Miracle-dz/UniFAR-FTUs huggingface dataset:
Cohort versus patient level simulation for the economic evaluation of single versus combination immuno-oncology therapies in metastatic melanoma

Abstract Background: Model structure, despite being a key source of uncertainty in economic evaluations, is often not treated as a priority for model development. In oncology, partitioned survival models (PSMs) and Markov models, both types of cohort model, are commonly used, but patient responses to newer immuno-oncology (I-O) agents suggest that more innovative model frameworks should be explored. Objective: A discussion of the theoretical pros and cons of cohort level vs patient level simulation (PLS) models provides the background for an illustrative comparison of I-O therapies, namely nivolumab/ipilimumab combination and ipilimumab alone using patient level data from the CheckMate 067 trial in metastatic melanoma. PSM, Markov, and PLS models were compared on the basis of coherence with short-term clinical trial endpoints and long-term cost per QALY outcomes reported. Methods: The PSM was based on Kaplan-Meier curves from CheckMate 067 with 3-year data on progression free survival (PFS) and overall survival (OS). The Markov model used time independent transition probabilities based on the average trajectory of PFS and OS over the trial period. The PLS model was developed based on baseline characteristics hypothesized to be associated with disease as well as significant mortality and disease progression risk factors identified through a proportional hazards model. Results: The short-term Markov model outputs matched the 1–3 year clinical trial results approximately as well as the PSMs for OS but not PFS. The fixed (average) cohort PLS results corresponded as well as the PSMs for OS in the combination therapy arm and PFS in the monotherapy arm. Over the lifetime horizon, the PLS produced an additional 5.95 quality adjusted life years (QALYs) associated with combination therapy relative to ipilimumab alone, resulting in an incremental cost-effectiveness ratio (ICER) of £6,474 per QALY, compared with £14,194 for the PSMs which gave an incremental benefit of between 2.2 and 2.4 QALYs. The Markov model was an outlier (∼ £49,000 per QALY in the base case). Conclusions: The 4- and 5-state versions of the PSM cohort model estimated in this study deviate from the standard 3-state approach to better capture I-O response patterns. Markov and PLS approaches, by modeling state transitions explicitly, could be more informative in understanding I-O immune response, the PLS particularly so by reflecting heterogeneity in treatment response. However, both require a number of assumptions to capture the immune response effectively. Better I-O representation with surrogate endpoints in future clinical trials could yield greater model validity across all models.
Effect of chicken meat replacement by spent laying hen meat on physicochemical properties and sensorial characteristics of fresh sausage

ABSTRACT 1. Sausages were used to assess the effects of chicken meat replacement by spent laying hen meat on the quality parameters and sensorial properties. 2. Five formulations were developed: control (CON) containing 100% chicken meat and 4 levels of chicken meat replacement with spent laying hen meat: 25% (T25), 50% (T50), 75% (T75) and 100% (T100). 3. Appearance, texture, succulence, flavour and overall consumer acceptance were analysed. Parameters such as moisture, ash, fat and protein content, pH, cooking loss and colour parameters (lightness (L*), redness (a*), yellowness (b*)) were analysed, as well as the texture properties (hardness, elasticity, cohesiveness and chewiness). 4. Statistical analysis did not reveal significant (P > 0.05) differences in chemical composition and colour parameters among formulations. On the other hand, CON treatment showed the lowest (P < 0.05) cooking loss (20.45%) that increased as spent laying hen meat increased in the formulation (24.92% vs. 27.65% vs. 28.12% vs. 33.05%, for T25, T50, T75 and T100 batches, respectively). 5. Regarding textural parameters, T75 and T100 formulations presented higher (P < 0.05) hardness and chewiness compared to the other ones. 6. Concerning to sensorial characteristics, the T100 formulation presented the lowest average scores (P < 0.05) for all attributes studied. However, the other batches (T25, T50 and T75) did not show significant differences for appearance, texture, succulence, flavour and overall acceptability attributes compared with the CON formulation. 7. The results indicated that the substitution of up to 75% of chicken meat by spent laying hen meat did not decrease the sensory acceptance of the sausages by consumers, demonstrating that this level of substitution in sausages allows better use of spent laying hen meat.
5-Year Survival Rates and Prognostic Factors in Patients with Synchronus and Metachronus Breast Cancer from 2010 to 2015

Introduction: Currently breast (BC) cancer is a serious medical problem in all countries of the world. Survival depends on many factors. The present study focused on 5-year survival and its related factors in patients with BC in Iran. Material and methods. The present analytical retrospective study was performed (from March 2010 until March 2015) on patients with BC followed for at least 6 months. The main variables assessed were tumor size, grade of lymph node involvement, metastasis, stage, history, human epidermal growth factor receptor expression, and tumor origin. Analysis of survival was accomplished using the Kaplan- Meier method. Results: Some 351 (80.2%) of the total of 438 individuals had unilateral and 87(19.8%) had bilateral cancer, 28 (35.6%) of the latter being synchronous and 56(64.4%) metachronous. Mean duration of follow-up was 47.44±28.19 months, during which 61 (17.3%) patients with unilateral and 18 with bilateral cancer eventually died. The 5-year survival rate in patients with unilateral BC was significantly higher than those with bilateral BC (Log-rank Test chi2= 3.11, p=0.032). In addition, with metachronous cases, the survival rate was 64.2% in comparison with 51.6% for synchronous BCs. Survival rate was significantly (p value =0.038) higher with metachronous than with synchronous cancers (Log-rank Test chi2=3.54, p=0.038). The highest survival rate was reported for BCs originating from lobule tissue and the lowest rate examples of interstitial tissue origin (Log-rank Test chi2=11.54, p=0.0001). Patients with earl stage lesions (M1) survived longer than with other stages (Log-rank Test chi2= 9.55, p=0.001). Conclusion: In this study, most women with BC had a positive family history and were married. The 5-year survival rate was lower with advanced stages of cancer. According to our findings, survival rates might improve if patients undergo screening and diagnosis is made at an early stage of the disease.
Conscientiousness Is Associated with Lower Risk of Dementia among Black and White Older Adults

Background: While some personality traits may reduce risk of dementia, this is controversial and has not been studied as much among diverse populations. We examined associations between 2 traits – Conscientiousness and Openness to Experience – and risk of dementia among black and white older adults. Methods: We studied 875 older adults (ages 71–82, 47% black) without prevalent dementia from the Health, Aging and Body Composition study, who completed the NEO Five-Factor Inventory for Conscientiousness and Openness to Experience. Incident dementia over 8 years (mean = 6.9 years) was determined by hospital records, medications, or ≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination. In adjusted models, we investigated associations between each trait and risk of dementia, including for race interactions. Results: Associations between personality traits and dementia risk did not differ by race (interactions: p > 0.7). Higher Conscientiousness was associated with lower dementia risk (adjusted HR per 1SD = 0.78; 95% CI 0.65–0.94). There was no association for Openness to Experience (adjusted HR per 1SD = 0.88; 95% CI 0.71–1.08). Conclusions: Higher Conscientiousness is associated with lower dementia risk, even among diverse populations. Higher Conscientiousness may be protective, or lower Conscientiousness may be an early symptom of neurodegenerative disease.
Mental disorders and the risk of adult violent and psychological victimisation: a prospective, population-based study

Abstract Aims Psychiatric patients are at increased risk to become victim of violence. It remains unknown whether subjects of the general population with mental disorders are at risk of victimisation as well. In addition, it remains unclear whether the risk of victimisation differs across specific disorders. This study aimed to determine whether a broad range of mood, anxiety and substance use disorders at baseline predict adult violent (physical and/or sexual) and psychological victimisation at 3-year follow-up, also after adjustment for childhood trauma. Furthermore, this study aimed to examine whether specific types of childhood trauma predict violent and psychological victimisation at follow-up, after adjustment for mental disorder. Finally, this study aimed to examine whether the co-occurrence of childhood trauma and any baseline mental disorder leads to an incrementally increased risk of future victimisation. Methods Data were derived from the first two waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2): a psychiatric epidemiological cohort study among a nationally representative adult population. Mental disorders were assessed using the Composite International Diagnostic Interview version 3.0. Longitudinal associations between 12 mental disorders at baseline and violent and psychological victimisation at 3-year follow-up (n = 5303) were studied using logistic regression analyses, with adjustment for sociodemographic characteristics and childhood trauma. Furthermore, the moderating effect of childhood trauma on these associations was examined. Results Associations with victimisation varied considerably across specific mental disorders. Only alcohol dependence predicted both violent and psychological victimisation after adjustment for sociodemographic characteristics and childhood trauma. Depression, panic disorder, social phobia, generalised anxiety disorder and alcohol dependence predicted subsequent psychological victimisation in the fully adjusted models. All types of childhood trauma independently predicted violent and psychological victimisation after adjustment for any mental disorder. The presence of any childhood trauma moderated the association between any anxiety disorder and psychological victimisation, whereas no interaction between mental disorder and childhood trauma on violent victimisation existed. Conclusions The current study shows that members of the general population with mental disorders are at increased risk of future victimisation. However, the associations with violent and psychological victimisation vary considerably across specific disorders. Clinicians should be aware of the increased risk of violent and psychological victimisation in individuals with these mental disorders – especially those with alcohol dependence – and individuals with a history of childhood trauma. Violence prevention programmes should be developed for people at risk. These programmes should not only address violent victimisation, but also psychological victimisation.
The Use of Smartphone Applications (Apps) for Enhancing Communication With Surgical Patients: A Systematic Review of the Literature

Background. The widespread use and development of smartphones and mHealth apps has the potential to overcome communication deficiencies in health care. Objective. To carry out a literature review of studies that evaluate patients’ experience on the use of perioperative mHealth apps. Methods. An up-to-date systematic review on studies assessing patients’ use of mHealth apps for communicating with the health care team in the perioperative period was performed following the PRISMA statement. Results. Ten studies (in 11 articles) were identified: 8 feasibility studies and 2 randomized controlled trials. Nine studies included apps used for postoperative monitoring while 1 study also provided preoperative guidance. Discussion. An analysis of barriers and motivations of patients and health care professionals to the use of perioperative mHealth apps was performed. Barriers included patients’ lack of confidence when using apps and potential lack of time from health care professionals to monitor information submitted by patients. Motivations included patients’ sense of being looked after and potential cost-effectiveness and increased efficiency of health care services. This analysis led to the concept of the “ideal app” that would need to be developed following adequate protocols and security standards. Features of the ideal app include preoperative advice on medications and investigations, information on surgery, and a remote follow-up tool to improve safety and to minimize unnecessary clinic appointments and associated costs. Conclusion. There is an overall positive impression of the use of perioperative mHealth apps. However, further studies are required to assess the impact that they have on patients’ care and healthcare professional services.
Common and dissociable contributions of alexithymia and autism to domain-specific interoceptive dysregulations – a dimensional neuroimaging approach

Alexithymia represents a transdiagnostic marker across psychiatric entities associated with emotional impairments, including autism spectrum disorders (ASD). Accumulating evidence suggests that interoceptive dysfunctions that underpin the core symptomatic emotion recognition and empathy deficits in ASD may be contributed to by high levels of alexithymia rather than autistic symptoms per se. However, previous findings are hampered by generally elevated alexithymia in ASD patients, and thus were not able to differentiate common and distinct contributions across the entire spectrum of variations of autism and alexithymia. Moreover, the multi-factorial nature of the domains affected, such as distinct neural reactivity towards perceiving physical and affective pain, has not been accounted for. Against this background the present fMRI study employed a dimensional trait approach in n = 242 healthy subjects to determine common and distinct associations between both traits and pain empathic responses towards physical and affective pain. Higher levels of alexithymia associated with increased left anterior insula pain empathic reactivity. Disentangling these effects revealed a positive association during perceived physical pain, but a negative one during affective pain. No significant associations with trait autism were found, but an interaction effect between the trait dimensions was observed in the mid-cingulate cortex. Moderation analysis demonstrated that trait autism only impacted mid-cingulate reactivity towards physical pain in high alexithymia subjects, whereas reactivity towards affective pain was specifically associated with trait autism in low alexithymia subjects. Findings confirm previous patient studies suggesting that alexithymia rather than autism per se may drive altered insula pain empathic reactivity. Importantly, the present approach allowed for the first time to demonstrate that the impact of alexithymia on insula reactivity varies as a function of the pain empathic domain and that effects on other core empathy nodes evolve in interaction with trait autism.
Action 3:30R: Results of a Cluster Randomised Feasibility Study of a Revised Teaching Assistant-Led Extracurricular Physical Activity Intervention for 8 to 10 Year Olds

Many children are not sufficiently physically active. We conducted a cluster-randomised feasibility trial of a revised after-school physical activity (PA) programme delivered by trained teaching assistants (TAs) to assess the potential evidence of promise for increasing moderate-to-vigorous physical activity (MVPA). Participants (n = 335) aged 8–10 years were recruited from 12 primary schools in South West England. Six schools were randomised to receive the intervention and six acted as non-intervention controls. In intervention schools, TAs were trained to deliver an after-school programme for 15 weeks. The difference in mean accelerometer-assessed MVPA between intervention and control schools was assessed at follow-up (T1). The cost of programme delivery was estimated. Two schools did not deliver the intervention, meaning four intervention and six control schools were analysed at T1. There was no evidence for a difference in MVPA at T1 between intervention and control groups. Programme delivery cost was estimated at £2.06 per pupil per session. Existing provision in the 12 schools cost £5.91 per pupil per session. Action 3:30 was feasible to deliver and considerably cheaper than existing after-school provision. No difference in weekday MVPA was observed at T1 between the two groups, thus progression to a full trial is not warranted.
Sex differences in the severity of neuropsychiatric symptoms and their relationship with clinico-demographic and psychosocial factors in patients with amnestic mild cognitive impairment and mild Alzheimer’s disease

Abstract Objectives: We examined differences in the severity of neuropsychiatric symptoms (NPS) according to sex and identified NPS-related clinico-demographic and psychosocial factors among community-living patients with amnestic-mild cognitive impairment (a-MCI) or mild Alzheimer’s disease (AD). Method: Overall, 111 patients (44 males, 67 females) with mild a-MCI (n = 64) or mild AD (n = 47) were included. We divided the patients according to sex and compared their clinico-demographic and psychosocial factors, explored the severity of NPS using the subscales from the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and further identified variables related to NPS. Results: Significant differences in several clinico-demographic and psychosocial characteristics were observed between the sexes. The severity of delusions was higher among females (mean, 0.48; SD, 1.60) than males (mean, 0.23; SD, 1.07; p = .02), while the severity of irritability was higher among males (mean, 0.97; SD, 1.92) than females (mean, 0.49; SD, 1.40; p = .03). The severity of delusions among females was related to the duration of cognitive decline (B = 0.37, p = .03), while the severity of irritability among males was related to general cognition (B = -0.40, p = .003). Conclusion: The severity of NPS among patients with a-MCI or mild AD differed according to sex. We identified NPS-related clinico-demographic factors among these patients. Sex differences should be considered when determining the need for NPS interventions.
18F-Fluciclovine PET/CT Detection of Recurrent Prostate Carcinoma in Patients With Serum PSA ⩽ 1 ng/mL After Definitive Primary Treatment

Purpose The aims of this study were to report on our initial experience using 18F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings. Patients and Methods In this retrospective study, 18F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSA values of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test. Results At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative 18F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively). Conclusions Detection of recurrent prostate cancer using 18F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.
Selenoprotein P in Patients with Nonalcoholic Fatty Liver Disease.

OBJECTIVE Main aim of this study was to evaluate circulating selenoprotein P (SEPP) levels in patients with simple steatosis (SS) and nonalcoholic steatohepatitis (NASH) compared with healthy controls. METHODS Thirty-one patients with biopsy-proven NAFLD (15 with SS, 10 with borderline NASH, 6 with definite NASH) and 27 matched controls without NAFLD were enrolled. Serum SEPP levels and liver function tests plus biochemical parameters were measured with ELISA and standard methods, respectively. Homeostatic model of assessment - insulin resistance (HOMA-IR) was calculated. RESULTS SEPP levels were statistically different between groups (p-value for trend=0.043). In pairwise comparisons, SEPP was lower in definite NASH compared with controls (p=0.029), but not SS (p=0.18) or borderline NASH (p=0.35). SEPP was not different between controls, SS and borderline NASH. The unadjusted trend between the controls, SS and NASH patients remained essentially unchanged after adjustment for age, sex, log(ALT) and waist circumference, but it marginally lost significance when log(HOMA-IR) entered into the model. SEPP levels were not different between groups of different severity of steatosis, fibrosis, hepatocellular ballooning, lobular and portal inflammation. CONCLUSIONS Lower SEPP levels were observed in patients with definite NASH compared with controls, a finding warranting larger studies.