Comprehensive Longitudinal Database Research Articles

Science and technology evaluation reform and universities’ innovation performance

Does science and technology evaluation (STE) policy reform improve universities' innovation performance? Research typically argues that more upstream R&D investment leads to more downstream innovation performance, but it is less clear what the trade-offs over time might be for targeted investments in universities influenced by STE reform. In 2013, China proposed STE reform measures focused on ‘innovation quality, efficiency, and contribution’. Using a difference-in-differences research design on a comprehensive longitudinal database of 62 universities spanning from 2009 to 2016, we show that this STE policy positively affects university basic research outputs and quality but weakens applied research outputs. This effect is pronounced in pilot universities with better resources. Empirical evidence suggests that the STE policy works mainly through mobilising the enthusiasm of human capital, improving R&D intensity in science and technology funds, and promoting industrialisation-oriented R&D projects. We consider the following possible perspectives on the mechanisms of change: knowledge asset development, economic competition, and a socio-political process. This analysis leads to theoretical developments about how basic versus applied science produces outputs in the Chinese context. The paper also shows that the STE policy promotes technology transfer in universities.

The Child & Youth CompreHensIve Longitudinal Database for Deep Brain Stimulation (CHILD-DBS).

Deep brain stimulation (DBS) is a common tool for the treatment of movement disorders in adults; however, it remains an emerging treatment modality in children with a growing number of indications, including epilepsy and dystonia. The Child & Youth CompreHensIve Longitudinal Database of DBS (CHILD-DBS) study aims to prospectively collect relevant data on quality of life (QoL), safety, efficacy, and long-term neurodevelopmental outcomes following DBS in children. Data are collected and managed using the Research Electronic Data Capture (REDCap). This database aims to collect multicentre comprehensive and longitudinal clinical, QoL, imaging and electrophysiologic data for children under the age of 19 undergoing DBS. Both general and indication-specific measures are collected at baseline and at four time points postoperatively: 6 months, 1 year, 2 years, and 3 years. The database encompasses QoL metrics for children, including the PedsQL (Pediatric Quality of Life Inventory, generic), QOLCE (Quality of Life in Childhood Epilepsy Questionnaire, parent-rated), CHU 9D (Child Health Utility 9D), and KIDSCREEN. Caregiver clinical and QoL metrics, including QIDS (Quick Inventory of Depressive Symptomatology), GAD-7 (Generalized Anxiety Disorder 7-item scale), and CarerQoL-7D (The Care-related Quality of Life Instrument), are similarly prospectively collected. Healthcare resource utilization is also assessed before and after DBS. Lastly, stimulation parameters and radiographic and electrophysiologic data are collected within the database. The development of the current prospective paediatric DBS database with carefully selected physical and psychosocial outcomes and assessments will complement existing efforts to enhance and facilitate multisite collaboration to further understand the role of DBS in childhood.

Efficacy and safety of mycophenolate mofetil in progressive multiple sclerosis patients.

There are increasingly effective therapies for relapsing forms of multiple sclerosis (MS); however, the options for the progressive patient population are limited. The effect of mycophenolate mofetil (MMF), a disease-modifying agent for several autoimmune diseases, in progressive MS has not been explored effectively. We performed a prospective study to assess the safety and efficacy of MMF in progressive MS patients. We identified 64 patients enrolled in the comprehensive longitudinal database at the Partners MS Center, who fulfilled our inclusion criteria. They were exposed to MMF for at least 1year with recorded clinical outcomes. Efficacy was assessed by comparing the absolute relapse rate (ARR), and the mean Expanded Disability Status Scale (EDSS) and timed 25 foot walk (T25FW) test scores before and after MMF treatment. At the start of MMF, 78% of patients (n = 50) were in the 4-7.5 EDSS range. There was a slight increase in mean EDSS from 5.49 ± 1.65 (n = 48) 1year before MMF start to 5.85 ± 1.56 (n = 48) 1year after (p = 0.020). The mean T25FW score increased 1year before MMF from 12.3 ± 9.6s (n = 38) to 15.6 ± 12.3s (n = 38) 1year after (p = 0.009). The ARR in the 2years pre-MMF period was 0.30 ± 0.63, which decreased to a 0.09 ± 0.29 (p = 0.022) 2years post MMF. MMF did not affect disease progression but did influence relapse rate. We believe that other medication options should be considered before MMF in advanced progressive patients.

National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System: Review of Program and Database

The Burn Model System (BMS) centers program was created in 1994 to evaluate the long-term outcomes of burn injuries. As part of this multicenter program, a comprehensive longitudinal database was developed to facilitate the study of a number of functional and psychosocial outcomes after burn injury. In this article, we provide an overview of the data collection procedures, measures selection process, and an overview of the participant data collected between 1994 and 2016. Surveys were administered during hospitalization and at 6, 12, and 24 months after discharge, and in the most recent funding cycle, data collection at every 5 years postinjury was added. More than 7200 people with burn injury were eligible to participate in the BMS National Longitudinal Database. Of these, >5900 (82%) were alive at discharge and consented to follow-up data collection. The BMS National Longitudinal Database represents a large sample of people with burn injury, including information on demographic characteristics, injury characteristics, and health outcomes. The database is publicly available and can be used to examine the effect of burn injury on long-term outcomes.

Financial markets and firm size: The role of employment protection laws and barriers to entrepreneurship

ABSTRACTThis article provides evidence on the institutional determinants of firm size for the period 1980–1998. Using a comprehensive longitudinal database across 29 industrial sectors in 15 Organisation for Economic Co-operation and Development (OECD) countries, we study how labour regulations and barriers to entrepreneurship (BE) affect industrial organization in the presence of capital market frictions. We show that strict employment protection laws (EPL) and high BE negatively affect firm size in sectors that are more dependent on external funds. Our findings demonstrate that the interaction between market regulations and financial market imperfections help to explain some of the differences in firm structure across countries.

A population based study of the epidemiology of Herpes Zoster and its complications

To assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN). A retrospective database search for newly diagnosed cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox-proportional hazards models were used to assess associations between risk factors and HZ and PHN. During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person-years in the total population and 12.8 per 1000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥ 65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socioeconomic status, diabetes mellitus, cancer history, and HIV treatment. Extrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.

Dosing patterns for octreotide LAR in neuroendocrine tumor (NET) patients: NCCN NET outcomes database.

4142 Background: Among patients (pts) with neuroendocrine histology, 10 mg – 30 mg of octreotide-LAR administered intramuscularly every 4 weeks is FDA-approved for the long term treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and pancreatic VIPomas. In clinical practice, higher doses and/or more frequent administration is often prescribed for pts who experience refractory symptoms (e.g., flushing and/or diarrhea) on the maximal labeled dose. Methods: National Comprehensive Cancer Network (NCCN) created a comprehensive longitudinal database to characterize pts treated for NETs. This database was queried to identify pts presenting to 7 NCCN institutions, from 2004 to 2010, with a confirmed carcinoid or pancreatic NET (pNET) diagnosis who received octreotide LAR. The primary aim of this analysis was to describe octreotide LAR dosing patterns when beyond label recommendations, clinical characteristics, reasons for dose increase, and maximal dose. Results: Among 1,886 pts in the database, 271 carcinoid and pNET pts received octreotide LAR. 40% of carcinoid pts (n=82) and 23% of pNET pts (n=15) received octreotide LAR above-label dosing, defined by dose and/or frequency greater than 30 mg every 4 weeks. The primary tumor sites among carcinoid pts receiving above label dosing were small bowel (n=40), colorectal (n=4), and unknown (n=34). Reasons for above label dosing among carcinoid pts included uncontrolled symptoms (n=53, 65%), tumor progression (n=21, 25%), high urine 5-HIAA (n=1, 1%) and unknown (n=7, 9%). The most common dose/frequency combinations for carcinoid pts were 40 mg every 4 weeks (32 pts, 39%), 40 mg every 3 weeks (15 pts, 18%), and 30 mg every 2 weeks (14 pts 17%). Among pNET pts, reasons for change included uncontrolled symptoms (n=5, 33%), tumor progression (n=9, 60%), and unknown (n=1, 7%). The most common maximal dose/frequency combinations among pNET pts were 40mg every 4 weeks (n=5, 33%), 30mg every 2 weeks (n=4, 27%), and 60 mg every 4 weeks (n=4, 27). Conclusions: Above label dosing of octreotide LAR is common in NCCN institutions. The primary indication is refractory carcinoid syndrome. Prospective studies are planned to validate this strategy.

Development of biomarkers to chart all Alzheimer's disease stages: The royal road to cutting the therapeutic Gordian Knot

The aim of this perspective article is to stimulate radical shifts in thinking and foster further discussion on the effective discovery, development, validation, and qualification process of biological markers derived from all available technical modalities that meet the complex conceptual and pathophysiological challenges across all stages of the complex, nonlinear, dynamic, and chronically progressive sporadic Alzheimer's disease (AD). This perspective evaluates the current state of the science regarding a broad spectrum of hypothesis-driven and exploratory technologies and "markers" as candidates for all required biomarker functions, in particular, surrogate indicators of adaptive to maladaptive and compensatory to decompensatory, reversible to irreversible brain "systems failure." We stress the future importance of the systems biology (SB) paradigm (next to the neural network paradigm) for substantial progress in AD research. SB represents an integrated and deeper investigation of interacting biomolecules within cells and organisms. This approach has only recently become feasible as high-throughput technologies and mass spectrometric analyses of proteins and lipids, together with rigorous bioinformatics, have evolved. Existing high-content data derived from clinically and experimentally derived neural tissues point to convergent pathophysiological pathways during the course of AD, transcending traditional descriptive studies to reach a more integrated and comprehensive understanding of AD pathophysiology, derived systems biomarkers, and "druggable" system nodes. The discussion is continued on the premise that the lack of integration of advanced biomarker technologies and transfertilization from more mature translational research fields (e.g., oncology, immunology, cardiovascular), which satisfy regulatory requirements for an accurate, sensitive, and well-validated surrogate marker of specific pathophysiological processes and/or clinical outcomes, is a major rate-limiting factor for the successful development and approval of effective treatments for AD prevention. We consider the conceptual, scientific, and technical challenges for the discovery-development-validation-qualification process of biomarker tools and analytical algorithms for detection of the earliest pathophysiological processes in asymptomatic individuals at elevated risk during preclinical stages of AD. The most critical need for rapid translation of putative markers into validated (performance) and standardized (harmonized standard operating procedures) biomarker tools that fulfill regulatory requirements (qualify for use in treatment trials: e.g., safety, target engagement, mechanism of action, enrichment, stratification, secondary and primary outcome, surrogate outcome) is the availability of a large-scale worldwide comprehensive longitudinal database that includes the following cohorts: (a) healthy aging, (b) people at elevated risks (genetic/epigenetic/lifestyle/comorbid conditions), and (c) asymptomatic-preclinical/prodromal-mild cognitive impairment/syndromal mild, moderate, or severe AD. Our proposal, as initial strategic steps for integrating markers into future development of diagnostic and therapy trial technologies, is to work toward: (a) creating the essential research and development infrastructure as an international shared resource, (b) building the organizational structure for managing such a multinational shared resource, and (c) establishing an integrated transsectoral multidisciplinary global network of collaborating investigators to help build and use the shared research resource.

Baseline demographics of patients with neuroendocrine tumors presenting to seven National Comprehensive Cancer Network (NCCN) institutions: Development of a multi-institutional outcomes database.

187 Background: Diagnostic strategies, management paradigms, and clinical outcomes of patients with neuroendocrine tumors (NETs) are diverse and poorly characterized. The National Comprehensive Cancer Network (NCCN) created a comprehensive longitudinal database to characterize patients treated for NETs at seven participating institutions. Preliminary results from the database are reported. Methods: Member IRB approval was obtained to identify patients at least 18 years of age presenting to each of seven NCCN institutions between 2004 and 2007 with pathologically confirmed newly or previously diagnosed NETs via hospital medical records. Eligible patients included those with carcinoid (any site); goblet cell or adenocarcinoid; composite carcinoid; poorly differentiated gastrointestinal small cell tumor; pancreatic NET; NET of unknown primary site; pheochromocytoma; and paraganglioma. Baseline demographic characteristics were summarized for this analysis. Results: Among the 2,542 patients identified with a NET diagnosis, patients most frequently presented with carcinoid tumor (51%), pancreatic NET (27%) and NET of unknown primary site (8%). Median age at diagnosis was 55 (SD=13) and median age at first presentation to the NCCN was 57 (SD=13). Fifty-three percent of patients were female. Most (88%) were Caucasian and 8% were African American. Forty percent of patients were diagnosed with NET before presenting to the NCCN. Among these, the median time between initial NET diagnosis and presentation to the NCCN was 2 years (SD=6). Significant differences in provider specialty referral patterns were observed between institutions. Conclusions: The baseline demographic characteristics of NET patients in this new database are consistent with those previously reported in population-based registries. The NCCN database will provide a valuable resource for further exploration of patterns of diagnosis, treatment, consistency with established guidelines, as well as clinical outcomes in patients with this condition. Existing differences among institutions in referral patterns will be further explored.

HIV Pandemic, Medical Brain Drain, and Economic Development in Sub-Saharan Africa

Country-level longitudinal data at three-year intervals over 1990–2004 are used to analyze the factors affecting emigration of physicians from Sub-Saharan countries and the effects of this medical brain drain on life expectancy and number of deaths due to AIDS. Data are compiled on emigrating African physicians from 16 receiving Organisation for Economic Co-operation and Development (OECD) countries. A comprehensive longitudinal database is developed by merging the medical brain drain variables with recent data on HIV prevalence rates, public health expenditures, physicians' wages, and economic and demographic variables. A triangular system of equations is estimated in a random effects framework using five time observations for medical brain drain rates, life expectancy, and number of deaths due to AIDS, taking into account the interdependence of these variables. Lower wages and higher HIV prevalence rates are strongly associated with the brain drain of physicians from Sub-Saharan African to OECD countries. In countries in which the HIV prevalence rate exceeds 3 percent, a doubling of the medical brain drain rate is associated with a 20 percent increase in adult deaths from AIDS; medical brain drain does not appear to affect life expectancy. These findings underscore the need to improve economic conditions for physicians in order to retain physicians in Sub-Saharan Africa, especially as antiretroviral treatment becomes more widely available.

Start-up size and industrial dynamics: some evidence from Italian manufacturing

The aim of this paper is to shed some light on industry dynamics in Italy. For this purpose we use a large and comprehensive longitudinal data base, identifying the start-up of new manufacturing firms and their subsequent post-entry performance. This enables us to link the survival and growth of firms in each manufacturing industry specifically to their start-up size. While in a tobit regression (at the two-digit level) we find no evidence to link start-up size with survival, the growth rates are negatively and significantly correlated with initial size. As in previous studies dealing with other countries, this evidence suggests that Gibrat's Law fails to hold, at least for small, new-born manufacturing firms.

Start-up size and post-entry performance: the case of tourism services in Italy

A large and comprehensive longitudinal database is used to identify the start-up of new firms in the Italian tourist industry and their subsequent post-entry performance. Analysed in particular is the link between the survival of hotels, restaurants, and catering firms in each Italian region and their start-up size. By using logit estimation, it is found that for eighteen out of twenty regions the relationship has the expected sign, although only for twelve regions and the country as a whole did it turn out to be statistically significant.

Effect of vidarabine and acyclovir on acute herpetic pain treated with sympathetic nerve block

To assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN).A retrospective database search for newly diagnosed cases of HZ and of PHN during 2006–2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox-proportional hazards models were used to assess associations between risk factors and HZ and PHN.During 2006–2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person-years in the total population and 12.8 per 1000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socioeconomic status, diabetes mellitus, cancer history, and HIV treatment.Extrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.