Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

Background: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA).

Objectives: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes.

Methods: RWE requirements were summarized based on HTAbs' guidelines.

Cross-hemispheric recruitment during action planning with increasing task demand.

The recruitment of cross-hemispheric counterparts of lateralized prefrontal brain regions with increasing processing demand is thought to increase memory performance despite cognitive aging, but was recently reported to be present also in young adults working at their capacity limit. Here we ask if cross-hemispheric recruitment is a general strategy of the adult brain in that executive task demand would modulate bilateral activation beyond prefrontal cortex and across cognitive tasks. We analyzed data sets from two fMRI experiments investigating retrospective working memory maintenance and prospective action planning.

Bounded rational decision-making models suggest capacity-limited concurrent motor planning in human posterior parietal and frontal cortex.

While traditional theories of sensorimotor processing have often assumed a serial decision-making pipeline, more recent approaches have suggested that multiple actions may be planned concurrently and vie for execution. Evidence for the latter almost exclusively stems from electrophysiological studies in posterior parietal and premotor cortex of monkeys. Here we study concurrent prospective motor planning in humans by recording functional magnetic resonance imaging (fMRI) during a delayed response task engaging movement sequences towards multiple potential targets.

Electrodermal Activity Biofeedback Alters Evolving Functional Brain Networks in People With Epilepsy, but in a Non-specific Manner.

There is evidence that biofeedback of electrodermal activity (EDA) can reduce seizure frequency in people with epilepsy. Prior studies have linked EDA biofeedback to a diffuse brain activation as a potential functional mechanism. Here, we investigated whether short-term EDA biofeedback alters EEG-derived large-scale functional brain networks in people with epilepsy.

Impact of Transcutaneous Auricular Vagus Nerve Stimulation on Large-Scale Functional Brain Networks: From Local to Global.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for a wide range of diseases. Although first promising findings were obtained so far, the exact mode of action of taVNS is not fully understood yet. We recently developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks.

Visual surround suppression in people with epilepsy correlates with attentional-executive functioning, but not with epilepsy or seizure types.

Purpose: Following reports that an index of visual surround suppression (SI) may serve as a biomarker for an imbalance of cortical excitation and inhibition in different psychiatric and neurological disorders including epilepsy, we evaluated whether SI is associated with seizure susceptibility, seizure spread, and inhibitory effects of antiseizure medication (ASM).

Methods: In this prospective controlled study, we examined SI with a motion discrimination task in people with genetic generalized epilepsy (GGE) and focal epilepsy with and without focal to bilateral tonic-clonic seizures. Cofactors such as GABAergic ASM, attentional-executive functioning, and depression were taken into account.

Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour.

[DNVF Memorandum Health Services Research in Oncology].

Health services research in oncology deals with all situations which cancer patients face. It looks at the different phases of care, i. e.

Quantifying Motor Task Performance by Bounded Rational Decision Theory.

Expected utility models are often used as a normative baseline for human performance in motor tasks. However, this baseline ignores computational costs that are incurred when searching for the optimal strategy. In contrast, bounded rational decision-theory provides a normative baseline that takes computational effort into account, as it describes optimal behavior of an agent with limited information-processing capacity to change a prior motor strategy (before information-processing) into a posterior strategy (after information-processing).

Reducing the probability of false positive research findings by pre-publication validation - experience with a large multiple sclerosis database.

Background: Published false positive research findings are a major problem in the process of scientific discovery. There is a high rate of lack of replication of results in clinical research in general, multiple sclerosis research being no exception. Our aim was to develop and implement a policy that reduces the probability of publishing false positive research findings.

Pooled historical MRI data as a basis for research in multiple sclerosis--a statistical evaluation.

Pooled data from placebo groups of different trials can serve as historical control for ongoing or future therapeutic studies and as a reference for power calculations. In order to assess their usefulness for this purpose, we investigated the degree of heterogeneity of placebo arm data from 14 controlled studies included in the database of the Sylvia Lawry Centre for Multiple Sclerosis Research. Since different criteria for the inclusion/exclusion of patients were used in these studies, an attempt was made to adjust the distribution of magnetic resonance imaging (MRI) measures for the differences in the study populations.

[Quality of primary medical care after in-patient stroke rehabilitation].

Purpose: Since only insufficient information concerning the further development of patients after stroke and rehabilitation is currently available, and since the quality of care provided by family doctors is often classified as insufficient, this quality of care was to be examined on the basis of the rehabilitation results. Of particular interest were the co-operation, the therapeutical quality standards and the risk management, as well as the quality of life and compliance of the patients.

Methods: In 2000, all 223 stroke patients were asked prior to their discharge from three large rehabilitation clinics in North Baden, and subsequently their 210 family doctors, whether they were prepared to participate in this follow-up study.

Treosulfan in the treatment of advanced ovarian cancer: a randomised co-operative multicentre phase III-study.

Background: In August 1988 a randomised phase III multicenter trial was started in order to compare cisplatinum/treosulfan (PT) with standard cisplatinum/cyclophosphamide (PC) in advanced ovarian carcinoma, aiming at lower toxicity and maintained efficiency.

Patients And Methods: Five hundred and nineteen patients were enrolled into the protocol. Final evaluation after a median observation time of more than five years was made in July 1996 and included 398 eligible patients, of whom 366 were evaluable regarding efficiency and 290 in respect of toxicity.

Duration of breastfeeding and associated factors in Western and Eastern Germany.

Unlabelled: Ten years after the German political reunification, specific lifestyle habits still vary between the former Western (FRG) and Eastern (GDR) sectors of Germany. We have analysed data from the first nationwide SuSe Study on breastfeeding 1997-1998 (n = 1593 healthy, term German infants) stratified in a Western (80.3%) and Eastern (19.

Quinoline 2-oxidoreductase and 2-oxo-1,2-dihydroquinoline 5,6-dioxygenase from Comamonas testosteroni 63. The first two enzymes in quinoline and 3-methylquinoline degradation.

The enzymes catalysing the first two steps of quinoline and 3-methylquinoline degradation by Comamonas testosteroni 63 were investigated. Quinoline 2-oxidoreductase, which catalyses the hydroxylation of (3-methyl-)quinoline to (3-methyl-)2-oxo-1,2-dihydroquinoline, was purified to apparent homogeneity. The native enzyme, with a molecular mass of 360 kDa, is composed of three non-identical subunits (87, 32, and 22 kDa), occurring in a ratio of 1.

Microbial metabolism of quinoline and related compounds. XVII. Degradation of 3-methylquinoline by Comamonas testosteroni 63.

A bacterial strain which utilizes 3-methylquinoline as sole source of carbon, nitrogen and energy was isolated from activated sludge. On the basis of its morphological and physiological characteristics, this isolate was classified as Comamonas testosteroni. Four metabolites of 3-methylquinoline degradation were isolated from the culture supernatant and identified as 3-methyl-2-oxo-1,2-dihydroquinoline, 6-hydroxy-3-methyl-2-oxo-1,2-dihydroquinoline, 5,6-dihydroxy-3-methyl-2-oxo-1,2-dihydroquinoline and 2,5,6-trihydroxy-3-methylpyridine.

[Frequency of medical consultation as reflected in 2 representative surveys: DHP-Survey and EVaS-Study (German Cardiovascular Disease Prevention and Survey of Ambulatory Care)].

The frequency of patient-doctor contacts in outpatient care is determined via two representative inquiries supplying complementary perspectives. They concern, on the one hand, a sample of contacts in the consultation room, and, on the other hand, contacts as stated in a population-based survey. In the 25-69 years age bracket, both surveys yielded a contact incidence of 2 to more than 5 contacts per person and quarter of a year.

Social mechanisms in the population genetics of Tay-Sachs and other lethal autosomal recessive diseases: a computer simulation model.

A computer simulation model was developed to study the effects of various feudal social customs on the incidence of lethal autosomal recessive genes. Populations of 500 individuals were created in which each person was characterized by sibship, genotype, and sex. The numbered sibships were sorted into numerical order.

ENDO-LAB: an integrated, portable endocrinology laboratory software system.

ENDO-LAB is an IBM PC-based system which performs calculations and record-keeping for the Vanderbilt University Medical Center Endocrinology Laboratory. It manages maintenance and quality control, and prints reports for regulatory agencies. The system was designed to minimize paperwork without changing laboratory procedures in any way.

A reappraisal of the use of the phi-coefficient in multiple choice examinations.

The phi-coefficient of an item in a multiple choice question (MCQ) examination is often used to determine whether that item is suitable for re-use in future examinations. In order to be of value in this regard, the coefficient must be shown to be an objective and consistent index of the discriminating power of an MCQ item. The behaviour of the phi-coefficient (phi) was investigated in two one-from-five MCQ and two true/false examinations.

Marital mores as a mechanism for the maintenance of ethnic variations of lethal gene frequencies.

A computer simulation model was developed to study the effects of various marital mores on the incidence of lethal autosomal recessive genes in populations that are subdivided into small isolates. The problem was studied in isolates where initial generation size was 30, 40, and 50 individuals. In each of these, the mean fertility rate was varied from 2.

On the perpetuation of relic genes having an inviable homozygote.

Reproductive compensation may be prezygotic or postzygotic. Prezygotic compensation is the replacement of inviable infants by one or more additional births. When the marital fertility rates are greater than necessary to replace the parents, however, many traditional societies ensured that any surviving progeny in excess of two (on average) did not marry, or married only if they replaced an older sib as heir to the family estate.