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{"title"=>"Healthy Volunteers Can Be Phenotyped Using Cutaneous Sensitization Pain Models", "type"=>"journal", "authors"=>[{"first_name"=>"Mads U.", "last_name"=>"Werner", "scopus_author_id"=>"7402991866"}, {"first_name"=>"Karin L.", "last_name"=>"Petersen", "scopus_author_id"=>"7202488405"}, {"first_name"=>"Michael C.", "last_name"=>"Rowbotham", "scopus_author_id"=>"7005612625"}, {"first_name"=>"Jørgen B.", "last_name"=>"Dahl", "scopus_author_id"=>"7202282549"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"368882631", "pmid"=>"23671631", "doi"=>"10.1371/journal.pone.0062733", "sgr"=>"84877329693", "scopus"=>"2-s2.0-84877329693"}, "id"=>"c943a573-d1d6-3f7e-90e6-c0b7f36dcb50", "abstract"=>"BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models.\\n\\nMETHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models.\\n\\nRESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st) quartile [<25%]) and 'large area' (4(th) quartile [>75%]) responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models.\\n\\nCONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.", "link"=>"http://www.mendeley.com/research/healthy-volunteers-phenotyped-using-cutaneous-sensitization-pain-models", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Nursing and Health Professions"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>15, "Agricultural and Biological Sciences"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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• http://doi.org/10.1097/j.pain.0000000000000460
• http://doi.org/10.1111/anae.12717
• http://doi.org/10.1371/journal.pone.0099507
• http://doi.org/10.1371/journal.pone.0201642
• http://doi.org/10.1097/SPC.0000000000000045
• http://doi.org/10.1097/MD.0000000000005336
• http://doi.org/10.1186/s12871-016-0193-2
• http://doi.org/10.2196/resprot.5680
• http://doi.org/10.1371/journal.pone.0134441
• http://doi.org/10.1186/s13063-015-1021-6
• http://doi.org/10.1097/PSY.0000000000000638
• http://doi.org/10.1097/ALN.0000000000001000
• http://doi.org/10.1111/aas.12492
• http://doi.org/10.1371/journal.pone.0155284
• http://doi.org/10.1097/PR9.0000000000000697
• http://doi.org/10.1371/journal.pone.0114840
• http://doi.org/10.1016/j.jneumeth.2015.08.018
• http://doi.org/10.1016/j.joen.2015.12.010

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• 4640219
• 4050052
• 4304709
• 4549112
• 3555550

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1058347"], "description"=>"<p>Measure 1 is from Day 1 (or placebo day if no day order was specified) and Measure 2 is the first measurement from the next day where measures were repeated. Measure 1 is the first measurement from Day 1 (or placebo day if no day order was specified) and Measure 2 is the first measurement from the next day where measures were repeated.</p>§<p> = unpublished study.</p>*<p>Measure 1 is from the placebo day, measure 2 is from treatment day. Day order was randomized, so measurement 1 may not have come before measurement 2.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "hyperalgesia", "paired", "t-tests", "coefficient", "intra-class"], "article_id"=>701101, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t002", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Areas_of_secondary_hyperalgesia_for_measurement_1_and_2_mean_SD_P_values_for_paired_t_tests_between_measurements_Spearman_s_rank_correlation_coefficient_rho_coefficient_of_variation_CV_mean_SD_intra_class_correlation_coefficient_ICC_95_CI_for_2_measureme/701101", "title"=>"Areas of secondary hyperalgesia for measurement 1 and 2 (mean +/− SD), <i>P</i>-values for paired t-tests between measurements, Spearman’s rank correlation coefficient (rho), coefficient of variation (CV, mean +/− SD), intra-class correlation coefficient (ICC, 95% CI) for 2 measurements and for data with more than 2 measurements.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:21"}
• {"files"=>["https://ndownloader.figshare.com/files/1058346"], "description"=>"<p>Data indicate the distribution of observations split into quartiles (<25%, 25–50%, 51–75%, >75%) giving a 4×4 contingency table (total number of observations for each quartile are indicated in lower row [Measurement 2] and right-hand column [Measurement 1]). The numbers in the lower right-hand corner, in each panel, are the total number of observations. The numbers in bold indicate completely agreement between observations: Measurement 1 and Measurement 2. Perfect agreement for the heat/capsaicin (<b>A</b>), brief thermal stimulation (<b>B</b>) and the burn injury (<b>C</b>) models were seen in 51%, 54% and 49% of the observations, respectively. The weighted Cohen’s kappa statistics were 0.66 (95% CI: 0.57–0.74) for the heat/capsaicin model, 0.74 (0.65–0.82) for the brief thermal stimulation and 0.74 (0.65–0.82) for the burn injury model.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "hyperalgesia", "areas", "thermal", "sensitization"], "article_id"=>701100, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Agreement_of_secondary_hyperalgesia_areas_in_the_heat_capsaicin_left_part_of_table_brief_thermal_sensitization_BTS_middle_part_of_table_and_the_burn_injury_right_part_of_model_model_at_Measurement_1_rows_and_Measurement_2_columns_/701100", "title"=>"Agreement of secondary hyperalgesia areas in the heat/capsaicin (<b>left part of table</b>), brief thermal sensitization (BTS [<b>middle part of table</b>]) and the burn injury (<b>right part of model</b>) model, at <b>Measurement</b><b>1</b> (rows) and <b>Measurement 2</b> (columns).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:20"}
• {"files"=>["https://ndownloader.figshare.com/files/1058343"], "description"=>"<p>The kappa statistics were significantly different from zero (what would be expected from chance alone) for 1 comparison.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "weighted", "kappa", "statistic", "pooled", "showed"], "article_id"=>701097, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_weighted_Cohen_8217_s_kappa_statistic_for_the_pooled_analyses_showed_moderate_agreement_for_measurement_1_0_44_and_substantial_agreement_for_measurement_2_0_62_/701097", "title"=>"The weighted Cohen’s kappa statistic for the pooled analyses showed moderate agreement for measurement 1 (0.44) and substantial agreement for measurement 2 (0.62).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:17"}
• {"files"=>["https://ndownloader.figshare.com/files/1058339"], "description"=>"<p>The Spearman’s rank correlation coefficient (rho) and line of identity are indicated.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "scatterplots", "hyperalgesia", "pooled", "studies", "thermal", "stimulation"], "article_id"=>701095, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Basic_scatterplots_of_area_of_secondary_hyperalgesia_cm_2_first_vs_second_measurement_in_the_heat_capsacin_model_panel_A_pooled_data_from_eight_studies_n_8202_8202_189_the_brief_thermal_stimulation_model_panel_B_pooled_data_from_four_studies_n_8202_8202_/701095", "title"=>"Basic scatterplots of area of secondary hyperalgesia (cm²), first vs. second measurement, in the heat/capsacin model (panel A, pooled data from eight studies [n = 189]), the brief thermal stimulation model (panel B, pooled data from four studies [n = 120]) and the burn injury model (panel C, data from one study [n = 100]).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-09 00:18:15"}
• {"files"=>["https://ndownloader.figshare.com/files/1058341"], "description"=>"<p>The solid vertical line (mean of difference) indicate bias between the methods and the dashed vertical lines indicate the upper and lower 95% confidence interval (CI [±1.96×SD = limits of agreement]).</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "illustrating", "plotted", "hyperalgesia", "areas", "induced", "pooled", "studies", "thermal", "stimulation"], "article_id"=>701096, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bland_Altman_plots_illustrating_the_mean_of_measurement_1_and_measurement_2_x_axis_plotted_against_the_difference_between_measurement_1_and_measurement_2_y_axis_for_secondary_hyperalgesia_areas_induced_by_the_heat_capsacin_model_panel_A_pooled_data_from_/701096", "title"=>"Bland-Altman plots illustrating the mean of measurement 1 and measurement 2 (x-axis) plotted against the difference between measurement 1 and measurement 2 (y-axis) for secondary hyperalgesia areas induced by the heat/capsacin model (panel A, pooled data from eight studies [n = 189]), the brief thermal stimulation model (panel B, pooled data from four studies [n = 120]) and the burn injury model (panel C, data from one study [n = 100]).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-09 00:18:16"}
• {"files"=>["https://ndownloader.figshare.com/files/1058348"], "description"=>"<p>BTS = brief thermal sensitization, CB = complete block design, DB = double-blind, PC = placebo-controlled, P = parallel, R = randomized, X = cross-over.</p>▵<p>data from intention-to-treat population,</p>§<p>4-period, 4-treatment, and 4-sequence study.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "unpublished", "studies", "induced", "hyperalgesia"], "article_id"=>701102, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Published_2_4_8211_8_11_8211_13_and_unpublished_volunteer_studies_on_induced_secondary_hyperalgesia_areas_/701102", "title"=>"Published (2,4–8,11–13) and unpublished volunteer studies on induced secondary hyperalgesia areas.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:22"}
• {"files"=>["https://ndownloader.figshare.com/files/1058345"], "description"=>"<p>The distribution of the lowest (<25%) and highest (>75%) quartiles (rows [split into <b>Measurement 1</b> and <b>Measurement 2</b> observations]) divided in the 2 higher (≥50%) and the 2 lower (<50%) quartiles (columns), across the 3 different models. As an example: in the heat/capsaicin model the number of observations <b>Measurement 1</b> with areas in the highest quartile (>75% [n = 47]) corresponded at <b>Measurement 2</b> to 41 observations at or above the median (≥50%) and 6 observations below median value (<50%).</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "illustrates", "probability", "moving", "quartile", "vice", "versa", "thermal", "sensitization"], "article_id"=>701099, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t004", "stats"=>{"downloads"=>4, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_table_illustrates_the_probability_of_measurement_2_moving_more_than_one_quartile_away_from_measurement_1_and_vice_versa_for_the_heat_capsaicin_brief_thermal_sensitization_BTS_and_burn_injury_models_/701099", "title"=>"The table illustrates the probability of measurement 2 moving more than one quartile away from measurement 1 and vice versa for the heat/capsaicin, brief thermal sensitization (BTS) and burn injury models.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:19"}
• {"files"=>["https://ndownloader.figshare.com/files/1058344"], "description"=>"<p>The agreement in classification to small-, mid- or large areas across induction methods was 59% for measurement 1 and 69% for measurement 2.</p>", "links"=>[], "tags"=>["anesthesiology", "Pain management", "Clinical research design", "clinical trials", "Preclinical models", "Drugs and devices", "Clinical pharmacology", "Drug research and development", "Pharmacodynamics", "neurology", "Neuropharmacology", "categorizations", "thermal", "sensitization", "methods"], "article_id"=>701098, "categories"=>["Medicine"], "users"=>["Mads U. Werner", "Karin L. Petersen", "Michael C. Rowbotham", "Jørgen B. Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0062733.t005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparing_the_area_categorizations_small_mid_large_between_the_heat_capsaicin_and_the_brief_thermal_sensitization_methods_when_measured_on_the_same_subject_at_the_same_time_/701098", "title"=>"Comparing the area categorizations (small, mid, large) between the heat/capsaicin and the brief thermal sensitization methods when measured on the same subject at the same time.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-09 00:18:18"}

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• {"unique-ip"=>"11", "full-text"=>"2", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
• {"unique-ip"=>"10", "full-text"=>"2", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Engineering and technology", "average_usage"=>[254, 440, 558, 675, 785, 883, 972, 1061, 1154, 1248, 1336, 1414, 1489]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}]}

F1000Prime