bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of choroidal thickness in juvenile systemic lupus erythematosus and its correlation with laboratory tests
Authors: Ru Li , Xu Jinping , Lin Zhongjing , Cao Lanfang , Zhang Lin
Published: April 2023

Background

The aim of this study is to investigate the alterations of choroidal thickness (CT) in juvenile systemic lupus erythematosus (JSLE) using enhanced depth imaging optical coherence tomography (EDI-OCT). We also aimed to assess whether CT parameters correlated with systemic health status in JSLE patients.

Methods

JSLE patients and age- and sex-matched healthy subjects were recruited. A detailed ophthalmological examination was applied to all participants. CT measurements were acquired in the macular region using EDI-OCT. Moreover, a spectrum of laboratory tests was examined to evaluate the systemic conditions, and the Th1/Th2/Th17/Treg cytokine profiles in the peripheral blood were also analyzed in JSLE group.

Results

A total of 45 JSLE patients with no visual impairment and 50 healthy individuals were enrolled in the study. CT values in the macular region were decreased in JSLE patients when compared with healthy controls, even adjusting for age, axial length and refraction. There were no significant correlations between CT and cumulative dose of hydroxychloroquine or duration of hydroxychloroquine use (all P > 0.05). The average macular, temporal and subfoveal CT in JSLE group was negatively correlated with IL-6 and IL-10 (all P < 0.05), but had no significant correlations with other laboratory results (all P > 0.05).

Conclusions

JSLE patients without ocular involvement may have significant variations in choroidal thickness at the macular area. Choroidal alterations might be associated with the systemic cytokine profiles in JSLE.
Health-related quality of life in children under treatment for overweight, obesity or severe obesity: a cross-sectional study in the Netherlands
Authors: van der Voorn Bibian , Camfferman R. , Seidell J. C. , Halberstadt J.
Published: April 2023

Background

It is unknown whether weight class is associated with impairment of health-related quality of life (HRQOL) for children in the Netherlands. The aim of this study was to explore generic and weight-specific HRQOL in a clinical cohort of children with overweight, obesity or severe obesity aged 5–19 years in the Netherlands.

Methods

803 children from three clinical cohorts participated: mean age 11.5 (SD 2.9) years, 61.1% girls. The influence of weight class was explored in a subgroup of 425 children (25.2% with overweight, 32.5% obesity and 42.3% severe obesity), of whom the exact International Obesity Task Force (IOTF) BMI class was known. Generic HRQOL was measured by the PedsQL child report. Weight-specific HRQOL was measured by the IWQOL-Kids child or parent report. Average total, subscale and item scores were reported and the influence of the IOTF BMI class analyzed by multiple linear regression, corrected for age and sex.

Results

Children with severe obesity had lower generic and weight-specific HRQOL scores than those with obesity or overweight. IOTF BMI class was negatively associated with item scores from all subscales, especially physical, social and emotional functioning. Children with overweight reported similar HRQOL total, subscale and item scores to children with obesity.

Conclusions

In the Netherlands, children treated for overweight, obesity or severe obesity experience problems on the majority of items within all subscales of generic and weight-specific HRQOL. Children with severe obesity especially report significantly more challenges due to their weight than children with obesity or overweight.
Sex differences in impact of cumulative systolic blood pressure from childhood to adulthood on albuminuria in midlife: a 30-year prospective cohort study
Authors: Wang Dan , Kou Pu-qing , Liao Yue-yuan , Wang Ke-ke , Yan Yu , Chen Chen , Chu Chao , Wang Yang , Niu Ze-Jiaxin , Ma Qiong , Sun Yue , Mu Jian-jun
Published: April 2023

Background and objectives

Albuminuria is recognized as being a predictor of cardiovascular and renal disease. We aimed to identify the impact of the long-term burden and trends of systolic blood pressure on albuminuria in midlife, as well as to explore sex differences concerning this relationship.

Methods

This longitudinal study consisted of 1,683 adults who had been examined 4 or more times for blood pressure starting in childhood, with a follow-up time period of 30 years. The cumulative effect and longitudinal trend of blood pressure were identified by using the area under the curve (AUC) of individual systolic blood pressure measurement with a growth curve random effects model.

Results

Over 30 years of follow-up, 190 people developed albuminuria, including 53.2% males and 46.8% females (aged 43.39 ± 3.13 years in the latest follow-up). The urine albumin-to-creatinine ratio (uACR) values increased as the total and incremental AUC values increased. Additionally, women had a higher albuminuria incidence in the higher SBP AUC groups than men do (13.3% for men vs. 33.7% for women). Logistic regression showed that the ORs of albuminuria for males and females in the high total AUC group were 1.34 (0.70–2.60) and 2.94 (1.50–5.74), respectively. Similar associations were found in the incremental AUC groups.

Conclusions

Higher cumulative SBP was correlated with higher uACR levels and a risk of albuminuria in middle age, especially in women. The identification and control of cumulative SBP levels from an early age may assist in reducing the incidences of renal and cardiovascular disease for individuals in later life.
A qualitative study on the feasibility and acceptability of institutionalizing health technology assessment in Malawi
Authors: Mfutso-Bengo Joseph , Jeremiah Faless , Kasende-Chinguwo Florence , Ng’ambi Wingston , Nkungula Nthanda , Kazanga-Chiumia Isabel , Juma Mercy , Chawani Marlen , Chinkhumba Jobiba , Twea Pakwanja , Chirwa Emily , Langwe Kate , Manthalu Gerald , Ngwira Lucky Gift , Nkhoma Dominic , Colbourn Tim , Revill Paul , Sculpher Mark
Published: April 2023

Objective

The objective of this study was to assess the feasibility and acceptability of institutionalizing Health Technology Assessment (HTA) in Malawi.

Methods

This study employed a document review and qualitative research methods, to understand the status of HTA in Malawi. This was complemented by a review of the status and nature of HTA institutionalization in selected countries.Qualitative research employed a Focus Group Discussion (FGD ) with 7 participants, and Key Informant Interviews (KIIs) with12 informants selected based on their knowledge and expertise in policy processes related to HTA in Malawi.Data extracted from the literature was organized in Microsoft Excel, categorized according to thematic areas and analyzed using a literature review framework. Qualitative data from KIIs and the FGD was analyzed using a thematic content analysis approach.

Results

Some HTA processes exist and are executed through three structures namely: Ministry of Health Senior Management Team, Technical Working Groups, and Pharmacy and Medicines Regulatory Authority (PMRA) with varyingdegrees of effectiveness.The main limitations of current HTA mechanisms include limited evidence use, lack of a standardized framework for technology adoption, donor pressure, lack of resources for the HTA process and technology acquisition, laws and practices that undermine cost-effectiveness considerations. KII and FGD results showed overwhelming demand for strengthening HTA in Malawi, with a stronger preference for strengthening coordination and capacity of existing entities and structures.

Conclusion

The study has shown that HTA institutionalization is acceptable and feasible in Malawi. However, the current committee based processes are suboptimal to improve efficiency due to lack of a structured framework. A structured HTA framework has the potential to improve processes in pharmaceuticals and medical technologies decision-making.In the short to medium term, HTA capacity building should focus on generating demand and increasing capacity in cost-effectiveness assessments. Country-specific assessments should precede HTA institutionalization as well as recommendations for new technology adoptions.
Electronic cigarette menthol flavoring is associated with increased inhaled micro and sub-micron particles and worse lung function in combustion cigarette smokers
Authors: Chandra Divay , Bogdanoff Rachel F. , Bowler Russell P. , Benam Kambez H.
Published: April 2023

Flavored electronic cigarettes (ECs) present a serious health challenge globally. Currently, it is unknown whether the addition of highly popular menthol flavoring to e-liquid is associated with changes in the number of aerosolized particles generated or altered lung function. Here, we first performed preclinical studies using our novel robotic platform Human Vaping Mimetic Real-Time Particle Analyzer (HUMITIPAA). HUMITIPAA generates fresh aerosols for any desired EC in a very controlled and user-definable manner and utilizes an optical sensing system to quantitate and analyze sub-micron and microparticles from every puff over the course of vaping session in real-time while emulating clinically relevant breathing mechanics and vaping topography. We discovered that addition of menthol flavoring to freshly prepared e-liquid base propylene glycol–vegetable glycerin leads to enhanced particle counts in all tested size fractions, similar to the effect of adding vitamin E acetate to e-liquid we previously reported. Similarly, we found that menthol vs. non-menthol (tobacco) flavored pods from commercially available ECs leads to generation of significantly higher quantities of 1–10 µm particles upon inhalation. We then retrospectively analyzed data from the COPDGene study and identified an association between the use of menthol flavored ECs and reduced FEV1% predicted and FEV1/FVC independent of age, gender, race, pack-years of smoking, and use of nicotine or cannabis-containing vaping products. Our results reveal an association between enhanced inhaled particle due to menthol addition to ECs and worse lung function indices. Detailed causal relation remains to be demonstrated in future large-scale prospective clinical studies. Importantly, here we demonstrate utility of the HUMITIPAA as a predictive enabling technology to identify inhalation toxicological potential of emerging ECs as the chemical formulation of e-liquid gets modified.
Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Authors: Kang Ji Young , Han Kyungdo , Lee Seung-Hwan , Kim Mee Kyoung
Published: April 2023

Background

Many have the rising coincidence of diabetes mellitus (DM) and endemic tuberculosis (TB). We evaluated whether the severity of diabetes is associated with an increased risk of active TB infection.

Methods

 Using a nationally representative database from the Korean National Health Insurance System, 2, 489, 718 people with type 2 DM who underwent a regular health checkup during 2009–2012 were followed up until the end of 2018. The diabetes severity score parameters included the number of oral hypoglycemic agents (≥ 3), insulin use, diabetes duration (≥ 5 years), and the presence of chronic kidney disease (CKD) or cardiovascular disease. Each of these characteristics was scored as one point, and their sum (0–5) was used as the diabetes severity score.

Results

We identified 21, 231 cases of active TB during a median follow-up of 6.8 years. Each parameter of the diabetes severity score was associated with an increased risk of active TB (all P < 0.001). Insulin use was the most significant factor related to the risk of TB, followed by CKD. The risk of TB increased progressively with increasing diabetes severity score. After adjusting for possible confounding factors, the hazard ratio (95% confidence interval) for TB were 1.23 (1.19–1.27) in participants with one parameter, 1.39 (1.33–1.44) in those with two parameters, 1.65 (1.56–1.73) in those with three parameters, 2.05 (1.88–2.23) in those with four parameters, and 2.62 (2.10–3.27) in those with five parameters compared with participants with no parameters.

Conclusion

Diabetes severity was strongly associated in a dose-dependent manner with the occurrence of active TB. People with a higher diabetes severity score may be a targeted group for active TB screening.
Gold-nanosphere mitigates osteoporosis through regulating TMAO metabolism in a gut microbiota-dependent manner
Authors: Chen Yueqi , Yang Chuan , Dai Qijie , Tan Jiulin , Dou Ce , Luo Fei
Published: April 2023

Osteoporosis (OP) is a metabolic bone disease characterized by decreased bone mass and increased bone fragility. The imbalance of bone homeostasis modulated by osteoclasts and osteoblasts is the most crucial pathological change in osteoporosis. As a novel treatment strategy, nanomedicine has been applied in drug delivery and targeted therapy due to its high efficiency, precision, and fewer side effects. Gold nanospheres (GNS), as a common kind of gold nanoparticles (GNPs), possess significant antimicrobial and anti-inflammatory activity, which have been applied for the treatment of eye diseases and rheumatoid arthritis. However, the effect of GNS on osteoporosis remains elusive. In this study, we found that GNS significantly prevented ovariectomy (OVX)-induced osteoporosis in a gut microbiota-dependent manner. 16S rDNA gene sequencing demonstrated GNS markedly altered the gut microbial diversity and flora composition. In addition, GNS reduced the abundance of TMAO-related metabolites in OVX mice. Low TMAO levels might alleviate the bone loss phenomenon by reducing the inflammation response. Therefore, we investigated the alteration of cytokine profiles in OVX mice. GNS inhibited the release of pro-osteoclastogenic or proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-6, and granulocyte colony-stimulating factor (G-CSF) in the serum. In conclusion, GNS suppressed estrogen deficiency-induced bone loss by regulating the destroyed homeostasis of gut microbiota so as to reduce its relevant TMAO metabolism and restrain the release of proinflammatory cytokines. These results demonstrated the protective effects of GNS on osteoporosis as a gut microbiota modulator and offered novel insights into the regulation of the “gut–bone” axis.
Associations between treatment burden, self-reported treatment qualities, antiretroviral therapy obtainment, and health-related quality of life among Ugandan PLWH
Authors: Guan Ming , Guan Hongyi
Published: April 2023

Background

Understanding related risk factors of health-related quality of life (HRQoL) could avoid treatment failure and provide an insight of personalized treatment approach among people living with HIV/AIDS (PLWH). The objective of this study was to identify factors associated with self-reported treatment qualities and domains of health-related quality of life (HRQoL) among PLWH in Uganda.

Method

Data were from “Life on antiretroviral therapy: People’s adaptive coping and adjustment to living with HIV as a chronic condition in Wakiso District, Uganda” in English. The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire was used to assess the HRQoL of 263 PLWH in the sample. Considering variance inflation factors, multiple regression analyses were performed to assess the associations between demographic factors, ART obtainment, treatment burden, and self-reported treatment qualities, associations between demographic factors, self-reported treatment qualities, and HRQoL, and association between ART obtainment and HRQoL. Controlling for the confounding effects, several regression anatomies were employed to explore the associations between self-reported treatment qualities and six domains of HRQoL.

Results

In the sample, the geographical distribution were urban (5.70%), semi-urban (37.26%), and rural (57.03%). 67.30% of the participants were females. The mean age of the sample was 39.82 years (standard deviation = 9.76) ranging from 22 to 81 years. Multiple logistic regressions reported statistically significant associations of distance to ART facility with self-reported quality of services, advice, manners, and counseling, statistically significant association between self-reported manners quality and four domains of HRQoL, and statistically significant association between TASO membership and domains of HRQoL. Plots from regression anatomies reported that self-reported treatment qualities had statistically significant associations with six domains of HRQoL.

Conclusions

Treatment burden, self-reported treatment qualities, ART obtainment, and TASO were possible determinants of individual domains of HRQoL among PLWH in Uganda. PLWH’s HRQoL might be improved by promoting medical quality and optimizing ART obtainment in the healthcare providers’ practice. Findings in this study had important implications for the redesign of clinical guidelines, healthcare delivery, and health care co-ordination among PLWH globally.
Toward the next generation EGFR inhibitors: an overview of osimertinib resistance mediated by EGFR mutations in non-small cell lung cancer
Authors: Li Yufeng , Mao Tianyu , Wang Jing , Zheng Hongrui , Hu Ziyi , Cao Pingping , Yang Suisui , Zhu Lingyun , Guo Shunyao , Zhao Xinfei , Tian Yue , Shen Hua , Lin Fan
Published: April 2023

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently the standard first-line therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). The life quality and survival of this subgroup of patients were constantly improving owing to the continuous iteration and optimization of EGFR-TKI. Osimertinib, an oral, third-generation, irreversible EGFR-TKI, was initially approved for the treatment of NSCLC patients carrying EGFR T790M mutations, and has currently become the dominant first-line targeted therapy for most EGFR mutant lung cancer. Unfortunately, resistance to osimertinib inevitably develops during the treatment and therefore limits its long-term effectiveness. For both fundamental and clinical researchers, it stands for a major challenge to reveal the mechanism, and a dire need to develop novel therapeutics to overcome the resistance. In this article, we focus on the acquired resistance to osimertinib caused by EGFR mutations which account for approximately 1/3 of all reported resistance mechanisms. We also review the proposed therapeutic strategies for each type of mutation conferring resistance to osimertinib and give an outlook to the development of the next generation EGFR inhibitors.
Patients’ physiological reactions to competitive rehabilitation therapies assisted by robotic devices
Authors: Catalán José M. , Blanco-Ivorra Andrea , García-Pérez José V. , Vales Yolanda , Martínez-Pascual David , Ezquerro Santiago , Garrote Alicia , Costa Teresa , Lledó Luis D. , García-Aracil Nicolás
Published: April 2023

Background

The aging of the population and the progressive increase in life expectancy in developed countries is leading to a high incidence of cerebrovascular diseases. Several studies have demonstrated that robot-assisted rehabilitation therapies combined with serious games can improve rehabilitation outcomes. Social interaction in the form of multiplayer games has been highlighted as a potential element to increase patient’s motivation and exercise intensity, which professionals have described as one of the determining factors in maximizing rehabilitation outcomes. Despite this, it has not been widely studied. Physiological measures have been proven as an objective tool to evaluate patients’ experience in robot-assisted rehabilitation environments. However, they have not been used to evaluate patients’ experience in multiplayer robot-assisted rehabilitation therapies. The main objective of this study is to analyze whether the interpersonal interaction inherent in a competitive game mode affects the patients’ physiological responses in robot-assisted rehabilitation environments.

Methods

A total of 14 patients participated in this study. The results of a competitive game mode were compared with a single-player game mode with different difficulty levels. Exercise intensity and performance were measured through parameters extracted from the game and the information provided by the robotic rehabilitation platforms. The physiological response of patients in each game mode was measured by the heart rate (HR) and the galvanic skin response (GSR). Patients were asked to fill out the IMI and the overall experience questionnaire.

Results

The exercise intensity results show that high-difficulty single-player game mode is similar in terms of intensity level to a competitive game mode, based on velocity values, reaction time and questionnaire results. However, the results of the physiological responses of the patients measured by GSR and HR are lower in the case of the competitive mode compared to the high-difficulty single-player game mode, obtaining results similar to those obtained in the low-difficulty single-player game mode.

Conclusions

Patients find the competitive game mode the most fun, which is also the mode they report experiencing the most effort and stress level. However, this subjective evaluation is not in line with the results of physiological responses. This study concludes that interpersonal interaction inherent to a competitive game mode influences patients’ physiological responses. This could mean that social interaction is an important factor to consider when interpreting the results obtained from physiological measurements.
K-line tilt as a novel potential risk factor for cervical Modic change: a retrospective study
Authors: Zhou Qingsong , Deng Wei , Wang Shengtao , Cai Jieyong , Feng Junfei , Chen Qian , Yin Yong
Published: April 2023

Background

Cervical sagittal parameters are important parameters that reflect the mechanical stress in the sagittal plane of the cervical spine and are an important basis for predicting the clinical status and prognosis of patients. Although it has been confirmed that there is a significant correlation between cervical Modic changes and some sagittal parameters. However, as a newly discovered sagittal parameter, there is no report on the relationship between the K-line tilt and the Modic changes of cervical spine.

Methods

A retrospective analysis was performed for 240 patients who underwent cervical magnetic resonance imaging scan for neck and shoulder pain. Among them, 120 patients with Modic changes, namely the MC(+) group, were evenly divided into three subgroups of 40 patients in each group according to different subtypes, namely MCI subgroup, MCII subgroup and MCIII subgroup. One hundred twenty patients without Modic changes were included in MC(−) group. We measured and compared the sagittal parameters of cervical spine among different groups, including K-line tilt, C2–C7 sagittal axial vertical distance (C2–C7 SVA), T1 slope and C2–7 lordosis. Logistic regression was used to analyse the risk factors of cervical Modic changes.

Results

The K-line tilt and C2–7 lordosis were significantly different between MC(+) group and MC(−) group (P < 0.05). The K-line tilt greater than 6.72° is a risk factor for Modic changes in cervical spine (P < 0.05). At the same time, the receiver operating characteristic curve showed that this change had moderate diagnostic value when the area under the curve was 0.77.

Conclusion

This study shows that the K-line tilt greater than 6.72° is a potential risk factor for Modic changes in cervical spine. When the K-line tilt is greater than 6.72°, we should be alert to the occurrence of Modic changes.

Trial registration number: 2022ER023-1.
Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial
Authors: Forlani Luca , De Cecco Loris , Simeon Vittorio , Paolini Biagio , Bagnoli Marina , Cecere Sabrina Chiara , Spina Anna , Citeroni Eleonora , Bignotti Eliana , Lorusso Domenica , Arenare Laura , Russo Daniela , De Angelis Carmine , Ardighieri Laura , Scognamiglio Giosuè , Del Sesto Michele , Tognon Germana , Califano Daniela , Schettino Clorinda , Chiodini Paolo , Perrone Francesco , Mezzanzanica Delia , Pignata Sandro , Tomassetti Antonella
Published: April 2023

Background

Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients.

Methods

EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation.

Results

Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib.

Conclusions

Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach.
“I've got a spring in my step” participants experience of action observation therapy and eccentric exercises, a telehealth study for mid‐portion Achilles Tendinopathy: a qualitative study
Authors: Ryan Deirdre , Rio Ebonie , O'Donoghue Grainne , O'Sullivan Cliona
Published: April 2023

Background

Quantitative research has dominated the field of Achilles Tendinopathy. The use of qualitative research allows in‐depth exploration of participants' perspectives, offering great insight in the evaluation of a trial's processes, particularly when exploring a novel intervention such as Action Observation Therapy combined with eccentric exercises which has not been previously researched. This study aimed to qualitatively explore participants' experiences of partaking in a telehealth study including the acceptability of the intervention, motivators for participation, and perspectives on the trial processes.

Method

A thematic analysis as guided by Braun and Clarke was used to analyse the semi‐structured interviews conducted on a purposive sample of participants with mid‐portion Achilles Tendinopathy who recently completed a pilot feasibility study. The study adhered to the criteria for reporting qualitative research guidelines (COREQ).

Results/Discussion

Sixteen participants were interviewed. The five themes identified were: (i) The impact of Achilles Tendinopathy is commonly not prioritised with ‘The acceptance and minimisation of pain’ as a sub‐theme (ii) Therapeutic alliance has the greatest impact on support (iii) Factors which influenced adherence (iv) Action Observation Therapy is valued and recommended (v) Recommendations for future interventions.

Conclusion

This study provides insightful recommendations around; exploring the use of Action Observation Therapy in Achilles Tendinopathy, the relative importance of therapeutic alliance rather than mode of therapy delivery, and that sufferers of Achilles Tendinopathy may not prioritise health seeking for this condition.
Differential diagnosis and cause-specific treatment during out-of-hospital cardiac arrest: a retrospective descriptive study
Authors: Heikkilä Elina , Jousi Milla , Nurmi Jouni
Published: April 2023

Background

The cardiopulmonary resuscitation (CPR) guidelines recommend identifying and correcting the underlying reversible causes of out-of-hospital cardiac arrest (OHCA). However, it is uncertain how often these causes can be identified and treated. Our aim was to estimate the frequency of point of care ultrasound examinations, blood sample analyses and cause-specific treatments during OHCA.

Methods

We performed a retrospective study in a physician-staffed helicopter emergency medical service (HEMS) unit. Data on 549 non-traumatic OHCA patients who were undergoing CPR at the arrival of the HEMS unit from 2016 to 2019 were collected from the HEMS database and patient records. We also recorded the frequency of ultrasound examinations, blood sample analyses and specific therapies provided during OHCA, such as procedures or medications other than chest compressions, airway management, ventilation, defibrillation, adrenaline or amiodarone.

Results

Of the 549 patients, ultrasound was used in 331 (60%) and blood sample analyses in 136 (24%) patients during CPR. A total of 85 (15%) patients received cause-specific treatment, the most common ones being transportation to extracorporeal CPR and percutaneous coronary intervention (PCI) (n = 30), thrombolysis (n = 23), sodium bicarbonate (n = 17), calcium gluconate administration (n = 11) and fluid resuscitation (n = 10).

Conclusion

In our study, HEMS physicians deployed ultrasound or blood sample analyses in 84% of the encountered OHCA cases. Cause-specific treatment was administered in 15% of the cases. Our study demonstrates the frequent use of differential diagnostic tools and relatively infrequent use of cause-specific treatment during OHCA. Effect on protocol for differential diagnostics should be evaluated for more efficient cause specific treatment during OHCA.
The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis
Authors: Li Zheng , Cai Jianghui , Lu Jing , Wang Mingju , Yang Chenmei , Zeng Zheng , Tang Qian , Li Jianhong , Tang Wen , Luo Huiling , Pan Gaofeng , Zeng Xingmao
Published: April 2023

Background

The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients.

Methods

We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1–2 months of follow-up.

Results

27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50–2.15; P < .00001; I2 = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40–0.80; P = .001; I2 = 76%). There was a lower risk of CALs during 1–2 months follow-up for those who started IVIG administration within 10 days from the onset.

Conclusions

Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.
Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial
Authors: Yuan Xueyan , Zhang Rui , Wang Yuxuan , Chen Dongyu , Chao Yali , Xu Jingyuan , Guo Lanqi , Liu Airan , Xie Jianfeng , Pan Chun , Yang Yi , Qiu Haibo , Liu Ling
Published: April 2023

Background

Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table.

Methods

This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA).

Discussion

As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date.

Trial registration

ClinicalTrial.gov NCT05207202. First published on January 26, 2022.
Functions and regulatory mechanisms of resting hematopoietic stem cells: a promising targeted therapeutic strategy
Authors: Tang Xinyu , Wang Zhenzhen , Wang Jingyi , Cui Siyuan , Xu Ruirong , Wang Yan
Published: April 2023

Hematopoietic stem cells (HSCs) are the common and essential precursors of all blood cells, including immune cells, and they are responsible for the lifelong maintenance and damage repair of blood tissue homeostasis. The vast majority (> 95%) of HSCs are in a resting state under physiological conditions and are only activated to play a functional role under stress conditions. This resting state affects their long-term survival and is also closely related to the lifelong maintenance of hematopoietic function; however, abnormal changes may also be an important factor leading to the decline of immune function in the body and the occurrence of diseases in various systems. While the importance of resting HSCs has attracted increasing research attention, our current understanding of this topic remains insufficient, and the direction of clinical targeted treatments is unclear. Here, we describe the functions of HSCs, analyze the regulatory mechanisms that affect their resting state, and discuss the relationship between resting HSCs and different diseases, with a view to providing guidance for the future clinical implementation of related targeted treatments.
Adolescent borderline personality traits and dyadic behavior shape mother-adolescent cortisol synchrony
Authors: Fleck Leonie , Fuchs Anna , Lerch Stefan , Möhler Eva , Koenig Julian , Resch Franz , Kaess Michael
Published: April 2023

Background

Associations between parent and child cortisol levels (“cortisol synchrony”) are often reported and positive synchrony may mark dyadic regulation on a physiological level. Although dyadic behavior during interaction and adolescent borderline personality disorder (BPD) traits are linked with individual and dyadic regulatory capacities, little is known about how both factors influence parent-adolescent cortisol synchrony. We hypothesized that cortisol synchrony would differ depending on behavioral synchrony, i.e., smooth reciprocal dyadic interaction patterns, adolescent BPD traits, and their interactions.

Methods

Multilevel state-trait modeling was implemented to investigate associations between concurrent mother-adolescent state cortisol and mother-adolescent average cortisol levels in a community sample of 76 mother-adolescent dyads. Three saliva samples were collected across interaction paradigms. Behavioral synchrony was observed, and adolescent BPD traits were evaluated using clinical interviews.

Results

First, behavioral synchrony and absence of BPD traits were linked with positive associations between adolescent and maternal state cortisol (positive synchrony), BPD traits with negative associations (negative synchrony). When interaction effects were examined, results were more nuanced. In low-risk dyads (higher behavioral synchrony, no BPD traits) asynchrony was found. When risk (BPD traits) and resource (higher behavioral synchrony) were combined, synchrony was positive. Lastly, in high-risk dyads (lower behavioral synchrony, adolescent BPD traits), negative synchrony was observed. Average adolescent and maternal cortisol levels were consistently positively associated in dyads with higher risk.

Conclusions

Positive dyadic interaction patterns are associated with positive state cortisol synchrony in mother-adolescent dyads and could buffer the effect of BPD traits, possibly supporting the process of physiological regulation.
Influence of low-velocity superficial layer on long-period basin-induced surface waves in eastern Osaka basin
Authors: Oprsal Ivo , Sekiguchi Haruko , Iwata Tomotaka , Burjanek Jan
Published: April 2023

The long-period strong ground motions with periods above 1 s have, in the case of farther or deeper earthquakes, potential to cause serious damage to structures with low eigen frequency, such as long bridges, oil tanks, or artificially damped structures, such as high-rise buildings. This work focuses on wave propagation due to the deep large earthquake representing rare deep damaging events of the region, with relatively sparse data coverage, studied for simple geological models computed by 2D finite differences. We model the wave propagation by finite differences using up-to-date 3D structural model of the Osaka basin. The strong surface waves in the region are not directly generated by these deep sources, but they originate by refraction mostly at the edges of the bedrock–sediments interface. The objective of this research is to model observed surface Love wave generated in the eastern part of the basin that propagates approximately westwards and is recorded by several surface stations. At these stations, the 3D finite-difference modeling provides a good fit with the observed surface wave in terms of waveform, amplitude, and arrival time for the most detailed 3D velocity model that contains topmost 50–250 m structure with the lowest S-wave velocities of 250 m/s. The semblance analysis of the synthetic wave field reveals that the respective synthetic surface wave is a result of interfering waves arriving in OSA and WOS stations from NE and SE directions. Performed tests reveal that such a synthetic wave field is extremely sensitive to the presence of the superficial 50—250 m thick low-velocity structure which is only a small fraction of the propagating surface wave length and occupies only part of the surface area. The ability to model the surface wave in terms of amplitude and time arrival validates the 3D structural model for long-period Osaka Bay earthquake scenario computations.

Graphical Abstract
Closed‐leg standing long leg radiographs can be a useful tool to assess whether the joint line is parallel to the ground in restricted kinematic alignment total knee arthroplasty
Authors: Kobayashi Takashi , Goto Kazumi , Otsu Masayoshi , Michishita Kazuhiko
Published: April 2023

Purpose

Restricted kinematic alignment (rKA) is a modified technique of kinematic alignment (KA) total knee arthroplasty (TKA) for patients with an outlier or atypical knee anatomy, striving to preserve the native knee joint line parallel to the ground in a bipedal stance. This study aimed to evaluate the accuracy of rKA TKA with a computed tomography (CT)‐based patient‐specific instrument (PSI) to achieve the preoperative plan with the joint line parallel to the ground level.

Methods

Using a CT‐based PSI, 74 closed‐leg standing long‐leg radiographs were obtained before and after rKA TKA. The hip‐knee‐ankle angle (HKA), joint line orientation angle (JLOA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. Bone resection accuracy was evaluated by postoperative HKA deviations from the planned alignment and joint line by postoperative JLOA deviations from the ground level.

Results

The mean postoperative JLOA and HKA were 2.1° valgus (range, standard deviation: 6.0° valgus to 3.0° varus, 2.0) and 2.6° varus (3.5° valgus to 12.5° varus, 3.2), respectively. Postoperative JLOA and HKA were within ± 3° of the planned alignment for 69% and 86% of cases, respectively.

Conclusions

Despite a static verification, we clarified how the joint line after rKA TKA was reproduced in the closed‐leg long leg radiographs to mimic the limb position during gait. However, this imaging method is not well‐established, and lack of long‐term survivorship and the relationship between joint line inclination and clinical outcomes represented limitations of this study.

Level of evidence

Level IV.
Update of global maps of Alisov’s climate classification
Authors: Shimabukuro Ryu , Tomita Tomohiko , Fukui Ken-ichi
Published: April 2023

Proposed in 1954, Alisov’s climate classification (CC) focuses on climatic changes observed in January–July in large-scale air mass zones and their fronts. Herein, data clustering by machine learning was applied to global reanalysis data to quantitatively and objectively determine air mass zones, which were then used to classify the global climate. The differences in air mass zones between two half-year seasons were used to determine climatic zones, which were then subdivided into continental or maritime climatic regions or according to east–west climatic differences. This study renews Alisov’s CC for the first time in almost 70 years and employs data-driven machine learning to establish a standard for causal CC based on air masses.
Investigating and preventing scientific misconduct using Benford’s Law
Authors: Eckhartt Gregory M. , Ruxton Graeme D.
Published: April 2023

Integrity and trust in that integrity are fundamental to academic research. However, procedures for monitoring the trustworthiness of research, and for investigating cases where concern about possible data fraud have been raised are not well established. Here we suggest a practical approach for the investigation of work suspected of fraudulent data manipulation using Benford’s Law. This should be of value to both individual peer-reviewers and academic institutions and journals. In this, we draw inspiration from well-established practices of financial auditing. We provide synthesis of the literature on tests of adherence to Benford’s Law, culminating in advice of a single initial test for digits in each position of numerical strings within a dataset. We also recommend further tests which may prove useful in the event that specific hypotheses regarding the nature of data manipulation can be justified. Importantly, our advice differs from the most common current implementations of tests of Benford’s Law. Furthermore, we apply the approach to previously-published data, highlighting the efficacy of these tests in detecting known irregularities. Finally, we discuss the results of these tests, with reference to their strengths and limitations.
Climate change impact on the healthcare provided to patients
Authors: Al-Marwani Sabah
Published: April 2023

Background

The last several years have shed light on the fact that changes in the global climate pose one of the greatest dangers to mankind and life on Earth. Even though a growing amount of attention is being paid to the acute consequences of climate change on human health, there is still very little that is recognized or understood about the impacts of climate change events on patient-related aspects, especially patient care and safety.

Aim

This study aims to fill the gap in the literature and provide a comprehensive synopsis and critical investigation of the effects of climate change on patient care and safety.

Methodology

This research is based on a narrative review which was more appropriate to provide a descriptive analysis of the topic of interest and to be suitable for the wide scope of the study. The research was conducted using several databases with no restriction on the date of the publication of searched documents and resulted in 34 articles which were then further assessed by removing any duplications and repetitions to have by the end 15 publications. The references of all included documents were further checked for additional relevant items. The study lasted for four months starting from 09/09/2022 to the last search date 10/01/2023.

Main results

Losing access to healthcare facilities, shortage in drugs due to disruption of supply chains resulting from climate extreme events, infections spread, increasing occurrence of medical errors, the emergence of new diseases, raising many problems with the safety of drug use, increasing patients vulnerability, delay in cancer detection and management, and worsening prognosis of cancer cases, are examples of the catastrophic effects that climate change poses on the health and patients care.

Conclusions

This study highlights the catastrophic impacts of climate change on patient care and safety and emphasizes the critical need for immediate action to reduce climate change and build more resilient healthcare systems.