Reporting of systematic searches.

Documenting systematic searches promotes transparency, reproducibility, and integrity in research. In recent years, various reporting guidelines have gained widespread recognition and adoption, and some journals and funders require researchers to provide a detailed account of their search strategies. Documentation of systematic searches vary depending on the search strategies and types of reviews. This review provides an overview of principles of reporting search strategies for key review types and search strategies, and furthermore an overview of existing reporting guidelines.

Supplementary strategies identified additional eligible studies in qualitative systematic reviews.

BACKGROUND AND OBJECTIVES: There is an increasing number of qualitative systematic reviews being produced. Searching for qualitative literature to include in these systematic reviews is, however, more challenging and may result in less than favorable recall. Database searches relying solely on key elements of the research question may not retrieve all relevant qualitative studies for synthesis, and supplementary searches may be pertinent to complement the searches. This study aimed to determine, if a) supplementary search strategies (citation searches and alternative search strategies) were able to identify relevant publications for qualitative systematic reviews that were nonretrievable, when conducting traditional database searches based on key elements; and b) to investigate the total number of identified publications when combining traditional database searches with these supplementary search strategies. METHODS: From a previous study, a gold standard of 12 qualitative reviews including 101 PubMed-indexed publications was used. One of the reviews had only one included publication and in one review, the two included studies were identifiable in PubMed. In the remaining 10 reviews, 61 publications were retrievable through traditional database searches, and 37 were nonidentifiable. The 61 publications were used as basis for possible identification of the 37 publications by using the supplementary search strategies: citations searches (review of reference lists, PubMed "Cited by" function; Scopus "Cited by" function, Citationchaser, CoCites plugin for PubMed) and alternative search strategies (PubMed "similar articles" function; Scopus "Related documents based on references"). RESULTS: Traditional database searches retrieved 62.4% of the 101 publications. Citations searches in Scopus, Citationchaser and CoCites identified 21 (56.8%) of the 37 remaining publications. The PubMed "Cited by" function did not identify any of the 37 publications. The alternative search strategies, the PubMed "Similar articles" together with Scopus "Related documents based on references"-function) identified 15 (40.5%) of the 37 publications. Together, these supplementary search strategies identified 25 (67.6%) of the 37 publications, resulting in an overall retrieval of 87.1%, when combining traditional database searches and supplementary search strategies. CONCLUSION: The results of this study indicate that supplementary search strategies (citation searches and alternative search strategies) increase the retrieval potential, when searching for qualitative publications and should be included, when identifying literature for qualitative reviews.

Avoiding searching for outcomes called for additional search strategies: a study of Cochrane review searches.

OBJECTIVES: A search strategy for a systematic review that uses the Population, Intervention, Comparison, and Outcome framework should include the population, the intervention(s), and the type(s) of study design. According to existing guidelines, outcome should generally be excluded from the search strategy unless the search is multistranded. However, a recent study found that approximately 10% (51) of recent Cochrane reviews on interventions included outcomes in their literature search strategies. This study aims to analyze the alternatives to including outcomes in a search strategy by analyzing these recent Cochrane reviews. STUDY DESIGN AND SETTING: This study analyzes the 51 Cochrane reviews that included outcomes in their literature search strategies and analyzes the results of alternative search strategies that follow current recommendations. RESULTS: Despite a small study sample of 51 reviews the results show that many of the reviews excluded some of the recommended elements due to very broadly defined elements (e.g., all interventions or all people). Furthermore, excluding outcomes from the search strategy is followed by an enormous increase in the number of retrieved records making it unmanageable to screen, if using a single-stranded search strategy. CONCLUSION: Recommendations for search strategies in difficult cases are called for.

[The use of search filtersin systematic searches].

In this review, we provide an overview of search filters, which are pre-formulated search strategies developed to help identify articles within a given topic or with a particular study design. We present the rationale behind search filters and how they are used. Using a search filter may however, result in missing relevant publications and they should be used with care. Therefore, we describe how these search filters are developed and evaluated. Finally, we provide guidance on how the use of a search filter is reported in a systematic search.

Performance of conceptual framework elements for the retrieval of qualitative health literature: a case study.

OBJECTIVE: A growing volume of studies address methods for performing systematic reviews of qualitative studies. One such methodological aspect is the conceptual framework used to structure the review question and plan the search strategy for locating relevant studies. The purpose of this case study was to evaluate the retrieval potential of each element of conceptual frameworks in qualitative systematic reviews in the health sciences. METHODS: The presence of elements from conceptual frameworks in publication titles, abstracts, and controlled vocabulary in CINAHL and PubMed was analyzed using a set of qualitative reviews and their included studies as a gold standard. Using a sample of 101 publications, we determined whether particular publications could be retrieved if a specific element from the conceptual framework was used in the search strategy. RESULTS: We found that the relative recall of conceptual framework elements varied considerably, with higher recall for patient/population (99%) and research type (97%) and lower recall for intervention/phenomenon of interest (74%), outcome (79%), and context (61%). CONCLUSION: The use of patient/population and research type elements had high relative recall for qualitative studies. However, other elements should be used with great care due to lower relative recall.

Using Embase as a supplement to PubMed in Cochrane reviews differed across fields.

OBJECTIVE: Medline/PubMed is often first choice for health science researchers when doing literature searches. However, Medline/PubMed does not cover the health science research literature equally well across specialties. Embase is often considered an important supplement to Medline/PubMed in health sciences. The present study analyzes the coverage of Embase as a supplement to PubMed, and the aim of the study is to investigate if searching Embase can compensate for low PubMed retrieval. STUDY DESIGN AND SETTING: The population in this study is all the included studies in all Cochrane reviews from 2012 to 2016 across the 53 Cochrane groups. The analyses were performed using two units of analysis (study and publication). We are examining the coverage in Embase of publications and studies not covered by PubMed (25,119 publications and 9,420 studies). RESULTS: The results showed that using Embase as a supplement to PubMed resulted in a coverage of 66,994 publications out of 86,167 and a coverage rate of 77.7, 95% CI [75.05, 80.45] of all the included publications. Embase combined with PubMed covered 48,326 out of 54,901 studies and thus had a coverage rate of 88.0%, 95% CI [86.2, 89.9] of studies. The results also showed that supplementing PubMed with Embase increased coverage of included publications by 6.8 percentage points, and the coverage of studies increased by 5.5 percentage points. Substantial differences were found across and within review groups over time. CONCLUSION: The included publications and studies in some groups are covered considerably better by supplementing with Embase, whereas in other groups, the difference in coverage is negligible. However, due to the variation over time, one should be careful predicting the benefit from supplementing PubMed with Embase to retrieve relevant publications to include in a review.

Using the full PICO model as a search tool for systematic reviews resulted in lower recall for some PICO elements.

OBJECTIVES: The use of the four-part PICO model to facilitate search strategy development for a precise answer is recommended for structuring searches for systematic reviews. Existing guidelines generally recommend that a search strategy should include the population, intervention(s), and types of study design. Consequently, comparison and outcome are not recommended as a part of the search strategy. There is evidence that comparison and particularly outcome is not represented in enough detail, but this needs to be confirmed. STUDY DESIGN AND SETTING: The present study examines the presence of PICO elements in the records in two commonly used databases for health sciences research: Embase and PubMed. We examine the field of upper GI and pancreatic diseases as well as the field of pregnancy and childbirth by extracting the included studies as well as the related PICO elements from a random selection of Cochrane reviews within these two areas. RESULTS: We find that the PICO elements C and O had a lower retrieval potential across the two Cochrane groups and databases also when combining text words and subject headings. In particular, we find a lower retrieval when searching for both primary and secondary outcomes. CONCLUSION: Our results support the existing recommendation not to search for outcomes.

Research Integrity Among PhD Students at the Faculty of Medicine: A Comparison of Three Scandinavian Universities.

This study investigates research integrity among PhD students in health sciences at three universities in Scandinavia (Stockholm, Oslo, Odense). A questionnaire with questions on knowledge, attitudes, experiences, and behavior was distributed to PhD students and obtained a response rate of 77.7%. About 10% of the respondents agreed that research misconduct strictly defined (such as fabrication, falsification, and plagiarism, FFP) is common in their area of research, while slightly more agreed that other forms of misconduct is common. A nonnegligible segment of the respondents was willing to fabricate, falsify, or omit contradicting data if they believe that they are right in their overall conclusions. Up to one third reported to have added one or more authors unmerited. Results showed a negative correlation between "good attitudes" and self-reported misconduct and a positive correlation between how frequent respondents thought that misconduct occurs and whether they reported misconduct themselves. This reveals that existing educational and research systems partly fail to foster research integrity.

[Planning the searches for a systematic review].

The planning of a systematic search is of great importance to the results. The systematic searches are planned as part of a protocol, which is developed to minimise bias. The development of the search strategy uses elements from a conceptualisation model. The information sources are selected based on the review question and should include more than one bibliographic database and possibly grey literature. Search terms are defined, and the thesauri of the databases should be used if possible. Any alternative search strategies may be considered. Finally, the searches must be reported in detail. Those points are discussed in this review.

[Questionable journals and how to avoid them].

The purpose of this review is to provide an overview of tools, which health-science researchers can use when assessing, whether a journal is legitimate or questionable. Researchers are regularly contacted by journals encouraging them to submit manuscripts. Many of these contacts are phishing e-mails sent by questionable journals, who offer the publication of manuscripts for a fee but without performing peer review or carrying out other processes normally associated with a scientific journal. Determining whether a journal is questionable or legitimate can be challenging.

PubMed coverage varied across specialties and over time: a large-scale study of included studies in Cochrane reviews.

OBJECTIVE: PubMed is one of the most commonly used search tools in biomedical and life sciences. Existing studies of database coverage generally conclude that searching PubMed may not be sufficient although some find that the contributions from other databases are modest at best. However, generalizability of the studies of the coverage of PubMed is typically restricted. The objective of this study is to analyze the coverage of PubMed across specialties and over time. STUDY DESIGN AND SETTING: We use the more than 50,000 included studies in all Cochrane reviews published from 2012 to 2016 as our population and examine if the studies and resulting publications can be identified in PubMed. RESULTS: The results show that PubMed has a coverage of 70.9, 95% confidence interval (CI) (68.40, 73.30) of all the included publications and 82.8%, 95% CI (80.9, 84.7) of the included studies. There are huge differences in coverage across and within specialties. In addition, coverage varies within groups over time. CONCLUSION: Databases used for searching topics within the groups with highly varying or low coverage should be chosen with care as PubMed may have a relatively low coverage.

The impact of patient, intervention, comparison, outcome (PICO) as a search strategy tool on literature search quality: a systematic review.

OBJECTIVE: This review aimed to determine if the use of the patient, intervention, comparison, outcome (PICO) model as a search strategy tool affects the quality of a literature search. METHODS: A comprehensive literature search was conducted in PubMed, Embase, CINAHL, PsycINFO, Cochrane Library, Web of Science, Library and Information Science Abstracts (LISA), Scopus, and the National Library of Medicine (NLM) catalog up until January 9, 2017. Reference lists were scrutinized, and citation searches were performed on the included studies. The primary outcome was the quality of literature searches and the secondary outcome was time spent on the literature search when the PICO model was used as a search strategy tool, compared to the use of another conceptualizing tool or unguided searching. RESULTS: A total of 2,163 records were identified, and after removal of duplicates and initial screening, 22 full-text articles were assessed. Of these, 19 studies were excluded and 3 studies were included, data were extracted, risk of bias was assessed, and a qualitative analysis was conducted. The included studies compared PICO to the PIC truncation or links to related articles in PubMed, PICOS, and sample, phenomenon of interest, design, evaluation, research type (SPIDER). One study compared PICO to unguided searching. Due to differences in intervention, no quantitative analysis was performed. CONCLUSIONS: Only few studies exist that assess the effect of the PICO model vis-a-vis other available models or even vis-a-vis the use of no model. Before implications for current practice can be drawn, well-designed studies are needed to evaluate the role of the tool used to devise a search strategy.

Research integrity among PhD students within clinical research at the University of Southern Denmark.

INTRODUCTION: Responsible conduct of research is the basis for the credibility of all research. Research misconduct is defined as the fabrication, falsification or plagiarism committed willfully or grossly negligently in the planning, performing or reporting of research. We undertook a survey of knowledge of the attitudes towards and experiences with research misconduct among PhD students in clinical research. METHODS: A questionnaire previously used in Swedish and Norwegian studies was distributed to PhD students (n = 330) affiliated with the Department of Clinical Research or Department of Regional Health Research, University of Southern Denmark. RESULTS: A total of 165 PhD students completed the questionnaire in full or in part, yielding an overall response rate of 50%. 18-34% reported to have heard (within the past year) about researchers who had plagiarised, falsified or fabricated data, or plagiarised publications. None reported this to occur in their own department. Few stated that they had felt under pressure to either falsify data (1%) or present results in a misleading way (3%). However, 22% stated to have felt an unethical pressure (within the past year) regarding the inclusion or order of authors. CONCLUSIONS: Results indicate that, albeit at a low frequency, research misconduct involving PhD students is taking place. Likewise, a high fraction of respondents reported to have been under pressure regarding authorships, which points to questionable research practices in clinical research. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Embase is a central resource for literature search in health science].

PubMed is often first choice for searching health sciences literature. However, even though Embase tends to be overlooked it is an important supplement to PubMed. The present paper provides an overview of the literature dealing with the significance of using Embase for systematic reviews and metaanalyses. Furthermore, the differences in the coverage of the two databases are described and the search process in Embase is presented using examples.

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism.

Universal screening for hepatitis B among pregnant women led to 96% vaccination coverage among newborns of HBsAg positive mothers in Denmark.

In Denmark selective screening programs of pregnant women for hepatitis B missed 30-50% of high-risk groups and in late 2005 a universal screening of pregnant women for HBsAg was implemented. During a 2-year period a prospective enhanced surveillance of the universal screening was performed to examine the effectiveness of universal HBV-screening of pregnant women and HBV-immunizations of their newborn, and to provide a prevalence-estimate for HBV in Denmark. On a opt out basis all women in Denmark attending antenatal care were tested for hepatitis B serology. Vaccination data of the newborns and households of HBsAg positive pregnant women were assembled. Among 140,376 HBsAg tests of pregnant women, 371 (0.26%) were positive. The prevalence among women of Danish origin was 0.012% and 2.74% among foreign born women, highest for women from Southeast Asia (14.5%). Genotype C was the most prevalent (37%) and 13% had a HBVDNA ≥10(8) IU/ml. The prevalence estimate of chronic hepatitis B in Denmark was 0.2-0.3% in the general population. Among children born within the project period, 96% received vaccination at birth compared to 50% of siblings born prior to universal screening. During 3 years of passive follow-up two transmissions (0.5%) have been notified. Among children born of the positive mothers prior to the trial-period 7.3% had been notified. Thus the prevalence of HBV positive mothers has more than doubled in Denmark over the last 40 years, but among women of Danish origin it has decreased 10-fold. By replacing selective screening with universal, identification of newborns in need of HBV-immunization was increased from 50% to almost complete coverage, and also identifies mothers with high viral load for evaluation of pre-term treatment to interrupt in utero transmission.

Intact primary mitochondrial function in myotubes established from women with PCOS.

CONTEXT: Polycystic ovary syndrome (PCOS) affects 5-8% of fertile women and is often accompanied by insulin resistance, leading to increased risk of developing type 2 diabetes. Skeletal muscle from insulin-resistant PCOS subjects display reduced expression of nuclear encoded genes involved in mitochondrial oxidative metabolism. OBJECTIVE: We aimed to investigate whether there was a primary mitochondrial dysfunction or difference in mitochondria content that might contribute to the in vivo detected insulin resistance. DESIGN: The ATP synthesis with and without ATP use and the mitochondrial mass was determined in mitochondria isolated from myotubes established from PCOS subjects and control subjects. PATIENTS: Myotubes were established from eight insulin-resistant PCOS subjects (verified by euglycemic hyperinsulinemic clamp) and eight healthy weight- and age-matched controls. RESULTS: Mitochondrial mass and measurable mitochondrial ATP synthesis, with and without ATP use, were not different between PCOS subjects and control subjects. CONCLUSION: We found no evidence for a primary impaired mitochondrial function or content in myotubes established from PCOS subjects, and our results suggest that reduced expression of oxidative genes in PCOS subjects is an adaptive trait.

Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark.

The prevalence of hepatitis C virus (HCV) genotype 4 has increased throughout Europe. This is an epidemiological study of patients infected chronically with HCV genotype 4 in Denmark. The HCV strains analyzed originated from patient samples collected between 1999 and 2007 as part of the national Danish hepatitis B and C network, DANHEP. Sequence analyses were based on the envelope 1 region of HCV. Results from a total of 72 patients indicated a high degree of genetic heterogeneity. Fifty-six patients (78%) were infected with one of the three dominating subtypes: 4d, 4a, or 4r. The remaining 16 patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes. No single transmission event could be confirmed, but the pairwise nucleotide identity within the patients of Danish origin was relatively high (∼95%), suggesting a recent introduction into Denmark. (2) The 21 patients infected with subtype 4a all came from Northern Africa, Egypt, Pakistan, or the Middle East. (3) Patients from Southern Africa dominated among patients infected with subtype 4r (10 of 12 patients). This study demonstrates that HCV genotype 4d has been introduced in and spread among Danish intravenous drug users. The remaining subtypes show restricted distribution, infecting almost exclusively patients from geographical areas with a relatively high prevalence of HCV genotype 4 infections.

Postmortem detection of hepatitis B, C, and human immunodeficiency virus genomes in blood samples from drug-related deaths in Denmark*.

Blood-borne viral infections are widespread among injecting drug users; however, it is difficult to include these patients in serological surveys. Therefore, we developed a national surveillance program based on postmortem testing of persons whose deaths were drug related. Blood collected at autopsy was tested for anti-HBc, anti-HBs, anti-hepatitis C virus (HCV), or anti-human immunodeficiency virus (HIV) antibodies using commercial kits. Subsets of seropositive samples were screened for viral genomes using sensitive in-house and commercial polymerase chain reaction (PCR) assays. Hepatitis B virus (HBV) DNA was detected in 20% (3/15) of anti-HBc-positive/anti-HBs-negative samples, HCV RNA was found in 64% (16/25) of anti-HCV-positive samples, and HIV RNA was detected in 40% (6/15) of anti-HIV-positive samples. The postmortem and antemortem prevalences of HBV DNA and HCV RNA were similar. Postmortem HIV RNA testing was less sensitive than antemortem testing. Thus, postmortem PCR analysis for HBV and HBC infection is feasible and relevant for demonstrating ongoing infections at death or for transmission analysis during outbreaks.