Miracle-dz/UniFAR-FTUs huggingface dataset:
Telling the patients about diagnosis and outcome of schizophrenia: what, when and how?

A review of the disclosure of the mental health diagnosis found that the service users suffering from schizophrenia were far less likely to be informed about their diagnosis, with 45% not receiving any information, compared to an average of 20% for other diagnoses. The caregivers of those suffering from schizophrenia have also described the ‘long and difficult pathway to being given a diagnosis’ and the ‘haphazard mean of finding diagnoses’. Based on a large survey in Scotland, Clafferty et al. reported that only 59% of psychiatrists would tell the diagnosis in a first episode; however, 89% of psychiatrists would disclose the diagnosis in recurrent episodes. Studies showed that clinicians sometimes offered a ‘substitute’ diagnosis instead of schizophrenia including terms such as neurasthenia, neurosis and psychogenic reaction. Recent literature on clinical practices in this area is limited, and it is therefore not clear whether clinicians still withhold diagnosis or offer a more ‘acceptable’ alternative to patients and carers. The cross-cultural issues pose another challenge. Some Chinese American psychiatrists believed that they were being culturally competent by not disclosing diagnoses and considered diagnostic nondisclosure as one of the most effective treatment approaches when working with Chinese American patients. Another cross-cultural study revealed that 70% of North Americans and less than 30% of Japanese psychiatrists would inform patients about the diagnosis of schizophrenia. Communicating diagnosis is an even greater problem in the first-episode psychosis. In view of diagnostic heterogeneity in first-episode psychoses and diagnostic instability over time, it is understandable that most early intervention services prefer the term psychosis instead of schizophrenia. Indeed, the Japanese Society of Psychiatry and Neurology renamed schizophrenia to ‘Togo Shitcho Sho’, which literally means integration disorder. It is not clear, though, how these alternative diagnostic entities are communicated with service users and how these are accepted.
Development of multiplex real-time PCR screens for the diagnosis of feline and canine infectious disease

Infectious disease is a significant cause of morbidity and mortality in cats and dogs. The diagnosis of the causative agent is essential to allow for the appropriate clinical intervention, to reduce infection spread, and also to support epidemiological studies which in turn will better the understanding of infectious disease transmission and control. The polymerase chain reaction (PCR) has replaced traditional detection methods as the gold standard diagnostic technique for many pathogens, however replacing traditional detection methods with panels of internally controlled multiplex real-time PCR screens designed along syndromic lines is not widespread. The aim of this thesis is to undertake the development phase of a wider project that intends to develop a broad panel of syndrome based real-time PCR multiplex assays for infectious diseases in cats and dogs. In order to achieve this, appropriate extraction and real-time PCR platforms and reagents were chosen. The aim of this project was to begin the development of five syndrome based panels of multiplex screens:- feline respiratory disease, feline conjunctivitis, feline anaemia, feline gingivitis, and feline and canine gastroenteritis. The multiplex assays were optimised and then evaluated through a series of experiments to determine the endpoint sensitivity, specificity and robustness of each multiplex in comparison to the single assays. The full optimisation and pre-clinical validation assessment of five multiplex assays was completed in the timescale of this project; the feline respiratory screen, the feline conjunctivitis screen and the feline/canine gastroenteritis 1, 2 and 3 screens. This study highlighted some of the difficulties that can be encountered when developing in-house multiplex real-time PCR assays. The main limitations were the lack of readily available positive control material, published assays and sequence data. The results of this study highlight that the development of an in-house multiplex real-time PCR diagnostic service can be at times difficult and occasionally time-consuming. A significant finding of this study was that PCR may not be as sensitive as virus isolation in the detection of feline calicivirus (FCV). It is hoped that further work including additional sequencing will aid in the development of a more sensitive FCV PCR assay. In-house multiplex real-time PCR should bring many advantages over current veterinary diagnostic assays. This will in turn aid in the treatment and clinical management of the animal, and increase our understanding of infectious disease in cats and dogs.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine

Background The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication‐competent, recombinant vesicular stomatitis virus (rVSV)–based vaccine candidate designed to prevent EVD. Methods We conducted two phase 1, placebo‐controlled, double‐blind, dose‐escalation trials of an rVSV‐based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV‐ZEBOV vaccine (3 million plaque‐forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. Results The most common adverse events were injection‐site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme‐linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV‐Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. Conclusions This Ebola vaccine candidate elicited anti‐Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV&Dgr;G‐ZEBOV‐GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408.)
Effects of red-cell storage duration on patients undergoing cardiac surgery.

BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
Long-term effect of gene therapy on Leber's congenital amaurosis.

BACKGROUND Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).
Does co‐occurring borderline personality disorder influence acute phase treatment for first‐episode psychosis?

This aims of this study were: (1) to determine the prevalence of co‐occurring borderline personality disorder (BPD) in a first‐episode psychosis (FEP) sample; (2) to determine differences between patients with and without BPD on demographics, comorbidities and clinical risks and other variables; and (3) to examine whether BPD comorbidity influenced treatment received by patients for FEP during their first 3 months after service entry to a specialist early psychosis service.
Fresh Fruit Consumption and Major Cardiovascular Disease in China.

BACKGROUND In Western populations, a higher level of fruit consumption has been associated with a lower risk of cardiovascular disease, but little is known about such associations in China, where the consumption level is low and rates of stroke are high. METHODS Between 2004 and 2008, we recruited 512,891 adults, 30 to 79 years of age, from 10 diverse localities in China. During 3.2 million person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523 intracerebral hemorrhages were recorded among the 451,665 participants who did not have a history of cardiovascular disease or antihypertensive treatments at baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit consumption to disease rates. RESULTS Overall, 18.0% of participants reported consuming fresh fruit daily. As compared with participants who never or rarely consumed fresh fruit (the "nonconsumption" category), those who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels (by 0.5 mmol per liter [9.0 mg per deciliter]) (P<0.001 for trend for both comparisons). The adjusted hazard ratios for daily consumption versus nonconsumption were 0.60 (95% confidence interval [CI], 0.54 to 0.67) for cardiovascular death, and 0.66 (95% CI, 0.58 to 0.75), 0.75 (95% CI, 0.72 to 0.79), and 0.64 (95% CI, 0.56 to 0.74), respectively, for incident major coronary events, ischemic stroke, and hemorrhagic stroke. There was a strong log-linear dose-response relationship between the incidence of each outcome and the amount of fresh fruit consumed. These associations were similar across the 10 study regions and in subgroups of participants defined by baseline characteristics. CONCLUSIONS Among Chinese adults, a higher level of fruit consumption was associated with lower blood pressure and blood glucose levels and, largely independent of these and other dietary and nondietary factors, with significantly lower risks of major cardiovascular diseases. (Funded by the Wellcome Trust and others.).
Prostate Cancer Patient Outcomes and Choice of Providers: Development of an Infrastructure for Quality Assessment

Abstract : Prostate cancer is the most common solid malignancy diagnosed in American men. More than half of the new cases identified each year are localized prostate cancer, an early stage of the disease in which the tumor is confined to the prostate. The usual approach to localized prostate cancer includes radical prostatectomy, radiation therapy, or watchful waiting. Unfortunately, clear evidence about the comparative efficacy of these treatments is lacking; and, even untreated, most men with early stage prostate cancer have a life expectancy comparable to similarly aged men without prostate cancer. The most common potential long-term complications after treatment include urinary incontinence, impotence, and bowel dysfunction. The rates of these complications reported by different researchers and institutions in the scientific literature vary substantially. Although this variability may simply reflect differences in the patients included (case-mix) or the ways in which the data were collected, it does raise concern that widespread variation exists in the quality of treatment provided for men with prostate cancer across the United States.
Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations.

BACKGROUND BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. METHODS We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. RESULTS In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. CONCLUSIONS BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.).
Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood.

BACKGROUND In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood. METHODS We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used. RESULTS During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular causes, after adjustment for sex, age, birth year, sociodemographic characteristics, and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses. CONCLUSIONS A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood. (Funded by the Environment and Health Fund.).
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.

BACKGROUND Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer. METHODS This phase 3 study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred. RESULTS The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib-fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). The most common grade 3 or 4 adverse events in the palbociclib-fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. CONCLUSIONS Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone. (Funded by Pfizer; PALOMA3 ClinicalTrials.gov number, NCT01942135.).
Brainstem projections to motoneurons in the lumbar spinal cord : an ultrastructural study in rat

textabstractThis thesis deals with an ultrastructural study in rat on the descending projections from the ventro-lateral medullary medial reticular formation, the medullary raphe nuclei and the area of the nucleus coeruleus and subcoeruleus to the motoneuronal cell groups in the lumbar spinal cord. Since these projections te~inate not only in the intermediate zone, bu~ also directly on motoneurons, they constitute a special subgroup of the descending pathways to the spinal cord (reviewed briefly in Ch I.5).
The Role and Impact of Cooperative Extension in Diabetes Self-Management Education

OF THESIS THE ROLE AND IMPACT OF COOPERATIVE EXTENSION IN DIABETES SELFMANAGEMENT EDUCATION Diabetes is increasing globally and nationally. Diabetes complications and costs can be reduced through modification of lifestyle risks and diabetes self-management education (DSME). The Cooperative Extension System (CES) is uniquely positioned to implement DSME. This study assessed the role and impact of the Cooperative Extension System (CES) in DSME. A survey was sent to CES professionals throughout the U.S. a total of 43 participants provided information on 73 DSME programs. Most participants were from the South (n=22, 51.16%) and Midwest (n=12, 27.91%) and most programs targeted adults with and at risk for type 2 diabetes. Most programs were developed and taught by registered dietitians and family and consumer science agents and were focused on healthy eating and cooking techniques. Few programs addressed medications, mental and physical health, influenza and pneumococcal vaccinations. Implementation challenges were related to recruitment, attrition, and funding and most suggestions for the future of CES in DSME were related to funding. CES has a wide reach in terms of DSME with over 29 states. Future CES efforts should target children with type 2 diabetes and should form/continue partnerships with health care professionals.