bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the “obesity paradox” exist after transcatheter aortic valve implantation?
Authors: Luo Zeng-Rong , Chen Liang-wan , Qiu Han-Fan
Published: June 2022

Background

Transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis is considered a minimally invasive procedure. Body mass index (BMI) has been rarely evaluated for pulmonary complications after TAVI. This study aimed to assess the influence of BMI on pulmonary complications and other related outcomes after TAVI.

Methods

The clinical data of 109 patients who underwent TAVI in our hospital from May 2018 to April 2021 were retrospectively analyzed. Patients were divided into three groups according to BMI: low weight (BMI < 21.9 kg/m2, n = 27), middle weight (BMI 21.9–27.0 kg/m2, n = 55), and high weight (BMI > 27.0 kg/m2, n = 27); and two groups according to vascular access: through the femoral artery (TF-TAVI, n = 94) and through the transapical route (TA-TAVI, n = 15). Procedure endpoints, procedure success, and adverse outcomes were evaluated according to the Valve Academic Research Consortium (VARC)-2 definitions.

Results

High-weight patients had a higher proportion of older (p < 0.001) and previous percutaneous coronary interventions (p = 0.026), a higher percentage of diabetes mellitus (p = 0.026) and frailty (p = 0.032), and lower glomerular filtration rate (p = 0.024). Procedure success was similar among the three groups. The 30-day all-cause mortality of patients with low-, middle-, and high weights was 3.7% (1/27), 5.5% (3/55), and 3.7% (1/27), respectively. In the multivariable analysis, middle- and high-weight patients exhibited similar overall mortality (middle weight vs. low weight,p = 0.500; high weight vs. low weight,p = 0.738) and similar intubation time compared with low-weight patients (9.1 ± 7.3 h vs. 8.9 ± 6.0 h vs. 8.7 ± 4.2 h in high-, middle-, and low-weight patients, respectively,p = 0.872). Although high-weight patients had a lower PaO2/FiO2ratio than low-weight patients at baseline, transitional extubation, and post extubation 12th hour (p = 0.038, 0.030, 0.043, respectively), there were no differences for post extubation 24th hour, post extubation 48th hour, and post extubation 72nd hour (p = 0.856, 0.896, 0.873, respectively). Chronic lung disease [odds ratio (OR) 8.038,p = 0.001] rather than high weight (OR 2.768,p = 0.235) or middle weight (OR 2.226,p = 0.157) affected postoperative PaO2/FiO2after TAVI.

Conclusions

We did not find the existence of an obesity paradox after TAVI. BMI had no effect on postoperative intubation time. Patients with a higher BMI should be treated similarly without the need to deliberately extend the intubation time for TAVI.
Recommendations for the diagnosis and management of childhood Prader-Willi syndrome in China
Authors: Yang-Li Dai , Fei-Hong Luo , Hui-Wen Zhang , Ming-Sheng Ma , Xiao-Ping Luo , Li Liu , Yi Wang , Qing Zhou , Yong-Hui Jiang , Chao-Chun Zou ,   PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Xiao-Ou Shan , Yu Yang , Hui-Feng Zhang , Zhi-Liang Tian , Bo Sun , Mei Lu , Ya-Ying Cheng , Ying Yang , Xiong-Ying Yu , Jing Zhang , Xiao-Hong Chen , Fan Yang , Hong-Wei Ma , Maimaiti MireguIi , Gai-Xiu Zhang , Xiao-Hong Chen , Gui-Mie Li , Fan Tong ,   Zhejiang Expert Group for PWS, Ming-Qiang Zhi , Qiong Zhou , Yuan Gao , Kan Wang , Xiao-Ming Ying , Jian-Ping Zhang , Chun-Lin Wang , Chun-Ming Jiang , Rui Xiao
Published: June 2022

Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on chromosome15q11.2-q13.1. The clinical manifestations of PWS vary with age. It is characterized by severe hypotonia with poor suck and feeding difficulties in the early infancy, followed by overeating in late infancy or early childhood and progressive development of morbid obesity unless the diet is externally controlled. Compared to Western PWS patients, Chinese patients have a higher ratio of deletion type. Although some rare disease networks, including PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Zhejiang Expert Group for PWS, were established recently, misdiagnosis, missed diagnosis and inappropriate intervention were usually noted in China. Therefore, there is an urgent need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy. Our purpose is to evaluate the current literature and evidences on diagnosis and management of PWS in order to provide evidence-based guidelines for this disease, specially from China.
Analysis of 55 patients with multiple endocrine neoplasia type 1-associated insulinoma from a single center in China
Authors: Zhao Yuan , Yu Jie , Liu Yiwen , Lyu Lu , Ping Fan , Xu Lingling , Li Wei , Wang Ou , Xu Qiang , Wu Wenming , Zhang Huabing , Li Yuxiu
Published: June 2022

Objective

To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis.

Methods

“MEN1” and “insulinoma” were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data.

Results

A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p < 0.001) during hypoglycemic episodes. However, serum C-peptide level at 0.5 h and serum insulin level at 1 h was higher in patients with hypercalcemia than in patients with normal serum Ca levels in the oral glucose tolerance test (OGTT), although the differences were not statistically significant. Multifocal pancreatic neuroendocrine tumors (pNETs) were present in 38 (69.1%) patients; most of them (55.6%, 20/36) underwent multiple enucleations, and 45% (9/20) had a postoperative recurrence. Five patients (10%) who underwent distal pancreatectomy developed pancreatic insufficiency after an average of seven years. patients who underwent genetic testing, 23 (95.8%) were positive for MEN1 mutation, with mutations most commonly found in exons 2 (21.7%) and 3 (13%).

Conclusions

In our study, the rates of postoperative recurrence and long-term complications in patients with MEN1 with multifocal pNETs were significantly different from those in other international centers and might be related to the choice of surgical method. In addition, elevated serum Ca levels in patients with primary hyperparathyroidism may affect insulin secretion.
Analysis of the genotypic profile and its relationship with the clinical manifestations in people with cystic fibrosis: study from a rare disease registry
Authors: Rueda-Nieto Senay , Mondejar-Lopez Pedro , Mira-Escolano María-Pilar , Cutillas-Tolín Ana , Maceda-Roldán Luis Alberto , Arense-Gonzalo Julián Jesús , Palomar-Rodríguez Joaquín A.
Published: June 2022

Background

Cystic fibrosis (CF) has a vast and heterogeneous mutational spectrum in Europe. This variability has also been described in Spain, and there are numerous studies linking CFTR variants with the symptoms of the disease. Most of the studies analysed determinate clinical manifestations or specific sequence variants in patients from clinical units. Others used registry data without addressing the genotype–phenotype relationship. Therefore, the objective of this study is to describe the genetic and clinical characteristics of people with CF and to analyse the relationship between both using data from the rare disease registry of a region in southeastern Spain.

Methods

A cross-sectional study was carried out in people with a confirmed diagnosis of CF registered in the Rare Diseases Information System (SIER) of the Region of Murcia (Spain). The patients were classified into two genotypes according to the functional consequence that the genetic variants had on the CFTR protein.

Results

There were 192 people diagnosed with CF reported in the Region of Murcia as of 31 December 2018. Seventy-six genotypes and 49 different variants were described, with c.1521_1523delCTT (p. Phe508del) being the most common in 58.3% of the CF patients and 37.0% of the alleles. In addition, 67% of the patients were classified as a high-risk genotype, which was associated with a lower percentage of FEV1 (OR: 5.3; 95% CI: 1.2, 24.4), an increased risk of colonization by Pseudomonas aeruginosa (OR: 7.5; 95% CI: 1.7, 33.0) and the presence of pancreatic insufficiency (OR: 28.1; 95% CI: 9.3, 84.4) compared to those with a low-risk genotype.

Conclusions

This is the first study in Spain that describes the mutational spectrum and its association with clinical manifestations in patients with CF using data from a rare disease registry. The results obtained allow planning for the health resources needed by people with this disease, thus contributing to the development of personalized medicine that helps to optimize health care in CF patients.
Health technology assessment and price negotiation alignment for rare disorder drugs in Canada: Who benefits?
Authors: Rawson Nigel S. B.
Published: June 2022

Background

Since 2014, the Canadian Agency for Drugs and Technologies in Health (CADTH), which performs health technology assessments for all federal, provincial and territorial government drug programs (except Quebec’s) and the pan-Canadian Pharmaceutical Alliance (pCPA), which conducts price negotiations with manufacturers for all government drug programs, have been aligning their processes.

Objective

To examine trends in CADTH recommendations for non-oncology drugs for rare disorders (DRDs) released between 2014 and 2021, results of pCPA negotiations for the same drugs, and listings in government drug plans to assess who benefits from the alignment.

Results

Recommendations were positive in 87% of the reviews, although all included clinical criteria for use and/or economic conditions. Almost 90% of the DRDs with a positive recommendation had a successful price negotiation and 71% of those with a negative recommendation had no negotiation. Although no recommendation published before mid-2016 had a specified price reduction, almost 95% of those issued afterwards included the price reduction required to achieve a specific low cost-effectiveness threshold. The median time between the DRDs receiving marketing approval and a completed price negotiation was 663 days. Negotiations for DRDs completed after 2017 generally had fewer listings in government drug plans, but there was no distinct trend. The drug’s price likely played a role in listing decisions. When DRDs were listed, drug plans had access criteria consistent with CADTH’s or stronger for all the DRDs.

Conclusions

The governments who own, fund and manage CADTH and the pCPA benefit from their alignment. The alignment is less beneficial for patients waiting for access to the DRDs. The time taken by CADTH and pCPA actions and individual government drug plans to make listing decisions delays access. CADTH’s clinical criteria have become more extensive and are applied rigorously by drug plans which restricts patient access to DRDs. Canadians with rare disorders urgently need their governments to implement a long-overdue, comprehensive rare disease strategy to ensure DRDs are reviewed and reimbursed quickly and equitably to provide adequate health care to all who need them.
Social support, perceived stigma, and depression among PLHIV on second-line antiretroviral therapy using structural equation modeling in a multicenter study in Northeast Ethiopia
Authors: Wedajo Shambel , Degu Getu , Deribew Amare , Ambaw Fentie
Published: June 2022

Background

Depression has a multitude of clinical and public health consequences for HIV patients. The magnitude of HIV patients who failed first-line antiretroviral treatment and switched to second-line therapy is becoming a growing public health concern. However, unlike first-line therapy, to date, little attention has been given to mental health problems in such patients, particularly in the era of the COVID-19 pandemic. Thus, this research was conducted to determine the magnitude of depression and its determinants among HIV patients on second-line antiretroviral therapy.

Methods

A multi-centered cross-sectional study was conducted on 714 HIV patients on second-line therapy who were selected via systematic random sampling. Data were collected in personal interviews as well as document reviews. The nine-item patient health questionnaire score was used to assess depression, while the three-item Oslo Scale was used to assess social support. The associations between exogenous, mediating, and endogenous variables were identified simultaneously using structural equation modeling. Statistical significance was declared at a P-value less than 0.05, and the effect sizes were presented using 95% CI.

Results

Depression was reported in 27.7% of HIV patients on second-line therapy [95% CI: 24.7–31.1%]. Social support has a direct [$$\widehat{\beta }$$

β
^

= − 0.9, (95% CI: − 1.11 to − 0.69)] and indirect [$$\widehat{\beta }$$

β
^

= − 0.22, (95% CI: − 0.31 to − 0.13)] negative effect on depression. Perceived stigma was a mediator variable and significantly associated with depression [$$\widehat{\beta }$$

β
^

= 0.40, (95% CI: 0.23–0.57)]. Co-morbid illness [$$\widehat{\beta }$$

β
^

= 0.49, (95% CI: 0.35–0.63)], high viremia [$$\widehat{\beta }$$

β
^

= 0.17, (95% CI: 0.08–0.26], moderate and high-risk substance use [$$\widehat{\beta }$$

β
^

= 0.29, (95% CI: 0.18–0.39)], and not-workable functional status [$$\widehat{\beta }$$

β
^

= 0.2, (95% CI: 0.1–0.31)] were all positively associated with depression.

Conclusions

This study revealed that there was a high prevalence of depression among HIV patients on second-line antiretroviral therapy. Social and clinical factors were associated with depression risk. As a result, screening, prevention, and control strategies, including psychosocial support, should be strengthened in routine clinical care.
RETRACTED ARTICLE: Immune characteristics of children with autoimmune encephalitis and the correlation with a short-term prognosis
Authors: Huang Jin-Yue , Fan Wen-Xuan , Meng Jing , Cai Chun-Quan , Li Dong
Published: June 2022

Background

Autoimmune encephalitis (AE) is a type of encephalopathy mediated by an antigenic immune response in the central nervous system. Most research related to autoimmune encephalitis (AE) is focused on early diagnosis, treatment and prognosis analysis; there has been little research conducted on the characteristics of immune function, and the relationship between immune function and prognoses of patients with autoimmune encephalitis needs to be studied further.

Methods

A total of 33 children with autoimmune encephalitis were identified through the clinic database and inpatient consults at Tianjin Children’s Hospital from January 2013 to January 2021. Based on the one-year follow-up and the modified Rankin Scale (mRS) prognosis score, they were divided into a good prognosis group and a poor prognosis group. The immune function characteristics of the two groups of children with autoimmune encephalitis (AE) were compared using Spearman correlation to analyse the mRS score and immune function indicators (IgA, IgG, IgM, CD4, CD8, CD4/CD8), and binary logistic regression was used to analyse the independent risk factors of the prognoses in patients with autoimmune encephalitis (AE).

Results

The differences in abnormal mental disorders and limb dyskinesia, cognitive impairment, onset types, modified Rankin Scale (mRS) scores at admission, and immune function status during remission between the two groups were statistically significant (p < 0.05).

Conclusion

There is a close correlation between modified Rankin Scale (mRS) scores and the immune function index CD4/CD8 in children with autoimmune encephalitis (AE) when they are admitted to the hospital. A young age, disturbance of consciousness, limb dyskinesia, abnormal immune function in remission and anti-NMDAR encephalitis are risk factors for poor prognoses in children with autoimmune encephalitis (AE). Clinical treatment requires more attention.
Impact of dexamethasone on the incidence of ventilator-associated pneumonia in mechanically ventilated COVID-19 patients: a propensity-matched cohort study
Authors: Scaravilli Vittorio , Guzzardella Amedeo , Madotto Fabiana , Beltrama Virginia , Muscatello Antonio , Bellani Giacomo , Monti Gianpaola , Greco Massimiliano , Pesenti Antonio , Bandera Alessandra , Grasselli Giacomo
Published: June 2022

Objective

To assess the impact of treatment with steroids on the incidence and outcome of ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 patients.

Design

Propensity-matched retrospective cohort study from February 24 to December 31, 2020, in 4 dedicated COVID-19 Intensive Care Units (ICU) in Lombardy (Italy).

Patients

Adult consecutive mechanically ventilated COVID-19 patients were subdivided into two groups: (1) treated with low-dose corticosteroids (dexamethasone 6 mg/day intravenous for 10 days) (DEXA+); (2) not treated with corticosteroids (DEXA−). A propensity score matching procedure (1:1 ratio) identified patients' cohorts based on: age, weight, PEEP Level, PaO2/FiO2 ratio, non-respiratory Sequential Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index (CCI), C reactive protein plasma concentration at admission, sex and admission hospital (exact matching).

Intervention

Dexamethasone 6 mg/day intravenous for 10 days from hospital admission.

Measurements and main results

Seven hundred and thirty-nine patients were included, and the propensity-score matching identified two groups of 158 subjects each. Eighty-nine (56%) DEXA+ versus 55 (34%) DEXA− patients developed a VAP (RR 1.61 (1.26–2.098), p = 0.0001), after similar time from hospitalization, ICU admission and intubation. DEXA+ patients had higher crude VAP incidence rate (49.58 (49.26–49.91) vs. 31.65 (31.38–31.91)VAP*1000/pd), (IRR 1.57 (1.55–1.58), p < 0.0001) and risk for VAP (HR 1.81 (1.31–2.50), p = 0.0003), with longer ICU LOS and invasive mechanical ventilation but similar mortality (RR 1.17 (0.85–1.63), p = 0.3332). VAPs were similarly due to G+ bacteria (mostly Staphylococcus aureus) and G− bacteria (mostly Enterobacterales). Forty-one (28%) VAPs were due to multi-drug resistant bacteria. VAP was associated with almost doubled ICU and hospital LOS and invasive mechanical ventilation, and increased mortality (RR 1.64 [1.02–2.65], p = 0.040) with no differences among patients' groups.

Conclusions

Critically ill COVID-19 patients are at high risk for VAP, frequently caused by multidrug-resistant bacteria, and the risk is increased by corticosteroid treatment.

Trial registration: NCT04388670, retrospectively registered May 14, 2020.
Communication Bridge™-2 (CB2): an NIH Stage 2 randomized control trial of a speech-language intervention for communication impairments in individuals with mild to moderate primary progressive aphasia
Authors: Roberts Angela C. , Rademaker Alfred W. , Salley Elizabeth Ann , Mooney Aimee , Morhardt Darby , Fried-Oken Melanie , Weintraub Sandra , Mesulam Marsel , Rogalski Emily
Published: June 2022

Background

Primary progressive aphasia (PPA) is a clinical dementia syndrome. Impairments in language (speaking, reading, writing, and understanding) are the primary and persistent symptoms. These impairments progress insidiously and devastate communication confidence, participation, and quality of life for persons living with PPA. Currently, there are no effective disease modifying treatments for PPA. Speech-language interventions hold promise for mitigating communication challenges and language symptoms. However, evidence regarding their efficacy in PPA is of low quality and there are currently no rigorous randomized trials.

Method

Communication Bridge™-2 (CB2) is a Stage 2, superiority, single-blind, randomized, parallel group, active-control, behavioral clinical trial delivered virtually within a telehealth service delivery model to individuals with PPA. Ninety carefully characterized participants with clinically confirmed PPA will be randomized to one of two speech-language intervention arms: (1) Communication Bridge™ a dyadic intervention based in communication participation therapy models that incorporates salient training stimuli or (2) the control intervention a non-dyadic intervention based in impairment therapy models addressing word retrieval and language production that incorporates fixed stimuli. The superiority of Communication Bridge™ over the Control arm will be evaluated using primary outcomes of communication confidence and participation. Other outcomes include accuracy for trained words and scripts. Participants complete two therapy blocks over a 12-month period. Outcomes will be measured at baseline, at each therapy block, and at 12 months post enrollment.

Discussion

The CB2 trial will supply Level 2 evidence regarding the efficacy of the Communication Bridge™ intervention delivered in a telehealth service delivery model for individuals with mild to moderate PPA. An important by-product of the CB2 trial is that these data can be used to evaluate the efficacy of speech-language interventions delivered in both trial arms for persons with PPA. The impact of these data should not be overlooked as they will yield important insights examining why interventions work and for whom, which will advance effectiveness trials for speech-language interventions in PPA.

Trial Registration

ClinicalTrials.govNCT03371706. Registered prospectively on December 13, 2017.
TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II–III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis
Authors: Berry Catherine , du Cros Philipp , Fielding Katherine , Gajewski Suzanne , Kazounis Emil , McHugh Timothy D. , Merle Corinne , Motta Ilaria , Moore David A. J. , Nyang’wa Bern-Thomas
Published: June 2022

Background

Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9–24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis.

Methods

TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site.

Discussion

TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment.

Trial registration

Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.
Establishing a core outcome set for neurogenic bladder trials: study protocol for a scoping review and Delphi surveys
Authors: Zhang Yan , Chen Yamin , Niu Mingming , Li Yuanyuan , Zhang Jiaoyan , Zhang Li , Wu Fangfang , Chen Qingyun , Yu Huijin , Tian Jinhui
Published: June 2022

Background

Neurogenic bladder (NGB) is a chronic and disabling condition with a high prevalence rate, which can cause economic burden on patients and their families and reduce the quality of life of patients. Researchers have carried out a large number of clinical trials on the effectiveness and safety of different interventions for the treatment of NGB. The published clinical trials of NGB generally suffered from inconsistent and irregular reporting of outcome indicators. To facilitate future research studies of NGB, a core outcome set (COS) is required, which helps translate the results into high-quality evidence.

Methods and analysis

This mixed-method project has four phases instrument: in phase 1, a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of clinical trials of interventions for NGB; in phase 2, a qualitative component using interviews to obtain the views of NGB patients, families, and their caregivers; in phase 3, Delphi survey among stakeholders to prioritize the core outcomes; and in phase 4, a face-to-face consensus meeting to discuss and agree on the final NBG COS.

Conclusions

We will develop a COS that should be reported in future clinical trials of NGB.

Trial registration

Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration:http://www.comet-initiative.org/studies/details/1985. Registered on 02 January 2022. INPLASY INPLASY202210007
Effect of smartphone app-based health care intervention for health management of high-risk mothers: a study protocol for a randomized controlled trial
Authors: Kim Bora , Moon Jong Youn , Shin Jae Yong , Jeon Hae Rin , Oh So Yeon , Kim Suk Young
Published: June 2022

Background

The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life.

Methods

This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework.

Discussion

These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers.

Trial registration

Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows:

Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193. Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022.
Efficacy of dexmedetomidine on postoperative pain in patients undergoing gastric and esophageal endoscopic submucosal dissection: a study protocol for a randomized controlled prospective trial
Authors: Luo Xin , An Li-Xin , Chen Pei-Shan , Chang Xin-Lu , Li Yang
Published: June 2022

Background

Endoscopic submucosal dissection (ESD) is widely used as an effective treatment of early gastric and esophageal tumors, as it is minimally invasive, safe, and convenient. Epigastric pain is a common complication of ESD. In the traditional cognition, the postoperative pain of ESD is not serious and does not attach too much attention. However, previous studies found that the incidence of moderate to severe pain after ESD can be as high as 44.9~62.8%. At present, there is no unified understanding of how to carry out good postoperative analgesia in patients undergoing ESD of stomach and esophagus. The purpose of present study is to investigate the efficacy of intraoperative dexmedetomidine (DEX) using on postoperative pain though observing the postoperative visual analog scale (VAS) score within 48 h after ESD surgery, so as to explore an effective analgesia and anesthetic method in patients undergoing gastric and esophagus ESD.

Methods/design

This study is a prospective, single-center, two-arm, randomized control trail. In total, 120 patients undergoing endoscopic submucosal dissection were stratified by type of surgery (i.e., gastric or esophagus ESD) and randomized into two treatment groups, DEX group (group D, n = 60) and control group (group C, n = 60). Patients in the experimental group (DEX group) will be administrated a loading dose of DEX at 1 μg/kg for 15 min and a continuous infusion at 0.6 μg/kg/h until 30 min before the end of operation. In control group, the same volume of normal saline was infused. The primary outcome is VAS at 2 h after ESD surgery. The secondary outcome will be VAS at 1 h, 4 h, 6 h,18 h, 24 h, and 48 h, the status of perioperative hemodynamics, the use of remedial analgesics, sedation score, shivering, postoperative nausea and vomiting (PONV), and satisfaction scores of patient and complication of ESD (such as bleeding, perforation, aspiration pneumonia).

Discussion

The results of this study will demonstrate that intraoperative application of DEX is beneficial for postoperative pain treatment in patients undergoing ESD. This study will not only confirm that postoperative pain treatment is necessary for patients undergoing ESD but also provides an effective anesthesia method for postoperative analgesia.

Trial registration

Chinese Clinical Trial Registry, ID: ChiCTR2100043837, registered on March 4, 2021, http://www.chictr.org.cn.
Influence on study outcomes of an inpatient study by the behavior of the study staff (PINgPOng): study protocol for a randomized clinical trial
Authors: Coenen Martin , Bingel Ulrike , Zunhammer Matthias , Berdaguer Maria Soledad , Fuhrmann Christine , Fimmers Rolf , Rengelshausen Jens , Hartmann Gunther , Schedlowski Manfred , Coch Christoph
Published: June 2022

Background

The placebo effect as the symptom improvement following inert treatments is a fixed component of RCTs to differentiate between specific effects of the tested pharmacological substance from other unspecific effects. The PINgPOng study was set up to analyze the influence of a study team trained to either minimize the placebo response and optimize drug-placebo differences or to maximize the placebo response to increase drug efficacy by unspecific factors on the study results of a RCT in a classical early clinical trial setting.

Methods/design

PINgPOng is a single-center, prospective, randomized, double-blind, placebo-controlled study in a 3-group, 2-sequence, 2-period cross-over design. The study is conducted according to the principles of ICH-GCP and the Declaration of Helsinki on the Phase I-Unit of the University Hospital Bonn. The primary endpoint is the pain intensity in the cold pressor test before and after the administration of 15 mg oxycodone or placebo. The pain intensity is compared between three study conditions: 32 healthy volunteers in each study arm will be treated either by an untrained study team (arm A), by a study team trained to maximize (arm B), or to minimize placebo responses (arm C). Neuroendocrine factors (alpha-amylase activity, salivary cortisol), characteristic traits (anxiety, depression, stress), and somatic reactions are analyzed as covariates of the pain perception.

Discussion

The PINgPOng study will allow to answer the question whether and to what extent the behavior of a trained study team (neutral vs. maximize vs. minimize placebo responses) will differentially affect placebo responses in a setting of a highly standardized early clinical trial. The results will help to control the placebo effects by education of the clinical study team and to avoid unnecessary high placebo effects in clinical development.

Trial registration

German Clinical Trials Register DRKS00013586. Registered on December 22, 2017.
Amplification of LTRs of extrachromosomal linear DNAs (ALE-seq) identifies two active Oryco LTR retrotransposons in the rice cultivar Dongjin
Authors: Koo Hyunjin , Kim Soomin , Park Hyun-Seung , Lee Sang-Ji , Paek Nam-Chon , Cho Jungnam , Yang Tae-Jin
Published: June 2022

Long terminal repeat retrotransposons (LTR-RTs) make up a considerable portion of plant genomes. New insertions of these active LTR-RTs modify gene structures and functions and play an important role in genome evolution. Therefore, identifying active forms of LTR-RTs could uncover the effects of these elements in plants. Extrachromosomal linear DNA (eclDNA) forms during LTR-RT replication; therefore, amplification LTRs of eclDNAs followed by sequencing (ALE-seq) uncover the current transpositional potential of the LTR-RTs. The ALE-seq protocol was validated by identification of Tos17 in callus of Nipponbare cultivar. Here, we identified two active LTR-RTs belonging to the Oryco family on chromosomes 6 and 9 in rice cultivar Dongjin callus based on the ALE-seq technology. Each Oryco family member has paired LTRs with identical sequences and internal domain regions. Comparison of the two LTR-RTs revealed 97% sequence identity in their internal domains and 65% sequence identity in their LTRs. These two putatively active Oryco LTR-RT family members could be used to expand our knowledge of retrotransposition mechanisms and the effects of LTR-RTs on the rice genome.
KNIME workflow for retrieving causal drug and protein interactions, building networks, and performing topological enrichment analysis demonstrated by a DILI case study
Authors: Füzi Barbara , Malik-Sheriff Rahuman S. , Manners Emma J. , Hermjakob Henning , Ecker Gerhard F.
Published: June 2022

As an alternative to one drug-one target approaches, systems biology methods can provide a deeper insight into the holistic effects of drugs. Network-based approaches are tools of systems biology, that can represent valuable methods for visualizing and analysing drug-protein and protein–protein interactions. In this study, a KNIME workflow is presented which connects drugs to causal target proteins and target proteins to their causal protein interactors. With the collected data, networks can be constructed for visualizing and interpreting the connections. The last part of the workflow provides a topological enrichment test for identifying relevant pathways and processes connected to the submitted data. The workflow is based on openly available databases and their web services. As a case study, compounds of DILIRank were analysed. DILIRank is the benchmark dataset for Drug-Induced Liver Injury by the FDA, where compounds are categorized by their likeliness of causing DILI. The study includes the drugs that are most likely to cause DILI (“mostDILI”) and the ones that are not likely to cause DILI (“noDILI”). After selecting the compounds of interest, down- and upregulated proteins connected to the mostDILI group were identified; furthermore, a liver-specific subset of those was created. The downregulated sub-list had considerably more entries, therefore, network and causal interactome were constructed and topological pathway enrichment analysis was performed with this list. The workflow identified proteins such as Prostaglandin G7H synthase 1 and UDP-glucuronosyltransferase 1A9 as key participants in the potential toxic events disclosing the possible mode of action. The topological network analysis resulted in pathways such as recycling of bile acids and salts and glucuronidation, indicating their involvement in DILI. The KNIME pipeline was built to support target and network-based approaches to analyse any sets of drug data and identify their target proteins, mode of actions and processes they are involved in. The fragments of the pipeline can be used separately or can be combined as required.
Commentary: the first twelve years of the Journal of Cheminformatics
Authors: Willett Peter
Published: June 2022

This commentary provides an overview of the publications in, and the citations to, the first twelve volumes of the Journal of Cheminformatics, covering the period 2009–2020. The analysis is based on the 622 articles that have appeared in the journal during that time and that have been indexed in the Clarivate Web of Science Core Collection database. It is clear that the journal has established itself as one of the most important publications in the field of cheminformatics: it attracts citations not only from other journals in its specialist field but also from biological and chemical journals more widely, and moreover from journals that are far removed in focus from it but that are still able to benefit from the articles that it publishes.
Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health
Authors: Taillieu Emily , Chiers Koen , Amorim Irina , Gärtner Fátima , Maes Dominiek , Van Steenkiste Christophe , Haesebrouck Freddy
Published: June 2022

This article focuses on the pathogenic significance ofHelicobacterspecies naturally colonizing the stomach of dogs, cats and pigs. These gastric “non-Helicobacter(H.)pylori Helicobacterspecies” (NHPH) are less well-known than the human adaptedH. pylori.Helicobacter suishas been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of thepars oesophageaof the porcine stomach.The stomach of dogs and cats can be colonized by severalHelicobacterspecies but their pathogenic significance for these animals is probably low.Helicobacter suisas well as several canine and feline gastricHelicobacterspecies may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, forH. suis, also consumption of contaminated pork. It has been described that standardH. pylorieradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcineH. suisstrains are intrinsically less susceptible to aminopenicillins than non-human primateH. suisstrains and other gastricHelicobacterspecies. Virulence factors ofH. suisand the canine and feline gastricHelicobacterspecies include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors inH. pylori.It can be concluded that besidesH. pylori, gastricHelicobacterspecies associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.
Loop diuretics in adult intensive care patients with fluid overload: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis
Authors: Wichmann Sine , Barbateskovic Marija , Liang Ning , Itenov Theis Skovsgaard , Berthelsen Rasmus Ehrenfried , Lindschou Jane , Perner Anders , Gluud Christian , Bestle Morten Heiberg
Published: June 2022

Background

Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients.

Methods

We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799).

Results

We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49–1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15–3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66–0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55–1.20).

Conclusions

The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.
Joint high-dimensional soft bit estimation and quantization using deep learning
Authors: Arvinte Marius , Vishwanath Sriram , Tewfik Ahmed H. , Tamir Jonathan I.
Published: June 2022

Forward error correction using soft probability estimates is a central component in modern digital communication receivers and impacts end-to-end system performance. In this work, we introduce EQ-Net: a deep learning approach for joint soft bit estimation (E) and quantization (Q) in high-dimensional multiple-input multiple-output (MIMO) systems. We propose a two-stage algorithm that uses soft bit quantization as pretraining for estimation and is motivated by a theoretical analysis of soft bit representation sizes in MIMO channels. Our experiments demonstrate that a single deep learning model achieves competitive results on both tasks when compared to previous methods, with gains in quantization efficiency as high as$$20\%$$20%and reduced estimation latency by at least$$21\%$$21%compared to other deep learning approaches that achieve the same end-to-end performance. We also demonstrate that the quantization approach is feasible in single-user MIMO scenarios of up to$$64 \times 64$$64×64and can be used with different soft bit estimation algorithms than the ones during training. We investigate the robustness of the proposed approach and demonstrate that the model is robust to distributional shifts when used for soft bit quantization and is competitive with state-of-the-art deep learning approaches when faced with channel estimation errors in soft bit estimation.
Existence and stability results for non-hybrid single-valued and fully hybrid multi-valued problems with multipoint-multistrip conditions
Authors: Rezapour Shahram , Ahmad Bashir , Boutiara Abdellatif , Nonlaopon Kamsing , Etemad Sina
Published: June 2022

In this paper, we study a new class of non-hybrid single-valued fractional boundary value problems equipped with integro-non-hybrid-multiterm-multipoint-multistrip conditions and a fully hybrid integro-multi-valued fractional boundary value problem by some new methods including the Kuratowski measures based on Sadovskii’s theorem, Krasnoselskii–Zabreiko criterion, and Dhage’s technique. We generalize the Gronwall inequality in relation to a non-hybrid single-valued fractional boundary value problem, and then we investigate the stability notions in two versions. To examine the correctness of the results, we provide some examples.
Incorporating fantasy into gamification promotes student learning and quality of online interaction
Authors: Bai Shurui , Hew Khe Foon , Gonda Donn Emmanuel , Huang Biyun , Liang Xinyi
Published: June 2022

We used the design-based research approach to test and refine a theoretically grounded goal-access-feedback-challenge-collaboration gamification model. The testbed was a 10-week, university-level e-learning design course offered in two consecutive semesters. In Study 1, we implemented the initial goal-access-feedback-challenge-collaboration model in semester one of the 2020–2021 academic year (N = 26). The aim was to enhance student behavioral engagement in online discussion forums, affective engagement in the class, and learning performance. The results of Study 1 showed that although most participants were engaged in this gamified learning experience during the first two sessions, they gradually lost interest and their participation in online discussions dropped over the next eight weeks. Thus, we introduced a new element, fantasy, into the original model. In Study 2, we tested the effectiveness of the goal-access-feedback-challenge-collaboration-fantasy model on students’ learning outcomes in semester two of 2020–2021 (N = 23). The results of Study 2 suggested that, compared to the original model, the goal-access-feedback-challenge-collaboration-fantasy model can better promote students’ engagement in online discussion, as measured by increased interaction with peers, learning experience, and learning performance.