Unmet need in major depressive disorder and acute suicidal ideation/behavior: findings from a longitudinal electronic health record data analysis

Using a national electronic health records (EHR) database, the current study describes treatments, depression severity, and health care resource utilisation (HRU) among patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (MDSI) prior to, during, and following a suicide-related event in the United States. This retrospective matched cohort study used data collected from the Optum electronic health record de-identified database for patients with diagnosis codes for MDD and acute suicidal ideation or behavior, and a propensity-score matched cohort of patients without MDD or a suicide-related event. The study period was 31/10/2015-30/9/2019. MDD-related treatments and 9-item Patient Health Questionnaire (PHQ-9) scores, when available, were assessed at the first health care encounter for a suicide-related event (index period), 12 months before (pre-period), and 6 months after (post-period). All-cause and MDD-related HRU were assessed during the post-period. The mean (SD) age of patients with MDSI was 39 (16) years; 55.0% were female. Index events occurred as follows: inpatient stay, 38.9%; observation unit stay, 4.6%; emergency department (ED) visit, 46.5%; and outpatient visit, 10.1%. Antidepressants and psychotherapy were the most common pharmacologic and nonpharmacologic treatments, respectively, prescribed during the pre- (31.3%, 9.5%, respectively) and index (41.2%, 18.7%, respectively) periods. Post-period data (n = 40,261) revealed only 43.4% received an antidepressant and 20.5% had psychotherapy after the suicide-related event. Few patients had PHQ-9 scores recorded during the pre- (4.4%), index (1.3%), and post- (7.6%) periods. During the post-period, 11.8%, 5.0%, and 33.1% of patients had ≥1 all-cause inpatient stay, observation unit stay, and emergency department visit, respectively; 61.0% had ≥1 all-cause, and 33.4% ≥1 MDD-related, outpatient visit. Most patients with MDSI and an inpatient encounter or ED visit were discharged to home or self-care (65.4%). Odds of an all-cause hospital encounter during the post-period were higher for patients with, versus without MDSI (by 30.1, 33.5, and 33.9 times for inpatient stay, ED visit and observation unit stay, respectively). This analysis highlights an opportunity to improve outcomes for this vulnerable population. More complete data on patient outcomes is needed to inform strategies designed to optimize screening and treatment.</p

Quantitative Phosphoproteomics Studies Using Stable Isotope Dimethyl Labeling Coupled with IMAC-HILIC-nanoLC−MS/MS for Estrogen-Induced Transcriptional Regulation

17β-Estradiol (E2) regulates transcriptional activity partly by inducing protein-kinase cascades, leading to the phosphorylation of estrogen receptors (ERs) and other functional proteins. Many of these phosphorylation events are also modulated by growth factors. To gain an insight into E2-modulated protein phosphorylation, we applied quantitative phosphoproteomics to investigate global changes in protein phosphorylation induced by E2 in MCF-7 cells. Proteomic analyses using stable isotope dimethyl labeling coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography (IMAC-HILIC) fractionation and nanoLC−MS/MS identified and quantified 2857 unique phosphorylation sites in 1338 phosphoproteins from 1 mg of total cellular protein. In addition to S118 of ERα, a 30-min E2 treatment significantly altered the status of 403 phosphorylation sites, including 112 novel sites. Interestingly, the substrate motifs for ERK1/2 were largely enriched in both the up-regulated and down-regulated phosphorylation sites. An increase in the phosphorylation on either the T202 or Y204 sites of ERK1 was observed after E2 treatment, while dual phosphorylation on both sites were not detected, implying that a feedback loop to deactivate MAPK signaling was achieved during a 30-min E2 treatment. In contrast, the PKA and CKII substrate motifs were majorly enriched among the up-regulated phosphorylation sites. Western blot analysis confirmed that E2 increased the phosphorylation level of S226 within a CKII motif of HSP90β by a factor of 2- to 3-fold without changing the total protein expression level. E2 also up-regulated phosphorylations of S255 in HSP90β and S353 within a CKII motif of HSP90α. These results indicated that E2 may modulate gene transcription by affecting the stability, function, and activity of many regulators through a HSP90 phosphorylation-mediated chaperoning process. This study, using a quantitative, multidimensional separation phosphoproteomic approach that required a relatively low amount of cells, provides new insights into the diversity, variability, and dynamic nature of the protein phosphorylation/dephosphorylation elicited by E2

Additional file 4: of Hematoma block or procedural sedation and analgesia, which is the most effective method of anesthesia in reduction of displaced distal radius fracture?

Figure S1. Funnel plot of meta-analysis of different pain during reduction procedure. (PNG 91 kb

Quantitative Phosphoproteomics Studies Using Stable Isotope Dimethyl Labeling Coupled with IMAC-HILIC-nanoLC−MS/MS for Estrogen-Induced Transcriptional Regulation

17β-Estradiol (E2) regulates transcriptional activity partly by inducing protein-kinase cascades, leading to the phosphorylation of estrogen receptors (ERs) and other functional proteins. Many of these phosphorylation events are also modulated by growth factors. To gain an insight into E2-modulated protein phosphorylation, we applied quantitative phosphoproteomics to investigate global changes in protein phosphorylation induced by E2 in MCF-7 cells. Proteomic analyses using stable isotope dimethyl labeling coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography (IMAC-HILIC) fractionation and nanoLC−MS/MS identified and quantified 2857 unique phosphorylation sites in 1338 phosphoproteins from 1 mg of total cellular protein. In addition to S118 of ERα, a 30-min E2 treatment significantly altered the status of 403 phosphorylation sites, including 112 novel sites. Interestingly, the substrate motifs for ERK1/2 were largely enriched in both the up-regulated and down-regulated phosphorylation sites. An increase in the phosphorylation on either the T202 or Y204 sites of ERK1 was observed after E2 treatment, while dual phosphorylation on both sites were not detected, implying that a feedback loop to deactivate MAPK signaling was achieved during a 30-min E2 treatment. In contrast, the PKA and CKII substrate motifs were majorly enriched among the up-regulated phosphorylation sites. Western blot analysis confirmed that E2 increased the phosphorylation level of S226 within a CKII motif of HSP90β by a factor of 2- to 3-fold without changing the total protein expression level. E2 also up-regulated phosphorylations of S255 in HSP90β and S353 within a CKII motif of HSP90α. These results indicated that E2 may modulate gene transcription by affecting the stability, function, and activity of many regulators through a HSP90 phosphorylation-mediated chaperoning process. This study, using a quantitative, multidimensional separation phosphoproteomic approach that required a relatively low amount of cells, provides new insights into the diversity, variability, and dynamic nature of the protein phosphorylation/dephosphorylation elicited by E2

Quantitative Phosphoproteomics Studies Using Stable Isotope Dimethyl Labeling Coupled with IMAC-HILIC-nanoLC−MS/MS for Estrogen-Induced Transcriptional Regulation

17β-Estradiol (E2) regulates transcriptional activity partly by inducing protein-kinase cascades, leading to the phosphorylation of estrogen receptors (ERs) and other functional proteins. Many of these phosphorylation events are also modulated by growth factors. To gain an insight into E2-modulated protein phosphorylation, we applied quantitative phosphoproteomics to investigate global changes in protein phosphorylation induced by E2 in MCF-7 cells. Proteomic analyses using stable isotope dimethyl labeling coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography (IMAC-HILIC) fractionation and nanoLC−MS/MS identified and quantified 2857 unique phosphorylation sites in 1338 phosphoproteins from 1 mg of total cellular protein. In addition to S118 of ERα, a 30-min E2 treatment significantly altered the status of 403 phosphorylation sites, including 112 novel sites. Interestingly, the substrate motifs for ERK1/2 were largely enriched in both the up-regulated and down-regulated phosphorylation sites. An increase in the phosphorylation on either the T202 or Y204 sites of ERK1 was observed after E2 treatment, while dual phosphorylation on both sites were not detected, implying that a feedback loop to deactivate MAPK signaling was achieved during a 30-min E2 treatment. In contrast, the PKA and CKII substrate motifs were majorly enriched among the up-regulated phosphorylation sites. Western blot analysis confirmed that E2 increased the phosphorylation level of S226 within a CKII motif of HSP90β by a factor of 2- to 3-fold without changing the total protein expression level. E2 also up-regulated phosphorylations of S255 in HSP90β and S353 within a CKII motif of HSP90α. These results indicated that E2 may modulate gene transcription by affecting the stability, function, and activity of many regulators through a HSP90 phosphorylation-mediated chaperoning process. This study, using a quantitative, multidimensional separation phosphoproteomic approach that required a relatively low amount of cells, provides new insights into the diversity, variability, and dynamic nature of the protein phosphorylation/dephosphorylation elicited by E2

Quantitative Phosphoproteomics Studies Using Stable Isotope Dimethyl Labeling Coupled with IMAC-HILIC-nanoLC−MS/MS for Estrogen-Induced Transcriptional Regulation

17β-Estradiol (E2) regulates transcriptional activity partly by inducing protein-kinase cascades, leading to the phosphorylation of estrogen receptors (ERs) and other functional proteins. Many of these phosphorylation events are also modulated by growth factors. To gain an insight into E2-modulated protein phosphorylation, we applied quantitative phosphoproteomics to investigate global changes in protein phosphorylation induced by E2 in MCF-7 cells. Proteomic analyses using stable isotope dimethyl labeling coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography (IMAC-HILIC) fractionation and nanoLC−MS/MS identified and quantified 2857 unique phosphorylation sites in 1338 phosphoproteins from 1 mg of total cellular protein. In addition to S118 of ERα, a 30-min E2 treatment significantly altered the status of 403 phosphorylation sites, including 112 novel sites. Interestingly, the substrate motifs for ERK1/2 were largely enriched in both the up-regulated and down-regulated phosphorylation sites. An increase in the phosphorylation on either the T202 or Y204 sites of ERK1 was observed after E2 treatment, while dual phosphorylation on both sites were not detected, implying that a feedback loop to deactivate MAPK signaling was achieved during a 30-min E2 treatment. In contrast, the PKA and CKII substrate motifs were majorly enriched among the up-regulated phosphorylation sites. Western blot analysis confirmed that E2 increased the phosphorylation level of S226 within a CKII motif of HSP90β by a factor of 2- to 3-fold without changing the total protein expression level. E2 also up-regulated phosphorylations of S255 in HSP90β and S353 within a CKII motif of HSP90α. These results indicated that E2 may modulate gene transcription by affecting the stability, function, and activity of many regulators through a HSP90 phosphorylation-mediated chaperoning process. This study, using a quantitative, multidimensional separation phosphoproteomic approach that required a relatively low amount of cells, provides new insights into the diversity, variability, and dynamic nature of the protein phosphorylation/dephosphorylation elicited by E2

Additional file 1: of Hematoma block or procedural sedation and analgesia, which is the most effective method of anesthesia in reduction of displaced distal radius fracture?

Table S1. PRISMA checklist of current meta-analysis. (DOCX 27 kb

Additional file 2: of Hematoma block or procedural sedation and analgesia, which is the most effective method of anesthesia in reduction of displaced distal radius fracture?

Table S2. Excluded studies and reason. (DOCX 17 kb

Additional file 3: of Hematoma block or procedural sedation and analgesia, which is the most effective method of anesthesia in reduction of displaced distal radius fracture?

Table S3. Jadad scores of recruited studies. (DOCX 16 kb

Additional file 5: of Hematoma block or procedural sedation and analgesia, which is the most effective method of anesthesia in reduction of displaced distal radius fracture?

Table S4. Summary of secondary outcome among the reference. (DOCX 20 kb