The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement.

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. There is increasing attention for responsible research practices and implementation of reporting guidelines, but whether these efforts have improved the methodological quality of RCTs (e.g., lower risk of bias) is unknown. We, therefore, mapped risk-of-bias trends over time in RCT publications in relation to journal and author characteristics. Meta-information of 176,620 RCTs published between 1966 and 2018 was extracted. The risk-of-bias probability (random sequence generation, allocation concealment, blinding of patients/personnel, and blinding of outcome assessment) was assessed using a risk-of-bias machine learning tool. This tool was simultaneously validated using 63,327 human risk-of-bias assessments obtained from 17,394 RCTs evaluated in the Cochrane Database of Systematic Reviews (CDSR). Moreover, RCT registration and CONSORT Statement reporting were assessed using automated searches. Publication characteristics included the number of authors, journal impact factor (JIF), and medical discipline. The annual number of published RCTs substantially increased over 4 decades, accompanied by increases in authors (5.2 to 7.8) and institutions (2.9 to 4.8). The risk of bias remained present in most RCTs but decreased over time for allocation concealment (63% to 51%), random sequence generation (57% to 36%), and blinding of outcome assessment (58% to 52%). Trial registration (37% to 47%) and the use of the CONSORT Statement (1% to 20%) also rapidly increased. In journals with a higher impact factor (>10), the risk of bias was consistently lower with higher levels of RCT registration and the use of the CONSORT Statement. Automated risk-of-bias predictions had accuracies above 70% for allocation concealment (70.7%), random sequence generation (72.1%), and blinding of patients/personnel (79.8%), but not for blinding of outcome assessment (62.7%). In conclusion, the likelihood of bias in RCTs has generally decreased over the last decades. This optimistic trend may be driven by increased knowledge augmented by mandatory trial registration and more stringent reporting guidelines and journal requirements. Nevertheless, relatively high probabilities of bias remain, particularly in journals with lower impact factors. This emphasizes that further improvement of RCT registration, conduct, and reporting is still urgently needed.

Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?

BACKGROUND: The last decade was characterized by a growing awareness about the severity of dementia in the field of age-related and no age-related diseases and about the importance to invest resources in the research of new, effective treatments. Among the dementias, Alzheimer's plays a substantial role because of its extremely high incidence and fatality. Several pharmacological strategies have been tried but still now, Alzheimer keeps being an untreatable disease. In literature, the number of QSAR related drug design attempts about new treatments for Alzheimer is huge, but only few results can be considered noteworthy. Providing a detailed analysis of the actual situation and reporting the most notable results in the field of drug design and discovery, the current review focuses on the potential of molecular topology as a reliable tool in finding new anti-Alzheimer lead compounds. METHODS: Published works on QSAR applied to the search of anti-Alzheimer's drugs during the last 10 years has been tracked. 2D and 3D-QSAR, HQSAR, topological indexes, etc. have been analyzed, as well as different mechanisms of action, such as MAO, AchE, etc. An example of topological indexes' application to the search of potential anti-Alzheimer drugs is reported. RESULTS: Results show that QSAR methods during the last decade represented an excellent approach to the search of new effective drugs against Alzheimer's. In particular, QSAR based on molecular topology allows the establishment of a direct structure-property link that results in the identification of new hits and leads. CONCLUSION: Molecular topology is a powerful tool for the discovery of new anti-Alzheimer drugs covering simultaneously different mechanisms of action, what may help to find a definitive cure for the disease.

Henry Hollingsworth Smith and His Bibliographical Index and Historical Record: The Beginning of American Surgical Historiography.

OBJECTIVE: To explore the details of Henry Hollingsworth Smith's (1815-1890) achievement as the first physician to organize in a systematic and chronologic manner the details of the history of surgery in America and prepare a register of men who performed surgical operations. BACKGROUND: The life of Smith, the earliest of the nation's surgeons to elucidate the history of American surgery, is little known. His boosting the image of the scalpel wielder helped shape the future of the craft, in particular, surgery's rise as a specialty and profession. METHODS: An analysis of the published medical literature and unpublished documents relating to Smith and his work to document the history of American surgery. RESULTS: During the 1850 s, a time when surgery was not considered a separate branch of medicine but a mere technical mode of treatment, Smith's efforts in surgical history provided much needed encouragement to surgeons in their pursuit of professional recognition. CONCLUSIONS: Although Smith's accomplishment as the nation's first compiler of the history of American surgery has long been forgotten, his effort afforded the men who performed surgical operations their earliest measure of self-respect. As such, Smith belongs in America's pantheon of surgical heroes.

[Acupoints selection rules analysis of ancient acupuncture for urinary incontinence based on data mining technology].

Based on ancient literature of acupuncture in Canon of Chinese Medicine (4th edition), the articles regarding acupuncture for urinary incontinence were retrieved and collected to establish a database. By Weka data mining software, the multi-level association rules analysis method was applied to analyze the acupoints selection characteristics and rules of ancient acupuncture for treatment of urinary incontinence. Totally 356 articles of acupuncture for urinary incontinence were collected, involving 41 acupoints with a total frequency of 364. As a result, (1) the acupoints in the yin-meridian of hand and foot were highly valued, as the frequency of acupoints in yin-meridians was 2.6 times than that in yang-meridians, and the frequency of acupoints selected was the most in the liver meridian of foot-jueyin; (2) the acupoints in bladder meridian of foot-taiyang were also highly valued, and among three yang-meridians of foot, the frequency of acupoints in the bladder meridian of foot-taiyang was 54, accounting for 65.85% (54/82); (3) more acupoints selected were located in the lower limbs and abdomen; (4) specific acupoints in above meridians were mostly selected, presenting 73.2% (30/41) to the ratio of number and 79.4% (289/364) to the frequency, respectively; (5) Zhongji (CV 3), the front-mu point of bladder meridian, was seldom selected in the ancient acupuncture literature, which was different from modern literature reports. The results show that urinary incontinence belongs to external genitalia diseases, which should be treated from yin, indicating more yin-meridians be used and special acupoints be focused on. It is essential to focus inheritance and innovation in TCM clinical treatment, and applying data mining technology to ancient literature of acupuncture could provide classic theory basis for TCM clinical treatment.

Analysis of the most highly cited articles from the 50-year history of CCA.

BACKGROUND: The 50th anniversary of CCA in 2006 prompted analysis of the most highly cited articles from the Journal's history. METHODS: Lists of most highly cited CCA articles were obtained from Current Contents (1974, 1991) and CCA (2006); all based on the ISI/Thomson Scientific database. PubMed search identified country of origin. RESULTS: Distribution of the most highly cited CCA articles was skewed towards those with high total citations. From the beginning, these articles originated from a diverse group of countries. This diversity increased with time to include countries from 4 continents. The most highly cited articles emerged at least 8-16 years following their publication. During the first 35 years of the Journal, there was a significant positive correlation between the total number of citations and the publication date of cited articles. Initially, virtually all most highly cited articles were methods papers, whereas during the past 25 years less than half of them reported methods; clinical research papers and reviews making up the rest. CONCLUSIONS: Results of this analysis may help in editorial policy-making and marketing of the Journal and in assessing the impact of individual countries on the field, and may guide authors' decision in submitting articles to the Journal.

Nursing Record/British Journal of Nursing archives, 1888-1956.

This article centres on the experience of using a new database comprising a digitised historical journal - the Nursing Record/British Journal of Nursing from 1888 to 1956, when the journal ceased publication. The project was initiated by the UK Centre for the History of Nursing, a collaboration between a number of academic bodies, including the Wellcome Trust and the Royal College of Nursing (RCN). The database was launched at Oxford in September 2003 and is freely available via the RCN website. The database was searched for material concerning emotion, as there has been increasing interest in this topic among service professionals, including nurses, during the past few decades (Hochschild, 1983; Smith, 1992; James et al, 2003). It seemed interesting to explore the same topic, as discussed in the late 19th and first half of the 20th centuries. Search terms used were "emotion", "feeling", "sympathy", "comfort" and "compassion". Most hits were achieved with "sympathy" and "feeling", but the majority of these were not strictly relevant to the discussion. This pilot search indicates that hand searching of paper copies still represents the "gold standard", in terms of identifying relevant material and interesting context data, not necessarily found when feeding specific search terms into a computer. The main advantages of the digitized journal are much wider access to this source and protection of fragile archival material.

A short history of INAHTA. International Network of Agencies for Health Technology Assessment.

The need for better communication and collaboration between health technology assessment agencies led to the formation of an International Network of Agencies for Health Technology Assessment (INAHTA). The network now comprises 27 agencies and has been successful in improving exchange of information and in undertaking joint health technology assessment projects. Issues for the future include possible changes to criteria for membership and identification of resources for more extensive programs.