Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study
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{"title"=>"Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study", "type"=>"journal", "authors"=>[{"first_name"=>"Søeren Søgaard", "last_name"=>"Lund", "scopus_author_id"=>"18537038500"}, {"first_name"=>"Lise", "last_name"=>"Tarnow", "scopus_author_id"=>"7006204047"}, {"first_name"=>"Anne Sofie", "last_name"=>"Astrup", "scopus_author_id"=>"8987335700"}, {"first_name"=>"Peter", "last_name"=>"Hovind", "scopus_author_id"=>"6701384355"}, {"first_name"=>"Peter Karl", "last_name"=>"Jacobsen", "scopus_author_id"=>"7101913318"}, {"first_name"=>"Amra Ciric", "last_name"=>"Alibegovic", "scopus_author_id"=>"22984490100"}, {"first_name"=>"Ida", "last_name"=>"Parving", "scopus_author_id"=>"25622672400"}, {"first_name"=>"Lotte", "last_name"=>"Pietraszek", "scopus_author_id"=>"15766466200"}, {"first_name"=>"Merete", "last_name"=>"Frandsen", "scopus_author_id"=>"6603145798"}, {"first_name"=>"Peter", "last_name"=>"Rossing", "scopus_author_id"=>"7005170096"}, {"first_name"=>"Hans Henrik", "last_name"=>"Parving", "scopus_author_id"=>"35355625800"}, {"first_name"=>"Allan Arthur", "last_name"=>"Vaag", "scopus_author_id"=>"7006759757"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"352553383", "sgr"=>"54449097429", "issn"=>"19326203", "pmid"=>"18852875", "scopus"=>"2-s2.0-54449097429", "doi"=>"10.1371/journal.pone.0003363", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"035e3e4a-cb7c-364b-87aa-ba18eb9ddee9", "abstract"=>"BACKGROUND Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control. METHODOLOGY/PRINCIPAL FINDINGS One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated. CONCLUSIONS/SIGNIFICANCE In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted. TRIAL REGISTRATION ClinicalTrials.gov NCT00118937.", "link"=>"http://www.mendeley.com/research/effect-adjunct-metformin-treatment-patients-type1-diabetes-persistent-inadequate-glycaemic-control-r", "reader_count"=>41, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>8, "Student > Master"=>6, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>8, "Student > Master"=>6, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Nursing and Health Professions"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Brazil"=>1, "Germany"=>1}, "group_count"=>3}

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  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"2"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/919488"], "description"=>"<p>Follow-up HbA<sub>1c</sub> data were obtained from planned study visits as well as from intermediate non-study outpatient clinic visits during the intervention period. All HbA<sub>1c</sub> measurements obtained at least one month post-randomization were evaluated. Data are shown for the subgroup of 72 patients having available follow-up HbA<sub>1c</sub> measurements from one to four months post-randomization. Data at baseline (0 month) and follow-up are raw absolute values given as mean (standard deviation) or median (range). Data for ΔMetformin and ΔPlacebo represent the mean (95% confidence interval) estimated changes from baseline as predicted by the statistical model.</p>a<p>The first available follow-up HbA<sub>1c</sub> measurement (in the group of 72 patients presented here, all the “first available” HbA<sub>1c</sub> data were obtained at intermediate outpatient clinic visits). Given change from baseline estimates (i.e., ΔMetformin, ΔPlacebo and ΔMetformin versus ΔPlacebo) represent data without adjustment for time. Additional adjustment for time did not change conclusions substantially (data not shown).</p>b<p>Time from randomization until the first available HbA<sub>1c</sub> measurement.</p>c<p>The last available follow-up HbA<sub>1c</sub> measurement (obtained from study visits or intermediate outpatient clinic visits, that is, equal to EOT levels including last observation carried forward).</p>d<p>Total daily insulin dose represents the last reported dose at the intermediate telephone consultations within the first three months post-randomization. The total insulin doses corrected for body weight (i.e. Units/kg) are not shown since data for body weight at the date of reporting insulin doses (i.e. at the intermediate telephone consultations) were not available.</p><p>Abbreviations:</p><p>EOT: End of treatment.</p><p>HbA<sub>1c</sub>: HaemoglobinA<sub>1c</sub>.</p>", "links"=>[], "tags"=>["metformin", "placebo", "follow-up", "levels", "insulin", "doses", "72", "patients", "type-1"], "article_id"=>589922, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t006", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_metformin_versus_placebo_on_follow_up_intermediate_and_study_visit_levels_of_HbA_1c_and_insulin_doses_in_72_patients_with_type_1_diabetes_during_a_one_year_period_/589922", "title"=>"Effect of metformin versus placebo on follow-up (intermediate and study visit) levels of HbA<sub>1c</sub> and insulin doses in 72 patients with type-1 diabetes during a one year period.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:45:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/454067", "https://ndownloader.figshare.com/files/454079", "https://ndownloader.figshare.com/files/454086", "https://ndownloader.figshare.com/files/454095"], "description"=>"<div><h3>Background</h3><p>Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.</p><h3>Methodology/Principal Findings</h3><p>One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA<sub>1c</sub> (HbA<sub>1c</sub>) ≥8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA<sub>1c</sub> after one year of treatment. At enrolment, mean (standard deviation) HbA<sub>1c</sub> was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA<sub>1c</sub>, 0.13% (−0.19; 0.44), p = 0.422; Total daily insulin dose, −5.7 U/day (−8.6; −2.9), p<0.001; body weight, −1.74 kg (−3.32; −0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.</p><h3>Conclusions/Significance</h3><p>In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov <a href=\"http://clinicaltrials.gov/ct2/show/NCT00118937\">NCT00118937</a></p></div>", "links"=>[], "tags"=>["adjunct", "metformin", "patients", "type-1", "persistent", "inadequate", "glycaemic", "randomized"], "article_id"=>149445, "categories"=>["Chemistry", "Cancer", "Biological Sciences"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003363.s001", "https://dx.doi.org/10.1371/journal.pone.0003363.s002", "https://dx.doi.org/10.1371/journal.pone.0003363.s003", "https://dx.doi.org/10.1371/journal.pone.0003363.s004"], "stats"=>{"downloads"=>16, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_Adjunct_Metformin_Treatment_in_Patients_with_Type_1_Diabetes_and_Persistent_Inadequate_Glycaemic_Control_A_Randomized_Study/149445", "title"=>"Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-10-09 02:37:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/919389"], "description"=>"a<p>p = 0.151 and p = 0.287 between metformin versus placebo for the total number of events and total number of patients with events, respectively.</p>", "links"=>[], "tags"=>["adverse", "events", "100", "patients", "type-1", "allocated", "metformin", "placebo"], "article_id"=>589831, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Non_hypoglycaemia_related_serious_adverse_events_in_100_patients_with_type_1_diabetes_allocated_treatment_with_metformin_or_placebo_for_one_year_/589831", "title"=>"Non-hypoglycaemia-related serious adverse events in 100 patients with type-1 diabetes allocated treatment with metformin or placebo for one year.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:43:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/919297"], "description"=>"<p>Data at baseline (0 month) and EOT (12 months) are raw absolute values given as mean (standard deviation). Data for ΔMetformin and ΔPlacebo represent the mean (95% confidence interval) estimated changes from baseline as predicted by the statistical model. The numbers of patients represent the maximum number of patients included in each analysis. Data are presented as intention-to-treat including last observation carried forward.</p><p>Abbreviations:</p><p>EOT: End of treatment.</p>", "links"=>[], "tags"=>["variables", "100", "patients", "type-1", "metformin"], "article_id"=>589738, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Metabolism_related_variables_in_100_patients_with_type_1_diabetes_before_and_after_one_year_of_treatment_with_metformin_or_placebo_/589738", "title"=>"Metabolism-related variables in 100 patients with type-1 diabetes before and after one year of treatment with metformin or placebo.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:42:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/919082"], "description"=>"<p>Patient flow scheme.</p>", "links"=>[], "tags"=>["diabetes and endocrinology", "diabetes and endocrinology/obesity", "diabetes and endocrinology/type 1 diabetes"], "article_id"=>589525, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.g001", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_flow_scheme_/589525", "title"=>"Patient flow scheme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-10-09 02:38:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/919338"], "description"=>"<p>Data represent number of patients [%], mean (standard deviation) or median (range).</p>a<p>Information about daily alcohol intake was missing in 23 and 24 patients allocated metformin and placebo, respectively. The percentage of patients refers to those for whom data were available.</p>b<p>Not compared statistically due to equal proportions of patients or too few patients in treatment groups.</p>c<p>Previous ischaemic heart disease, stroke, transient ischaemic attack or peripheral arterial disease.</p>d<p>Normo-, micro- and macro-albuminuria: 24-hour urinary albumin-excretion≤29 mg, 30–299 mg and ≥300 mg, respectively, in two out of three consecutive samples. One patient, in the metformin group, had a kidney transplant five years prior to enrolment due to polycystic kidney disease. The patient presented with normal levels of creatinine and microalbuminura. Due to having prior kidney disease, the patient is included in the macroalbuminuria group.</p>e<p>Symptomatic peripheral or autonomic neuropathy or clinical signs thereof.</p>f<p>One patient, in the metformin group, received continuous subcutaneous insulin-infusions. The patient is included in the group with four daily injections.</p>g<p>During the run-in period, in the metformin group, one patient changed from thiazid to loop diuretics, one patient initiated statin treatment and two patients initiated dietary (n = 1) or potassium (n = 1) supplementations, respectively, whereas, in the placebo group, one patient was temporarily treated with non-steroid anti-inflammatory drugs. Thus, at baseline (0 months), in the metformin and placebo groups, respectively, a total of 24 (49%) and 14 (27%) patients received ongoing statin treatment (<b>p = 0.039</b> between treatments); five (10%) and one (2%) patients received dietary supplementations (p = 0.108 between treatments) and 15 (31%) and 12 (24%) patients received potassium supplementations (p = 0.502 between treatments). In contrast, for the whole group of thiazid or loop diuretics as well as for non-steroid anti-inflammatory drugs, despite changes herein during the run-in period, a similar number of patients received such treatments at baseline compared to enrolment. Otherwise, patients did not start and/or stop other non-study medications as listed during the run-in period.</p>h<p>Over-the-counter vitamin pills with unspecified cobalamin and folic acid content.</p><p>Abbreviation: ACE: Angiotensin converting enzyme.</p>", "links"=>[], "tags"=>["characteristics", "enrolment", "100", "patients", "type-1"], "article_id"=>589781, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Subject_characteristics_at_enrolment_8722_1_month_for_100_patients_with_type_1_diabetes_/589781", "title"=>"Subject characteristics at enrolment (−1 month) for 100 patients with type-1 diabetes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:43:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/919436"], "description"=>"<p>Data are included for at total of 99 patients (one patient, in the placebo group, out of a total of 100 randomized patients, had missing data on hypoglycaemia).</p>a<p>Not compared statistically due to equal proportions of patients in treatment groups.</p>b<p><b>p<0.05</b> compared to enrolment (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003363#pone-0003363-t002\" target=\"_blank\">Table 2</a>).</p>c<p>Levels of circulating glucose were captured periodically by patients estimating average levels of blood/plasma glucose during hypoglycaemic events. The calibration (plasma or whole blood glucose) of hand held devices was not registrated, nor was devices calibrated at enrolment. Hence, data represent non-standardized plasma and/or blood glucose measurements. Not all patients had available glucose measurements during events. The total number of patients with available measurement was: Minor hypoglycaemia: metformin: n = 47; placebo: n = 49; Major hypoglycaemia: metformin: n = 11; placebo: n = 8.</p>d<p><b>p = 0.011</b> and p = 0.209 compared to enrolment for metformin and placebo, respectively (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003363#pone-0003363-t002\" target=\"_blank\">Table 2</a>).</p>e<p>p = 0.049888455.</p>", "links"=>[], "tags"=>["hypoglycaemic", "episodes", "patients", "type-1", "metformin"], "article_id"=>589878, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reported_hypoglycaemic_episodes_in_patients_with_type_1_diabetes_during_one_year_of_treatment_with_metformin_or_placebo_/589878", "title"=>"Reported hypoglycaemic episodes in patients with type-1 diabetes during one year of treatment with metformin or placebo.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/919246"], "description"=>"a<p>See reference <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003363#pone.0003363-World1\" target=\"_blank\">[33]</a>.</p>b<p>At enrolment, the level of C-peptide was determined in non-fasting samples. In the case of non-fasting C-peptide levels≥300 pmol/l, a fasting sample and/or a glucagon-stimulated C-peptide measure was obtained to evaluate beta cell function. According to local guidelines, suggested cut-off levels for C-peptide indicative of type-1 diabetes were: Fasting<300 pmol/l; after 1 mg i.v. glucagon: ≤600 pmol/l.</p><p>Abbreviations:</p><p>HbA<sub>1c</sub>: HaemeglobinA<sub>1c</sub></p><p>AST: Aspartate aminotransferase</p>", "links"=>[], "tags"=>["exclusion"], "article_id"=>589695, "categories"=>["Chemistry", "Infectious Diseases", "Computational Biology"], "users"=>["Søren Søgaard Lund", "Lise Tarnow", "Anne Sofie Astrup", "Peter Hovind", "Peter Karl Jacobsen", "Amra Ciric Alibegovic", "Ida Parving", "Lotte Pietraszek", "Merete Frandsen", "Peter Rossing", "Hans-Henrik Parving", "Allan Arthur Vaag"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003363.t001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inclusion_exclusion_and_withdrawal_criteria_/589695", "title"=>"Inclusion, exclusion and withdrawal criteria", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-10-09 02:41:35"}

PMC Usage Stats | Further Information

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Relative Metric

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