bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of limited sample size and follow-up on single event survival extrapolation for health technology assessment: a simulation study
Authors: Beca Jaclyn M. , Chan Kelvin K. W. , Naimark David M. J. , Pechlivanoglou Petros 
Published: December 2021

Abstract
Introduction
Extrapolation of time-to-event data from clinical trials is commonly used in decision models for health technology assessment (HTA). The objective of this study was to assess performance of standard parametric survival analysis techniques for extrapolation of time-to-event data for a single event from clinical trials with limited data due to small samples or short follow-up.

Methods
Simulated populations with 50,000 individuals were generated with an exponential hazard rate for the event of interest. A scenario consisted of 5000 repetitions with six sample size groups (30–500 patients) artificially censored after every 10% of events observed. Goodness-of-fit statistics (AIC, BIC) were used to determine the best-fitting among standard parametric distributions (exponential, Weibull, log-normal, log-logistic, generalized gamma, Gompertz). Median survival, one-year survival probability, time horizon (1% survival time, or 99th percentile of survival distribution) and restricted mean survival time (RMST) were compared to population values to assess coverage and error (e.g., mean absolute percentage error).

Results
The true exponential distribution was correctly identified using goodness-of-fit according to BIC more frequently compared to AIC (average 92% vs 68%). Under-coverage and large errors were observed for all outcomes when distributions were specified by AIC and for time horizon and RMST with BIC. Error in point estimates were found to be strongly associated with sample size and completeness of follow-up. Small samples produced larger average error, even with complete follow-up, than large samples with short follow-up. Correctly specifying the event distribution reduced magnitude of error in larger samples but not in smaller samples.

Conclusions
Limited clinical data from small samples, or short follow-up of large samples, produce large error in estimates relevant to HTA regardless of whether the correct distribution is specified. The associated uncertainty in estimated parameters may not capture the true population values. Decision models that base lifetime time horizon on the model’s extrapolated output are not likely to reliably estimate mean survival or its uncertainty. For data with an exponential event distribution, BIC more reliably identified the true distribution than AIC. These findings have important implications for health decision modelling and HTA of novel therapies seeking approval with limited evidence.
The automation of relevant trial registration screening for systematic review updates: an evaluation study on a large dataset of ClinicalTrials.gov registrations
Authors: Surian Didi , Bourgeois Florence T. , Dunn Adam G. 
Published: December 2021

Abstract
Background
Clinical trial registries can be used as sources of clinical evidence for systematic review synthesis and updating. Our aim was to evaluate methods for identifying clinical trial registrations that should be screened for inclusion in updates of published systematic reviews.

Methods
A set of 4644 clinical trial registrations (ClinicalTrials.gov) included in 1089 systematic reviews (PubMed) were used to evaluate two methods (document similarity and hierarchical clustering) and representations (L2-normalised TF-IDF, Latent Dirichlet Allocation, and Doc2Vec) for ranking 163,501 completed clinical trials by relevance. Clinical trial registrations were ranked for each systematic review using seeding clinical trials, simulating how new relevant clinical trials could be automatically identified for an update. Performance was measured by the number of clinical trials that need to be screened to identify all relevant clinical trials.

Results
Using the document similarity method with TF-IDF feature representation and Euclidean distance metric, all relevant clinical trials for half of the systematic reviews were identified after screening 99 trials (IQR 19 to 491). The best-performing hierarchical clustering was using Ward agglomerative clustering (with TF-IDF representation and Euclidean distance) and needed to screen 501 clinical trials (IQR 43 to 4363) to achieve the same result.

Conclusion
An evaluation using a large set of mined links between published systematic reviews and clinical trial registrations showed that document similarity outperformed hierarchical clustering for identifying relevant clinical trials to include in systematic review updates.
How frail is frail? A systematic scoping review and synthesis of high impact studies
Authors: Gordon E. H. , Reid N. , Khetani I. S. , Hubbard R. E. 
Published: December 2021

Abstract
Aims
While the frailty index (FI) is a continuous variable, an FI score of 0.25 has construct and predictive validity to categorise community-dwelling older adults as frail or non-frail. Our study aimed to explore which FI categories (FI scores and labels) were being used in high impact studies of adults across different care settings and why these categories were being chosen by study authors.

Methods
For this systematic scoping review, Medline, Cochrane and EMBASE databases were searched for studies that measured and categorised an FI. Of 1314 articles screened, 303 met the eligibility criteria (community: N = 205; residential aged care: N = 24; acute care: N = 74). For each setting, the 10 studies with the highest field-weighted citation impact (FWCI) were identified and data, including FI scores and labels and justification provided, were extracted and analysed.

Results
FI scores used to distinguish frail and non-frail participants varied from 0.12 to 0.45 with 0.21 and 0.25 used most frequently. Additional categories such as mildly, moderately and severely frail were defined inconsistently. The rationale for selecting particular FI scores and labels were reported in most studies, but were not always relevant.

Conclusions
High impact studies vary in the way they categorise the FI and while there is some evidence in the community-dweller literature, FI categories have not been well validated in acute and residential aged care. For the time being, in those settings, the FI should be reported as a continuous variable wherever possible. It is important to continue working towards defining frailty categories as variability in FI categorisation impacts the ability to synthesise results and to translate findings into clinical practice.
Challenges in providing ethically competent health care to incarcerated older adults with mental illness: a qualitative study exploring mental health professionals’ perspectives in Canada
Authors: Mussie Kirubel Manyazewal , Pageau Félix , Merkt Helene , Wangmo Tenzin , Elger Bernice Simone 
Published: December 2021

Abstract
Background
The population of incarcerated older adults is the fastest growing demographic in prisons. Older persons in custody have poorer health as compared with those in the community. The unmet and complex health care needs of incarcerated older adults with mental illness raise justice, safety, dignity and fairness in care as ethical concerns. As there exists research gap to better understand these concerns, the current study aimed at exploring the perspectives of mental health professionals on challenges in delivering ethically competent care to mentally ill incarcerated older adults in Canada.

Methods
Thirty-four semi-structured interviews were conducted between August 2017 and November 2018 with prison mental health professionals in Canada who were selected using purposive and convenience sampling techniques. The audio recorded interviews were transcribed verbatim and analysed inductively to generate themes.

Results
The results were distilled into three main categories and seven subcategories that related to ethical issues in the provision of health care for mentally ill incarcerated older adults. The main categories included imprisoned older persons with special care needs, lack of resources, and the peer-support program.

Conclusions
Results of this study showed that existing practices of care of mentally ill incarcerated older adults are characterised by challenges that increase their vulnerability to worse health conditions. It is imperative for local authorities, policy makers and representatives to prepare for and respond to the challenges that compromise ethically competent health care for, and healthy ageing of, mentally ill incarcerated older adults.
Effect of food insecurity on the cognitive problems among elderly in India
Authors: Kumar Shubham , Bansal Anjali , Shri Neha , Nath Nayan Jyoti , Dosaya Divya 
Published: December 2021

AbstractBackgroundFood Insecurity (FI) is a crucial social determinant of health, independent of other socioeconomic factors, as inadequate food resources create a threat to physical and mental health especially among older person. The present study explores the associations between FI and cognitive ability among the aged population in India.MethodsTo measure the cognitive functioning we have used two proxies, word recall and computational problem. Descriptive analysis and multivariable logistic regression was used to understand the prevalence of word recall and computational problem by food security and some selected sociodemographic parameters. All the results were reported at 95% confidence interval.ResultsWe have used the data from the first wave of longitudinal ageing study of India (LASI), with a sample of 31,464 older persons 60 years and above. The study identified that 17 and 5% of the older population in India experiencing computational and word recall problem, respectively. It was found that respondents from food secure households were 14% less likely to have word recall problems [AOR:0.86, 95% CI:0.31–0.98], and 55% likely to have computational problems [AOR:0.45, 95% CI:0.29–0.70]. We also found poor cognitive functioning among those experiencing disability, severe ADL, and IADL. Further, factors such as age, education, marital status, working status, health related factors were the major contributors to the cognitive functioning in older adults.ConclusionThis study suggest that food insecurity is associated with a lower level of cognition among the elderly in India, which highlight the need of food policy and interventional strategies to address food insecurity, especially among the individuals belonging to lower wealth quintiles. Furthermore, increasing the coverage of food distribution may also help to decrease the burden of disease for the at most risk population. Also, there is a need for specific programs and policies that improve the availability of nutritious food among elderly.
Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases
Authors: Shi Min , Yang Zhongyin , Lu Sheng , Liu Wentao , Ni Zhentian , Yao Xuexin , Hua Zichen , Feng Runhua , Zheng Yanan , Wang Zhenqiang , Sah Birendra Kumar , Chen Mingmin , Zhu Zhenglun , He Changyu , Li Chen , Zhang Jun , Yan Chao , Yan Min , Zhu Zhenggang 
Published: December 2021

Abstract
Background
In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases.

Patients and methods
Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks.

Results
Of all these 30 patients, the median number of cycles was 6 (range 2–16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7–8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4–17.8 months). The grade 3–4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3–4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%).

Conclusions
SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3–4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy.

Trail registration
ChiCTR, ChiCTR-IIR-16009802. Registered 9 November 2016,
High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas
Authors: Raymond Perrine , Klein Marc , Cuny Thomas , Klein Olivier , Salleron Julia , Bernier-Chastagner Valérie 
Published: December 2021

Abstract
Background
Cranial irradiation represents one of the first line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas.

Methods
Fifty-two adults receiving photon-beam therapy for skull base meningiomas between 2003 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8 am-Cortisol, IGF-1, fT3, fT4, 17βestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated.

Results
Mean age at diagnosis was 56 +/− 14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37, 28, 18 and 15% of patients, respectively. Hyperprolactinemia was found in 13% of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥40 mm significantly increased the risk of developing hypopituitarism.

Conclusions
Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥4 cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.
Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model
Authors: Yoneda Junya , Nishikawa Sachiko , Kurihara Shigekazu 
Published: December 2021

Abstract
Background
Chemotherapy is frequently used in cancer treatment; however, it may cause adverse events, which must be managed. Reactive oxygen species (ROS) have been reported to be involved in the induction of intestinal mucositis and diarrhea, which are common side effects of treatment with fluoropyrimidine 5-fluorouracil (5-FU). Our previous studies have shown that oral administration of cystine and theanine (CT) increases glutathione (GSH) production in vivo. In the present study, we hypothesized that CT might inhibit oxidative stress, including the overproduction of ROS, and attenuate 5-FU-induced mucositis and diarrhea.

Methods
We investigated the inhibitory effect of CT administration on mucositis and diarrhea, as well as its mechanism, using a mouse model of 5-FU-induced intestinal mucositis.

Results
CT administration suppressed 5-FU-induced diarrhea and weight loss in the studied mice. After 5-FU administration, the GSH level and the GSH/GSSG ratio in the small intestine mucosal tissue decreased compared to normal control group; but CT administration improved the GSH/GSSG ratio to normal control levels. 5-FU induced ROS production in the basal region of the crypt of the small intestine mucosal tissue, which was inhibited by CT. CT did not affect the antitumor effect of 5-FU.

Conclusions
CT administration suppressed intestinal mucositis and diarrhea in a mouse model. This finding might be associated with the antioxidant characteristics of CT, including the improved rate of GSH redox and the reduced rate of ROS production in the small intestine mucosal tissue. CT might be a suitable candidate for the treatment of gastrointestinal mucositis associated with chemotherapy.
Interpersonal trauma and its relation to childhood psychopathic traits: what does ADHD and ODD add to the equation?
Authors: Marshall John J. , Sörman Karolina , Durbeej Natalie , Thompson L. , Lundström Sebastian , Minnis Helen , Hellner Clara , Gillberg Christopher 
Published: December 2021

Abstract
Background
Childhood trauma has demonstrated associations with callous-unemotional traits (e.g., reflecting lack of remorse and guilt, unconcern about own performance). Less is known about associations between trauma and multiple domains of child psychopathic traits. There has also been limited focus on the role of co-occurring disorders to psychopathy traits among children, namely, attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) and how they interact with childhood trauma.

Methods
We examined to what degree childhood interpersonal trauma can predict parent-rated psychopathic traits in a large population based Swedish twin sample (N = 5057), using a stringent definition of interpersonal trauma occurring before age 10. Two hundred and fifty-one participants met the interpersonal trauma criteria for analysis. The study explored the additional impact of traits of attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD).

Results
Linear regressions demonstrated statistically significant but clinically negligible effects of interpersonal trauma on total and subscale scores of parent-rated psychopathic traits. When exploring interaction effects of ADHD and ODD into the model, the effect increased. There were interaction effects between ODD and trauma in relation to psychopathic traits, suggesting a moderating role of ODD. Having been exposed to trauma before age 10 was significantly associated with higher parent rated psychopathy traits as measured by The Child Problematic Traits Inventory-Short Version (CPTI-SV), however the explained variance was small (0.3–0.9%).

Conclusions
The results challenge the notion of association between interpersonal trauma and youth psychopathic traits. They also highlight the need to gain an improved understanding of overlap between psychopathic traits, ADHD and ODD for clinical screening purposes and the underlying developmental mechanisms.
A cross-sectional study of community perceptions of stigmatization amongst women affected by UN-peacekeeper perpetrated sexual exploitation and abuse
Authors: Gray Samantha , Bartels Susan A. , Lee Sabine , Stuart Heather 
Published: December 2021

Abstract
Background
Sexual exploitation and abuse (SEA) by UN peacekeepers perpetrated against local women and girls is a concern in the Democratic Republic of Congo (DRC). While stigma associated with sexual and gender-based violence is well documented more broadly, little is known about stigma associated with peacekeeper-perpetrated SEA.

Methods
The aim of this study was to examine how the degree of exposure to SEA affects community perceptions of a woman or girl’s (1) social status (public stigma) and (2) institutional support in her community (structural stigma). Two poisson regression models with robust variance estimation were constructed utilizing community survey data of SEA experiences from eastern DRC (n = 2867) to quantify these associations. Relevant demographic variables were assessed for confounding and effect modification.

Results
The prevalence of public and structural stigma were 62.9 and 19.3% respectively across the sample. A positive relationship was demonstrated between level of exposure of SEA and diminished social status in which women and girls experiencing moderate levels of SEA were at the greatest risk of public stigmatization after adjusting for confounding (RR: 1.94; CI: 1.66–2.26). Similarly, a positive relationship between exposure to SEA and inadequate institutional support was shown for female narrators wherein women and girls experiencing a high degree of SEA were 6.53 times as likely to receive inadequate support (RR: 6.53; CI: 3.63, 11.73). This contrasted with male narrated stories for whom there was no significant association between the SEA exposure level and institutional support.

Conclusions
Women/girls with high exposure levels to UN peacekeeper-perpetrated SEA are at the highest risk of public and structural stigmatization, which should be more routinely considered when conceptualizing the consequences of SEA in peacekeeping contexts. The frequent occurrence of both public and structural stigma, coupled with the varying perceptions by sex, demonstrates the need for a multi-faceted approach for stigma reduction.
The performance of COVID-19 Surveillance System as timely containment strategy in Western Oromia, Ethiopia
Authors: Tamiru Afework , Regassa Bikila , Alemu Tamirat , Begna Zenebu 
Published: December 2021

AbstractBackgroundCOVID-19 has been swiftly spreading throughout the world ever since it emerged in Wuhan, China, in late December 2019. Case detection and contact identification remain the key surveillance objectives for effective containment of the pandemic. This study was aimed at assessing performance of surveillance in early containment of COVID 19 in Western Oromia, Ethiopia.MethodsA cross-sectional study was conducted from August 1 to September 30, 2020, in the 7 kebeles of Nekemte and 2 kebeles of Shambu Town. Residents who lived there for at least the past six months were considered eligible for this study. Data were collected from community and health system at different levels using semi structured questionnaire and checklist, respectively. Participants’ health facility usage (dependent variable) and perceived risk, awareness, Socioeconomic Status, and practices (independent variable) were assessed. Bivariable analysis was computed to test the presence of an association between dependent and independent variables. Independent predictors were identified on multivariable logistic regression using a p-value of (<0.05) significance level. We have checked the model goodness of fit test by Hosmer-lemeshow test.ResultsOne hundred seventy-nine (41%) of the participants believe that they have a high risk of contracting COVID-19 and 127 (29%) of them reported they have been visited by health extension worker. One hundred ninety-seven (45.2%) reported that they were not using health facilities for routine services during this pandemic. Except one hospital, all health facilities (92%) were using updated case definition. Three (33%) of the assessed health posts didn’t have community volunteers. On multivariable logistic regression analysis, the source of income AOR=0.30, 95% CI (0.11, 0.86), perceived level of risk AOR=3.42, 95% CI (2.04, 5.7) and not visited by health extension workers AOR=0.46, 95% CI (0.29, 0.74) were found to be independent predictors of not using health facilities during this pandemic.ConclusionEvent based surveillance, both at community and health facility level, was not performing optimally in identifying potential suspects. Therefore, for effective early containment of epidemic, it is critical to strengthen event based surveillance and make use of surveillance data for tailored intervention in settings where mass testing is not feasible.