Although modern medicine has been routinely used in treatment of various diseases, it is less than 100 years old. Traditional medicine, in comparison, has served mankind for thousands of years, is quite safe and effective. The mechanism or the scientific basis of traditional medicine, however, is less well understood.
13.6.1. In Vitro Studies with Turmeric
Throughout the Orient, turmeric is traditionally used for both prevention and therapy of diseases. Modern in vitro studies reveal that turmeric is a potent antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and anticancer agent (Table 13.3). Turmeric, used in cooking and in home remedies, has significant antioxidant abilities at different levels of action. Studies indicate that sufficient levels of turmeric may be consumed from curries in vivo to ensure adequate antioxidant protection. (Tilak et al. 2004). As an antioxidant, turmeric extracts can scavenge free radicals, increase antioxidant enzymes, and inhibit lipid peroxidation. Turmeric (100 μg/mL) inhibits lipid peroxidation in renal cells against hydrogen peroxide-induced injury when incubated with cells for 3 hours (Cohly et al. 1998). Using Salmonella typhimurium strains TA 100 and TA 1535, a mutagenicity study showed that turmeric inhibits the mutagenicity produced by direct-acting mutagens such as N-methyl N’-nitro-N-nitrosoguanidine and sodium azide. Turmeric extracts were found to inhibit microsomal activation-dependent mutagenicity of 2-acetamidofluorene (Soudamini et al. 1995).
In Vitro Effects of Turmeric against Various Diseases/Disorders.
Numerous lines of evidence suggest that turmeric exhibits anti-inflammatory activity. In one study, crude organic extracts of turmeric were found to inhibit lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)-α (median inhibitory concentration [IC50] value = 15.2 μg/mL) and prostaglandin E2 (PGE2; IC50 value = 0.92 μg/mL) from HL-60 cells. A combination of several fractions that contained the turmeric oils was more effective than curcuminoids in inhibiting PGE2 production (Lantz et al. 2005). A hydroethanolic extract of turmeric was recently found to inhibit activation of human dendritic cells in response to inflammatory cytokines (Krasovsky et al. 2009).
Besides these properties, turmeric has strong antimicrobial properties. The growth of histamine-producing bacteria (Vibrio parahaemolyticus, Bacillus cereus, Pseudomonas aeruginosa, and Proteus mirabilis) was inhibited by garlic and turmeric extracts at a 5% concentration (Paramasivam, Thangaradjou, and Kannan 2007). Turmeric was also found to inhibit histamine production in Morganella morganii (potent histamine-producing bacteria). However, inhibition of histamine production and histidine decarboxylase activity of turmeric is less than that of clove and cinnamon (Shakila, Vasundhara, and Rao 1996). Turmeric extract was found to inhibit growth of the foodborne pathogen V. parahaemolyticus with good sensitivity (Yano, Satomi, and Oikawa 2006). A methanolic extract of turmeric inhibited the growth of different strains of Helicobacter pylori with a minimum inhibitory concentration range of 6.25–50.0 μg/mL (Mahady et al. 2002). Among the various plant extracts that killed H. pylori, such as cumin, ginger, chili, borage, black caraway, oregano, and licorice, turmeric was found to be the most efficient (O’Mahony et al. 2005).
Ethanolic extracts of C. longa have good antifungal activity against Trichophyton longifusus (Khattak et al. 2005). Tests using the agar disc diffusion method for detecting antifungal activity showed that a crude ethanolic extract of turmeric killed all 29 tested clinical strains of dermatophytes. This extract exhibited an inhibition zone range of 6.1–26.0 mm (Wuthi-udomlert et al. 2000).
The anticancer activities of turmeric include inhibiting cell proliferation and inducing apoptosis of cancer cells. Ar-turmerone, which is isolated from turmeric, induced apoptosis in human leukemia Molt 4B and HL-60 cells by fragmenting DNA to oligonucleosome-sized fragments, a known step in the process of apoptosis (Aratanechemuge et al. 2002). Moreover, the nucleosomal DNA fragmentation induced by ar-turmerone was associated with induction of Bax and p53 proteins, rather than B cell lymphoma 2 (Bcl-2) and p21, and activation of mitochondrial cytochrome c and caspase-3 (Lee 2009). This study showed that turmeric extract repressed the production and secretion of hepatitis B surface antigen from HepG 2.2.15 cells, an activity that is mediated through the enhancement of cellular accumulation of p53 protein by transactivating the transcription of the p53 gene as well as increasing the stability of the p53 protein (Kim et al. 2009).
13.6.2. In Vivo Studies with Turmeric
Both the preventive and therapeutic effects of turmeric have been examined in animal models (Table 13.4). These studies report that this yellow spice exhibits anticancer (Azuine and Bhide 1994; Deshpande, Ingle, and Maru 1997; Garg, Ingle, and Maru 2008), hepatoprotective (Miyakoshi et al. 2004), cardioprotective (Mohanty, Arya, and Gupta 2006), hypoglycemic (Kuroda et al. 2005; Honda et al. 2006), and antiarthritic properties (Funk et al. 2006).
In Vivo Effect of Turmeric against Development of Various Diseases/Disorders.
In various models, turmeric has been reported to exhibit activity against the development of skin cancer (Villaseñlor, Simon, and Villanueva 2002), breast cancer (Deshpande, Ingle, and Maru 1998a), oral cancer (Azuine and Bhide 1992a), and stomach cancer (Azuine and Bhide 1992b). It prevents carcinogenesis at various steps, including inhibiting mutation (Polasa et al. 1991), detoxifying carcinogens (Thapliyal, Deshpande, and Maru 2001), decreasing cell proliferation, and inducing apoptosis of tumor cells (Garg, Ingle, and Maru 2008). Turmeric extract prevents animal tumors induced by Dalton’s lymphoma (Kuttan et al. 1985). In this study, mice were injected with Dalton’s lymphoma cells intraperitoneally and treated with turmeric extract (10–40 mg/animal) for 10 days. After 30 days, the authors found up to 80% decrease in tumor formation in comparison with nontreated mice (Figure 13.2a). They also observed that up to 75% of animals survived after 30 days and 50% after 60 days of treatment (Figure 13.2b). In a 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch model of carcinogenesis, dietary turmeric (1%) decreased tumor burden and multiplicity and enhanced the latency period in parallel. The mechanisms of anticarcinogenesis were mediated through inhibition of DMBA-induced expression of the ras oncogene product, induction of p21 and its downstream targets, mitogen-activated protein kinases, and reduction of proliferating cell nuclear antigen and Bcl-2 expression. Turmeric also enhanced apoptosis (increased expression of Bax, caspase-3, and apoptotic index), decreased inflammation (levels of cyclooxygenase [COX]-2, the downstream target of activator protein-1/nuclear factor KB [NF-KB], and PGE2), and induced aberrant expression of known differentiation markers, that is, cytokeratins (Garg, Ingle, and Maru 2008).
Inhibition of tumor growth in mice by turmeric extracts in a dose-dependent manner. Mice were injected with Dalton’s lymphoma cells (1 million) intraperitoneally. After randomization, turmeric was given to the mice (n = 8) at indicated concentration (more...)
Topical application of turmeric was found to decrease multiplicity and onset of skin tumors (Villaseñor, Simon, and Villanueva 2002). Dietary administration of 1% turmeric per 0.05% ethanolic turmeric extract was found to inhibit DMBA-induced mammary tumorigenesis in female Sprague–Dawley rats (Deshpande, Ingle, and Maru 1998a). Dietary turmeric inhibited ethyl(acetoxymethyl) nitrosamine-induced oral carcinogenesis in Syrian hamsters. However, the inhibitory effect of a combination of turmeric and betel leaf extract was found to be higher than that of the individual constituents (Azuine and Bhide 1992a). Administration of turmeric extract at a dose of 3 mg/animal 18 hours prior to intraperitoneal (i.p.) injection of benzo[a]pyrene (BaP; 250 mg/kg) significantly inhibited bone marrow micronuclei formation in female Swiss mice. Moreover, the incidence and multiplicity of BaP-induced forestomach tumors in female Swiss mice were significantly inhibited by turmeric extract (Azuine, Kayal, and Bhide 1992). Chandra Mohan, Abraham, and Nagini (2004) also showed that pretreatment with turmeric alone and in combination with tomato and garlic extract significantly lowered the frequencies of DMBA-induced bone marrow micronuclei, as well as the extent of lipid peroxidation. They revealed that these changes may be mediated by the antioxidant-enhancing effects of the dietary agents. Combined treatment of urethane, a well-known mutagen, and turmeric displayed an inhibition of the genotoxic effect of urethane by turmeric (el Hamss et al. 1999). Decrease in tumorigenesis caused by turmeric is also associated with inhibition of DNA adduct formation. Turmeric inhibited the levels of BaP-induced DNA adducts in the livers of rats. Inclusion of turmeric at 0.1%, 0.5%, and 3.0% in the diet for 4 weeks significantly decreased the level of BaP–DNA adducts, including the major adduct dG-N2-BaP, formed within 24 hours in response to a single i.p. BaP injection (Mukundan et al. 1993). Irrespective of whether turmeric was included in the diet or applied locally, it significantly decreased DMBA-induced DNA adducts at the target site and consequently lowered the number of tumors and tumor burden in the studied animals (Krishnaswamy et al. 1998). Turmeric contains several substances capable of inhibiting chemical carcinogenesis. It enhanced the xenobiotic-metabolizing enzymes in the hepatic tissue of rats fed with 0.5–1.0% turmeric in the diet. Detoxifying enzymes such as uridine diphosphate (UDP), glucuronyl transferase, and glutathione-S-transferase significantly increased in turmeric-fed mice as compared with control animals (Goud, Polasa, and Krishnaswamy 1993).
Ethanolic turmeric extract was found to have opposing actions on murine lymphocytes and on Ehlrich ascitic carcinoma cells. Turmeric enhances lymphocyte viability and blastogenesis, but induces formation of cytoplasmic blebs and plasma membrane disintegration of tumor cells. Thus, it is suggested that turmeric is a conducive agent for lymphocytes and inhibitory as well as apoptosisinducing for tumor cells (Chakravarty and Yasmin 2005). A comparative study of edible plants like C. longa and F. caraica, and herbaceous plants like Gossypium barbadense and Ricinus communis extracts for their antitumor activities showed that the edible plant extracts exhibited higher antitumorigenic activities. Thus, edible plants that show in vivo antitumor activities may be recommended as safe sources of antitumor compounds (Amara, El-Masry, and Bogdady 2008).
Turmeric showed antioxidant potential by lowering oxidative stress in animals. A study showed that a diet containing 0.1% turmeric fed for 3 weeks to retinol-deficient rats lowered lipid peroxidation rates by 22.6% in liver, 24.1% in kidney, 18.0% in spleen, and 31.4% in brain (Kaul and Krishnakantha 1997). A study conducted on mice showed that turmeric extract inhibited membrane phospholipid peroxidation and increased liver lipid metabolism, which indicates turmeric extract has the ability to prevent the deposition of triacylglycerols in the liver. Dietary supplementation for one week (1% w/w of diet) with a turmeric extract showed lower phospholipids hydroperoxide level in mice red blood cells (RBC). The liver lipid peroxidizability induced with Fe2+/ascorbic acid was effectively suppressed by dietary supplementation with turmeric (Asai, Nakagawa, and Miyazawa 1999). Oral administration of a nutritional dose of turmeric extract decreased susceptibility to oxidation of erythrocyte and liver microsome membranes in vitro. When turmeric hydroalcoholic extract (1.66 mg/kg of body weight) was given to rabbits fed a high-fat diet, oxidation of erythrocyte membranes was found to be significantly lower than that in membranes of control animals. Levels of hydroperoxides and thiobarbituric acid-reactive substances in liver microsomes were also low (Mesa et al. 2003). Turmeric also seems beneficial in preventing diabetes-induced oxidative stress. In diabetic rats, an AIN93 diet containing 0.5% turmeric was found to control oxidative stress by inhibiting increases in thiobarbituric acid-reactive substances and protein carbonyls and reversing altered antioxidant enzyme activities without altering the hyperglycemic state (Arun and Nalini 2002; Suryanarayana et al. 2007). This diet also inhibited expression of vascular endothelial growth factor in diabetic rats (Mrudula et al. 2007). Further, it suppressed increase in blood glucose level in type 2 diabetic KK-Ay mice. A dose of 0.2 or 1.0 g of ethanol extract, 0.5 g of hexane extract, and 0.5 g of hexane-extraction residue per 100 g of diet in the mice feed suppressed significant increase in blood glucose levels. The ethanol extract of turmeric also stimulated human adipocyte differentiation, and it showed human peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligand-binding activity (Nishiyama et al. 2005). Further, turmeric appeared to minimize osmotic stress. Most importantly, aggregation and insolubilization of lens proteins due to hyperglycemia was prevented by turmeric, indicating that it prevents or delays the development of cataracts (Suryanarayana et al. 2005).
Turmeric has been reported to be hepatoprotective. Diets containing turmeric extract suppressed increases in lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels caused by D-galactosamine-induced liver injury in rats (Miyakoshi et al. 2004). A 5% turmeric extract decreased carbon tetrachloride–induced increases in serum levels of bilirubin, cholesterol, AST, ALT, and alkaline phosphatase (ALP) in mice (Deshpande et al. 1998b). In female Wistar rats fed a diet containing 0%, 0.2%, 1.0%, or 5.0% turmeric, nitrosodiethylamineinduced hepatocarcinogenesis was inhibited. This effect was detected by measuring the numbers of γ-glutamyl transpeptidase–positive foci, a marker of hepatocarcinogenesis (Thapliyal et al. 2003).
Turmeric is also effective against neuronal, cardiac, and kidney disorders. The effect of turmeric on myocardial apoptosis and cardiac function was examined in an ischemia and reperfusion model of myocardial injury. Turmeric at 100 mg/kg administered for 1 month afforded significant cardioprotection and functional recovery that was attributed to reduction in cell death (Mohanty, Arya, and Gupta 2006).
Turmeric is also useful against depression (Yu, Kong, and Chen 2002; Xia et al. 2006; Xia et al. 2007). Its ethanolic extract markedly attenuated swim stress–induced decreases in serotonin, 5-hydroxyindoleacetic acid, and noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Also, this extract significantly reversed swim stress–induced increases in serum corticotropin-releasing factor and cortisol levels and thus regulated neurochemical and neuroendocrine systems in mice (Xia et al. 2007). In another study, administration of aqueous extracts of turmeric to mice (140–560 mg/kg for 14 days) reduced immobility in the tail suspension test and the forced swimming test (Yu, Kong, and Chen 2002). The effects of 560-mg/kg turmeric were found to be more potent than those of the antidepressant fluoxetine. The extracts significantly inhibited brain monoamine oxidase (MAO)-A activity at a low dose, but at a higher dose, they inhibited brain MAO-B activity. In comparison, fluoxetine showed only a tendency to inhibit MAO-A and -B activity in animal brains. These results demonstrate that turmeric has specific antidepressant effects in vivo. However, since curcumin is not water soluble, the agent in aqueous extracts of turmeric responsible for this activity is not clear.
The antiarthritic effects of turmeric include inhibition of joint inflammation and periarticular joint destruction. In vivo treatment with turmeric extract prevented local activation of NF-κB and the subsequent expression of NF-κB-regulated genes mediating joint inflammation and destruction, including chemokines, COX-2, and the receptor activator of NF-κB ligand (RANKL). It also inhibited inflammatory cell influx, joint levels of PGE2, and periarticular osteoclast formation in rats (Funk et al. 2006). Turmeric was found to be effective against carrageenan-induced edema in rats (Yegnanarayan, Saraf, and Balwani 1976), and water extracts of turmeric were more active than alcohol extracts in the inhibition of carrageenan-induced edema. Turmeric extract, when given intraperitoneally, was found to be more active than hydrocortisone (Ghatak and Basu 1972). The yellow powder of turmeric is known to have potent vasorelaxant activity and to decrease the atherogenic properties of cholesterol. A study showed that supplementation of turmeric in the diet controlled arterial blood pressure in animals and enhanced vasorelaxant responses to adenosine, acetylcholine, and isoproterenol (Zahid Ashraf, Hussain, and Fahim 2005). Turmeric’s antiatherosclerotic effect is associated with inhibition of low-density lipoprotein oxidation, prevention of lipoperoxidation, and reduction in levels of cholesterol (Quiles et al. 1998; Ramírez-Tortosa et al. 1999). A study showed that feeding an ethanolic extract of turmeric to rats elevated the high-density lipoprotein (HDL)-cholesterol/total cholesterol ratio. The extract also caused a significant decrease in the ratio of total cholesterol/phospholipids. Turmeric extract exhibited better cholesterol and triglyceride lowering (85% and 88%, respectively) as compared to Nardostachys jatamansi extract in tritoninduced hyperlipidemic rats (Dixit, Jain, and Joshi 1988). Turmeric suppresses Freund’s adjuvantinduced arthritis and acute edema in rats, and it has also been reported that oil extract of turmeric is more active than cortisone (Chandra and Gupta 1972).
Another interesting property of turmeric is its wound-healing ability. Gujral, Chowdhury, and Saxena (1953) found that turmeric has the property of healing wounds and ulcers in rats and rabbits. Other studies in rabbits revealed that stimulation of mucin secretion could protect the stomach from ulcer (Mukerji, Zaidi, and Singh 1961).
Besides causing these effects, addition of turmeric to the diet significantly improved weight gain of broiler chicks and reduced their relative liver weight. Turmeric also ameliorated the adverse effects of aflatoxin on some serum chemistry parameters (total protein, albumin, cholesterol, calcium) in broiler chicks and restored antioxidant functions in terms of level of peroxides, superoxide dismutase activity, and total antioxidant concentration in their livers (Gowda et al. 2008).
Turmeric acts as a digestive stimulant. As a dietary supplement, it favorably enhanced the activities of pancreatic lipase, chymotrypsin, and amylase. Moreover, turmeric mixed with other spices such as coriander, red chili, black pepper, and cumin brought about a pronounced stimulation of bile flow and bile acid secretion (Platel et al. 2002). Mukerji, Zaidi, and Singh (1961) showed that turmeric increases the mucin content of gastric juice in rabbits. Studies conducted by Farnsworth and Bunyapraphatsara (1992), Supniewski and Hano (1935), and Prucksunand et al. (2001) explain that turmeric has local anesthetic action. After eating turmeric, secretion of gastrin hormone from the antrum of the stomach may be inhibited. Turmeric may possess local membrane-anesthetizing activity at the antrum of the stomach, which then inhibits secretion of gastrin in the same way as oxethazaine, the active ingredient of strocain (Masuda 1973). This is the reason turmeric is administered before meals.
13.6.3. Clinical Studies Using Turmeric
Turmeric has been tested against various diseases in humans (Table 13.5). In one study, the antimutagenic effects of turmeric were examined in 16 chronic smokers (Polasa et al. 1992). Turmeric was given in doses of 1.5 g/day for 30 days, and this was found to significantly reduce the urinary excretion of mutagens in these smokers. In six nonsmokers, on the other hand, no change in urinary excretion of mutagens was noted. These results suggest that dietary turmeric is an effective antimutagen and may be useful in chemoprevention. In another study, the effect of turmeric was examined on patients with irritable bowel syndrome. When 1 or 2 tablets of a standardized turmeric extract were given daily for 8 weeks, the prevalence of irritable bowel syndrome was significantly decreased, as was the abdominal pain/discomfort score (Bundy et al. 2004). Alcoholic extract of turmeric offered protection against BaP-induced increase in micronuclei in circulating lymphocytes of healthy individuals (Hastak et al. 1997). In a subsequent study, the authors treated patients suffering from oral submucous fibrosis (OSF) with turmeric extract (3 g/day) for 3 months. The number of micronuclei from oral exfoliated cells of OSF patients before and after treatment with turmeric extract was recorded. They found that the number of micronuclei in oral exfoliated cells decreased substantially and was comparable with that of normal, healthy individuals (Figure 13.3).
Inhibition of micronuclei formation in oral submucous fibrosis (OSF) patients: (a) Incidence of micronuclei in exfoliated buccal mucosal cells of OSF patients before and after treatment with turmeric and of normal healthy individuals. (b) Incidence of (more...)
Turmeric was also found useful in healing peptic ulcers. In a phase II clinical trial, 45 patients with peptic ulcer received capsule-filled turmeric orally in the dose of 2 capsules (300 mg each) five times daily. After 4 weeks of treatment, ulcers were found to be absent in 48% of cases. After 12 weeks of treatment, ulcer-free cases increased to 76% (Prucksunand et al. 2001). A double-blind trial found turmeric to be helpful for people with indigestion and for people with stomach or intestinal ulcers, but it was shown to be less effective than antacids (Kositchaiwat, Kositchaiwat, and Havanondha 1993). An ethanol extract of turmeric was found to produce remarkable symptomatic relief in patients with external cancerous lesions. In a study of 62 patients, reduction in smell was noted in 90% of the cases and reduction of itching in almost all cases. Some patients (10%) had a reduction in lesion size and pain (Kuttan, Sudheeran, and Joseph 1987).
A study on eight healthy subjects showed that the presence of turmeric in curry increases bowel motility and activates hydrogen-producing bacterial flora in the colon, thereby increasing the concentration of breath hydrogen (Shimouchi et al. 2008). Turmeric paste is used to heal wounds or to protect against infection. In certain parts of Bangladesh, turmeric is the most common application on the cut umbilical cord after delivery (Alam et al. 2008).
Identifying and removing duplicate records from systematic review searches
Yoojin Kwon, MLIS, Michelle Lemieux, MLIS, Jill McTavish, PhD, MLIS, and Nadine Wathen, PhD
This article has been cited by other articles in PMC.
The purpose of this study was to compare effectiveness of different options for de-duplicating records retrieved from systematic review searches.
Using the records from a published systematic review, five de-duplication options were compared. The time taken to de-duplicate in each option and the number of false positives (were deleted but should not have been) and false negatives (should have been deleted but were not) were recorded.
The time for each option varied. The number of positive and false duplicates returned from each option also varied greatly.
The authors recommend different de-duplication options based on the skill level of the searcher and the purpose of de-duplication efforts.
Keywords: Biomedical Research, Standards, Duplicate Publication as Topic, Publications, Standards, Review Literature as Topic
Systematic reviews continue to gain prevalence in health care primarily because they summarize and appraise vast amounts of evidence for busy health care providers [1, 2]. Because they are used as the foundation for clinical and policy-related decision-making processes, it is critical to ensure that the methods used in systematic reviews are explicit and valid. The Cochrane Collaboration, for example, places a heavy emphasis on minimizing bias with a thorough, objective, and reproducible multi-database search , which has become the standard in systematic review processes . Searching multiple databases, however, results in the retrieval of numerous duplicate citations. Also, due to the nature of the publishing cycle in the field of medicine, conference abstracts and full-text articles reporting the same information are often retrieved concurrently. In addition, although many have called out against such practice, some authors “slice, reformat, or reproduce material from a study” , which creates repetitive, duplicate, and redundant publications. As Kassirer and Angell argued, “multiple reports of the same observations can over emphasize the importance of the findings, overburden busy reviewers, fill the medical literature with inconsequential material, and distort the academic reward system” . Removing these duplicate citations, also known as de-duplication, can be a time-consuming process but is necessary to ensure a valid and reliable pool of studies for inclusion in a systematic review.
The aim of this study was to explore and compare the effectiveness of various de-duplication features. Specifically, the authors examined and compared two categories of de-duplication strategies: de-duplicating in the Ovid and EBSCO database platforms and de-duplicating in three selected reference management software packages: RefWorks, EndNote, and Mendeley.
Five de-duplication options were examined in this study:
Ovid multifile search: Searchers are able to de-duplicate in the Ovid platform across various Ovid products, such as Ovid MEDLINE and Ovid Embase.
CINAHL (EBSCO) and Ovid multifile search: Searchers are able to exclude MEDLINE records in the CINAHL database.
Refworks: Searchers are able to de-duplicate all records from various sources in this citation manager.
Mendeley: This citation manager automatically identifies duplicates among imported references, which can be deleted.
Endnote: When de-duplicating, this citation manager creates a separate group for duplicate references only. It is possible for searchers to view this group and delete the duplicates.
To create the citation samples used for this study, we reran the search strategies that were developed for a systematic review on ward closure as an infection control practice in Ovid MEDLINE, Ovid Embase, and CINAHL from the database inception to September 11, 2014 (Appendix, online only) .
For the Ovid multifile option (option 1), which allows de-duplication across various Ovid products, we opened up MEDLINE and Embase in the Ovid platform and ran a search using the strategies that were designed for the aforementioned systematic review. We ran the “use” command and database codes for MEDLINE and Embase, which are “pmoz” and “oemezd,” respectively, to ensure that the retrieved results were filtered appropriately (Appendix, online only). Then, we used the “remove duplicates” command for de-duplication.
For the EBSCO CINAHL option (option 2), we ran a search in CINAHL and limited the search results to non-MEDLINE citations. The results from the searches in Ovid and EBSCO were collated and recorded in two spreadsheets: the first one contained Ovid results only, and the second one contained both Ovid and EBSCO results.
For the other three options (RefWorks, Endnote, and Mendeley), we retrieved all citations from the systematic review and exported them to each de-duplication option. In RefWorks, we clicked on the “Exact Duplicates” and “Close Duplicates” buttons in the “View” tab and deleted all identified citations. In EndNote, we clicked on the “Find Duplicates” button under the “References” menu. We deleted everything in the EndNote library duplicate references group. We loaded references as a Research Information Systems (RIS) file into Mendeley, where they were automatically de-duplicated. “Check duplicates” from the tools menu was then run to check for close duplicates, all of which were merged. All sets of citations were downloaded and recorded on separate spreadsheets.
To investigate these five de-duplication options, we needed a sample set of citations and a “gold standard” file of de-duplicated references to compare against each option. To create the sample set of citations for this study, we reran search strategies that were developed for a systematic review on ward closure as an infection control practice in Ovid MEDLINE, Ovid Embase, and CINAHL from the database inception to September 11, 2014 . All of these search strategies are provided in the online appendix.
To develop the gold standard sets, we screened and de-duplicated the citations by hand, which were recorded on a Microsoft Excel spreadsheet. The detailed steps that we took to identify the duplicates in Excel are listed in the online appendix. To be considered duplicates, two or more citations had to share the same author, title, publication date, volume, issue, and start page information. The full-text versions of the citations were consulted when we were in doubt. In such cases, we also checked the population sizes, methodology, and outcomes to determine whether the citations were duplicates. Conference abstracts were deemed to be duplicates if full-text articles that shared the same study design, sample size, and conclusion were retrieved, even if their publication dates varied. Older versions of systematic reviews were deleted when there was a link between them and newer versions. All citations that were classified as duplicates were deleted from the spreadsheet. Ultimately, 2 gold standard sets were developed: one for just Ovid MEDLINE and Ovid Embase (1,087 citations) and the other for Ovid MEDLINE, Ovid Embase, and CINAHL (1,262 citations). The first gold standard set was developed for comparison against the results from the Ovid multifile search alone (option 1). The second gold standard set was developed for comparison against the other 4 options (options 2–5).
All sets of results from the de-duplication strategies outlined above were compared against the gold standard sets to identify false negatives (duplicate citations that should have been deleted but were not) and false positives (duplicate citations that were deleted but should not have been). We also recorded the time it took to de-duplicate results in each option (Table 1, online only). We took into consideration the results of this comparison and the time it took to de-duplicate with each option when determining the most effective strategy for de-duplication when searching the selected databases and using the selected reference management software.
The time spent on each de-duplication option varied (Table 1, online only). Including the time spent on reaching consensus, developing the gold standard samples of non-duplicate results took four hours and forty-five minutes. Carrying out Ovid multifile and CINAHL searches took less than three minutes to retrieve the results. Likewise, the Ovid multifile and CINAHL non-MEDLINE searches each took under three minutes. RefWorks took approximately ten minutes to delete exact and close duplicates. EndNote took three minutes to load and delete duplicates. Mendeley took five minutes. The majority of this time was spent merging the close duplicates.
The number of positive and false duplicates returned from each de-duplication option varied greatly (Table 2). The Ovid multifile search alone resulted in 1,178 citations. The comparison to the gold standard for Ovid MEDLINE and Ovid Embase revealed that simply de-duplicating in Ovid resulted in 91 false negatives but no false positives.
Number of de-duplicated citations and breakdown
As mentioned above, we developed a second gold standard set for the results retrieved from Ovid MEDLINE, Ovid Embase, and CINAHL. The de-duplicated datasets from Ovid multifile and CINAHL non-MEDLINE searches, RefWorks, EndNote, and Mendeley were compared against this gold standard set. Combining the search results from the Ovid multifile search and CINAHL non-MEDLINE search options increased not only the number of false negatives by 3, but also the number of false positives by 40. De-duplicating in RefWorks resulted in 94 false negatives and 3 false positives. EndNote resulted in 258 false negatives and 6 false positives. De-duplicating with Mendeley resulted in 36 false negatives and 4 false positives.
Our primary research question was to compare the effectiveness of various de-duplication options. We were particularly interested in verifying whether using the various de-duplication options resulted in false positives (duplicates that should not have been deleted). Similar to Jiang et al., we believe false positives are more detrimental than false negatives because systematic reviewers want to maintain the highest possible recall in retrieval . As running the Ovid multifile search command alone did not result in any false positives, we recommend using this option to further refine the search results before exporting to a citation manager. The limitation of this approach is that it only works if users subscribe to both MEDLINE and Embase through Ovid. PubMed users are not able to use this method.
Running the non-MEDLINE command in CINAHL, on the other hand, was the least effective method of de-duplication as it resulted in forty false positives, which was the highest number amongst all of the options. We found that using the non-MEDLINE option in CINAHL reduced the benefit of searching multiple databases. Multi-database searching is necessary because different articles are indexed differently in different databases, so there may be articles retrieved from CINAHL that are indexed in MEDLINE but are not retrieved by the MEDLINE search. The danger of the non-MEDLINE command is that it deletes these records, reducing some of the benefit of the multi-database search.
Beyond the desire to minimize false positives, there is as yet no definitive consensus regarding how best to find and delete duplicates, although the prevalence and potential impact of duplicates remains a critical issue for those undertaking systematic reviews . In 2014, Bramer et al. published a study testing the efficacy of de-duplicating with various reference managers, such as RefWorks, EndNote, Mendeley, and more . According to the authors, de-duplicating exact citations in RefWorks performed the worst and de-duplicating with their proposed algorithm, named the Bramer method, yielded the best results in terms of accuracy and speed . Because Bramer et al. did not distinguish the differences between false negatives and false positives, we were unable to directly compare their results to the results of our study.
A 2013 study by Qi et al. revealed that relying solely on the auto-searching feature of reference management software, such as EndNote, is inadequate when identifying duplicates for a systematic review .
Most recently, Rathbone et al. published a study comparing the Systematic Review Assistant-Deduplication Module (SRA-DM), a newly developed citation-screening program, against EndNote . By demonstrating the superiority of the SRA-DM method, Rathbone et al.'s study also exposed the limited performance of de-duplication features in reference management software . In our study, RefWorks produced the smallest number of false positives out of the citation management software that we used.
De-duplicating with Mendeley resulted in the smallest number of false negatives (citations that should have been deleted). Most notably, EndNote was the least effective citation management tool, with the highest number of false positives and false negatives. The results of our study not only confirm Qi et al.'s  and Rathbone et al.'s  findings that the automatic de-duplicating option in EndNote is inadequate and must be supplemented by hand-searching, but the results also reveal that using this option may lead to losses of articles that should not be deleted.
These data suggest that researchers will have to individually determine their own thresholds of acceptability for false positives. If none are acceptable, none of the citation management de-duplication options can be used. If the researcher is confident that all key articles would be found by hand-searching and deems a relatively low percentage of false negatives and positives to be acceptable (Table 3, online only), we recommend Mendeley as the most effective tool. Effort should be made to individually investigate all of the close duplicates in RefWorks and Mendeley to check for false positives. In addition, the results from any de-duplication technique should always be manually reviewed to check for remaining duplicates. Using formulas in Excel, such as highlighting duplicates, can be a useful tool to speed up this process.
Even with these preliminary recommendations, we must emphasize that de-duplication of results is complex. Examples of some technical issues causing difficulties in identifying duplicates automatically while creating the gold standard datasets are:
- ▪ differences in journal names (e.g., “and” instead of “&”)
- ▪ punctuation (e.g., some titles are exported with a period at the end, others are not)
- ▪ translation differences of non-English article titles
- ▪ author information or order of author names
These issues are often the result of unintentional human error that occurs during the processing of individual records, and eliminating them proves challenging. Nevertheless, as commercial service providers, database administrators need to be more vigilant. Elmagarmid et al.'s article provides an extensive list of duplicate detection algorithms and metrics that can be used to clean up databases .
This study does have limitations. Only two “gold standards” were used, and results may vary with other search topics. We were not able to explore the de-duplication options of other reference management software such as Zotero and Reference Manager. Future research may involve expanding the selection of reference management software.
There are many other directions that future research on this topic could take as well. For example, researchers could investigate the effectiveness of combining de-duplication codes (e.g., ..dedup) and options that can be used in bibliographic databases and refining those results with de-duplication features that various reference management software packages offer. Researchers could also test non-MEDLINE and non-MEDLINE journals commands in Embase to determine if these codes are more effective than the non-MEDLINE command in CINAHL. To foster further advancement in this field, more participation in research by librarians and information specialists is encouraged.
The authors thank the authors of the systematic review used in this study, in particular Holly Wong, Susan E. Powelson, AHIP, Dr. William A. Ghali, and Dr. John M. Conly.
Yoojin Kwon, MLIS,ac.yrarbilcilbupotnorot@nowky, Librarian, Toronto Public Library, 35 Fairview Mall Drive, Toronto, ON M2J 4S4, Canada; Michelle Lemieux, MLIS, firstname.lastname@example.org, Regulatory Coordinator, AltaLink, 2611 Third Avenue Southeast, Calgary, AB, T2A 7W7, Canada; Jill McTavish, PhD, MLIS, ac.no.cshl@hsivaTcM.lliJ, Clinical Librarian, Health Sciences Library, London Regional Cancer Program (LRCP), 790 Commissioners Road East, ON, N6A 4L6, Canada; Nadine Wathen, PhD, ac.owu@nehtawn, Associate Professor and Faculty Scholar, Faculty of Information & Media Studies, University of Western Ontario, North Campus Building, Room 240, London, ON, N6A 5B7, Canada
*Based on a poster session at Canadian Health Libraries Association/Association des bibliothéques de la santé du Canada (CHLA/ABSC) '15, Riding the Wave of Change; Vancouver, BC; June 20, 2015.
IRPThis article has been approved for the Medical Library Association's Independent Reading Program <http://www.mlanet.org/education/irp/>.
ECA supplemental appendix and supplemental Table 1 and Table 3 are available with the online version of this journal.
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