal outcome test (SNOT-22) scores from baseline to timepoints after receiving dupilumab.

Results

Forty-eight patients were considered for dupilumab therapy, and 27 (56%) received coverage or were able to fund the medication independently. Patients waited an average of 3.6 months to obtain access to the medication. The mean age of the patients was 43. Forty-one percent (11/27) of patients had aspirin exacerbated respiratory disease, and 96% (26/27) had a diagnosis of asthma. The mean length of time on dupilumab was 12.1 months. The baseline SNOT-22 score was 60.6. The mean decrease at 1 month, 3 months, 6 months, and 12 months after starting dupilumab was 8.8, 26.5, 42.8, and 33.8, respectively. There were no serious adverse events.

Conclusion

Patients treated with dupilumab in a Canadian tertiary care rhinology clinic demonstrated substantial clinical improvement as measured by disease-specific sinonasal outcomes. Further studies are needed to determine the longer-term effectiveness and adverse event profile of this novel therapy.
N-methyl-d-aspartate receptors induce M1 polarization of macrophages: Feasibility of targeted imaging in inflammatory response in vivo
Authors: Jeon Hui-Jeon , Byun Jun-Kyu , Lee Sang Bong , Son Kwang Hee , Lim Ji-Youn , Lee Da Sol , Kim Kil Soo , Park Jin Woo , Shin Gyeong Rim , Kim Ye Jin , Jin Jonghwa , Kim Daehoon , Kim Dong-Ho , Yu Ji Hoon , Choi Yeon-Kyung , Park Keun-Gyu , Jeon Yong Hyun
Published: March 2023

Background

N-methyl-d-aspartate receptors (NMDARs) are considered to be involved in several physiological and pathophysiological processes in addition to the progression of neurological disorders. However, how NMDARs are involved in the glycolytic phenotype of M1 macrophage polarization and the possibility of using them as a bio-imaging probe for macrophage-mediated inflammation remain unclear.

Methods

We analyzed cellular responses to NMDAR antagonism and small interfering RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced via the introduction of NMDAR antibody and the infrared fluorescent dye FSD Fluor™ 647. N-TIP binding efficiency was tested in intact and LPS-stimulated BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The anti-inflammatory effects of dexamethasone were evaluated using the N-TIP-mediated macrophage imaging technique.

Results

NMDARs were overexpressed in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. Mechanistically, NMDAR-mediated Ca2+ accumulation resulted in LPS-stimulated glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h post-inflammation, and the inflamed lesions could be detected until 24 h. Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully visualize the anti-inflammatory effects of dexamethasone in mice with inflammation.

Conclusion

This study demonstrates that NMDAR-mediated glycolysis plays a critical role in M1 macrophage-related inflammation. Moreover, our results suggest that NMDAR targeting imaging probe may be useful in research on inflammatory response in vivo.
The risks of adverse events with venlafaxine and mirtazapine versus ‘active placebo’, placebo, or no intervention for adults with major depressive disorder: a protocol for two separate systematic reviews with meta-analysis and Trial Sequential Analysis
Authors: Jørgensen Caroline Kamp , Juul Sophie , Siddiqui Faiza , Horowitz Mark Abie , Moncrieff Joanna , Munkholm Klaus , Hengartner Michael Pascal , Kirsch Irving , Gluud Christian , Jakobsen Janus Christian
Published: March 2023

Background

Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small and may not be important to the average patient. Moreover, previous reviews have not systematically assessed the occurrence of adverse events. Therefore, we aim to investigate the risks of adverse events with venlafaxine or mirtazapine versus ‘active placebo’, placebo, or no intervention for adults with major depressive disorder in two separate systematic reviews.

Methods

This is a protocol for two systematic reviews with meta-analysis and Trial Sequential Analysis. The assessments of the effects of venlafaxine or mirtazapine will be reported in two separate reviews. The protocol is reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, risk of bias will be assessed with the Cochrane risk-of-bias tool version 2, clinical significance will be assessed using our eight-step procedure, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. We will search for published and unpublished trials in major medical databases and trial registers. Two review authors will independently screen the results from the literature searches, extract data, and assess risk of bias. We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with ‘active placebo’, placebo, or no intervention for adults with major depressive disorder. The primary outcomes will be suicides or suicide attempts, serious adverse events, and non-serious adverse events. Exploratory outcomes will include depressive symptoms, quality of life, and individual adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses.

Discussion

Venlafaxine and mirtazapine are frequently used as second-line treatment of major depressive disorder worldwide. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder.

Systematic review registration

PROSPERO CRD42022315395.
The relationship between obstructive sleep apnea and asthma severity and vice versa: a systematic review and meta-analysis
Authors: Wang Donghao , Zhou Yanyan , Chen Riken , Zeng Xiangxia , Zhang Sun , Su Xiaofen , Luo Yateng , Tang Yongkang , Li Shiwei , Zhuang Zhiyang , Zhao Dongxing , Ren Yingying , Zhang Nuofu
Published: March 2023

Background

There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa.

Methods

We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger’s test for bias analysis.

Results

34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763–0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16–1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49–7.64).

Conclusion

OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.
Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues
Authors: Sun Ying , Jing Pengyu , Gan Helina , Wang Xuejiao , Zhu Ximing , Fan Jiangjiang , Li Haichao , Zhang Zhipei , Lin James Chi Jen , Gu Zhongping
Published: March 2023

Background

In recent years, there have been breakthroughs in the preclinical research of respiratory diseases, such as organoids and organ tissue chip models, but they still cannot provide insight into human respiratory diseases well. Human lung slices model provides a promising in vitro model for the study of respiratory diseases because of its preservation of lung structure and major cell types.

Methods

Human lung slices were manually prepared from small pieces of lung tissues obtained from lung cancer patients subjected to lung surgery. To evaluate the suitability of this model for lung fibrosis research, lung slices were treated with CdCl2 (30 μM), TGF-β1 (1 ng/ml) or CdCl2 plus TGF-β1 for 3 days followed by toxicity assessment, gene expression analysis and histopathological observations.

Results

CdCl2 treatment resulted in a concentration-dependent toxicity profile evidenced by MTT assay as well as histopathological observations. In comparison with the untreated group, CdCl2 and TGF-β1 significantly induces MMP2 and MMP9 gene expression but not MMP1. Interestingly, CdCl2 plus TGF-β1 significantly induces the expression of MMP1 but not MMP2, MMP7 or MMP9. Microscopic observations reveal the pathogenesis of interstitial lung fibrosis in the lung slices of all groups; however, CdCl2 plus TGF-β1 treatment leads to a greater alveolar septa thickness and the formation of fibroblast foci-like pathological features. The lung slice model is in short of blood supply and the inflammatory/immune-responses are considered minimal.

Conclusions

The results are in favor of the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated by tissue damage and abnormal repair. Induction of MMP1 gene expression and fibroblast foci-like pathogenesis suggest that this model might represent an early stage of IPF.
Family connections in the treatment of relatives of people with eating disorders and personality disorders: study protocol of a randomized control trial
Authors: Guillén Verónica , Arnal Antonio , Pérez Sandra , Garcia-Alandete Joaquín , Fernandez-Felipe Isabel , Grau Antoni , Botella Cristina , Marco José Heliodoro
Published: March 2023

Background

Eating disorders (EDs) are serious disorders that significantly affect not only the lives of patients, but also those of their family members who often experience high levels of burden, suffering and helplessness. If, in addition to ED, the patient has a personality disorder (PD), the psychological distress experienced by family members can be devastating. However, few treatments have been developed for family members of people with ED and PD. Family Connections (FC) is a programme that has been shown to be effective for family members of people with borderline personality disorder. The overall aims of this work are: (a) to adapt FC for application to family members of patients with BPD-PD (FC: ED-PD); (b) to analyse, in a randomised controlled clinical trial, the efficacy of this programme in a Spanish population, compared to a control condition consisting of treatment as usual optimised treatment (TAU-O); (c) to analyse the feasibility of the intervention protocol; (d) to analyse whether the changes that may occur in relatives are related to improvements in the family climate and/or improvements observed in patients; and (e) to analyse the perceptions and opinions of relatives and patients about the two intervention protocols.

Methods

The study uses a two-arm randomised controlled clinical trial with two experimental conditions: adaptation of FC programme (FC: ED-PD) or Treatment as usual optimised (TAU-O). Participants will be family members of patients who meet DSM-5 criteria for ED and PD or dysfunctional personality traits. Participants will be assessed before and after treatment and at one-year follow-up. The intention-to-treat principle will be used when analysing the data.

Discussion

The results obtained are expected to confirm the effectiveness of the programme and its good acceptance by family members.

Trial registration ClinicalTrials.gov Identifier: NCT05404035. Accepted: May 2022.
Shape-altering flexible plasmonics of in-situ deformable nanorings
Authors: Tao Wei , Laible Florian , Hmima Abdelhamid , Maurer Thomas , Fleischer Monika
Published: March 2023

Nanorings (NRs) with their intrinsic cavities have attracted interest as plasmonic nanoparticles for years, due to the uniform electric field enhancement inside the cavity, lower plasmon damping effects and comparatively high refractive index sensitivities. In the present work, we successfully fabricated a series of Au NR arrays on flexible polydimethylsiloxane substrates by taking advantage of state-of-the-art fabrication methods such as electron beam lithography and wet-etching transfer techniques. In-situ optical measurements on these flexible systems are enabled by implementing a homemade micro-stretcher inside an optical reflection spectroscopy setup. The corresponding dark-field spectra of thin-walled NR arrays exhibit a strong shift to longer wavelengths (i.e., ~ 2.85 nm per 1% strain) under polarization perpendicular to the traction, mainly resulting from the increasing shape deformation of the NRs under strain. Moreover, numerical simulations illustrate that the shifting plasmonic mode has a radially-symmetric charge distribution of the bonding mode and is rather sensitive to the tuning of the NRs’ shape as confirmed by a subsequent in-situ scanning electron microscope characterization. These results explore the possibilities of shape-altering flexible plasmonics for nanoparticles with a cavity and indicate potential applications for plasmonic colors and biochemical sensing in future work.

Graphical Abstract
Image sharpening algorithms improve clarity of surgical field during 3D heads-up surgery
Authors: Nakajima Kosuke , Inoue Makoto , Takahashi Aya , Yoshikawa Yuji , Mizuno Masaharu , Koto Takashi , Ishida Tomoka , Oshika Tetsuro
Published: March 2023

Background

Image-sharpening algorithms with color adjustments enable real-time processing of the surgical field with a delay of 4 msec for heads-up surgery using digital three-dimensional displays. The aim of this study was to investigate the usefulness of the algorithms with the Artevo 800® digital microscope.

Methods

Seven vitreoretinal surgeons evaluated the effects of image-sharpening processing on the clarity of the surgical field with the Artevo 800® system that is used for cataract and vitreous surgeries. The scorings were made on a 10-point scale for anterior capsulotomy, phacoemulsification, cortex aspiration, core vitrectomy, and peeling of an epiretinal membrane or an internal limiting membrane. In addition, the images during the internal limiting membrane peeling were processed with or without color adjustments. We also evaluated the skewness (asymmetry in the distribution of the pixels) and kurtosis (sharpness in the distribution of the pixel) of the images to evaluate the contrast with each intensity of image-sharpening.

Results

Our results showed that the mean visibility score increased significantly from 4.9 ± 0.5 at 0% (original image) to 6.6 ± 0.5 at 25% intensity of the image-sharpening algorithm (P < 0.01). The visibility scores of the internal limiting membrane increased significantly from 0% (6.8 ± 0.3, no color adjustments) to 50% after the color adjustments (7.4 ± 0.4, P = 0.012). The mean skewness decreased significantly from 0.83 ± 2.02 at 0% (original source) to 0.55 ± 1.36 at 25% intensity of the image-sharpening algorithm (P = 0.01). The mean kurtosis decreased significantly from 0.93 ± 2.14 at 0% (original image) to 0.60 ± 1.44 at 25% intensity of the image-sharpening algorithm (P = 0.02).

Conclusions

We conclude that the image-sharpening algorithms can improve the clarity of the surgical field during 3D heads-up surgery by decreasing the skewness and kurtosis.

Trial registration

This was a prospective clinical study performed at a single academic institution, and the procedures used were approved by the Institutional Review Committee of the Kyorin University School of Medicine (reference number, 1904). The procedures also conformed to the tenets of the Declaration of Helsinki.
REal-world treatment outcomes after delayed intRavitreal therapy in center-involving diabetic macular edema – RETORT study
Authors: Chitturi Sai Prashanti , Venkatesh Ramesh , Mangla Rubble , Parmar Yash , Sangoram Rohini , Yadav Naresh Kumar , Chhablani Jay
Published: March 2023

Purpose

To compare real-life data on delayed intravitreal treatment of diabetic macular edema (DME) patients to early treatment.

Methods

In this single-centre, retrospective, interventional, comparative study, DME patients were divided into two groups based on when they received treatment: Group 1 - received treatment within 24 weeks and Group 2 - at or after 24 weeks from the time of treatment advice. Visual acuity and central subfield thickness (CSFT) changes were compared at various time points. Reasons for delaying treatment were noted.

Results

The study included 109 (Group 1–94; Group 2–15) eyes. When treatment was advised, demographic profile, diabetes duration, glucose control and VA between two groups were comparable. At this point, CSFT was higher in Group 1 than in Group 2 (p = 0.036). At injection time, Group 2 had better VA and lower CSFT than Group 1 (p < 0.05). Group 2’s VA (53.4 ± 12.67) was significantly lower than Group 1’s (57.38 ± 20.01) after 1-year treatment. At 1-year, CSFT decreased in Group 1 and increased in Group 2. Group 1 had mean improvement of + 7.6 letters and Group 2 had a decline of -6.9 letters. Group 2 required more intravitreal anti-VEGF (median – 3; IQR: 2–4), steroid injections (median – 4; IQR: 2–4) and focal laser sessions (median – 4; IQR: 2–4).

Conclusion

Late-treated DME eyes needed more injections and focal laser sessions than early treated eyes. Adherence to early treatment of DME in real-life will help prevent long-term vision loss.
Content analysis of health-related subjects in the K12 school curricula of Japan, Indonesia, Philippines, Guam, Micronesia, Marshall Islands, Palau, and Fiji
Authors: Nishio Akihiro , Shibuya Fumiko , de los Reyes Calvin S. , Estrada Crystal Amiel M. , Gregorio Ernesto R. , Sari Dian Puspita , Warnaini Cut , Kadriyan Hamsu , Cruz Maria Sandra M. , Hattori-Uchima Margaret , Dacanay Paul , Dacanay Rudelyn , Enos Hillia Langrine , Ngirmang Tarmau Terry , Khalif Mohamed , Volavola Saula Golea , Tomokawa Sachi , Kigawa Mika , Kobayashi Jun
Published: March 2023

Background

As a component of health promoting school, a school curriculum for health education was considered a fundamental. This survey aimed to identify the components of health-related topics and in which subjects were they taught.

Methods

Four topics were chosen: (i) hygiene, (ii) mental health, (iii) nutrition-oral Health, and (iv) environmental education related to global warming in Education for Sustainable Development (ESD). Before gathering the curricula from partner countries, school health specialists were gathered to discuss the appropriate components of a curriculum that required evaluation. The survey sheet was distributed to and answered by our partner in each country.

Results

About hygiene, individual practices or items that improve health-related were widely covered. However, items that imparted health-related education from an environmental perspective were not widely covered. About mental health, two types of country groups were identified. The first group included countries that taught mental health topics mainly as part of morals or religion; the second group included countries that imparted mental health topics mainly as part of health. The first group focused mainly on communication skills or coping methods. The second group focused not only on communication and coping skill but also on basic knowledge of mental health. About nutrition-oral education, three types of country groups were identified. One group imparted nutrition-oral education mainly in terms of health or nutrition. Another group imparted this topic mainly in terms of morals, home economics, and social science. The third group was the intermediate group. About ESD, a solid structure for this topic was not identified in any country. Many items were taught as part of science, while some were taught as part of social studies. Climate change was the most commonly taught item across all countries. The items related to environment were relatively limited compared to those related to natural disasters.

Conclusions

Overall, two different approaches were identified: the cultural-based approach, which promotes healthy behaviors as moral codes or community-friendly behaviors and the science-based approach, which promotes children’s health through scientific perspectives. Policymakers should initially  consider the findings of this study while making decisions on which approach should be taken.
Outcomes of near-miss/adverse perioperative events during elective and emergency non-cardiac surgeries that required unplanned admissions to the intensive care unit of a tertiary care center: a retrospective cohort study
Authors: Mylavarapu Krishna Kumar , Joshi Aditya , Kapoor Rajan
Published: March 2023

Background

The near-miss/adverse events during elective and emergency non-cardiac surgeries requiring unplanned admissions to the intensive care unit (ICU) during the perioperative period are not known. Patients undergoing elective and emergency (E) noncardiac surgeries classified according to the American Society of Anesthesiologists physical status (ASA PS) (I–IV) were studied.

Results

From 01 January 2019 to 31 December 2020, 6584 patients above 18 years underwent non-cardiac surgeries at a tertiary care center in eastern India, of which 87.3% (n = 5754) were elective surgical cases, and 12.5% (n = 826) were emergency surgeries. 0.98% of the patients (n = 65) (26 men and 39 females) had serious adverse/near-miss events requiring unplanned admission to the ICU, of these, 50.7% (n = 33) were elective cases, in ASA PS I 12.3% (n = 8), ASA II 27.6% (n = 18) ASA III 9.2% (n = 6) and ASA IV 1.53% (n = 1) respectively and 49.3% (n = 32) were emergency cases in ASA PS I (E) 13.8% (n = 9) (13.8%), ASA II (E) 26.1% (n = 17), ASA III(E) 4.6% (n = 3) and ASA IV(E) 4.6% (n = 3) respectively. Near miss events were mainly due to (a) cardiac-related events seen in 37.5% (n = 25) patients, (b) hemorrhage seen in 25% (n = 16), and (c) airway-related issues seen in 16.1% (n = 11) patients respectively. The adverse events were mainly due to drug-related errors in 21.4% (n = 13) patients. 13.84% (n = 9) patients had died and 86.16% (n = 56) had survived due to the availability of critical care services.

Emergency surgeries 25% (8 out of 32 patients) had a higher mortality rate due to adverse/near-miss events compared to elective surgeries which were 3.03% (1 out of 33 cases) respectively.

Conclusions

Emergency non-cardiac surgeries were associated with higher rates of adverse/near-miss events. Early recognition and prompt management of critical adverse events during intraoperative and postoperative periods with the help of critical care facilities may improve clinical outcomes.