bluuebunny/crossref_metadata_2025 huggingface dataset:
A smoking cessation intervention for people with severe mental illness treated in ambulatory mental health care (KISMET): study protocol of a randomised controlled trial
Authors: Küçükaksu Müge H. , van Meijel Berno , Jansen Lola , Hoekstra Trynke , Adriaanse Marcel C.
Published: February 2023

Background

Smoking among people with severe mental illness (SMI) is highly prevalent and strongly associated with poor physical health. Currently, evidence-based smoking cessation interventions are scarce and need to be integrated into current mental health care treatment guidelines and clinical practice. Therefore, the present study aims to evaluate the implementation and effectiveness of a smoking cessation intervention in comparison with usual care in people with SMI treated by Flexible Assertive Community Treatment (FACT) teams in the Netherlands.

Methods

A pragmatic, cluster-randomised controlled trial with embedded process evaluation will be conducted. Randomisation will be performed at the level of FACT teams, which will be assigned to the KISMET intervention or a control group (care as usual). The intervention will include pharmacological treatment combined with behavioural counselling and peer support provided by trained mental health care professionals. The intervention was developed using a Delphi study, through which a consensus was reached on the core elements of the intervention. We aim to include a total of 318 people with SMI (aged 18–65 years) who smoke and desire to quit smoking. The primary outcome is smoking status, as verified by carbon monoxide measurements and self-report. The secondary outcomes are depression and anxiety, psychotic symptoms, physical fitness, cardiovascular risks, substance use, quality of life, and health-related self-efficacy at 12 months. Alongside the trial, a qualitative process evaluation will be conducted to evaluate the barriers to and facilitators of its implementation as well as the satisfaction and experiences of both patients and mental health care professionals.

Discussion

The results of the KISMET trial will contribute to the evidence gap of effective smoking cessation interventions for people treated by FACT teams. Moreover, insights will be obtained regarding the implementation process of the intervention in current mental health care. The outcomes should advance the understanding of the interdependence of physical and mental health and the gradual integration of both within the mental health care system.

Trial registration

Netherlands Trial Register, NTR9783. Registered on 18 October 2021.
Comprehensive sexuality education linked to sexual and reproductive health services reduces early and unintended pregnancies among in-school adolescent girls in Zambia
Authors: Mbizvo Michael T. , Kasonda Kondwani , Muntalima Nelly-Claire , Rosen Joseph G. , Inambwae Sophie , Namukonda Edith S. , Mungoni Ronald , Okpara Natasha , Phiri Chifundo , Chelwa Nachela , Kangale Chabu
Published: February 2023

Background

Advancing the health of adolescents, particularly their sexual and reproductive health, including HIV prevention and care, is a development imperative. A critical part for improving their wellbeing and economic development is the social status accorded to adolescent girls and young women (AGYW). However, AGYW in many countries including Zambia, encounter health challenges that stem from gender inequalities, lack of empowerment, inaccurate knowledge on sexuality, and poor access to sexual and reproductive health (SRH) services and information. Addressing the knowledge gaps through comprehensive sexuality education (CSE) and improving access to SRH services and appropriate information, should reduce school attrition from early and unintended pregnancies (EUP) and enhance realization of their full potential.

Methods

The aim was to reduce EUP and improve SRH outcomes among AGYW in Zambia through provision of CSE linked to receptive SRH services. A 3-Arm randomized control study collected cross-sectional data at baseline, midline and Endline. Schools where CSE was being routinely provided were randomized into a non-intervention arm (arm1), an intervention arm in which information on available SRH services was provided in schools by health workers to complement CSE, (arm 2), and arm 3 in which pupils receiving CSE were also encouraged or supported to access pre-sensitized, receptive SRH services.

Results

Following 3 years of intervention exposure (CSE-Health Facility linkages), findings showed a significant decline of in-school pregnancies amongst AGYW in both intervention arms, with arm two exhibiting a more significant decline, having recorded only 0.74% pregnancies at endline (p < 0.001), as well as arm 3, which recorded 1.34% pregnancies (p < 0.001). No significant decline was recorded in the CSE only control arm. Trends in decline of pregnancies started to show by midline, and persisted at endline (2020), and when difference in differences test was applied, the incident rate ratios (IRR) between the none and exposed arms were equally significant (p < 0.001).

Conclusion

Linking provision of CSE with accessible SRH services that are receptive to needs of adolescents and young people reduces EUP, which provides the opportunity for higher retention in school for adolescent girls.
Employees’ preferences on organisational aspects of psychotherapeutic consultation at work by occupational area, company size, requirement levels and supervisor function – a cross-sectional study in Germany
Authors: Kohl Fiona , Angerer Peter , Weber Jeannette
Published: February 2023

Background

Common mental disorders affect a significant proportion of the population worldwide at any given time. Psychotherapeutic consultation at work offers employees with mental distress short-term and low-threshold access to psychotherapeutic treatment. However, this offer is only accepted by one to two percent of the employees to whom it is offered. Taking into account employees ‘ preferences regarding organisational aspects might increase the use of psychotherapeutic consultation at work. This study therefore aimed to identify preferences on organisational aspects of psychotherapeutic consultation at work among employees of diverse occupational areas, company sizes, supervisor functions and job requirement levels.

Methods

A total of 755 employees were recruited via advertisements on social media (Instagram, Facebook and LinkedIn). Participants rated on a 5-point Likert scale their agreement to different implementation options of psychotherapeutic consultation at work: type (in-person/video/telephone), location (on/outside company premises), time (within/outside working hours), scope (diagnostic/diagnostic + treatment) and purpose (private/occupational). Additionally, the maximum accepted distance to the location of consultation was assessed. Various analyses of variances (ANOVA) were conducted to determine differences in agreement to implementation options within each organisational aspect and to analyse differences between occupational areas, company sizes, requirement levels and between employees with and without supervisor function.

Results

Participants indicated a preference for in-person psychotherapeutic consultation that takes places outside company premises and outside working hours. Furthermore, they preferred offers including diagnostic and treatment sessions compared to offers including diagnostic sessions only. Even though participants agreed that consultation should be offered for all purposes, agreement for occupational issues was stronger than for private issues. For some implementation options, the level of agreement varied according to occupational field, company size, supervisor function and level of requirement. However, these differences did not affect the key findings mentioned above.

Conclusion

Those findings give practical indications on the organisational design of psychotherapeutic consultation at work. The results suggest that in-person consultation outside company premises and working hours combining diagnostic and treatment sessions will be accepted by employees regardless of their occupational area, company size, supervisor function and requirement level.
High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients
Authors: Costa Guilherme M. J. , Lacerda Samyra M. S. N. , Figueiredo André F. A. , Wnuk Natália T. , Brener Marcos R. G. , Andrade Lídia M. , Campolina-Silva Gabriel H. , Kauffmann-Zeh Andrea , Pacifico Lucila G. G. , Versiani Alice F. , Antunes Maísa M. , Souza Fernanda R. , Cassali Geovanni D. , Caldeira-Brant André L. , Chiarini-Garcia Hélio , de Souza Fernanda G. , Costa Vivian V. , da Fonseca Flavio G. , Nogueira Maurício L. , Campos Guilherme R. F. , Kangussu Lucas M. , Martins Estefânia M. N. , Antonio Loudiana M. , Bittar Cintia , Rahal Paula , Aguiar Renato S. , Mendes Bárbara P. , Procópio Marcela S. , Furtado Thiago P. , Guimaraes Yuri L. , Menezes Gustavo B. , Martinez-Marchal Ana , Orwig Kyle E. , Brieño-Enríquez Miguel , Furtado Marcelo H.
Published: February 2023

Background

Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis.

Results

We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA’s presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis.

Conclusions

Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.
Gene expression differences consistent with water loss reduction underlie desiccation tolerance of natural Drosophila populations
Authors: Horváth Vivien , Guirao-Rico Sara , Salces-Ortiz Judit , Rech Gabriel E. , Green Llewellyn , Aprea Eugenio , Rodeghiero Mirco , Anfora Gianfranco , González Josefa
Published: February 2023

Background

Climate change is one of the main factors shaping the distribution and biodiversity of organisms, among others by greatly altering water availability, thus exposing species and ecosystems to harsh desiccation conditions. However, most of the studies so far have focused on the effects of increased temperature. Integrating transcriptomics and physiology is key to advancing our knowledge on how species cope with desiccation stress, and these studies are still best accomplished in model organisms.

Results

Here, we characterized the natural variation of European D. melanogaster populations across climate zones and found that strains from arid regions were similar or more tolerant to desiccation compared with strains from temperate regions. Tolerant and sensitive strains differed not only in their transcriptomic response to stress but also in their basal expression levels. We further showed that gene expression changes in tolerant strains correlated with their physiological response to desiccation stress and with their cuticular hydrocarbon composition, and functionally validated three of the candidate genes identified. Transposable elements, which are known to influence stress response across organisms, were not found to be enriched nearby differentially expressed genes. Finally, we identified several tRNA-derived small RNA fragments that differentially targeted genes in response to desiccation stress.

Conclusions

Overall, our results showed that basal gene expression differences across individuals should be analyzed if we are to understand the genetic basis of differential stress survival. Moreover, tRNA-derived small RNA fragments appear to be relevant across stress responses and allow for the identification of stress-response genes not detected at the transcriptional level.
Case report: a Chinese girl like atypical Rubinstein–Taybi syndrome caused by a novel heterozygous mutation of the EP300 gene
Authors: Bai Zhouxian , Li Gaopan , Kong Xiangdong
Published: February 2023

Background

Rubinstein–Taybi syndrome (RSTS) is an extremely rare autosomal dominant inheritable disorder caused by CREBBP and EP300 mutations, while atypical RSTS harbouring variant from the same genes but not obvious resembling RSTS. There are only a few cases of Menke–Hennekam syndrome (MKHK) with variant of exon 30 or 31 of CREBBP or EP300 gene have been reported that not resembling RSTS recent years. Atypical RSTS cannot be accurately classified as MKHK, nor is it easy to identify the obvious classic characteristics of RSTS. The clinical manifestations and genetic variation of atypical RSTS are not fully understood.

Case presentation

We present a Chinese core family with a girl had recurrent respiratory tract infection and developmental delay. The patient with language and motor mild development retardation, she has slight abnormal facial features, mild hirsutism and post-axial hexadactylia of left foot. Her cisterna magna is enlarged to connect with the fourth ventricle, and the ventricular system is enlarged. She has a malacia beside the posterior horn of the left lateral ventricle. The patient has primary low immunoglobulin G and A, but her level of immunoglobulin M content in blood is normal. The patient harbors a novel heterozygous frameshift variant of c.2499dupG in exon 14 of EP300 gene, that it is proved to de novo origin. The mutation is judged to be a pathogenic mutation, and it has high-grade pathogenic evidence.

Conclusion

The clinical and genetic evaluation of this case corroborates that clinical features caused by c.2499dupG in exon 14 of EP300 are less marked than RSTS2 patient although it is difficult to establish an accurate genotype–phenotype correlation. Our additional case also helps to deepen the clinical and genetic spectrum in this disorder. The case provides a novel mutation of EP300 and enriches the phenotypes related with the gene. We have contributed new variation and disease information for guardians and doctors to broaden the knowledge about EP300-RSTS genotype and phenotype, this may contribute to ameliorate the health management of patients and improve the genetic counseling to the families.
Hidden blood loss between percutaneous pedicle screw fixation and the mini-open Wiltse approach with pedicle screw fixation for neurologically intact thoracolumbar fractures: a retrospective study
Authors: Jiang Haitao , Sheng Wenbo , Yuan Hantao , Xu Jianhua , Chen Xiaochun , Gu Xiaohua , Li Sibo
Published: February 2023

Background

The aim of this study was to determine the proportion of hidden blood loss (HBL) in patients treated with minimally invasive surgery, and to compare the HBL between patients treated with percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF).

Methods

From January 2017 to January 2019, a total of 119 patients with thoracolumbar fractures were included in the analysis, of which 58 cases received PPSF and 61 cases received MWPSF. The clinical information and demographic results were collected and compared. And the HBL of the patients is calculated by the combination formulas of Nadler, Gross and Sehat.

Results

Compared with the PPSF group, operation time of MWPSF is shorter. The fluoroscopy times are 13.6 ± 3.0 in PPSF group and 5.6 ± 1.6 in MWPSF group (p < 0.001). As shown in Table 3, the intraoperative blood loss in PPSF group is 31.9 ± 9.6 ml, which is significantly less than that in the MWPSF group (44.0 ± 14.9 ml). The HBL (445.7 ± 228.9 ml), and HBL% (91.2 ± 7.7%) of the PPSF group are significantly higher than that in the MWPSF group (P < 0.05). And the total blood loss (TBL) of the PPSF group (477.6 ± 228.8 ml) is also more than that in the MWPSF group (401.0 ± 171.3 ml).

Conclusions

Our results suggest that in the minimally invasive surgical treatment of thoracolumbar fractures, the perioperative HBL is much higher than visible blood loss (VBL). Although PPSF has less intraoperative blood loss, it has higher TBL and HBL than those of MWPSF. Compared with MWPSF, we should pay more attention to the postoperative anemia status of patients with thoracolumbar fractures undergoing PPSF surgery.
An overview of DNA methylation-derived trait score methods and applications
Authors: Nabais Marta F. , Gadd Danni A. , Hannon Eilis , Mill Jonathan , McRae Allan F. , Wray Naomi R.
Published: February 2023

Microarray technology has been used to measure genome-wide DNA methylation in thousands of individuals. These studies typically test the associations between individual DNA methylation sites (“probes”) and complex traits or diseases. The results can be used to generate methylation profile scores (MPS) to predict outcomes in independent data sets. Although there are many parallels between MPS and polygenic (risk) scores (PGS), there are key differences. Here, we review motivations, methods, and applications of DNA methylation-based trait prediction, with a focus on common diseases. We contrast MPS with PGS, highlighting where assumptions made in genetic modeling may not hold in epigenetic data.
Immobilization techniques improve volumetric hydrogen productivity of Caldicellulosiruptor species in a modified continuous stirred tank reactor
Authors: Vongkampang Thitiwut , Sreenivas Krishnan , Grey Carl , van Niel Ed W. J.
Published: February 2023

Background

Co-cultures and cell immobilization have been used for retaining biomass in a bioreactor, with the aim to improve the volumetric hydrogen productivity (QH2). Caldicellulosiruptor kronotskyensis is a strong cellulolytic species that possesses tāpirin proteins for attaching on lignocellulosic materials. C. owensensis has its reputation as a biofilm former. It was investigated whether continuous co-cultures of these two species with different types of carriers can improve the QH2.

Results

QH2 up to 30 ± 0.2 mmol L−1 h−1 was obtained during pure culture of C. kronotskyensis with combined acrylic fibres and chitosan. In addition, the yield of hydrogen was 2.95 ± 0.1 mol H2 mol−1 sugars at a dilution rate (D) of 0.3 h−1. However, the second-best QH2 26.4 ± 1.9 mmol L−1 h−1 and 25.4 ± 0.6 mmol L−1 h−1 were obtained with a co-culture of C. kronotskyensis and C. owensensis with acrylic fibres only and a pure culture of C. kronotskyensis with acrylic fibres, respectively. Interestingly, the population dynamics revealed that C. kronotskyensis was the dominant species in the biofilm fraction, whereas C. owensensis was the dominant species in the planktonic phase. The highest amount of c-di-GMP (260 ± 27.3 µM at a D of 0.2 h−1) were found with the co-culture of C. kronotskyensis and C. owensensis without a carrier. This could be due to Caldicellulosiruptor producing c-di-GMP as a second messenger for regulation of the biofilms under the high dilution rate (D) to prevent washout.

Conclusions

The cell immobilization strategy using a combination of carriers exhibited a promising approach to enhance the QH2. The QH2 obtained during the continuous culture of C. kronotskyensis with combined acrylic fibres and chitosan gave the highest QH2 among the pure culture and mixed cultures of Caldicellulosiruptor in the current study. Moreover, it was the highest QH2 among all cultures of Caldicellulosiruptor species studied so far.
Research on monaural speech segregation based on feature selection
Authors: Xie Xiaoping , Chen Yongzhen , Shen Rufeng , Tian Dan
Published: February 2023

Speech feature model is the basis of speech and noise separation, speech expression, and different styles of speech conversion. With the development of signal processing methods, the feature types and dimensions increase. Therefore, it is difficult to select appropriate features. If a single feature is used, the representation of the speech signal will be incomplete. If multiple features are used, there will be redundancy between features, which will affect the performance of speech separation. The feature described above is a combination of parameters to characterize speech. A single feature means that the combination has only one parameter. In this paper, the feature selection method is used to select and combine eight widely used speech features and parameters. The Deep Neural Network (DNN) is used to evaluate and analyze the speech separation effect of different feature groups. The comparison results show that the speech segregation effect of the complementary feature group is better. The effectiveness of the complementary feature group to improve the performance of DNN speech separation is verified.
Screening method toward ClbP-specific inhibitors
Authors: Zhou Tao , Ando Takayuki , Kudo Akihiro , Sato Michio , Miyoshi Noriyuki , Mutoh Michihiro , Ishikawa Hideki , Wakabayashi Keiji , Watanabe Kenji
Published: February 2023

Background

Colibactin is a genotoxin produced by Escherichia coli and other Enterobacteriaceae that is believed to increase the risk of colorectal cancer (CRC) of their symbiosis hosts, including human. A peptidase ClbP is the key enzyme for activation of colibactin. Inhibition of ClbP is considered to impede maturation of precolibactin into genotoxic colibactin. Therefore, ClbP-specific inhibitors could potentially prevent the onset of CRC, one of the leading causes of cancer-related deaths in the world. This study intends to establish an efficient screening system for identifying inhibitors that are specific to ClbP.

Methods

Two types of assays were applied in the screening procedure: a probe assay and an LC–MS assay. For the probe assay, we employed the synthesized probe which we described in our previous report. This probe can be hydrolyzed efficiently by ClbP to release a fluorophore. Hence it was applied here for detection of inhibition of ClbP. For the LC–MS assay, formation of the byproduct of precolibactin maturation process, N-myristoyl-D-asparagine, was quantified using a liquid chromatography–mass spectrometry (LC–MS) technique. The probe assay can be performed much faster, while the LC–MS assay is more accurate. Therefore, our method employed the two assays in sequence to screen a large number of compounds for inhibition of ClbP.

Results

A library of 67,965 standard compounds was evaluated by the screening method established in the current study, and one compound was found to show a moderate inhibitory activity against ClbP.

Conclusion

A simple screening method for ClbP-specific inhibitors was established. It was proven to be reliable and is believed to be useful in developing potential prophylactic agents for CRC.
A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis
Authors: Jiang Fu-Yao , Zhang Yan-Zhu , Tai Yuan-Hong , Chou Chien-Yu , Hsieh Yu-Ching , Chang Ya-Chi , Huang Hsiao-Chen , Li Zhi-Qin , Hsieh Yuan-Chin , Chen I-Ju , Huang Bo-Cheng , Su Yu-Cheng , Lin Wen-Wei , Lin Hsin-Chieh , Chao Jui-I , Yuan Shyng-Shiou F. , Wang Yun-Ming , Cheng Tian-Lu , Tzou Shey-Cherng
Published: February 2023

Background

CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG1 that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment.

Methods

We linked albumin to the N-terminus of CTLA4Ig (termed Alb-CTLA4Ig) via a substrate sequence of matrix metalloproteinase (MMP). The binding activities and the biological activities of Alb-CTLA4Ig before and after MMP digestion were analyzed by a cell-based ELISA and an in vitro Jurkat T cell activation assay. The efficacy and safety of Alb-CTLA4Ig in treating joint inflammation were tested in mouse collagen-induced arthritis.

Results

Alb-CTLA4Ig is stable and inactive under physiological conditions but can be fully activated by MMPs. The binding activity of nondigested Alb-CTLA4Ig was at least 10,000-fold weaker than that of MMP-digested Alb-CTLA4Ig. Nondigested Alb-CTLA4Ig was unable to inhibit Jurkat T cell activation, whereas MMP-digested Alb-CTLA4Ig was as potent as conventional CTLA4Ig in inhibiting the T cells. Alb-CTLA4Ig was converted to CTLA4Ig in the inflamed joints to treat mouse collagen-induced arthritis, showing similar efficacy to that of conventional CTLA4Ig. In contrast to conventional CTLA4Ig, Alb-CTLA4Ig did not inhibit the antimicrobial responses in the spleens of the treated mice.

Conclusions

Our study indicates that Alb-CTLA4Ig can be activated by MMPs to suppress tissue inflammation in situ. Thus, Alb-CTLA4Ig is a safe and effective treatment for collagen-induced arthritis in mice.
An empirical elastic anisotropy prediction model in self-sourced reservoir shales and its influencing factor analysis
Authors: Zhao Luanxiao , Cai Zhenjia , Qin Xuan , Wang Yang , Long Teng , Han De-Hua , Zhang Fengshou , Geng Jianhua
Published: February 2023

Organic shales can split into laminae or thin layers due to their fissility and are usually characterized as transverse isotropic media. Understanding their elastic and anisotropic properties plays a significant role in geophysical modeling and imaging, reservoir geomechanics, and reservoir characterization. One can obtain their velocity anisotropy through laboratory and field measurements or rock-physics models. However, the measurements are scarce, and theoretical modeling of Thomsen’s anisotropy parameters generally requires extra inputs, which are sometimes difficult to obtain. We have compiled ultrasonic data from 159 self-sourced reservoir shale samples from the literature and our own measurements. Simple exponential models can capture the trends of the P- and S-wave anisotropy parameters [Formula: see text] and [Formula: see text] decreasing with the increasing vertical P- and S-wave velocities, with [Formula: see text] being above 0.84. The error in estimated anisotropy is small for high-velocity ([Formula: see text]) shales but relatively large for low-velocity ([Formula: see text]) shales. We analyze the influence of multiple geologic factors on the proposed anisotropy-velocity relationships. We observe that velocity anisotropy generally increases with clay content. In addition, mature shales (0.6 < Ro (%) < 1.4) generally have stronger anisotropy strength spreading in a broader range than overmature shales (Ro (%) > 1.4). Overall, no single parameter dominates the source of velocity anisotropy, which is jointly affected by the coupled factors of clay content, organic matter, porosity, maturity level, and geologic history. The empirical model has the potential to offer a fast and straightforward method of predicting P- and S-wave anisotropy strength from vertical P- and S-wave velocities.
Cost-Effectiveness of the First Line Treatment Options For Metastatic Renal Cell Carcinoma in India
Authors: Gupta Dharna , Singh Ashish , Gupta Nidhi , Mehra Nikita , Bahuguna Pankaj , Aggarwal Vipul , Krishnamurthy Manjunath Nookala , Roy Partha Sarathi , Malhotra Pankaj , Gupta Sudeep , Kumar Lalit , Kataki Amal , Prinja Shankar
Published: February 2023

PURPOSE

Tyrosine kinase inhibitors such as sunitinib and pazopanib are the mainstay of treatment of metastatic renal cell carcinoma (mRCC) in India. However, pembrolizumab and nivolumab have shown significant improvement in the median progression-free survival and overall survival among patients with mRCC. In this study, we aimed to determine the cost-effectiveness of the first-line treatment options for the patients with mRCC in India.

METHODS

A Markov state-transition model was used to measure the lifetime costs and health outcomes associated with sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab among patients with first-line mRCC. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost-effectiveness using a willingness to pay threshold of one-time per capita gross-domestic product of India. The parameter uncertainty was analyzed using the probabilistic sensitivity analysis.

RESULTS

We estimated the total lifetime cost per patient of ₹ 0.27 million ($3,706 US dollars [USD]), ₹ 0.35 million ($4,716 USD), ₹ 9.7 million ($131,858 USD), and ₹ 6.7 million ($90,481 USD) for the sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab arms, respectively. Similarly, the mean QALYs lived per patient were 1.91, 1.86, 2.75, and 1.97, respectively. Sunitinib incurs an average cost of ₹ 143,269 ($1,939 USD) per QALY lived. Therefore, sunitinib at current reimbursement rates (₹ 10,000 per cycle) has a 94.6% probability of being cost-effective at a willingness to pay threshold of 1-time per capita gross-domestic product (₹ 168,300) in the Indian context.

CONCLUSION

Our findings support the current inclusion of sunitinib under India's publicly financed health insurance scheme.
Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia
Authors: Farrar Jason E. , Smith Jenny L. , Othus Megan , Huang Benjamin J. , Wang Yi-Cheng , Ries Rhonda , Hylkema Tiffany , Pogosova-Agadjanyan Era L. , Challa Sneha , Leonti Amanda , Shaw Timothy I. , Triche Timothy J. , Gamis Alan S. , Aplenc Richard , Kolb E. Anders , Ma Xiaotu , Stirewalt Derek L. , Alonzo Todd A. , Meshinchi Soheil
Published: February 2023

PURPOSE

Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML.

METHODS

To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis.

RESULTS

Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays.

CONCLUSION

Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.
A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study
Authors: Grani Giorgio , Gentili Michele , Siciliano Federico , Albano Domenico , Zilioli Valentina , Morelli Silvia , Puxeddu Efisio , Zatelli Maria Chiara , Gagliardi Irene , Piovesan Alessandro , Nervo Alice , Crocetti Umberto , Massa Michela , Samà Maria Teresa , Mele Chiara , Deandrea Maurilio , Fugazzola Laura , Puligheddu Barbara , Antonelli Alessandro , Rossetto Ruth , D’Amore Annamaria , Ceresini Graziano , Castello Roberto , Solaroli Erica , Centanni Marco , Monti Salvatore , Magri Flavia , Bruno Rocco , Sparano Clotilde , Pezzullo Luciano , Crescenzi Anna , Mian Caterina , Tumino Dario , Repaci Andrea , Castagna Maria Grazia , Triggiani Vincenzo , Porcelli Tommaso , Meringolo Domenico , Locati Laura , Spiazzi Giovanna , Di Dalmazi Giulia , Anagnostopoulos Aris , Leonardi Stefano , Filetti Sebastiano , Durante Cosimo
Published: February 2023

Context

The risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features.

Objective

To develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors.

Methods

In a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction.

Results

By ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis.

Conclusion

Current risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.
Imaging of Central Nervous System Autoimmune, Paraneoplastic, and Neuro-rheumatologic Disorders
Authors: Wahed Lama Abdel , Cho Tracey A.
Published: February 2023

OBJECTIVE

This article provides an overview of the imaging modalities used in the evaluation of central nervous system (CNS) autoimmune, paraneoplastic, and neuro-rheumatologic disorders. An approach is outlined for interpreting imaging findings in this context, synthesizing a differential diagnosis based on certain imaging patterns, and choosing further imaging for specific diseases.

LATEST DEVELOPMENTS

The rapid discovery of new neuronal and glial autoantibodies has revolutionized the autoimmune neurology field and has elucidated imaging patterns characteristic of certain antibody-associated diseases. Many CNS inflammatory diseases, however, lack a definitive biomarker. Clinicians should recognize neuroimaging patterns suggestive of inflammatory disorders, as well as the limitations of imaging. CT, MRI, and positron emission tomography (PET) modalities all play a role in diagnosing autoimmune, paraneoplastic, and neuro-rheumatologic disorders. Additional imaging modalities such as conventional angiography and ultrasonography can be helpful for further evaluation in select situations.

ESSENTIAL POINTS

Knowledge of imaging modalities, both structural and functional, is critical in identifying CNS inflammatory diseases quickly and can help avoid invasive testing such as brain biopsy in certain clinical scenarios. Recognizing imaging patterns suggestive of CNS inflammatory diseases can also facilitate the early initiation of appropriate treatments to diminish morbidity and future disability.
Neuroimaging in Dementia
Authors: Risacher Shannon L. , Apostolova Liana G.
Published: February 2023

OBJECTIVE

Neurodegenerative diseases are significant health concerns with regard to morbidity and social and economic hardship around the world. This review describes the state of the field of neuroimaging measures as biomarkers for detection and diagnosis of both slowly progressing and rapidly progressing neurodegenerative diseases, specifically Alzheimer disease, vascular cognitive impairment, dementia with Lewy bodies or Parkinson disease dementia, frontotemporal lobar degeneration spectrum disorders, and prion-related diseases. It briefly discusses findings in these diseases in studies using MRI and metabolic and molecular-based imaging (eg, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]).

LATEST DEVELOPMENTS

Neuroimaging studies with MRI and PET have demonstrated differential patterns of brain atrophy and hypometabolism in different neurodegenerative disorders, which can be useful in differential diagnoses. Advanced MRI sequences, such as diffusion-based imaging, and functional MRI (fMRI) provide important information about underlying biological changes in dementia and new directions for development of novel measures for future clinical use. Finally, advancements in molecular imaging allow clinicians and researchers to visualize dementia-related proteinopathies and neurotransmitter levels.

ESSENTIAL POINTS

Diagnosis of neurodegenerative diseases is primarily based on symptomatology, although the development of in vivo neuroimaging and fluid biomarkers is changing the scope of clinical diagnosis, as well as the research into these devastating diseases. This article will help inform the reader about the current state of neuroimaging in neurodegenerative diseases, as well as how these tools might be used for differential diagnoses.
Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis
Authors: Zhong Shiyu , Liu Tao , Zhai Qingqing , Zhang Xudong , Jing Huiquan , Li Kunhang , Liu Shengyu , Liu Guojun , Wang Liang , Li Lishuai , Tao Shanwei , Ren Lijie , Shi Xin , Bao Yijun
Published: February 2023

BACKGROUND:

The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins.

OBJECTIVE:

To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH.

METHODS:

We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis.

RESULTS:

A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79).

CONCLUSION:

Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.
Effectiveness of precise and quantitative rapid pulmonary rehabilitation nursing program for elderly patients with lung cancer during the perioperative period: A randomized controlled trial
Authors: Chen Bei , Yan Xiaoxia , Wang Xiaojun , Mao Yanjun
Published: February 2023

Objective: Preoperative rehabilitation should improve the functional condition of patients. Improvements in metabolism, lung mechanics, cardiovascular function, and muscle-function can be achieved by pulmonary rehabilitation. Hence, we focused on elderly patients with lung cancer undergoing surgery, and assessed the effectiveness of a rapid and precise pulmonary rehabilitation nursing program during the perioperative period.

Methods: This randomized controlled trial at the department of thoracic surgery; Shanghai pulmonary hospital, China during 2021 was conducted amongst 218 elderly patients with lung cancer treated by surgical operation into either a precision quantitative nursing model nursing group (experimental group) or a perioperative routine nursing group (control group). After individual planning of the pulmonary rehabilitation nursing outpatient clinic, nurses distributed breathing trainers, instructed the patients in breathing training, and supervised the patients after the operation. For our evaluation we considered pulmonary function tests, postoperative thoracic drainage tube indwelling times, postoperative hospital stays, postoperative complication rates, and postoperative quality of life results.

Results: The experimental group showed better pulmonary function, length of hospital stay, and quality of life outcomes than the control group, but the differences were not statistically significant. However, we found a significantly higher postoperative complications rate in the control group (11.9%) than in the experimental group (3.7%; p=0.02).

Conclusion: Strengthening pulmonary rehabilitation nursing interventions for elderly patients with lung cancer during the perioperative period can reduce their postoperative complications and promote their rapid recovery.

Clinical Trial: Registration Number - ChiCTR2100042916.

doi: https://doi.org/10.12669/pjms.39.2.7103

How to cite this: Chen B, Yan X, Wang X, Mao Y. Effectiveness of precise and quantitative rapid pulmonary rehabilitation nursing program for elderly patients with lung cancer during the perioperative period: A randomized controlled trial. Pak J Med Sci. 2023;39(2):572-577.  doi: https://doi.org/10.12669/pjms.39.2.7103

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Biases in Assertions of Self-Rated Health
Authors: Lazarevič Patrick
Published: February 2023

Comparative analyses frequently examine respondents’ self-rated health (SRH), assuming that it is a valid and comparable measure of generic health. However, given SRH’s vagueness, this assumption is questionable due to (1) manifold non-health influences, such as personal characteristics including optimism, interviewer effects on the rating, and cultural contexts, as well as (2) potential gender, age- or country-specific expectations for one’s health or frames of reference. Conceptually, two major components of SRH can be distinguished: latent health and reporting behavior. While latent health exclusively refers to objective health status, reporting behavior collectively refers to non-health characteristics (NH) affecting SRH. The present paper is primarily concerned with the latter and aims to identify whether and how NH bias SRH, including possible differences by gender, age, and country of residence.

The presented analyses are based on data from 16,183 participants in five countries drawn from the fifth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE). Latent health is controlled via a wide array of health indicators and the residuals are examined with a model covering NH from three different sources: the interviewer, the respondent, and the country of residence. To identify subgroup-specific response behaviors, all analyses are carried out separately by gender, three age groups (50-64, 65-79, and 80+ years), and country of residence.

The analyses uncovered influences of – among others–the interviewer’s SRH, the respondent’s life satisfaction, and the country of residence on SRH, while other factors differed by subgroup. The amount of explained variance due to such reporting behavior (with a mean of seven percent) can be deemed meaningful, considering that controlling for latent health already explains around half of SRH’s variance. The greatest source of non-health influences was respondent characteristics, with the interviewer and country having smaller effects.

These results illustrate the importance of taking NH into account when using SRH measures. Future research on complementing SRH with factual questions in survey design is advisable.

* This article belongs to a special issue on “Levels and Trends of Health Expectancy: Understanding its Measurement and Estimation Sensitivity”.
Advising patients on management of nocturnal asthma
Authors: Henry Heather
Published: February 2023

Heather Henry explains how nurses can help patients to prevent asthma from disturbing sleep
Exploring the lived experiences of mothers of extremely preterm infants in the UK
Authors: Robinson Stephanie , Williams Sophie , Hallam Jenny , Jackson Jessica Eve
Published: February 2023

The adverse impact of preterm birth on maternal mental health is well documented, yet there is limited available research regarding the subjective experiences of mothers of extremely preterm infants as a distinct cohort. The aim of this study was to explore the lived experiences of mothers of extremely preterm infants, born alive at less than 28 weeks gestation, in the UK. Three mothers of extremely preterm infants participated in a semi-structured interview conducted online, which invited them to share their experiences of pregnancy, their time in neonatal intensive care unit, the transition home and their present-day experiences. An interpretative phenomenological analysis explored a delayed transition to mothering and experiences relating to initial disconnection, missed moments and establishing a maternal connection. Owing to the traumatic experiences associated with an extremely preterm birth, it is concluded that mothers would benefit from health visitor support relating to attachment, mental health and connecting to parenting communities.
Nervous Energy
Authors: Wade Andrew
Published: February 2023

An emerging wave of bioelectronic medicine is changing the way we treat disease, targeting everything from arthritis and diabetes to cancer and Crohn’s disease