bluuebunny/crossref_metadata_2025 huggingface dataset:
A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases
Authors: Myint Zin W. , El Khouli Riham , Lemieux Bryan , Yan Donglin , St. Clair William H. , Liu Xiaoqi , Kunos Charles A.
Published: April 2022

Background

Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.

Methods

The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival.

Discussion

Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline.

Trial registration.

ClincialTrials.gov Identifier: NCT04616547.
Using diffuse weighted image and apparent diffusion coefficient in MRI for diagnosis of posterior ischemic optic neuropathy in a young male: a case report and literature review
Authors: Yang Tzu-Hsuan , Lin Muh-Chiou
Published: April 2022

Background

Posterior ischemic optic neuropathy (PION) is a rare cause of visual loss, especially in young patients who are more prone to inflammatory demyelinating optic neuritis (ON) compared to other types of optic neuropathy. The diagnosis of PION is usually a diagnosis of exclusion; however, the emergence of modern neuroimaging technique with diffuse-weighted image (DWI) and apparent diffusion coefficient (ADC) sequences in Magnetic Resonance Imaging (MRI) provides more evidence for accurate diagnosis and management.

Case presentation

A 30-year-old man with a history of hypertension and chronic renal failure secondary to glomerulonephritis presented with sudden onset of blurred vision, dyschromatopsia, pain, and positive relative afferent pupillary defect (RAPD) in the left eye for 1 week. He was initially admitted for steroid pulse therapy and was further monitored due to suspicion of optic neuritis oculus sinister (OS). However, his brain MRI revealed a focal high hyperintensity signal at the left optic nerve on the T2 DWI series. The area was corresponded with the hypointensity area in the ADC series, which was a powerful clue for PION. We explained the poor visual prognosis of PION to the patient after finishing steroid pulse therapy and referred him to the Nephrology and Neurology department for hypertension control to prevent additional hypertension related complication.

Conclusions

The diagnosis of PION is usually a diagnosis of exclusion; however, carefully interpreting the DWI and ADC sequence in MRI may give the clinician more evidence for the definite diagnosis and leads to proper management.
Factors predicting serum clozapine levels in Middle Eastern patients: an observational study
Authors: Hassab Errasoul Ahmed , Alarabi Mohammed A.
Published: April 2022

Background

Despite its superiority over other drugs for psychosis, clozapine remains underused and is associated with many clinical challenges, including difficulties in predicting therapeutic serum levels (350-600 ng/mL). We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. Therefore, we investigated the association between clozapine dose and serum level, and the clinical predictors of the clozapine serum level, in Middle Eastern patients.

Methods

This cross-sectional study included 94 patients of Middle Eastern ethnicity who attended the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia. We used a single measure of the serum clozapine level, which was collected 12 h after the last oral dose of clozapine under steady-state conditions.

Results

The average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. The majority of patients (59.8%) had serum levels higher than 600 ng/mL. Clozapine dose and serum level were positively correlated (rs[94] = 0.32,p = 0.002). We generated a predictive model of the serum clozapine level, which revealed that the daily dose, smoking status, use of fluvoxamine or lamotrigine, and body mass index (BMI) predicted 43.6% of the variance in the serum level (p < 0.001). Using this model, we calculated that patients with a BMI of 25 kg/m2would require a clozapine dose between 50 to 275 mg/daily if they were non-smokers, and a dose of 200 to 450 mg/daily if they were smokers, in order to reach a serum clozapine level between 350 to 600 ng/mL. Patients with higher BMI and those receiving fluvoxamine would require lower doses.

Conclusions

This was a naturalistic study of the clozapine dose-level relationship and the clinical predictors of the serum clozapine level in a sample of Middle Eastern patients. The ratios of clozapine level to dose in our patients more closely resembled those reported in Asian samples than in European samples. These findings do not reduce the value of individualised therapeutic drug monitoring, but may assist clinicians when prescribing clozapine to Middle Eastern patients. Further psychopharmacological studies are needed on this demographic population.
Implementation of a novel malaria management strategy based on self-testing and self-treatment in remote areas in the Amazon (Malakit): confronting a-priori assumptions with reality
Authors: Galindo Muriel Suzanne , Lambert Yann , Mutricy Louise , Garancher Laure , Miller Jane Bordalo , Gomes José Hermenegildo , Sanna Alice , Peterka Cassio , Cairo Hedley , Hiwat Helene , Adenis Antoine , Nacher Mathieu , Suárez-Mutis Martha Cecilia , Vreden Stephen , Douine Maylis
Published: April 2022

Background

A novel strategy to combat malaria was tested using a methodology adapted to a complex setting in the Amazon region and a hard-to-reach, mobile community. The intervention strategy tested was the distribution, after training, of malaria self-management kits to gold miners who cross the Surinamese and Brazilian borders with French Guiana to work illegally in the remote mining sites in the forest of this French overseas entity.

Main text

This article aims at presenting all process and implementation outcomes following the Conceptual Framework of Implementation Fidelity i.e. adherence, including content and exposure, and moderators, comprising participant responsiveness, quality of delivery, facilitation strategies, and context. The information sources are the post-intervention survey, data collected longitudinally during the intervention, a qualitative study, data collected during an outreach mission to a remote gold mining site, supervisory visit reports, in-depth feedback from the project implementers, and videos self-recorded by facilitators based on opened ended questions.

As expected, being part of or close to the study community was an essential condition to enable deliverers, referred to as “facilitators”, to overcome the usual wariness of this gold mining population. Overall, the content of the intervention was in line with what was planned. With an estimated one third of the population reached, exposure was satisfactory considering the challenging context, but improvable by increasing ad hoc off-site distribution according to needs. Participant responsiveness was the main strength of the intervention, but could be enhanced by reducing the duration of the process to get a kit, which could be disincentive in some places. Regarding the quality of delivery, the main issue was the excess of information provided to participants rather than a lack of information, but this was corrected over time. The expected decrease in malaria incidence became a source of reduced interest in the kit. Expanding the scope of facilitators’ responsibilities could be a suitable response. Better articulation with existing malaria management services is recommended to ensure sustainability.

Conclusions

These findings supplement the evaluation outcomes for assessing the relevance of the strategy and provide useful information to perpetuate and transfer it in comparable contexts.

Trial registration

ClinicalTrials.gov. NCT03695770. 10/02/2018 “Retrospectively registered”.
Examining active aging among Iranian provinces: a TOPSIS analysis
Authors: Saberzadeh Vahid , Emamgholipour Sefiddashti Sara , Safaei Lari Majid
Published: April 2022

Background

Planning and decision-making for the elderly requires a special attention due to the beginning of aging process in Iran. By emphasizing the concept of active aging, determining the status of the elderly like their ability to continue work over time, to attain income and to participate in social and political life is significant. Active aging uses the indicators measuring the non-used potential of the elderly for having an active and healthy aging. This study aimed to determine the level of active aging among the provinces of Iran in 2018 by considering 11 indicators related to elderly’s health, well-being and socioeconomic participation.

Methods

The raw data were obtained from Statistical Center of Iran. After establishing the indicators based on the Global Age Watch approach, the provinces were ranked by the TOPSIS method in terms of aging status.

Results

The results indicated that only Tehran and Alborz had the highest development level of active aging while 16% of the provinces had a semi-developed status and 77% failed at experiencing a satisfactory welfare, economic and social status.

Conclusions

Four indicators had the highest importance included the percentage of the elderly with a diploma and academic degree, the percentage of the elderly with lower incomes than the median income, the median income of the elderly to the median income of the other people in society, and life expectancy among the 65-year old men. Studying the indicators deeply can result in the appropriate planning for each area in line with the improvement of the elderly status.
Validation of physician certified verbal autopsy using conventional autopsy: a large study of adult non-external causes of death in a metropolitan area in Brazil
Authors: de André Carmen Diva Saldiva , Bierrenbach Ana Luiza , Barroso Lucia Pereira , de André Paulo Afonso , Justo Lisie Tocci , Pereira Luiz Alberto Amador , Taniguchi Mauro T. , Minto Cátia Martinez , Takecian Pedro Losco , Kamaura Leonardo Tadashi , Ferreira João Eduardo , Hazard Riley H. , Mclaughlin Deirdre , Riley Ian , Lopez Alan D. , Ramos Ana Maria de Oliveira , de Souza Maria de Fatima Marinho , França Elisabeth Barboza , Saldiva Paulo Hilário Nascimento , da Silva Luiz Fernando Ferraz
Published: April 2022

Background

Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard.

Methods

The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level.

Results

There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49.

Conclusions

The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.
Trends over two decades in life expectancy with complex health problems among older Swedes: implications for the provision of integrated health care and social care
Authors: Meinow Bettina , Li Peng , Jasilionis Domantas , Oksuzyan Anna , Sundberg Louise , Kelfve Susanne , Wastesson Jonas W.
Published: April 2022

Background

Due to population aging, it is essential to examine to what extent rises in life expectancy (LE) consist of healthy or unhealthy years. Most health expectancy studies have been based on single health measures and have shown divergent trends. We used a multi-domain indicator, complex health problems (CHP), indicative of the need for integrated medical and social care, to investigate how LE with and without CHP developed in Sweden between 1992 and 2011. We also addressed whether individuals with CHP more commonly lived in the community in 2011 compared to earlier years.

Methods

CHP were defined as having severe problems in at least two of three health domains related to the need for medical and/or social care: symptoms/diseases, cognition/communication, and mobility. The Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD), a nationally representative survey of the Swedish population aged ≥ 77 years with waves in 1992, 2002 and 2011 (n≈2000), was used to estimate the prevalence of CHP. Age- and gender-specific death rates were obtained from the Human Mortality Database. The Sullivan method was deployed to calculate the remaining life expectancy with and without CHP. The estimates were decomposed to calculate the contribution of changes from morbidity and mortality to the overall trends in LE without CHP.

Results

Between 1992 and 2011, both total LE (+ 1.69 years [95% CI 1.56;1.83] and LE without CHP (+ 0.84 years [-0,87;2.55]) at age 77 increased for men, whereas LE at age 77 increased for women (+ 1.33 [1.21;1.47]) but not LE without CHP (-0.06 years [-1.39;1.26]). When decomposing the trend, we found that the increase in LE with CHP was mainly driven by an increase in the prevalence of CHP. Among individuals with CHP the proportion residing in care homes was lower in 2011 (37%) compared to 2002 (58%) and 1992 (53%).

Conclusions

The findings, that an increasing number of older people are expected to live more years with CHP, and increasingly live in the community, point towards a challenge for individuals and families, as well as for society in financing and organizing coordinated and coherent medical and social services.
Incarceration exposure during pregnancy and maternal disability: findings from the Pregnancy Risk Assessment Monitoring System
Authors: Testa Alexander , Fahmy Chantal , Jackson Dylan B. , Ganson Kyle T. , Nagata Jason M.
Published: April 2022

Background

Extant research reveals that currently and formerly incarcerated individuals exhibit higher rates of disability. Moreover, recent research highlights that women exposed to incarceration during pregnancy —either personally or vicariously through a partner— face poorer health. However, prior research has not detailed the connection between incarceration exposure and risk for maternal disability.

Methods

The aim of this study is to evaluate the association between a women’s exposure to incarceration during pregnancy and disability including difficulty with: communication, hearing, remembering, seeing, self-care, or walking. Data are from Pregnancy Risk Assessment Monitoring System (PRAMS), 2019 (N = 12,712). Logistic and negative binomial regression were used to assess the relationship between incarceration exposure and maternal disability.

Results

Among the sample of women who delivered a recent live birth, approximately 3.3% of the sample indicated they were personally or vicariously exposed to incarceration in the 12 months before birth. Compared to those who did not have incarceration exposure, women with incarceration exposure have elevated odds of several disabilities, including difficulty remembering (Adjusted Odds Ratio [AOR] = 1.971; 95% Confidence Interval [CI] = 1.429, 2.718), difficulty seeing (AOR = 1.642, 95% CI = 1.179, 2.288), difficulty walking (AOR = 1.896, 95% CI = 1.413, 2.544), and a greater number of cumulative disabilities (Incidence Risk Ratio [IRR] = 1.483; 95% CI = 1.271, 1.731).

Conclusions

Women personally or vicariously exposed to incarceration during pregnancy endure greater odds of having a disability. Considering both incarceration and disability are important public health issues with implications for maternal and child well-being, these findings highlight the need for further research that can better understand the connection between incarceration and disability.
Demographics of road injuries and micromobility injuries among China, India, Japan, and the United States population: evidence from an age-period-cohort analysis
Authors: Zhao Yudi , Cao Jinhong , Ma Yudiyang , Mubarik Sumaira , Bai Jianjun , Yang Donghui , Wang Kai , Yu Chuanhua
Published: April 2022

Background

Micromobility sharing platforms have involved skyrocketing numbers of users in multiple countries since 2010. However, few studies have examined the overall impact of the growing micromobility market on road injuries.

Method

We use road injury data from the Global Burden of Disease Study database to examine the effect of age, period, and cohort on micromobility injury-related deaths and incidence. We compared four countries that vary in demographic background and road infrastructure. By comparing the countries, we analyzed the relationship between the trends in road injuries and these factors.

Results

We found an overall upward trend in micromobility injuries. A higher risk of micromobility-related injuries was witnessed in China and the US in 2015-2019, and people older than 45 showed a growing micromobility-related mortality and incidence rate in China, India, and the US. Cohorts after 1960 showed higher micromobility injury incidence risks in China and India, but the population born after 1990 in India showed a slightly lower risk compared to those before it.

Conclusions

The boosted usage of micromobility devices explains these increasing trends. Road infrastructure and separated traffic ease the collisions from micromobility devices. The overall situation calls for improvement in legislation as well as road infrastructure.
Associations between quality of health care and clinical outcomes in patients with rheumatic and musculoskeletal diseases: a rehabilitation cohort study
Authors: Sand-Svartrud Anne-Lene , Berdal Gunnhild , Azimi Maryam , Bø Ingvild , Dager Turid Nygaard , Eppeland Siv Grødal , Fredheim Guro Ohldieck , Hagland Anne Sirnes , Klokkeide Åse , Linge Anita Dyb , Sexton Joseph , Tennebø Kjetil , Valaas Helene Lindtvedt , Mjøsund Kristin , Dagfinrud Hanne , Kjeken Ingvild
Published: April 2022

Background

The quality of provided health care may be an important source of variation in rehabilitation outcomes, increasing the interest in associations between quality indicators (QIs) and improved patient outcomes. Therefore, we examined the associations between the quality of rehabilitation processes and subsequent clinical outcomes among patients with rheumatic and musculoskeletal diseases (RMDs).

Methods

In this multicentre prospective cohort study, adults with RMDs undergoing multidisciplinary rehabilitation at eight participating centres reported the quality of rehabilitation after 2 months and outcomes after 2, 7, and 12 months. We measured perceived quality of rehabilitation by 11 process indicators that cover the domains of initial assessments, patient participation and individual goal-setting, and individual follow-up and coordination across levels of health care. The patients responded “yes” or “no” to each indicator. Scores were calculated as pass rates (PRs) from 0 to 100% (best score). Clinical outcomes were goal attainment (Patient-Specific Functional Scale), physical function (30 s sit-to-stand test), and health-related quality of life (EuroQoL 5D-5L). Associations between patient-reported quality of care and each outcome measure at 7 months was analysed by linear mixed models.

Results

A total of 293 patients were enrolled in this study (mean age 52 years, 76% female). Primary diagnoses were inflammatory rheumatic disease (64%), fibromyalgia syndrome (18%), unspecific neck, shoulder, or low back pain (8%), connective tissue disease (6%), and osteoarthritis (4%). The overall median PR for the process indicators was 73% (range 11–100%). The PR was lowest (median 40%) for individual follow-up and coordination across levels of care. The mixed model analyses showed that higher PRs for the process indicators were not associated with improved goal attainment or improved physical function or improved health-related quality of life.

Conclusions

The quality of rehabilitation processes was not associated with important clinical outcomes. An implication of this is that measuring only the outcome dimension of quality may result in incomplete evaluation and monitoring of the quality of care, and we suggest using information from both the structure, process, and outcome dimensions to draw inferences about the quality, and plan future quality initiatives in the field of complex rehabilitation.

Trial registration

The study is part of the larger BRIDGE trial (ClinicalTrials.govNCT03102814).
Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series
Authors: Zia-ul-Hussnain Hafiz M. , Kgosidialwa Oratile , Kennedy Carmel , Quinn Mark , Dolan Emma , Deignan Paul , Sherlock Mark , Thompson Chris J. , Smith Diarmuid , O’Neill James P. , Hill Arnold , Leader Mary , Barrett Helen , Ryan Cliona , Keeling Frank , Morrin Martina M. , Agha Amar
Published: April 2022

Background 

Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2).

Methods

We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria.

Results

The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%).

Conclusions

With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.
Identification and validation of transcription factor-driven enhancers of genes related to lipid metabolism in metastatic oral squamous cell carcinomas
Authors: Zhang Liru , Zhao Shuangling , Liu Yuanhang , Lv Feifei , Geng Xixue
Published: April 2022

Background

The role and mechanisms of lipid metabolism in oral squamous cell carcinomas (OSCC) metastasis have not been clarified. This study aims to identify lipid metabolism-related genes and transcription factors regulated by metastasis-associated enhancers (MAEs) in OSCC.

Methods

Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed for lipid metabolism enrichment. TCGA data were used to analyze the differentially expressed lipid metabolism-related genes. MAEs were analyzed using GSE120634. Overlapping analysis was used to screen the MAE-regulated lipid metabolism-related genes, and the prognosis of these genes was analyzed. Transcription factor prediction was performed for the MAE-regulated lipid metabolism-related genes with prognostic value. Validation of the metastatic specificity of MAEs at ACAT1, OXSM and VAPA locus was performed using GSE88976 and GSE120634. ChIP-qPCR, qRT-PCR and Western blotting were used to verify the regulation of ACAT1, OXSM and VAPA expression by CBFB. Effects of CBFB knockdown on proliferation, invasion and lipid synthesis in metastatic OSCC cells were analyzed.

Results

Lipid metabolism was significantly enhanced in metastatic OSCC compared to non-metastatic OSCC. The expression of 276 lipid metabolism-related genes was significantly upregulated in metastatic OSCC, which were functionally related to lipid uptake, triacylglycerols, phospholipids and sterols metabolism. A total of 6782 MAEs and 176 MAE-regulated lipid metabolism-related genes were filtered. Three MAE-regulated lipid metabolism-related genes, ACAT1, OXSM and VAPA, were associated with a poor prognosis in OSCC patients. Enhancers at ACAT1, OXSM and VAPA locus were metastasis-specific enhancers. CBFB regulated ACAT1, OXSM and VAPA expression by binding to the enhancers of these genes. Knockdown of CBFB inhibited proliferation, invasion and lipid synthesis in metastatic OSCC cells.

Conclusion

The MAE-regulated lipid metabolism-related genes (ACAT1, OXSM and VAPA) and the key transcription factor (CBFB) were identified. CBFB knockdown inhibited proliferation, invasion and lipid synthesis of OSCC cells. These findings provide novel candidates for the development of therapeutic targets for OSCC.
Longitudinal inconsistencies in women’s self-reports of lifetime experience of physical and sexual IPV: evidence from the MAISHA trial and follow-on study in North-western Tanzania
Authors: Abramsky Tanya , Harvey Sheila , Mosha Neema , Mtolela Grace , Gibbs Andrew , Mshana Gerry , Lees Shelley , Kapiga Saidi , Stöckl Heidi
Published: April 2022

Background

Intimate partner violence (IPV) against women is pervasive throughout the world, with profound consequences for women’s health. Research to understand the extent, causes and consequences of IPV relies on self-reported data on violence, and yet there is a paucity of research into the consistency with which women report lifetime IPV over time.

Methods

We use data from the control group of the cluster randomised trial and a follow-on longitudinal study in Tanzania to examine discrepancies in women’s reported experience of lifetime physical IPV and sexual IPV over three time-points (T0, T29, T53 months). Among those reporting lifetime history of IPV at T0, we calculate the proportion who subsequently report no lifetime history at T29 and/or T53 (‘discrepant’ reporting). We use logistic regression to explore associations between discrepant reporting and respondent baseline characteristics, the nature of their IPV experiences at baseline, and situational factors at T53.

Results

Complete IPV data were available for 301 women. At T0, 154 (51%) women reported lifetime history of physical IPV, of whom 62% gave a discrepant ‘never’ report in a subsequent round. Among 93 (31%) with lifetime history of sexual IPV at T0, 73% provided a subsequent discrepant report. 73% of women reported lifetime physical IPV, and 55% lifetime sexual IPV in at least one survey round. For both IPV outcomes, women were less likely to provide discrepant reports if they had recent IPV at baseline, poor mental health (T53) and poor communication with partner (T53). For physical IPV only, reduced discrepant reporting was also associated with baseline household-level financial hardship and more severe or extensive experience of IPV.

Conclusions

A large proportion of women provided discrepant reports over the course of the study. Prevalence estimates of lifetime IPV from one-off cross-sectional surveys are likely to be underestimates, biased towards more recent and severe cases. To improve the stability of IPV measures, researchers should explicitly clarify the meaning of reference periods such as ‘ever’, consider using shorter reference periods (e.g. past-year), and avoid filter questions that use positive reports of lifetime IPV as a gateway to asking about more recent experiences.

Trial registration: Maisha CRT01 registered at ClinicalTrials.gov #NCT02592252, registered retrospectively (13/08/2015).
Development of a career questionnaire for medical undergraduates using Mokken scale analysis
Authors: Gao Yizhuo , Bai Xue , Sun Le , Jia Dong
Published: April 2022

Background

Individual-centred career questionnaires are important for understanding the motivations of medical students. This study aimed to collect validity evidence of a questionnaire to measure the career choice of medical undergraduates.

Methods

A cross-sectional survey was sent to third-year undergraduate students at a Chinese university-affiliated hospital. The questionnaire was formed using items that were selected after a systematic literature review. Item reduction was conducted using Mokken scale analysis, followed by reliability and validity testing, which described the validity evidence of the content, response process and internal structure.

Results

The preliminary 20-item questionnaire was returned by 213 undergraduate students (response rate: 86.59%). To construct a monotone homogeneity model, 6 items were removed after testing for unidimensionality, local independence, and latent monotonicity according to the sequence. The final questionnaire included 14 items in two subscales: a 10-item ‘career advantage’ subscale and a 4-item ‘career disadvantage’ subscale. The questionnaire was judged to be acceptably reliable (Molenaar-Sijtsma method: 0.87 and 0.75, Cronbach’s alpha: 0.87 and 0.74) and to have good construct validity (χ2/df: 1.748, normed fit index: > 0.9, comparative fit index: > 0.9, root mean square error of approximation: 0.05–0.08). Male and female undergraduates had different responses regarding their salary, subspecialty, career prospects, and ability to serve their relatives. Male undergraduates might be more willing to accept on-call positions and have subspecialties with greater likelihoods of patient–physician conflict.

Conclusion

We used Mokken scale analysis to develop and collect evidence of the validity of a 14-item questionnaire regarding career preferences among Chinese medical undergraduate students. This short and simple questionnaire may provide a suitable tool for exploring insights regarding the motivations of Chinese medical students.
Developing an innovative medical ethics and law curriculum—constructing a situation-based, interdisciplinary, court-based learning course: a mixed methods study
Authors: Chen Wan-Ting , Fu Chung-Pei , Chang Yan-Di , Shiao Yi-Chih , Chen Po-Yi , Wang Chih-Chia
Published: April 2022

Background

Traditional lecture-based medical ethics and law courses deliver knowledge but may not improve students’ learning motivation. To bridge this theory-to-practice gap and facilitate students’ learning effectiveness, we applied situated-learning theory to design an interdisciplinary court-based learning (CBL) component within the curriculum. Our study aimed to investigate students’ learning feedbacks and propose a creative course design.

Methods

A total of 135 fourth-year medical students participated in this course. The CBL component included 1 h of introduction, 1 h of court attendance, and 2 h of interdisciplinary discussion with senior physicians, judges, and prosecutors. After the class, we conducted a survey using a mixed-methods approach to gauge students’ perceptions of engagement, performance, and satisfaction.

Results

A total of 97 questionnaires were received (72% response rate). Over 70% of respondents were satisfied and felt that the class was useful except for role-playing activities (60%). More than 60% reported a better understanding of the practical applications of medical law. Approximately half (54%) reported less anxiety about medical disputes. 73% reported that the lecture provided awareness of potential medical disputes, and most respondents expressed an interest in medical law courses after the court visit (78%). 80% of the respondents were able to display empathy and apply mediation skills. Qualitative analyses showed that students demonstrated new knowledge, including recognizing the significance of the medical profession, distinguishing the importance of physician-patient communication, having confidence in the fairness of the justice system, and being willing to increase their legal knowledge.

Conclusions

CBL curriculum increases students’ learning motivation in strengthening medical professionalism and medical law, develops students’ empathy for patients and communication skills, as well as builds up students’ trust in the justice system. This novel course design can be applied to teach medical ethics and law.
The organisational climate of NHS Early Intervention Services (EIS) for psychosis: a qualitative analysis
Authors: Lammas Francis , Phillips Alexandria , Dopson Sue , Joyce Eileen , Csipke Emese , Wykes Til
Published: April 2022

Background

Cognitive remediation (CR) therapy for psychosis significantly improves recovery but is yet to be widely implemented in NHS services. It is likely to be of value at the earliest stages of psychosis development – at the first episode. Organisational climate is one factor likely to affect implementation into Early Intervention Services (EIS), which serve those experiencing first episode psychosis. We aimed to understand the organisational climate within UK NHS Early Intervention for Psychosis (EIP) services and the barriers and facilitators for the introduction of CR.

Methods

We conducted semi structured interviews with 42 EIS members of four teams in four NHS Trusts. Thematic analysis was used to analyse the data.

Results

There were differences between teams, including leadership style, involvement in decision making and willingness to adopt CR. Resource shortages were considered the main barrier for implementation across all teams. The evidence base behind CR and the recognition of there being a clinical need was seen as the main facilitator. Teams with more democratic leadership, and knowledge of both the evidence base and need for CR, may feel better able to successfully incorporate it into their service.

Conclusion

Despite enthusiasm for novel treatments, EIS teams are limited by their resources. An understanding of the local organisational variables can help teams establish a culture that values innovation. Clear communication of the evidence base for CR is key to help enable staff to implement novel treatments successfully despite these limited resources and time pressures.
Senior manager leadership competencies for quality residential aged care: an Australian industry perspective
Authors: Dawes Nathan , Topp S. M.
Published: April 2022

Background

Documented poor quality and standards of care in Australia’s residential aged care (RAC) sector have highlighted a need to better understand the role of and skills required by, RAC senior management personnel to address these concerns. This study examined which senior management leadership skills and personal qualities are necessary to deliver and strengthen the quality of RAC, with the aim of improving understanding of the professional development needs of leaders in the sector.

Methods

We conducted 12 in-depth interviews with Australian aged care industry experts, including academics, and representatives from the primary health network, consumer, and provider advocate groups. Abductive, thematic analysis incorporated coding derived from existing leadership skills frameworks as well as inductively identified themes.

Results

Identified leadership skills were grouped into five domains including i) workforce development and retention, ii) governance and business acumen; iii) health systems knowledge; iv) stewardship and v) responding to regulatory and political contexts. Skills particularly emphasised by participants were those required to recruit and retain a skilled workforce, manage relationships, and promote a positive organisational culture and employee wellbeing.

Conclusions

RAC senior managers require a complex mix of business, human resource management, and clinical skills to deliver quality care in Australia’s complex RAC setting. The lack of any professional development framework to guide the acquisition or updating of those skills is a concern.
Deep immunophenotyping reveals endometriosis is marked by dysregulation of the mononuclear phagocytic system in endometrium and peripheral blood
Authors: Vallvé-Juanico Júlia , George Ashley F. , Sen Sushmita , Thomas Reuben , Shin Min-Gyoung , Kushnoor Divyashree , Vásquez Joshua J. , Vo Kim Chi , Irwin Juan C. , Roan Nadia R. , Combes Alexis J. , Giudice Linda C.
Published: April 2022

Background

Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single-cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages.

Methods

A case-control study was designed. Endometrial biopsies and blood (n = 60 total) were obtained from women with (n = 20, n = 17, respectively) and without (n = 14, n = 9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed: one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed.

Results

The broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91+ macrophages overexpressed SIRPα (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease.

Conclusions

A greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.
LINC00922 acts as a novel oncogene in gastric cancer
Authors: Ji Zeyu , Qiu Yuping , Cai Qingchun , Xu Chunfang
Published: April 2022

Background

Long non-coding RNAs (lncRNAs) have been discovered to participate in various cancer developments. However, the biological function of lncRNAs associated with gastric cancer (GC) has not been fully elucidated.

Methods

Quantitative RT-PCR (qRT-PCR) assay was performed to measure lncRNAs, microRNAs (miRNAs) and message RNA (mRNA) expression. Cell Counter Kit-8 (CCK-8), clone formation, wound healing, and transwell assays were performed to investigate cell proliferation, migration, invasion, and apoptosis. Fluorescence in situ hybridization (FISH) assay was used to analyze LINC00922 in either the cytoplasm or nucleus. The potential binding among lncRNA, miRNA, and mRNA was evidenced by bioinformatics, luciferase reporter assay. Mouse-xenograft experiments were used to explore the tumorigenesis in vivo.

Results

LINC00922 was upregulated in GC, and high LINC00922 expression was associated with poor prognosis. Inhibition of LINC00922 suppressed GC cell proliferation, migration, invasion, and activated cell apoptosis in vitro and inhibited tumorigenesis in vivo. Besides, LINC00922 was markedly located in the cytoplasm. The mechanistic analysis demonstrated that LINC00922 acted as a sponge of miR-204-5p, thereby inhibiting the expression of the target gene-High Mobility Group AT-hook 2 (HMGA2).

Conclusion

LINC00922 accelerated the progression of GC by miR-204-5p/HMGA2 axis. These findings support LINC00922 may be a promising option for the diagnosis and therapy of GC.
Advanced pharmacodynamics of cangrelor in healthy volunteers: a dose-finding, open-label, pilot trial
Authors: Gelbenegger Georg , Grafeneder Juergen , Gager Gloria M. , Siller-Matula Jolanta M. , Schwameis Michael , Jilma Bernd , Schoergenhofer Christian
Published: April 2022

Background

High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers.

Methods

We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator. Platelet function was assessed using multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P) and the platelet function analyzer. In an ex vivo experiment, epinephrine was used to counteract the antiplatelet effect of cangrelor.

Results

All cangrelor bolus infusions resulted in immediate and pronounced platelet inhibition. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition assessed by MEA for 20 min in 90% of subjects. Infusion of cangrelor via the IV flow regulator resulted in sufficient platelet inhibition throughout the course of administration. Ex vivo epinephrine, in concentrations of 200 and 500 ng/mL was able to partially reverse the antiplatelet effect of cangrelor in a dose-dependent manner.

Conclusions

Weight-adapted bolus infusions followed by a continuous infusion of cangrelor via IV flow regulator result in immediate and pronounced platelet inhibition in healthy subjects. Cangrelor given as weight-adapted bolus infusion followed by a continuous infusion using an IV flow regulator may be a viable treatment approach for effective and well controllable prehospital platelet inhibition.

Trial registration

EC (Medical University of Vienna) 1835/2019 and EudraCT 2019-002792-34.