The McMaster Health Information Research Unit: Over a Quarter-Century of Health Informatics Supporting Evidence-Based Medicine.

Evidence-based medicine (EBM) emerged from McMaster University in the 1980-1990s, which emphasizes the integration of the best research evidence with clinical expertise and patient values. The Health Information Research Unit (HiRU) was created at McMaster University in 1985 to support EBM. Early on, digital health informatics took the form of teaching clinicians how to search MEDLINE with modems and phone lines. Searching and retrieval of published articles were transformed as electronic platforms provided greater access to clinically relevant studies, systematic reviews, and clinical practice guidelines, with PubMed playing a pivotal role. In the early 2000s, the HiRU introduced Clinical Queries-validated search filters derived from the curated, gold-standard, human-appraised Hedges dataset-to enhance the precision of searches, allowing clinicians to hone their queries based on study design, population, and outcomes. Currently, almost 1 million articles are added to PubMed annually. To filter through this volume of heterogenous publications for clinically important articles, the HiRU team and other researchers have been applying classical machine learning, deep learning, and, increasingly, large language models (LLMs). These approaches are built upon the foundation of gold-standard annotated datasets and humans in the loop for active machine learning. In this viewpoint, we explore the evolution of health informatics in supporting evidence search and retrieval processes over the past 25+ years within the HiRU, including the evolving roles of LLMs and responsible artificial intelligence, as we continue to facilitate the dissemination of knowledge, enabling clinicians to integrate the best available evidence into their clinical practice.

History and Metamorphosis of Hand Surgery India.

The advent of hand surgery in India reads like a fortuitous saga, a continuum of the hand deformity correction on leprosy patients pioneered by Dr. Paul Wilson Brand at the Christian Medical College (CMC) Vellore, Madras State (Tamil Nadu [TN]), in 1948. The "Hand Research Unit," established in 1951, became the largest repository for hand reconstructive surgeries and with its head-start drew in most hand dysfunctions in the country. Early industrialization and disorderly road traffic generated hand injuries that threatened workforce in India. Propitiously, a hand injury service was opened in 1971 at the Government Stanley Medical College Hospital, Chennai. The inexorable growth of hand surgery continued and incorporated the gamut of conditions that required hand care and rehabilitation, including brachial plexus injuries. Continuing Medical Education programs, Hand Surgery workshops, Indian Society for Surgery of the Hand meetings, Hand Fellowships, etc., increased the number of "hand surgery" practitioners, which drew the attention of the Medical Council of India to commence a postgraduate Hand Surgery program that it eventually gazetted. The sagacity of the members of the Board of Studies of TN Medical University honored the historical role of CMC Vellore in hand surgery and allowed it to commence the first Master of Chirurgiae Hand Surgery course in India in 2015. An intuitive understanding of 70 years of hand surgery accomplishments that redesigned and restored deformed and injured hands and protected livelihoods have made young surgeons increasingly take hand surgery as a career.

Research unit network (RUN) as a learning research system.

The clinical research units (CRUs) are one of the main spaces where both translational research and science take place. However, there is a lack of information about both best practices for CRU operations and, ultimately, benchmarks to evaluate CRU performance. The Research Unit Network (RUN) was created with the purpose to enable direct communication and collaboration among CRUs. An online survey was administered to further illustrate the functionality and impact of RUN. Thirty-one individual survey responses (39.2%) were included in the final analysis. The members value RUN monthly meetings (87.1%) as the most useful aspect of this network and CRU budgeting (67.7%) and staffing (61.3%) were the most relevant topics discussed. This is followed by EPIC - Research (58.1%), delegation of authority logs, unit signatures, and policies (51.6%), COVID-19 pandemic response (41.9%), the implementation of clinical trial management system (29.0%), and protocol deviations (19.4%). The intermediate goal of RUN is to identify best practices CRUs are establishing, implementing, and sharing these experiences with the goal to adopt them in different CRUs. The network's long-term goal is to establish standard benchmarks that can be used for evaluating the performance of CRUs across the nation.

Uncovering the biogeographic pattern of the widespread nematode-trapping fungi Arthrobotrys oligospora: watershed is the key.

Studies of biogeographic patterns of fungi have long been behind those of plants and animals. The presence of worldwide species, the lack of systematic sampling design and adequate sampling effort, and the lack of research units are responsible for this status. This study investigates the biogeographical patterns of Arthrobotrys oligospora, the most widespread globally distributed nematode-trapping fungi (NTF), by stratified collecting and analyzing 2,250 samples from 228 sites in Yunnan Province, China. The A. oligospora was isolated, and 149 strains were subjected to ITS, TUB, TEF and RPB2 gene sequencing and multi-gene association phylogeographic analysis. The results show that at population level A. oligospora is randomly distributed throughout Yunnan Province and has no biogeographical distribution pattern. At the genetic level, the phylogenetic tree of A. oligospora diverges into five major evolutionary clades, with a low degree of gene flow between the five clades. However, the correlation between the phylogenetic diversity of A. oligospora and geographical factors was low. There was no clear pattern in the phylogenetic clades distribution of A. oligospora either without dividing the study unit or when the grid was used as the study unit. When watersheds were used as the study unit, 67.4%, 63.3%, 65.9%, 83.3%, and 66.7% of clade 1-5 strains were distributed in the Jinsha river, Red river, Peal river, Lancang river, and Nujiang-Irawaddy river watersheds, respectively. The clades distribution of A. oligospora was highly consistent with the watersheds distribution. Training predictions of the clades distributions using randomly generated polygons were also less accurate than watersheds. These results suggest that watersheds are key to discovering the biogeographic distribution patterns of A. oligospora. The A. oligospora populations are blocked by mountains in the watershed, and gene flow barriers have occurred, which may have resulted in the formation of multiple cryptic species. Watersheds are also ideal for understanding such speciation processes, explaining factors affecting biodiversity distribution and coupling studies of plant and animal and microbial diversity.

Size of science team at university and internal co-publications: science policy implications.

Scientific collaboration within a science team (unit, group, etc.) has been under scrutiny. Recently, science of team science has emerged to use science for deep understanding of the ways researchers jointly perform science to increase their team's performance. This article analyses internal scientific outputs with respect to the size of university's science team. The objective is to examine the science policy motive that is, if the team size increases, by encouraging academics to gather in larger teams, then their outputs increase. The method of the contrapositive of this conditional statement is adopted. Thus, 120 accredited teams, composed of about 1500 academics in four universities in Morocco, were analyzed using a cross-matrix of members' co-publications, an intra-collaboration index, Lorenz curve of both internal co-publications and sole-publications, with respect to team's size. Our findings show that internal co-publications and sole ones are higher for small size teams and that the Lorenz distributions of these two indicators are unequal in favor of small size teams. We discuss the implications of our findings for science policy, beyond size, such as the output- instead of input-based perspective to form a team, time requirement to build a collaborative team, inter- and intra-disciplinarity oriented research, team directorship, etc.

Impacts of potential evapotranspiration on drought phenomena in different regions and climate zones.

The present study is aimed at examining whether potential evapotranspiration (PET), which is important for drought assessment, influences a drought index (standardized precipitation evapotranspiration index; SPEI) for different regions and climate zones. The study regions were East Asia, Europe, the United States (US), and West Africa, and the climate zones considered were the arid, semiarid, subhumid, and humid zones. We examined the pattern of water deficits, spatial trend of the SPEI, area ratio of spatial extent, and temporal trend to provide an understanding of drought characteristics. Two datasets, Climate Research Unit (CRU) and National Centers for Environmental Prediction (NCEP), were used for assessing the drought phenomena. Two types of evapotranspiration obtained using Thornthwaite and Penman-Monteith equations were used to estimate the PET. Negative water deficit values were clearly observed in the arid and semiarid zones of the majority of regions, whereas positive water deficit values were observed in the subhumid and humid zones of the regions. The SPEI spatial trend largely presented a decreasing trend in East Asia and West Africa, a neutral or decreasing trend in Europe, and a neutral or increasing trend in the US. The area ratio of the spatial extent showed large values of a neutral or decreasing trend in East Asia and Europe, a neutral or increasing trend in the US, and a decreasing trend in West Africa. The temporal trend of the spatial extent primarily exhibited no trend or an increasing trend in the aforementioned regions, except in the case of the majority of West Africa. Although the results obtained from the two datasets appear to be slightly different, they show that the PET is predominant in regions, especially in the US. The PET trends are identified through comparisons and used to understand the drought phenomena while considering various geographic regions and climatic zones.

On the life and work of Korbinian Brodmann (1868-1918).

This study describes the life and work of early-twentieth-century German scientist Korbinian Brodmann (1868-1918). His medical training at universities in Munich, Würzburg, Berlin, and Freiburg and his further education are illustrated. His early Leipzig career and cooperation with brain researchers Oskar and Cécile Vogt in Berlin are portrayed, as are his contributions to a localization theory of the cerebral cortex-namely, Brodmann's cytoarchitectonic approach-and the invention of a cortex area nomenclature, further developed until the beginning of World War I. His Tübingen professorship and being nominated to manage a major department of Emil Kraepelin's Munich research unit represent further aspects of this study, a promising career ahead, harshly interrupted by an early and unexpected death.

Nutrition in transition: historical cohort analysis summarising trends in under- and over-nutrition among pregnant women in a marginalised population along the Thailand-Myanmar border from 1986 to 2016.

The objective of the present study is to summarise trends in under- and over-nutrition in pregnant women on the Thailand-Myanmar border. Refugees contributed data from 1986 to 2016 and migrants from 1999 to 2016 for weight at first antenatal consultation. BMI and gestational weight gain (GWG) data were available during 2004-2016 when height was routinely measured. Risk factors for low and high BMI were analysed for <18·5 kg/m2 or ≥23 kg/m2, respectively. A total of 48 062 pregnancies over 30 years were available for weight analysis and 14 646 pregnancies over 13 years (2004-2016) had BMI measured in first trimester (<14 weeks' gestational age). Mean weight at first antenatal consultation in any trimester increased over the 30-year period by 2·0 to 5·2 kg for all women. First trimester BMI has been increasing on average by 0·5 kg/m2 for refugees and 0·6 kg/m2 for migrants, every 5 years. The proportion of women with low BMI in the first trimester decreased from 16·7 to 12·7 % for refugees and 23·1 to 20·2 % for migrants, whereas high BMI increased markedly from 16·9 to 33·2 % for refugees and 12·3 to 28·4 % for migrants. Multivariate analysis demonstrated low BMI as positively associated with being Burman, Muslim, primigravid, having malaria during pregnancy and smoking, and negatively associated with refugee as opposed to migrant status. High BMI was positively associated with being Muslim and literate, and negatively associated with age, primigravida, malaria, anaemia and smoking. Mean GWG was 10·0 (sd 3·4), 9·5 (sd 3·6) and 8·3 (sd 4·3) kg, for low, normal and high WHO BMI categories for Asians, respectively.

Practical exploration of clinical research unit platform construction and management mode based on research-oriented hospitals:The case study of a tertiary hospital in Shanghai / 中华医学科研管理杂志

Objective To summarize the practical experiences of Clinical Research Unit (CRU) platform established by Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,provide reference for domestic institutions that have prepared or to prepare to establish CRU platform.Methods Oriented by demand,this platform has set up six modules including project management module,methodology support module,data management module,quality risk management module,project transformation module and training and international exchange module.Besides,it also establishes and improves the corresponding module system,quality assurance,technical support and information data platform system.Results With this platform,the enthusiasm of departments to carry out clinical research has been continuously enhanced,the talent pool of clinical research has been expanded;the awareness of clinical research cooperation has been improved and the international cooperation fields have been further extended;the number of clinical research projects and funding have increased rapidly.Conclusions CRU Platform in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine provides all-dimensional technical support and whole-process informatization management to improve clinical research quality and efficiency.While learning from the advanced international concepts,we still need to explore and improve the platform construction and management mode in line with general research-oriented hospitals in China,further to enhance the academic research internationally.

Translational Research Unit: Development of Nursing Standards and Practice Within a Specialized Unit for Participants in Early Phase Clinical Trials.

BACKGROUND: A growing need exists to ensure safe and skilled oncology nursing care for an increasing number of patients enrolled in phases 1 and 1/2 clinical trials and to provide detailed adherence to protocol administration. This can be best accomplished in a dedicated area for patients in early phase clinical trials. OBJECTIVES: Nursing standards and practice within a newly established translational research unit at an academic medical center were developed. METHODS: A portion of an existing outpatient infusion room composed of 13 beds and a sub-waiting room with 2 chairs was designated for placement of patients enrolled in early phase clinical trials. The functional and safety requirements needed to successfully care for these patients while meeting the demands of the trial protocol drove the creation of this dedicated unit. FINDINGS: Development of dedicated space provided opportunities to define the role of the nurse and hardwire patient and staff safety practices that assisted in reducing study deviations.

Transgenerational effects enhance specific immune response in a wild passerine.

Vertebrate mothers transfer diverse compounds to developing embryos that can affect their development and final phenotype (i.e., maternal effects). However, the way such effects modulate offspring phenotype, in particular their immunity, remains unclear. To test the impact of maternal effects on offspring development, we treated wild breeding house sparrows (Passer domesticus) in Sevilla, SE Spain with Newcastle disease virus (NDV) vaccine. Female parents were vaccinated when caring for first broods, eliciting a specific immune response to NDV. The immune response to the same vaccine, and to the PHA inflammatory test were measured in 11-day-old chicks from their following brood. Vaccinated chicks from vaccinated mothers developed a stronger specific response that was related to maternal NDV antibody concentration while rearing their chicks. The chicks' carotenoid concentration and total antioxidant capacity in blood were negatively related to NDV antibody concentration, whereas no relation with PHA response was found. Specific NDV antibodies could not be detected in 11-day-old control chicks from vaccinated mothers, implying that maternally transmitted antibodies are not directly involved but may promote offspring specific immunity through a priming effect, while other immunity components remain unaffected. Maternally transmitted antibodies in the house sparrow are short-lived, depend on maternal circulation levels and enhance pre-fledging chick specific immunity when exposed to the same pathogens as the mothers.

History and its contribution to understanding addiction and society.

This paper provides a personal memoir of historical work at the Addiction Research Unit, in particular the genesis of the book Opium and the People. This topic had policy significance for US drug policy and a competing US study was funded. The development of the substance use history field is surveyed, and its expansion in recent times through a focused professional association and a critical mass of researchers in the area, covering a wide range of topics. The politics of using history in this area can be problematic. History now sits at the policy table more easily, but there is still a tendency for professionals in the field to use (and misuse) it, rather than calling on the interpretive and challenging approach they would obtain from professional historians. The paper calls for historians and others to move beyond a substance specific focus and to avoid the tendency for 'naive history' implicit in using only digitized industry archives as the sole source.

Epidemiology, ecology and gene pool of influenza A virus in Egypt: will Egypt be the epicentre of the next influenza pandemic?

Outside Asia, Egypt is considered to be an influenza H5N1 epicentre and presents a far greater pandemic risk than other countries. The long-term endemicity of H5N1 and the recent emergence of H9N2 in poultry call attention to the need for unravelling the epidemiology, ecology and highly diverse gene pool of influenza A virus (IAV) in Egypt which is the aim of this review. Isolation of a considerable number of IAV subtypes from several avian and mammalian hosts was described. Co-infections of poultry with H5N1 and H9N2 and subclinical infections of pigs and humans with H1N1 and H5N1 may raise the potential for the reassortment of these viruses. Moreover, the adjustment of IAV genomes, particularly H5N1, to optimize their evolution toward efficient transmission in human is progressing in Egypt. Understanding the present situation of influenza viruses in Egypt will help in the control of the disease and can potentially prevent a possible pandemic.

Best practices sharing: Setting up a professional clinical research unit in India.

The Drug Controller General of India has recently come up with very stringent laws to tighten the regulatory framework around clinical trials. One-way of improving the credibility of India and its researchers in the eyes of the regulators, sponsors and the general public is through professional site management team or setting up clinical research unit (CRU). The CRU acts as a bridge between the sponsor and the investigator. The CRU model has been better explained with the help of a good example of a clinical research institute. Since, a successful clinical trial needs high quality data, timeliness and clear communication between all parties, a professional CRU with a team of dedicated and trained professionals and infrastructure with written procedures and policies may be a solution to the pain and agony of poor site performance and investigator insufficiency and pressure.

Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection: safety, antiviral activity, resistance, and pharmacokinetics.

Vaniprevir is a competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease that has potent anti-HCV activity in preclinical models. This placebo-controlled dose-ranging study assessed the safety, tolerability, and antiviral efficacy of vaniprevir monotherapy in patients with genotype 1 chronic HCV infection. Treatment-naive and treatment-experienced non-cirrhotic adult patients with baseline HCV RNA >10(6)IU/ml were randomized to receive placebo or vaniprevir at doses of 125 mg qd, 600 mg qd, 25mg bid, 75 mg bid, 250 mg bid, 500 mg bid, and 700 mg bid for 8 days. Forty patients (82.5% male, 75% genotype 1a) received at least one dose of placebo or vaniprevir. After 1 week of vaniprevir, the decrease in HCV RNA from baseline ranged from 1.8 to 4.6 log10IU/ml across all treatment groups, and there was a greater than dose-proportional increase in vaniprevir exposure at doses above 75 mg bid. The most commonly reported drug-related adverse events (AEs) were diarrhea (n=5) and nausea (n=5). No pattern of laboratory or ECG abnormalities was observed, all AEs resolved during the study, and there were no discontinuations due to AEs. No serious AEs were reported. Resistance-associated amino acid variants were identified at positions R155 and D168 in patients infected with genotype 1a virus. Vaniprevir monotherapy demonstrated potent antiviral activity in patients with chronic genotype 1 HCV infection, and was generally well tolerated with no serious AEs or discontinuations due to AEs. Further development of vaniprevir, including studies in combination with other anti-HCV agents, is ongoing.

The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

BACKGROUND & AIMS: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. METHODS: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 µg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). RESULTS: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. CONCLUSIONS: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

La unidad de investigación traslacional como sustento de la medicina actual / The translational research unit as support for the current practice of medicine

Se discuten los principios, fundamentos e importancia de la medicina traslacional en la calidad de la atención de la salud en la actualidad. Se ejemplifica la medicina traslacional con la aplicación y el beneficio de la oncología traslacional y la oncología personalizada en pacientes con cáncer. Se describe el proceso que ha permitido la expansión de la medicina traslacional en los países desarrollados y las condiciones globales que han impedido en nuestra nación iniciar formalmente el proceso de expansión de la medicina traslacional. Se propone establecer unidades de investigación traslacional en hospitales de tercer nivel que permitan el inicio formal de la medicina traslacional en México. La implantación de una política de investigación traslacional en la atención es absolutamente obligada en el momento actual, y compromete la participación del Estado, academias y sociedades médicas nacionales, centros hospitalarios del sector salud, centros de educación e investigación biomédicos, industrias farmacéuticas biotecnológicas y profesionales médicos, así como de todos los agentes que intervienen en el mejoramiento tácito del nivel de atención médica. Con el funcionamiento de las unidades de investigación traslacional se generará un sistema de atención al enfermo de mayor calidad y mejor nivel científico.

In the first part of the present paper the basis and importance of translational medicine (TM) on the current status of quality of health care is discussed. This is exemplified by the application and benefit of translational oncology and personalized oncology in cancer patients as a model of TM. The second part of this article discusses the processes that have allowed the expansion of TM in developed countries and, likewise, the global conditions that have disabled the installation and expansion of TM in Mexico. The author suggests the establishment of translational research (TR) units in third-level hospitals, which will allow the formal initiation of TM in Mexico. The author concludes that the policy of TR in regard to national public health care is currently necessary. This policy requires the participation of government, national medical academies and societies, health sector medical centers, medical and research educators, centers of investigation, pharmaceutical and biotechnology industries, medical and biomedical physicians, and any other persons or entities who participate in the implicit improvement of the level of medical care. The installation of TR units located in hospitals represents a common benefit for the entire society and, specifically, for patients through the generation of a health care system with a higher scientific level, as well as higher quality of care.

Consent and the social context.

A series of eight multidisciplinary conferences on consent to health care and research was held in London during the period 1992 to 1995. The aim was to present a rich and varied account of consent from the perspectives of academics (especially social scientists), practitioners, and people affected by personal experience. This report summarizes some of the main contributions.