ABSTRACT

The aim of this study was to provide clinical recommendations about the use of platelet-rich plasma (PRP) that was subjected to short-term storage at room temperature. We determined bioactive growth factor and cytokine concentrations as indicators of platelet and white blood cell degranulation in blood and PRP. Additionally, this study sought to validate the use of manual, direct smear analysis as an alternative to automated methods for platelet quantification in PRP.

Blood was used to generate low-leukocyte PRP (L^lo PRP) or high-leukocyte PRP (L^hi PRP). Blood was either processed immediately or kept at room temperature for 2 or 4 hours prior to generation of PRP, which was then held at room temperature for 0, 1, 2, or 4 hours. Subsequently, bioactive transforming growth factor beta-1 and matrix metalloproteinase-9 were measured by ELISA (enzyme-linked immunosorbent assay). Manual and automated platelet counts were performed on all blood and PRP samples.

There were no differences in growth factor or cytokine concentration when blood or L^lo PRP or L^hi PRP was retained at room temperature for up to 4 hours. Manual, direct smear analysis for platelet quantification was not different from the use of automated machine counting for PRP samples, but in the starting blood samples, manual platelet counts were significantly higher than those generated using automated technology.

When there is a delay of up to 4 hours in the generation of PRP from blood or in the application of PRP to the patient, bioactive growth factor and cytokine concentrations remain stable in both blood and PRP. A manual direct counting method is a simple, cost-effective, and valid method to measure the contents of the PRP product being delivered to the patient.

Platelet-rich plasma (PRP) is used to promote healing in many areas of medicine, such as dental surgery,^1,2 soft-tissue injury,^3,4 orthopedic surgery,^5,6 wound healing,⁷ and veterinary medicine.^8,9 Despite its extensive use, there are still questions about the clinical efficacy of PRP.^10-12 Due to biological heterogeneity between patients^13,14 and differences between available manufacturing kits,^13,15 PRP can be highly variable between patients. There are classification schemes to categorize the various types of PRP,^16-18 which can be divided broadly into low-leukocyte PRP (L^lo PRP) and high-leukocyte PRP (L^hi PRP). PRP can be used as a point of care therapy, prepared and used immediately, or it can be used during a surgical procedure. In some institutions, blood is drawn by a phlebotomist, processed in the hospital laboratory, and then delivered to the operating room. In other instances, PRP is generated patient-side by the primary attending physician’s team, who draws the blood and processes it for immediate use.^5,19 Delays at any step in these various scenarios could lead to the blood or the resultant PRP remaining at room temperature from minutes to several hours prior to administration to the patient. This variability in PRP protocols between clinical and surgical settings adds to concerns regarding the stability and efficacy of the biologic.

Continue to: When performing clinical or research...

The primary aim of this study was to determine if retention of blood or PRP at room temperature for various time intervals had an effect on final growth factor or catabolic cytokine concentration. Bioactive transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were measured as representatives of growth factors and catabolic cytokines, respectively. The secondary aim was to identify if manual platelet counts were an accurate reflection of automated counts. The outcomes of these experiments should provide immediately relevant information for the clinical application of PRP.

MATERIALS AND METHODS

Blood Collection and Generation of PRP

Under Institutional Review Board approval, blood (105 mL) was collected from healthy human volunteers (N = 5) into a syringe containing acid citrate dextrose anticoagulant to a final concentration of 10% acid citrate dextrose. Three 15-mL aliquots of blood were used to generate L^lo PRP (Autologous Conditioned Plasma Double Syringe, Arthrex) and three 20-mL aliquots were used to generate L^hi PRP (SmartPReP 2, Harvest Technologies) (Figure 1). 

Automated and Manual Counts

Automated complete blood counts were performed by a board certified clinical pathologist in the clinical pathology department of Cornell University on all blood, L^lo PRP, and L^hi PRP samples. A manual platelet count, using a modified Giemsa stain,²² was performed on smears of all blood and PRP samples (Video). Slides were scanned at 10x magnification to identify an area where many red blood cells were present while maintaining a clear field of view (Figure 2A). The magnification was then increased to 100x using oil immersion, and the total number of platelets was counted in 10 fields of view (Figure 2B). 

Growth Factor and Catabolic Cytokine Measurements

Blood and PRP samples were thawed for ELISA (enzyme-linked immunosorbent assay) analysis. TGF-β1 concentration was determined using the TGF-β1 Emax ImmunoAssay System (Promega Corporation), which measures biologically active TGF-β1. We chose TGF-β1 because it is commonly measured in PRP studies as an anabolic cytokine with multiple effects on tissue healing. The functions of TGF-β1 include stimulation of undifferentiated mesenchymal cell proliferation; regulation of endothelial, fibroblast, and osteoblast mitogenesis; coordination of collagen synthesis; promotion of endothelial chemotaxis and angiogenesis; activation of extracellular matrix synthesis in cartilage; and reduction of the catabolic activity of interluekin-1 and MMPs.^23-25 In addition, TGF-β1 concentration strongly correlates with platelet concentration.²⁶ MMP-9 concentration was determined using the MMP-9 Biotrak Activity Assay (GE Healthcare Biosciences) which measures both active and pro- forms of MMP-9. In PRP, MMP-9 was measured as an indicator of white blood cell (WBC) concentration.²⁶ A catabolic cytokine capable of degrading collagen,^13,27 MMP-9 has been linked to poor healing.²⁸ For both assays, samples were measured in duplicate using a multiple detection plate reader (Tecan Safire).

Continue to: Statistical Analysis...

Statistical Analysis

Data were tested for the normal distribution to determine the appropriate statistical test. Manual and automated platelet counts were compared to each other in whole blood, L^lo PRP, and L^hi PRP samples using a paired t test. Bioactive TGF-β1 concentrations in blood, L^lo PRP, and L^hi PRP, were compared using a Kruskal-Wallis one-way analysis of variance (ANOVA) with Dunn’s all-pairwise comparison. Bioactive and pro-MMP-9 concentrations measured in the retained blood or PRP samples were compared using a one-way ANOVA with Tukey’s all-pairwise comparison. Statistical analyses were performed using Statistix 9 software (Analytical Software). A P value of <0.05 was considered significant.

RESULTS

Validation of PRP

PRP, as defined by an increase in platelet concentration in PRP compared with blood, was successfully generated in all samples by both systems. There was an average 1.98 ± 0.14-fold increase in platelet concentration in L^lo PRP and an average 3.06 ± 0.24-fold increase in L^hi PRP. Platelet concentration was significantly higher in L^hi PRP than in L^lo PRP (P = 0.001). Compared to whole blood, WBC concentration was 0.47 ± 0.07-fold lower in L^lo PRP and 1.98 ± 0.14-fold greater in L^hi PRP. Similar to platelets, WBCs were significantly greater in L^hi PRP than in L^lo PRP (P = 0.02).

Bioactive TGF-β1 and MMP-9 Concentration in Blood Retained at Room Temperature

To reflect the clinical situation where blood would be drawn from a patient, but there would be a delay in processing the blood to generate PRP, blood samples were retained at room temperature for up to 4 hours prior to analysis. Neither bioactive TGF-β1 (Figure 3) nor bioactive/pro-MMP-9 concentrations (Figure 4) changed significantly over time when blood was retained at room temperature prior to centrifugation to generate PRP.

Bioactive TGF-β1 and MMP-9 Concentration in PRP Retained at Room Temperature

In order to mimic the clinical situation where PRP would be generated but might sit out prior to being administered to the patient, PRP samples were retained at room temperature for up to 4 hours prior to analysis. In these samples, bioactive TGF-β1 concentrations were not significantly different between PRP products analyzed immediately and those samples retained at room temperature for up to 4 hours (Figure 5). 

Automatic vs Manual Platelet Count

Manual platelet counts were compared to automated platelet counts to determine if a manual platelet smear analysis could be a reliable method for analyzing PRP in clinical and pre-clinical studies. There was a significant difference between the automated and manual platelet counts in blood samples (Table) (P = 0.05, N = 5) with the manual platelet count having a higher average (99.1 thou/uL) platelet concentration than automated counts. Platelet clumping was identified in 2 automated counts, which falsely decreased platelet concentration by an unknown quantity. Manual platelet counts for both L^lo PRP (n = 30) and L^hi PRP (n = 30) were not different from automated platelet counts. Platelet clumping was not reported on any manual platelet counts performed on PRP samples.

Table. Platelet Concentrations of Whole Blood, L^lo PRP, and L^hi PRP (N = 5)

A paired t test was performed to compare results obtained from an automated platelet count and those obtained from a manual count.

Abbreviations: L^hi PRP, high-leukocyte platelet-rich plasma; L^lo PRP, low-leukocyte platelet-rich plasma; SD, standard deviation.

Continue to:The primary aim of this study...

DISCUSSION

The primary aim of this study was to improve the clinical use of PRP by characterizing changes that might occur due to extended preparation times. Physicians commonly question the stability of blood or PRP if it is retained at room temperature prior to being administered to the patient. Clinical recommendations to optimize PRP preparation can be derived from a better understanding of the stability of platelets and WBCs, which contribute to the anabolic and catabolic cytokines in PRP.

The results of this study suggest that platelets and WBCs remain stable in blood and both L^lo PRP and L^hi PRP for up to 4 hours. The use of bioactive ELISAs to measure TGF-β1 and MMP-9 allows for determination of stability of the PRP product retained at room temperature for up to 4 hours. This provides a time buffer to allow for delays from either institutional logistics or unanticipated clinical delays, without adverse effects on the generation of the final PRP product. As with all biologics, there are many factors that contribute to variability, but a relatively short delay of up to 4 hours in either generation of PRP from blood or in administration of PRP to the patient does not appear to contribute to that variability. Similar studies have been performed on equine PRP and suggest that growth factor concentrations remain stable for up to 6 hours after preparation of PRP²⁹ and in human PRP, which implies that although samples degrade over time, platelet integrity might be acceptable for clinical use for up to 5 days after preparation, particularly if stored in oxygen.³⁰ In contrast to this study, neither of the previously published reports used assays to measure biological activity in the stored PRP. Regardless of the variability between the studies with respect to the type of PRP evaluated and the outcome measures used, all of the studies support the concept that PRP can be stored at room temperature for at least a few hours before clinical use.

Centrifugation of blood does not guarantee the generation of PRP.^13,14 In some cases, platelet counts in PRP are similar to or even less than that in the starting whole blood sample. To determine whether a clinical outcome is attributed to PRP, it is vital to know the platelet concentration and, arguably, the WBC concentration in the blood used to generate PRP and in the PRP sample administered to the patient. The platelet concentration in blood and PRP samples can be quantified using automated or manual methods. The use of automated methods can add significant cost to a study or procedure. Manually evaluating a blood smear is an accepted, though more time consuming, method of analyzing cellular components of a blood sample. Depending on the standard operating procedure of the laboratory, manual smears are often done in conjunction with an automated count. This identifies abnormalities in cellular shape or size, or platelet clumping, which are not consistently recognized by automated methods. Manually evaluating a blood smear does take some training, but the material cost is very low, which has added value for clinical or preclinical research studies. Interestingly, the results of this study indicate that manual platelet counts in blood may be more accurate than the count generated from an automated counter because the automated platelet counts were falsely low due to platelet clumping. Platelet clumping can occur as early as 1 hour after blood collection, regardless of the type of anticoagulant used.³¹

LIMITATIONS

The sample size of this study was small. However, variability in PRP has been well documented in multiple other studies using slightly larger sample sizes.^13,14,16 Another potential limitation of this study could be that only one growth factor, TGF-β1, and one catabolic cytokine, MMP-9, were used as surrogate measures to represent platelet and WBC stability, respectively. We chose TGF-β1 because it is correlated with platelet concentrations^14,15,26 and MMP-9 because it is an indicator of catabolic factors in PRP that have been correlated with WBC concentrations.²⁶

CONCLUSION

This study illustrated that growth factor and cytokine concentrations in both L^lo PRP and L^hi PRP are stable for up to 4 hours. The clinical implications of these results suggest that if the generation or administration of PRP is delayed by up to 4 hours, the resultant PRP retains its bioactivity and is acceptable for clinical application. However, given the known variability of PRP generated due to patient and manufacturer variability,^13,14 it is still important to ensure that the product is indeed PRP, with an increase in platelet number over the starting sample of blood. This validation can be performed with a simple and cost-effective manual smear analysis of blood and PRP. The results of this study provide information that can be immediately translated into clinical, surgical, and research practices.

ABSTRACT

The aim of this study was to provide clinical recommendations about the use of platelet-rich plasma (PRP) that was subjected to short-term storage at room temperature. We determined bioactive growth factor and cytokine concentrations as indicators of platelet and white blood cell degranulation in blood and PRP. Additionally, this study sought to validate the use of manual, direct smear analysis as an alternative to automated methods for platelet quantification in PRP.

Blood was used to generate low-leukocyte PRP (L^lo PRP) or high-leukocyte PRP (L^hi PRP). Blood was either processed immediately or kept at room temperature for 2 or 4 hours prior to generation of PRP, which was then held at room temperature for 0, 1, 2, or 4 hours. Subsequently, bioactive transforming growth factor beta-1 and matrix metalloproteinase-9 were measured by ELISA (enzyme-linked immunosorbent assay). Manual and automated platelet counts were performed on all blood and PRP samples.

There were no differences in growth factor or cytokine concentration when blood or L^lo PRP or L^hi PRP was retained at room temperature for up to 4 hours. Manual, direct smear analysis for platelet quantification was not different from the use of automated machine counting for PRP samples, but in the starting blood samples, manual platelet counts were significantly higher than those generated using automated technology.

When there is a delay of up to 4 hours in the generation of PRP from blood or in the application of PRP to the patient, bioactive growth factor and cytokine concentrations remain stable in both blood and PRP. A manual direct counting method is a simple, cost-effective, and valid method to measure the contents of the PRP product being delivered to the patient.

Platelet-rich plasma (PRP) is used to promote healing in many areas of medicine, such as dental surgery,^1,2 soft-tissue injury,^3,4 orthopedic surgery,^5,6 wound healing,⁷ and veterinary medicine.^8,9 Despite its extensive use, there are still questions about the clinical efficacy of PRP.^10-12 Due to biological heterogeneity between patients^13,14 and differences between available manufacturing kits,^13,15 PRP can be highly variable between patients. There are classification schemes to categorize the various types of PRP,^16-18 which can be divided broadly into low-leukocyte PRP (L^lo PRP) and high-leukocyte PRP (L^hi PRP). PRP can be used as a point of care therapy, prepared and used immediately, or it can be used during a surgical procedure. In some institutions, blood is drawn by a phlebotomist, processed in the hospital laboratory, and then delivered to the operating room. In other instances, PRP is generated patient-side by the primary attending physician’s team, who draws the blood and processes it for immediate use.^5,19 Delays at any step in these various scenarios could lead to the blood or the resultant PRP remaining at room temperature from minutes to several hours prior to administration to the patient. This variability in PRP protocols between clinical and surgical settings adds to concerns regarding the stability and efficacy of the biologic.

Continue to: When performing clinical or research...

The primary aim of this study was to determine if retention of blood or PRP at room temperature for various time intervals had an effect on final growth factor or catabolic cytokine concentration. Bioactive transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were measured as representatives of growth factors and catabolic cytokines, respectively. The secondary aim was to identify if manual platelet counts were an accurate reflection of automated counts. The outcomes of these experiments should provide immediately relevant information for the clinical application of PRP.

MATERIALS AND METHODS

Blood Collection and Generation of PRP

Under Institutional Review Board approval, blood (105 mL) was collected from healthy human volunteers (N = 5) into a syringe containing acid citrate dextrose anticoagulant to a final concentration of 10% acid citrate dextrose. Three 15-mL aliquots of blood were used to generate L^lo PRP (Autologous Conditioned Plasma Double Syringe, Arthrex) and three 20-mL aliquots were used to generate L^hi PRP (SmartPReP 2, Harvest Technologies) (Figure 1). 

Automated and Manual Counts

Automated complete blood counts were performed by a board certified clinical pathologist in the clinical pathology department of Cornell University on all blood, L^lo PRP, and L^hi PRP samples. A manual platelet count, using a modified Giemsa stain,²² was performed on smears of all blood and PRP samples (Video). Slides were scanned at 10x magnification to identify an area where many red blood cells were present while maintaining a clear field of view (Figure 2A). The magnification was then increased to 100x using oil immersion, and the total number of platelets was counted in 10 fields of view (Figure 2B). 

Growth Factor and Catabolic Cytokine Measurements

Blood and PRP samples were thawed for ELISA (enzyme-linked immunosorbent assay) analysis. TGF-β1 concentration was determined using the TGF-β1 Emax ImmunoAssay System (Promega Corporation), which measures biologically active TGF-β1. We chose TGF-β1 because it is commonly measured in PRP studies as an anabolic cytokine with multiple effects on tissue healing. The functions of TGF-β1 include stimulation of undifferentiated mesenchymal cell proliferation; regulation of endothelial, fibroblast, and osteoblast mitogenesis; coordination of collagen synthesis; promotion of endothelial chemotaxis and angiogenesis; activation of extracellular matrix synthesis in cartilage; and reduction of the catabolic activity of interluekin-1 and MMPs.^23-25 In addition, TGF-β1 concentration strongly correlates with platelet concentration.²⁶ MMP-9 concentration was determined using the MMP-9 Biotrak Activity Assay (GE Healthcare Biosciences) which measures both active and pro- forms of MMP-9. In PRP, MMP-9 was measured as an indicator of white blood cell (WBC) concentration.²⁶ A catabolic cytokine capable of degrading collagen,^13,27 MMP-9 has been linked to poor healing.²⁸ For both assays, samples were measured in duplicate using a multiple detection plate reader (Tecan Safire).

Continue to: Statistical Analysis...

Statistical Analysis

Data were tested for the normal distribution to determine the appropriate statistical test. Manual and automated platelet counts were compared to each other in whole blood, L^lo PRP, and L^hi PRP samples using a paired t test. Bioactive TGF-β1 concentrations in blood, L^lo PRP, and L^hi PRP, were compared using a Kruskal-Wallis one-way analysis of variance (ANOVA) with Dunn’s all-pairwise comparison. Bioactive and pro-MMP-9 concentrations measured in the retained blood or PRP samples were compared using a one-way ANOVA with Tukey’s all-pairwise comparison. Statistical analyses were performed using Statistix 9 software (Analytical Software). A P value of <0.05 was considered significant.

RESULTS

Validation of PRP

PRP, as defined by an increase in platelet concentration in PRP compared with blood, was successfully generated in all samples by both systems. There was an average 1.98 ± 0.14-fold increase in platelet concentration in L^lo PRP and an average 3.06 ± 0.24-fold increase in L^hi PRP. Platelet concentration was significantly higher in L^hi PRP than in L^lo PRP (P = 0.001). Compared to whole blood, WBC concentration was 0.47 ± 0.07-fold lower in L^lo PRP and 1.98 ± 0.14-fold greater in L^hi PRP. Similar to platelets, WBCs were significantly greater in L^hi PRP than in L^lo PRP (P = 0.02).

Bioactive TGF-β1 and MMP-9 Concentration in Blood Retained at Room Temperature

To reflect the clinical situation where blood would be drawn from a patient, but there would be a delay in processing the blood to generate PRP, blood samples were retained at room temperature for up to 4 hours prior to analysis. Neither bioactive TGF-β1 (Figure 3) nor bioactive/pro-MMP-9 concentrations (Figure 4) changed significantly over time when blood was retained at room temperature prior to centrifugation to generate PRP.

Bioactive TGF-β1 and MMP-9 Concentration in PRP Retained at Room Temperature

In order to mimic the clinical situation where PRP would be generated but might sit out prior to being administered to the patient, PRP samples were retained at room temperature for up to 4 hours prior to analysis. In these samples, bioactive TGF-β1 concentrations were not significantly different between PRP products analyzed immediately and those samples retained at room temperature for up to 4 hours (Figure 5). 

Automatic vs Manual Platelet Count

Manual platelet counts were compared to automated platelet counts to determine if a manual platelet smear analysis could be a reliable method for analyzing PRP in clinical and pre-clinical studies. There was a significant difference between the automated and manual platelet counts in blood samples (Table) (P = 0.05, N = 5) with the manual platelet count having a higher average (99.1 thou/uL) platelet concentration than automated counts. Platelet clumping was identified in 2 automated counts, which falsely decreased platelet concentration by an unknown quantity. Manual platelet counts for both L^lo PRP (n = 30) and L^hi PRP (n = 30) were not different from automated platelet counts. Platelet clumping was not reported on any manual platelet counts performed on PRP samples.

Table. Platelet Concentrations of Whole Blood, L^lo PRP, and L^hi PRP (N = 5)

A paired t test was performed to compare results obtained from an automated platelet count and those obtained from a manual count.

Abbreviations: L^hi PRP, high-leukocyte platelet-rich plasma; L^lo PRP, low-leukocyte platelet-rich plasma; SD, standard deviation.

Continue to:The primary aim of this study...

DISCUSSION

The primary aim of this study was to improve the clinical use of PRP by characterizing changes that might occur due to extended preparation times. Physicians commonly question the stability of blood or PRP if it is retained at room temperature prior to being administered to the patient. Clinical recommendations to optimize PRP preparation can be derived from a better understanding of the stability of platelets and WBCs, which contribute to the anabolic and catabolic cytokines in PRP.

The results of this study suggest that platelets and WBCs remain stable in blood and both L^lo PRP and L^hi PRP for up to 4 hours. The use of bioactive ELISAs to measure TGF-β1 and MMP-9 allows for determination of stability of the PRP product retained at room temperature for up to 4 hours. This provides a time buffer to allow for delays from either institutional logistics or unanticipated clinical delays, without adverse effects on the generation of the final PRP product. As with all biologics, there are many factors that contribute to variability, but a relatively short delay of up to 4 hours in either generation of PRP from blood or in administration of PRP to the patient does not appear to contribute to that variability. Similar studies have been performed on equine PRP and suggest that growth factor concentrations remain stable for up to 6 hours after preparation of PRP²⁹ and in human PRP, which implies that although samples degrade over time, platelet integrity might be acceptable for clinical use for up to 5 days after preparation, particularly if stored in oxygen.³⁰ In contrast to this study, neither of the previously published reports used assays to measure biological activity in the stored PRP. Regardless of the variability between the studies with respect to the type of PRP evaluated and the outcome measures used, all of the studies support the concept that PRP can be stored at room temperature for at least a few hours before clinical use.

Centrifugation of blood does not guarantee the generation of PRP.^13,14 In some cases, platelet counts in PRP are similar to or even less than that in the starting whole blood sample. To determine whether a clinical outcome is attributed to PRP, it is vital to know the platelet concentration and, arguably, the WBC concentration in the blood used to generate PRP and in the PRP sample administered to the patient. The platelet concentration in blood and PRP samples can be quantified using automated or manual methods. The use of automated methods can add significant cost to a study or procedure. Manually evaluating a blood smear is an accepted, though more time consuming, method of analyzing cellular components of a blood sample. Depending on the standard operating procedure of the laboratory, manual smears are often done in conjunction with an automated count. This identifies abnormalities in cellular shape or size, or platelet clumping, which are not consistently recognized by automated methods. Manually evaluating a blood smear does take some training, but the material cost is very low, which has added value for clinical or preclinical research studies. Interestingly, the results of this study indicate that manual platelet counts in blood may be more accurate than the count generated from an automated counter because the automated platelet counts were falsely low due to platelet clumping. Platelet clumping can occur as early as 1 hour after blood collection, regardless of the type of anticoagulant used.³¹

LIMITATIONS

The sample size of this study was small. However, variability in PRP has been well documented in multiple other studies using slightly larger sample sizes.^13,14,16 Another potential limitation of this study could be that only one growth factor, TGF-β1, and one catabolic cytokine, MMP-9, were used as surrogate measures to represent platelet and WBC stability, respectively. We chose TGF-β1 because it is correlated with platelet concentrations^14,15,26 and MMP-9 because it is an indicator of catabolic factors in PRP that have been correlated with WBC concentrations.²⁶

CONCLUSION

This study illustrated that growth factor and cytokine concentrations in both L^lo PRP and L^hi PRP are stable for up to 4 hours. The clinical implications of these results suggest that if the generation or administration of PRP is delayed by up to 4 hours, the resultant PRP retains its bioactivity and is acceptable for clinical application. However, given the known variability of PRP generated due to patient and manufacturer variability,^13,14 it is still important to ensure that the product is indeed PRP, with an increase in platelet number over the starting sample of blood. This validation can be performed with a simple and cost-effective manual smear analysis of blood and PRP. The results of this study provide information that can be immediately translated into clinical, surgical, and research practices.

ABSTRACT

The aim of this study was to provide clinical recommendations about the use of platelet-rich plasma (PRP) that was subjected to short-term storage at room temperature. We determined bioactive growth factor and cytokine concentrations as indicators of platelet and white blood cell degranulation in blood and PRP. Additionally, this study sought to validate the use of manual, direct smear analysis as an alternative to automated methods for platelet quantification in PRP.

Blood was used to generate low-leukocyte PRP (L^lo PRP) or high-leukocyte PRP (L^hi PRP). Blood was either processed immediately or kept at room temperature for 2 or 4 hours prior to generation of PRP, which was then held at room temperature for 0, 1, 2, or 4 hours. Subsequently, bioactive transforming growth factor beta-1 and matrix metalloproteinase-9 were measured by ELISA (enzyme-linked immunosorbent assay). Manual and automated platelet counts were performed on all blood and PRP samples.

There were no differences in growth factor or cytokine concentration when blood or L^lo PRP or L^hi PRP was retained at room temperature for up to 4 hours. Manual, direct smear analysis for platelet quantification was not different from the use of automated machine counting for PRP samples, but in the starting blood samples, manual platelet counts were significantly higher than those generated using automated technology.

When there is a delay of up to 4 hours in the generation of PRP from blood or in the application of PRP to the patient, bioactive growth factor and cytokine concentrations remain stable in both blood and PRP. A manual direct counting method is a simple, cost-effective, and valid method to measure the contents of the PRP product being delivered to the patient.

Platelet-rich plasma (PRP) is used to promote healing in many areas of medicine, such as dental surgery,^1,2 soft-tissue injury,^3,4 orthopedic surgery,^5,6 wound healing,⁷ and veterinary medicine.^8,9 Despite its extensive use, there are still questions about the clinical efficacy of PRP.^10-12 Due to biological heterogeneity between patients^13,14 and differences between available manufacturing kits,^13,15 PRP can be highly variable between patients. There are classification schemes to categorize the various types of PRP,^16-18 which can be divided broadly into low-leukocyte PRP (L^lo PRP) and high-leukocyte PRP (L^hi PRP). PRP can be used as a point of care therapy, prepared and used immediately, or it can be used during a surgical procedure. In some institutions, blood is drawn by a phlebotomist, processed in the hospital laboratory, and then delivered to the operating room. In other instances, PRP is generated patient-side by the primary attending physician’s team, who draws the blood and processes it for immediate use.^5,19 Delays at any step in these various scenarios could lead to the blood or the resultant PRP remaining at room temperature from minutes to several hours prior to administration to the patient. This variability in PRP protocols between clinical and surgical settings adds to concerns regarding the stability and efficacy of the biologic.

Continue to: When performing clinical or research...

The primary aim of this study was to determine if retention of blood or PRP at room temperature for various time intervals had an effect on final growth factor or catabolic cytokine concentration. Bioactive transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were measured as representatives of growth factors and catabolic cytokines, respectively. The secondary aim was to identify if manual platelet counts were an accurate reflection of automated counts. The outcomes of these experiments should provide immediately relevant information for the clinical application of PRP.

MATERIALS AND METHODS

Blood Collection and Generation of PRP

Under Institutional Review Board approval, blood (105 mL) was collected from healthy human volunteers (N = 5) into a syringe containing acid citrate dextrose anticoagulant to a final concentration of 10% acid citrate dextrose. Three 15-mL aliquots of blood were used to generate L^lo PRP (Autologous Conditioned Plasma Double Syringe, Arthrex) and three 20-mL aliquots were used to generate L^hi PRP (SmartPReP 2, Harvest Technologies) (Figure 1). 

Automated and Manual Counts

Automated complete blood counts were performed by a board certified clinical pathologist in the clinical pathology department of Cornell University on all blood, L^lo PRP, and L^hi PRP samples. A manual platelet count, using a modified Giemsa stain,²² was performed on smears of all blood and PRP samples (Video). Slides were scanned at 10x magnification to identify an area where many red blood cells were present while maintaining a clear field of view (Figure 2A). The magnification was then increased to 100x using oil immersion, and the total number of platelets was counted in 10 fields of view (Figure 2B). 

Growth Factor and Catabolic Cytokine Measurements

Blood and PRP samples were thawed for ELISA (enzyme-linked immunosorbent assay) analysis. TGF-β1 concentration was determined using the TGF-β1 Emax ImmunoAssay System (Promega Corporation), which measures biologically active TGF-β1. We chose TGF-β1 because it is commonly measured in PRP studies as an anabolic cytokine with multiple effects on tissue healing. The functions of TGF-β1 include stimulation of undifferentiated mesenchymal cell proliferation; regulation of endothelial, fibroblast, and osteoblast mitogenesis; coordination of collagen synthesis; promotion of endothelial chemotaxis and angiogenesis; activation of extracellular matrix synthesis in cartilage; and reduction of the catabolic activity of interluekin-1 and MMPs.^23-25 In addition, TGF-β1 concentration strongly correlates with platelet concentration.²⁶ MMP-9 concentration was determined using the MMP-9 Biotrak Activity Assay (GE Healthcare Biosciences) which measures both active and pro- forms of MMP-9. In PRP, MMP-9 was measured as an indicator of white blood cell (WBC) concentration.²⁶ A catabolic cytokine capable of degrading collagen,^13,27 MMP-9 has been linked to poor healing.²⁸ For both assays, samples were measured in duplicate using a multiple detection plate reader (Tecan Safire).

Continue to: Statistical Analysis...

Statistical Analysis

Data were tested for the normal distribution to determine the appropriate statistical test. Manual and automated platelet counts were compared to each other in whole blood, L^lo PRP, and L^hi PRP samples using a paired t test. Bioactive TGF-β1 concentrations in blood, L^lo PRP, and L^hi PRP, were compared using a Kruskal-Wallis one-way analysis of variance (ANOVA) with Dunn’s all-pairwise comparison. Bioactive and pro-MMP-9 concentrations measured in the retained blood or PRP samples were compared using a one-way ANOVA with Tukey’s all-pairwise comparison. Statistical analyses were performed using Statistix 9 software (Analytical Software). A P value of <0.05 was considered significant.

RESULTS

Validation of PRP

PRP, as defined by an increase in platelet concentration in PRP compared with blood, was successfully generated in all samples by both systems. There was an average 1.98 ± 0.14-fold increase in platelet concentration in L^lo PRP and an average 3.06 ± 0.24-fold increase in L^hi PRP. Platelet concentration was significantly higher in L^hi PRP than in L^lo PRP (P = 0.001). Compared to whole blood, WBC concentration was 0.47 ± 0.07-fold lower in L^lo PRP and 1.98 ± 0.14-fold greater in L^hi PRP. Similar to platelets, WBCs were significantly greater in L^hi PRP than in L^lo PRP (P = 0.02).

Bioactive TGF-β1 and MMP-9 Concentration in Blood Retained at Room Temperature

To reflect the clinical situation where blood would be drawn from a patient, but there would be a delay in processing the blood to generate PRP, blood samples were retained at room temperature for up to 4 hours prior to analysis. Neither bioactive TGF-β1 (Figure 3) nor bioactive/pro-MMP-9 concentrations (Figure 4) changed significantly over time when blood was retained at room temperature prior to centrifugation to generate PRP.

Bioactive TGF-β1 and MMP-9 Concentration in PRP Retained at Room Temperature

In order to mimic the clinical situation where PRP would be generated but might sit out prior to being administered to the patient, PRP samples were retained at room temperature for up to 4 hours prior to analysis. In these samples, bioactive TGF-β1 concentrations were not significantly different between PRP products analyzed immediately and those samples retained at room temperature for up to 4 hours (Figure 5). 

Automatic vs Manual Platelet Count

Manual platelet counts were compared to automated platelet counts to determine if a manual platelet smear analysis could be a reliable method for analyzing PRP in clinical and pre-clinical studies. There was a significant difference between the automated and manual platelet counts in blood samples (Table) (P = 0.05, N = 5) with the manual platelet count having a higher average (99.1 thou/uL) platelet concentration than automated counts. Platelet clumping was identified in 2 automated counts, which falsely decreased platelet concentration by an unknown quantity. Manual platelet counts for both L^lo PRP (n = 30) and L^hi PRP (n = 30) were not different from automated platelet counts. Platelet clumping was not reported on any manual platelet counts performed on PRP samples.

Table. Platelet Concentrations of Whole Blood, L^lo PRP, and L^hi PRP (N = 5)

A paired t test was performed to compare results obtained from an automated platelet count and those obtained from a manual count.

Abbreviations: L^hi PRP, high-leukocyte platelet-rich plasma; L^lo PRP, low-leukocyte platelet-rich plasma; SD, standard deviation.

Continue to:The primary aim of this study...

DISCUSSION

The primary aim of this study was to improve the clinical use of PRP by characterizing changes that might occur due to extended preparation times. Physicians commonly question the stability of blood or PRP if it is retained at room temperature prior to being administered to the patient. Clinical recommendations to optimize PRP preparation can be derived from a better understanding of the stability of platelets and WBCs, which contribute to the anabolic and catabolic cytokines in PRP.

The results of this study suggest that platelets and WBCs remain stable in blood and both L^lo PRP and L^hi PRP for up to 4 hours. The use of bioactive ELISAs to measure TGF-β1 and MMP-9 allows for determination of stability of the PRP product retained at room temperature for up to 4 hours. This provides a time buffer to allow for delays from either institutional logistics or unanticipated clinical delays, without adverse effects on the generation of the final PRP product. As with all biologics, there are many factors that contribute to variability, but a relatively short delay of up to 4 hours in either generation of PRP from blood or in administration of PRP to the patient does not appear to contribute to that variability. Similar studies have been performed on equine PRP and suggest that growth factor concentrations remain stable for up to 6 hours after preparation of PRP²⁹ and in human PRP, which implies that although samples degrade over time, platelet integrity might be acceptable for clinical use for up to 5 days after preparation, particularly if stored in oxygen.³⁰ In contrast to this study, neither of the previously published reports used assays to measure biological activity in the stored PRP. Regardless of the variability between the studies with respect to the type of PRP evaluated and the outcome measures used, all of the studies support the concept that PRP can be stored at room temperature for at least a few hours before clinical use.

Centrifugation of blood does not guarantee the generation of PRP.^13,14 In some cases, platelet counts in PRP are similar to or even less than that in the starting whole blood sample. To determine whether a clinical outcome is attributed to PRP, it is vital to know the platelet concentration and, arguably, the WBC concentration in the blood used to generate PRP and in the PRP sample administered to the patient. The platelet concentration in blood and PRP samples can be quantified using automated or manual methods. The use of automated methods can add significant cost to a study or procedure. Manually evaluating a blood smear is an accepted, though more time consuming, method of analyzing cellular components of a blood sample. Depending on the standard operating procedure of the laboratory, manual smears are often done in conjunction with an automated count. This identifies abnormalities in cellular shape or size, or platelet clumping, which are not consistently recognized by automated methods. Manually evaluating a blood smear does take some training, but the material cost is very low, which has added value for clinical or preclinical research studies. Interestingly, the results of this study indicate that manual platelet counts in blood may be more accurate than the count generated from an automated counter because the automated platelet counts were falsely low due to platelet clumping. Platelet clumping can occur as early as 1 hour after blood collection, regardless of the type of anticoagulant used.³¹

LIMITATIONS

The sample size of this study was small. However, variability in PRP has been well documented in multiple other studies using slightly larger sample sizes.^13,14,16 Another potential limitation of this study could be that only one growth factor, TGF-β1, and one catabolic cytokine, MMP-9, were used as surrogate measures to represent platelet and WBC stability, respectively. We chose TGF-β1 because it is correlated with platelet concentrations^14,15,26 and MMP-9 because it is an indicator of catabolic factors in PRP that have been correlated with WBC concentrations.²⁶

CONCLUSION

This study illustrated that growth factor and cytokine concentrations in both L^lo PRP and L^hi PRP are stable for up to 4 hours. The clinical implications of these results suggest that if the generation or administration of PRP is delayed by up to 4 hours, the resultant PRP retains its bioactivity and is acceptable for clinical application. However, given the known variability of PRP generated due to patient and manufacturer variability,^13,14 it is still important to ensure that the product is indeed PRP, with an increase in platelet number over the starting sample of blood. This validation can be performed with a simple and cost-effective manual smear analysis of blood and PRP. The results of this study provide information that can be immediately translated into clinical, surgical, and research practices.

CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.

The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.

copyright Kativ/iStockphoto

SOURCE: Erdrich J et al. SSO 2018, Abstract 82.

CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.

The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.

copyright Kativ/iStockphoto

SOURCE: Erdrich J et al. SSO 2018, Abstract 82.

CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.

The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.

copyright Kativ/iStockphoto

SOURCE: Erdrich J et al. SSO 2018, Abstract 82.

ORLANDO – More than one-third of patients with treatment-resistant hypertension in U.S. cardiology practices are eligible for preferential consideration of spironolactone as their fourth-line agent in accord with the practice-changing findings of the PATHWAY-2 trial, Lauren Thompson, MD, said at the annual meeting of the American College of Cardiology.

She presented a study that harnessed the ACC’s National Cardiovascular Data Registry PINNACLE Registry – the largest observational outpatient cardiovascular registry in the world – to assess the potential impact of PATHWAY-2 on the management of treatment-resistant hypertension (TRH) in U.S. cardiology practices. And as she discovered, the potential implications for daily practice are huge.

Bruce Jancin/MDedge News

The most widely prescribed antihypertensive agents in PINNACLE registry patients with TRH were beta-blockers, in 87%; ACE inhibitors, in 72%; calcium channel blockers, in 71%; and thiazide diuretics, in 69%. Of note, 27% of patients with TRH were already on spironolactone.

Audience discussion centered around the uncertainties regarding treatment adherence in patients labeled as having TRH.

“I think sometimes clinicians are afraid to prescribe spironolactone in patients that they think might be nonadherent,” one cardiologist observed.

Dr. Thompson noted that it’s not possible to look at prescription-filling rates in the PINNACLE registry.

“Unfortunately, we can’t exclude white coat hypertension or nonadherence as reasons why patients in PINNACLE end up on multiple antihypertensive medication classes. We can see that a prescription was written, but we have no way to know if it was actually filled or not,” she observed.

Also, since patients in cardiology clinics typically have multiple cardiovascular comorbidities, it’s quite possible that patients with TRH who are on a beta-blocker, for example, might not have received that drug for blood pressure control.

Dr. Thompson’s study was supported by the ACC’s National Cardiovascular Disease Registry. She reported having no financial conflicts of interest.

[email protected]

Source: Thompson L. ACC 18. Abstract 1324M-09.

ORLANDO – More than one-third of patients with treatment-resistant hypertension in U.S. cardiology practices are eligible for preferential consideration of spironolactone as their fourth-line agent in accord with the practice-changing findings of the PATHWAY-2 trial, Lauren Thompson, MD, said at the annual meeting of the American College of Cardiology.

She presented a study that harnessed the ACC’s National Cardiovascular Data Registry PINNACLE Registry – the largest observational outpatient cardiovascular registry in the world – to assess the potential impact of PATHWAY-2 on the management of treatment-resistant hypertension (TRH) in U.S. cardiology practices. And as she discovered, the potential implications for daily practice are huge.

Bruce Jancin/MDedge News

The most widely prescribed antihypertensive agents in PINNACLE registry patients with TRH were beta-blockers, in 87%; ACE inhibitors, in 72%; calcium channel blockers, in 71%; and thiazide diuretics, in 69%. Of note, 27% of patients with TRH were already on spironolactone.

Audience discussion centered around the uncertainties regarding treatment adherence in patients labeled as having TRH.

“I think sometimes clinicians are afraid to prescribe spironolactone in patients that they think might be nonadherent,” one cardiologist observed.

Dr. Thompson noted that it’s not possible to look at prescription-filling rates in the PINNACLE registry.

“Unfortunately, we can’t exclude white coat hypertension or nonadherence as reasons why patients in PINNACLE end up on multiple antihypertensive medication classes. We can see that a prescription was written, but we have no way to know if it was actually filled or not,” she observed.

Also, since patients in cardiology clinics typically have multiple cardiovascular comorbidities, it’s quite possible that patients with TRH who are on a beta-blocker, for example, might not have received that drug for blood pressure control.

Dr. Thompson’s study was supported by the ACC’s National Cardiovascular Disease Registry. She reported having no financial conflicts of interest.

[email protected]

Source: Thompson L. ACC 18. Abstract 1324M-09.

ORLANDO – More than one-third of patients with treatment-resistant hypertension in U.S. cardiology practices are eligible for preferential consideration of spironolactone as their fourth-line agent in accord with the practice-changing findings of the PATHWAY-2 trial, Lauren Thompson, MD, said at the annual meeting of the American College of Cardiology.

She presented a study that harnessed the ACC’s National Cardiovascular Data Registry PINNACLE Registry – the largest observational outpatient cardiovascular registry in the world – to assess the potential impact of PATHWAY-2 on the management of treatment-resistant hypertension (TRH) in U.S. cardiology practices. And as she discovered, the potential implications for daily practice are huge.

Bruce Jancin/MDedge News

The most widely prescribed antihypertensive agents in PINNACLE registry patients with TRH were beta-blockers, in 87%; ACE inhibitors, in 72%; calcium channel blockers, in 71%; and thiazide diuretics, in 69%. Of note, 27% of patients with TRH were already on spironolactone.

Audience discussion centered around the uncertainties regarding treatment adherence in patients labeled as having TRH.

“I think sometimes clinicians are afraid to prescribe spironolactone in patients that they think might be nonadherent,” one cardiologist observed.

Dr. Thompson noted that it’s not possible to look at prescription-filling rates in the PINNACLE registry.

“Unfortunately, we can’t exclude white coat hypertension or nonadherence as reasons why patients in PINNACLE end up on multiple antihypertensive medication classes. We can see that a prescription was written, but we have no way to know if it was actually filled or not,” she observed.

Also, since patients in cardiology clinics typically have multiple cardiovascular comorbidities, it’s quite possible that patients with TRH who are on a beta-blocker, for example, might not have received that drug for blood pressure control.

Dr. Thompson’s study was supported by the ACC’s National Cardiovascular Disease Registry. She reported having no financial conflicts of interest.

[email protected]

Source: Thompson L. ACC 18. Abstract 1324M-09.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.

Clinical question: How does using procalcitonin levels for adults with acute respiratory infections (ARIs) affect patient outcomes?

Background: While the ARI diagnosis encompasses bacterial, viral, and inflammatory etiologies, as many as 75% of ARIs are treated with antibiotics. Procalcitonin is a biomarker released by tissues in response to bacterial infections. Its production is also inhibited by interferon-gamma, a cytokine released in response to viral infections, therefore, making procalcitonin a biomarker of particular interest to support the use of antibiotic therapy in the treatment of ARIs.

Study design: Cochrane Review.

Setting: Medical wards, intensive care units, primary care clinics, and emergency departments across 12 countries.

Synopsis: The review included 26 randomized control trials of 6,708 immunocompetent adults with ARIs who received antibiotics either based on procalcitonin-guided antibiotic therapy or routine care. Primary endpoints evaluated included all-cause mortality and treatment failure at 30 days. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. There were significantly fewer deaths in the procalcitonin-guided group than in the control group (286/8.6% vs. 336/10%; adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99; P = .037). Treatment failure was not statistically different between the procalcitonin-guided participants and the controls. Of the secondary endpoints, antibiotic use and antibiotic-related side effects were lower in the procalcitonin-guided group (5.7 days vs. 8.1 days; P less than .001; and 16.3% vs. 22.1%; P less than .001). Each of the RCTs had varying algorithms for the use of procalcitonin-guided therapy, so no specific treatment guidelines can be gleaned from this review.

Bottom line: Procalcitonin-guided algorithms are associated with lower mortality, lower antibiotic exposure, and lower antibiotic-related side effects. However, more research is needed to determine best practice algorithms for using procalcitonin levels to guide treatment decisions.

Citation: Schuetz P et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12. doi: 10.1002/14651858.cd007498.pub3.

Clinical question: How does using procalcitonin levels for adults with acute respiratory infections (ARIs) affect patient outcomes?

Background: While the ARI diagnosis encompasses bacterial, viral, and inflammatory etiologies, as many as 75% of ARIs are treated with antibiotics. Procalcitonin is a biomarker released by tissues in response to bacterial infections. Its production is also inhibited by interferon-gamma, a cytokine released in response to viral infections, therefore, making procalcitonin a biomarker of particular interest to support the use of antibiotic therapy in the treatment of ARIs.

Study design: Cochrane Review.

Setting: Medical wards, intensive care units, primary care clinics, and emergency departments across 12 countries.

Synopsis: The review included 26 randomized control trials of 6,708 immunocompetent adults with ARIs who received antibiotics either based on procalcitonin-guided antibiotic therapy or routine care. Primary endpoints evaluated included all-cause mortality and treatment failure at 30 days. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. There were significantly fewer deaths in the procalcitonin-guided group than in the control group (286/8.6% vs. 336/10%; adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99; P = .037). Treatment failure was not statistically different between the procalcitonin-guided participants and the controls. Of the secondary endpoints, antibiotic use and antibiotic-related side effects were lower in the procalcitonin-guided group (5.7 days vs. 8.1 days; P less than .001; and 16.3% vs. 22.1%; P less than .001). Each of the RCTs had varying algorithms for the use of procalcitonin-guided therapy, so no specific treatment guidelines can be gleaned from this review.

Bottom line: Procalcitonin-guided algorithms are associated with lower mortality, lower antibiotic exposure, and lower antibiotic-related side effects. However, more research is needed to determine best practice algorithms for using procalcitonin levels to guide treatment decisions.

Citation: Schuetz P et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12. doi: 10.1002/14651858.cd007498.pub3.

Clinical question: How does using procalcitonin levels for adults with acute respiratory infections (ARIs) affect patient outcomes?

Background: While the ARI diagnosis encompasses bacterial, viral, and inflammatory etiologies, as many as 75% of ARIs are treated with antibiotics. Procalcitonin is a biomarker released by tissues in response to bacterial infections. Its production is also inhibited by interferon-gamma, a cytokine released in response to viral infections, therefore, making procalcitonin a biomarker of particular interest to support the use of antibiotic therapy in the treatment of ARIs.

Study design: Cochrane Review.

Setting: Medical wards, intensive care units, primary care clinics, and emergency departments across 12 countries.

Synopsis: The review included 26 randomized control trials of 6,708 immunocompetent adults with ARIs who received antibiotics either based on procalcitonin-guided antibiotic therapy or routine care. Primary endpoints evaluated included all-cause mortality and treatment failure at 30 days. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. There were significantly fewer deaths in the procalcitonin-guided group than in the control group (286/8.6% vs. 336/10%; adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99; P = .037). Treatment failure was not statistically different between the procalcitonin-guided participants and the controls. Of the secondary endpoints, antibiotic use and antibiotic-related side effects were lower in the procalcitonin-guided group (5.7 days vs. 8.1 days; P less than .001; and 16.3% vs. 22.1%; P less than .001). Each of the RCTs had varying algorithms for the use of procalcitonin-guided therapy, so no specific treatment guidelines can be gleaned from this review.

Bottom line: Procalcitonin-guided algorithms are associated with lower mortality, lower antibiotic exposure, and lower antibiotic-related side effects. However, more research is needed to determine best practice algorithms for using procalcitonin levels to guide treatment decisions.

Citation: Schuetz P et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12. doi: 10.1002/14651858.cd007498.pub3.

The relationship between nonsteroidal anti-inflammatory drug (NSAID) use and exacerbations of inflammatory bowel disease (IBD) may not be as clear-cut as previously thought, according to the results of a systematic review and meta-analysis.

The report was published online in Alimentary Pharmacology and Therapeutics.

The researchers presented their analysis of 18 studies examining the association between acetaminophen, NSAIDs, and cyclo-oxygenase-2 (COX-2) inhibitors, and the risk of Crohn’s disease, ulcerative colitis flares, and IBD.

Five studies looked at the association between NSAIDS – such as naproxen and indomethacin – and the risk of Crohn’s disease exacerbation. While this showed a 42% increased risk of exacerbation with NSAID use, the authors noted that they saw substantial heterogeneity across the studies.

For example, two nonrandomized trials comparing NSAIDs and acetaminophen in patients with quiescent disease found NSAIDs were associated with frequent, early clinical relapse of IBD. But another study comparing patients with symptom flares and those in clinical remission found no difference between the two groups in the frequency of NSAID use.

©PhotoDisk

SOURCE: Moninuola O et al. Aliment Pharmacol Ther. 2018 Apr 5. doi: 10.1111/apt.14606.

The relationship between nonsteroidal anti-inflammatory drug (NSAID) use and exacerbations of inflammatory bowel disease (IBD) may not be as clear-cut as previously thought, according to the results of a systematic review and meta-analysis.

The report was published online in Alimentary Pharmacology and Therapeutics.

The researchers presented their analysis of 18 studies examining the association between acetaminophen, NSAIDs, and cyclo-oxygenase-2 (COX-2) inhibitors, and the risk of Crohn’s disease, ulcerative colitis flares, and IBD.

Five studies looked at the association between NSAIDS – such as naproxen and indomethacin – and the risk of Crohn’s disease exacerbation. While this showed a 42% increased risk of exacerbation with NSAID use, the authors noted that they saw substantial heterogeneity across the studies.

For example, two nonrandomized trials comparing NSAIDs and acetaminophen in patients with quiescent disease found NSAIDs were associated with frequent, early clinical relapse of IBD. But another study comparing patients with symptom flares and those in clinical remission found no difference between the two groups in the frequency of NSAID use.

©PhotoDisk

SOURCE: Moninuola O et al. Aliment Pharmacol Ther. 2018 Apr 5. doi: 10.1111/apt.14606.

The relationship between nonsteroidal anti-inflammatory drug (NSAID) use and exacerbations of inflammatory bowel disease (IBD) may not be as clear-cut as previously thought, according to the results of a systematic review and meta-analysis.

The report was published online in Alimentary Pharmacology and Therapeutics.

The researchers presented their analysis of 18 studies examining the association between acetaminophen, NSAIDs, and cyclo-oxygenase-2 (COX-2) inhibitors, and the risk of Crohn’s disease, ulcerative colitis flares, and IBD.

Five studies looked at the association between NSAIDS – such as naproxen and indomethacin – and the risk of Crohn’s disease exacerbation. While this showed a 42% increased risk of exacerbation with NSAID use, the authors noted that they saw substantial heterogeneity across the studies.

For example, two nonrandomized trials comparing NSAIDs and acetaminophen in patients with quiescent disease found NSAIDs were associated with frequent, early clinical relapse of IBD. But another study comparing patients with symptom flares and those in clinical remission found no difference between the two groups in the frequency of NSAID use.

©PhotoDisk

SOURCE: Moninuola O et al. Aliment Pharmacol Ther. 2018 Apr 5. doi: 10.1111/apt.14606.

Hospital Medicine: 10 years ago

My first Society of Hospital Medicine Annual Conference was HM08, and it changed the course of my professional career.

I was a first-year hospitalist from an academic program of fewer than 10 physicians. My knowledge about my field did not extend much beyond the clinical practice of hospital medicine. I remember sitting at the airport on my way to HM08 and excitedly looking over the schedule for the meeting. I diligently circled the sessions that I was looking forward to attending, the majority of which focused on the clinical tracks. But by the end of the meeting, in additional to valuable medical knowledge, I walked away with novel insights that launched me into my future.

New ideas in HM: In 2008, comanagement was still a new concept. As I attended sessions and spoke with hospitalists from across the country, it became clear that this was a collaboration that would be core to our specialty. Within a couple of months of returning home from the annual conference, I was approached by the chair of neurosurgery at my institution with a proposal to develop a quality program for his group. While at that time I was considering other competing interests, my experience at HM08 helped me recognize that this was a unique opportunity to build bridges across specialties and to collaborate. I subsequently became the executive director of quality for neurosurgery and over the years was able to create a strong relationship between our departments that led to building a nationally recognized program with exceptional performance in hospital-based quality.

Side note: If you’re interested in resources on comanagement, please check out SHM’s Resources for Effective Co-Management of Hospitalized Patients at https://www.hospitalmedicine.org/comanagement .

Emerging themes and trends in health care: While the quality movement had launched about a decade before HM08, many institutions still did not have robust programs. As I attended sessions during the annual meeting and spoke with thought leaders, one message became clear: Hospitalists would have to lead the quality movement at their institutions. When I returned home, I began learning about quality improvement and started to lead various initiatives. These efforts led to my appointment as associate chief medical officer for the health system. This position enabled me to leverage my knowledge of hospital-based care and collaborate across various specialties to reduce our mortality and readmission rates in the organization.

Side note: If you’re interested in learning more about quality improvement educational and mentorship opportunities, please visit https://www.hospitalmedicine.org/qi and look at the resources for each specific topic.

And, most importantly, friendships: By far the most important thing I took away from HM08 was the friendships that started at that meeting and have developed over the years since. A decade later, I continue to rely on, grow from, and be challenged by the same people I met at that meeting. They are the colleagues I call when I find myself in a tough spot at work and need advice, the collaborators I work with on grants and projects, and the friends I text when I travel to a new town and want to grab a bite to eat.

Side note: If you’re interested in connecting with colleagues who share similar interests, please visit https://www.hospitalmedicine.org/sigs and review SHM’s Special Interest Groups to find ones that are right for you. To connect on a more local level, find an SHM Chapter near you at https://www.hospitalmedicine.org/chapters.

I’ve shared these stories with you because for me my journey with our society has been a deeply personal one. And I feel indebted to SHM and the incredible people who drawn to it for helping me develop and enjoy a rich and rewarding career thus far. So, as I look forward to the next decade, I wanted to share my thoughts on HM and emerging themes in health care with you.
 

Hospital medicine: The next decade

New ideas in HM: Population health management

Building on our strong culture of collaboration as we move forward into this next decade, we have to define how we deliver value in the context of population health management. As hospitalists, we have to push the boundaries of the hospital and provide high-value care beyond our four walls.

How can we do that? I think technology will play a critical role in extending our reach beyond the hospital. As we move toward delivering greater value to our patients, lower acuity patients will receive care in their homes. Telehealth will enable us to monitor and manage these patients remotely while transferring our bedside management to patients’ bedrooms in their own homes. Virtual hospitals will further enable us to evaluate, triage, monitor, and manage patients remotely. Our active engagement in these efforts is critical to ensure the continued growth and value we bring to our patients, our organizations, and our society.
 

Emerging themes and trends in health care: Transitioning from quality to value

In the next decade, value will prevail. This is not a novel concept – much like how quality was not a new idea in 2008.

Value has been around for a while: There are some robust programs nationally, there is research around the topic, and there are policies with implications for reimbursements. However, the full potential of value has not yet been realized by health care – it exists in individual programs, not in everything we do. The unprecedented number of mergers and acquisitions in health care in 2018 support the fact that the future will belong to those institutions that can deliver the highest quality of care at the most appropriate cost throughout the entire continuum of care.

What are some of the tools that will help us get there? Artificial intelligence and machine learning will improve the predictive value for the care we deliver to individual patients; some preliminary work in this area has already revealed that factors that we previously associated with higher risk of readmissions are not truly predictive. Another emerging technology is blockchain: By creating a single source of truth for our patients’ medical information, it enables us to have dynamic, high-integrity records regardless of which health systems and EHRs have cared for those patients.

I wish you an energizing journey as you launch your future into the next dynamic decade of health care, and I look forward to connecting with you as we continue to build a society that prepares us for the challenges and opportunities ahead.
 

Dr. Afsar is the president of the Society of Hospital Medicine and the chief ambulatory officer and chief medical officer for the accountable care organizations at UC Irvine Health.

Hospital Medicine: 10 years ago

My first Society of Hospital Medicine Annual Conference was HM08, and it changed the course of my professional career.

I was a first-year hospitalist from an academic program of fewer than 10 physicians. My knowledge about my field did not extend much beyond the clinical practice of hospital medicine. I remember sitting at the airport on my way to HM08 and excitedly looking over the schedule for the meeting. I diligently circled the sessions that I was looking forward to attending, the majority of which focused on the clinical tracks. But by the end of the meeting, in additional to valuable medical knowledge, I walked away with novel insights that launched me into my future.

New ideas in HM: In 2008, comanagement was still a new concept. As I attended sessions and spoke with hospitalists from across the country, it became clear that this was a collaboration that would be core to our specialty. Within a couple of months of returning home from the annual conference, I was approached by the chair of neurosurgery at my institution with a proposal to develop a quality program for his group. While at that time I was considering other competing interests, my experience at HM08 helped me recognize that this was a unique opportunity to build bridges across specialties and to collaborate. I subsequently became the executive director of quality for neurosurgery and over the years was able to create a strong relationship between our departments that led to building a nationally recognized program with exceptional performance in hospital-based quality.

Side note: If you’re interested in resources on comanagement, please check out SHM’s Resources for Effective Co-Management of Hospitalized Patients at https://www.hospitalmedicine.org/comanagement .

Emerging themes and trends in health care: While the quality movement had launched about a decade before HM08, many institutions still did not have robust programs. As I attended sessions during the annual meeting and spoke with thought leaders, one message became clear: Hospitalists would have to lead the quality movement at their institutions. When I returned home, I began learning about quality improvement and started to lead various initiatives. These efforts led to my appointment as associate chief medical officer for the health system. This position enabled me to leverage my knowledge of hospital-based care and collaborate across various specialties to reduce our mortality and readmission rates in the organization.

Side note: If you’re interested in learning more about quality improvement educational and mentorship opportunities, please visit https://www.hospitalmedicine.org/qi and look at the resources for each specific topic.

And, most importantly, friendships: By far the most important thing I took away from HM08 was the friendships that started at that meeting and have developed over the years since. A decade later, I continue to rely on, grow from, and be challenged by the same people I met at that meeting. They are the colleagues I call when I find myself in a tough spot at work and need advice, the collaborators I work with on grants and projects, and the friends I text when I travel to a new town and want to grab a bite to eat.

Side note: If you’re interested in connecting with colleagues who share similar interests, please visit https://www.hospitalmedicine.org/sigs and review SHM’s Special Interest Groups to find ones that are right for you. To connect on a more local level, find an SHM Chapter near you at https://www.hospitalmedicine.org/chapters.

I’ve shared these stories with you because for me my journey with our society has been a deeply personal one. And I feel indebted to SHM and the incredible people who drawn to it for helping me develop and enjoy a rich and rewarding career thus far. So, as I look forward to the next decade, I wanted to share my thoughts on HM and emerging themes in health care with you.
 

Hospital medicine: The next decade

New ideas in HM: Population health management

Building on our strong culture of collaboration as we move forward into this next decade, we have to define how we deliver value in the context of population health management. As hospitalists, we have to push the boundaries of the hospital and provide high-value care beyond our four walls.

How can we do that? I think technology will play a critical role in extending our reach beyond the hospital. As we move toward delivering greater value to our patients, lower acuity patients will receive care in their homes. Telehealth will enable us to monitor and manage these patients remotely while transferring our bedside management to patients’ bedrooms in their own homes. Virtual hospitals will further enable us to evaluate, triage, monitor, and manage patients remotely. Our active engagement in these efforts is critical to ensure the continued growth and value we bring to our patients, our organizations, and our society.
 

Emerging themes and trends in health care: Transitioning from quality to value

In the next decade, value will prevail. This is not a novel concept – much like how quality was not a new idea in 2008.

Value has been around for a while: There are some robust programs nationally, there is research around the topic, and there are policies with implications for reimbursements. However, the full potential of value has not yet been realized by health care – it exists in individual programs, not in everything we do. The unprecedented number of mergers and acquisitions in health care in 2018 support the fact that the future will belong to those institutions that can deliver the highest quality of care at the most appropriate cost throughout the entire continuum of care.

What are some of the tools that will help us get there? Artificial intelligence and machine learning will improve the predictive value for the care we deliver to individual patients; some preliminary work in this area has already revealed that factors that we previously associated with higher risk of readmissions are not truly predictive. Another emerging technology is blockchain: By creating a single source of truth for our patients’ medical information, it enables us to have dynamic, high-integrity records regardless of which health systems and EHRs have cared for those patients.

I wish you an energizing journey as you launch your future into the next dynamic decade of health care, and I look forward to connecting with you as we continue to build a society that prepares us for the challenges and opportunities ahead.
 

Dr. Afsar is the president of the Society of Hospital Medicine and the chief ambulatory officer and chief medical officer for the accountable care organizations at UC Irvine Health.

Hospital Medicine: 10 years ago

My first Society of Hospital Medicine Annual Conference was HM08, and it changed the course of my professional career.

I was a first-year hospitalist from an academic program of fewer than 10 physicians. My knowledge about my field did not extend much beyond the clinical practice of hospital medicine. I remember sitting at the airport on my way to HM08 and excitedly looking over the schedule for the meeting. I diligently circled the sessions that I was looking forward to attending, the majority of which focused on the clinical tracks. But by the end of the meeting, in additional to valuable medical knowledge, I walked away with novel insights that launched me into my future.

New ideas in HM: In 2008, comanagement was still a new concept. As I attended sessions and spoke with hospitalists from across the country, it became clear that this was a collaboration that would be core to our specialty. Within a couple of months of returning home from the annual conference, I was approached by the chair of neurosurgery at my institution with a proposal to develop a quality program for his group. While at that time I was considering other competing interests, my experience at HM08 helped me recognize that this was a unique opportunity to build bridges across specialties and to collaborate. I subsequently became the executive director of quality for neurosurgery and over the years was able to create a strong relationship between our departments that led to building a nationally recognized program with exceptional performance in hospital-based quality.

Side note: If you’re interested in resources on comanagement, please check out SHM’s Resources for Effective Co-Management of Hospitalized Patients at https://www.hospitalmedicine.org/comanagement .

Emerging themes and trends in health care: While the quality movement had launched about a decade before HM08, many institutions still did not have robust programs. As I attended sessions during the annual meeting and spoke with thought leaders, one message became clear: Hospitalists would have to lead the quality movement at their institutions. When I returned home, I began learning about quality improvement and started to lead various initiatives. These efforts led to my appointment as associate chief medical officer for the health system. This position enabled me to leverage my knowledge of hospital-based care and collaborate across various specialties to reduce our mortality and readmission rates in the organization.

Side note: If you’re interested in learning more about quality improvement educational and mentorship opportunities, please visit https://www.hospitalmedicine.org/qi and look at the resources for each specific topic.

And, most importantly, friendships: By far the most important thing I took away from HM08 was the friendships that started at that meeting and have developed over the years since. A decade later, I continue to rely on, grow from, and be challenged by the same people I met at that meeting. They are the colleagues I call when I find myself in a tough spot at work and need advice, the collaborators I work with on grants and projects, and the friends I text when I travel to a new town and want to grab a bite to eat.

Side note: If you’re interested in connecting with colleagues who share similar interests, please visit https://www.hospitalmedicine.org/sigs and review SHM’s Special Interest Groups to find ones that are right for you. To connect on a more local level, find an SHM Chapter near you at https://www.hospitalmedicine.org/chapters.

I’ve shared these stories with you because for me my journey with our society has been a deeply personal one. And I feel indebted to SHM and the incredible people who drawn to it for helping me develop and enjoy a rich and rewarding career thus far. So, as I look forward to the next decade, I wanted to share my thoughts on HM and emerging themes in health care with you.
 

Hospital medicine: The next decade

New ideas in HM: Population health management

Building on our strong culture of collaboration as we move forward into this next decade, we have to define how we deliver value in the context of population health management. As hospitalists, we have to push the boundaries of the hospital and provide high-value care beyond our four walls.

How can we do that? I think technology will play a critical role in extending our reach beyond the hospital. As we move toward delivering greater value to our patients, lower acuity patients will receive care in their homes. Telehealth will enable us to monitor and manage these patients remotely while transferring our bedside management to patients’ bedrooms in their own homes. Virtual hospitals will further enable us to evaluate, triage, monitor, and manage patients remotely. Our active engagement in these efforts is critical to ensure the continued growth and value we bring to our patients, our organizations, and our society.
 

Emerging themes and trends in health care: Transitioning from quality to value

In the next decade, value will prevail. This is not a novel concept – much like how quality was not a new idea in 2008.

Value has been around for a while: There are some robust programs nationally, there is research around the topic, and there are policies with implications for reimbursements. However, the full potential of value has not yet been realized by health care – it exists in individual programs, not in everything we do. The unprecedented number of mergers and acquisitions in health care in 2018 support the fact that the future will belong to those institutions that can deliver the highest quality of care at the most appropriate cost throughout the entire continuum of care.

What are some of the tools that will help us get there? Artificial intelligence and machine learning will improve the predictive value for the care we deliver to individual patients; some preliminary work in this area has already revealed that factors that we previously associated with higher risk of readmissions are not truly predictive. Another emerging technology is blockchain: By creating a single source of truth for our patients’ medical information, it enables us to have dynamic, high-integrity records regardless of which health systems and EHRs have cared for those patients.

I wish you an energizing journey as you launch your future into the next dynamic decade of health care, and I look forward to connecting with you as we continue to build a society that prepares us for the challenges and opportunities ahead.
 

Dr. Afsar is the president of the Society of Hospital Medicine and the chief ambulatory officer and chief medical officer for the accountable care organizations at UC Irvine Health.

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.

Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).

Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1^{Ser241 (p-PDPK1)} in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.

Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).

Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1^{Ser241 (p-PDPK1)} in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.

Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).

Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1^{Ser241 (p-PDPK1)} in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.

It wasn’t something she planned to have happen but about 2 years ago, Vineet Arora, MD, MAPP, MHM, became what she calls an “accidental advocate” for gender parity in medicine.

“I was asked to review a paper around gender pay,” the University of Chicago Medical Center hospitalist said. “It was stunning to me just how different salaries were – between male and female physicians – even when the authors were attempting to control for various factors.”

That paper was published in the Journal of the American Medical Association (JAMA) in September 2016 by researchers at Harvard Medical School and Massachusetts General Hospital (MGH). It found that even after adjustment for age, experience, specialty, faculty rank, research productivity, and clinical revenue, female physicians at 24 public medical schools in 12 states earned nearly $20,000 less per year than their male colleagues.¹

Dr. Arora wrote an editorial to accompany that 2016 paper in JAMA, and in September 2017, she and her colleague at the University of Chicago, Jeanne Farnan, MD, MHPE, coauthored another piece in Annals of Internal Medicine titled, “Inpatient Notes: Gender Equality in Hospital Medicine – Are We There Yet?”²

In the 2017 paper, Dr. Arora and Dr. Farnan assessed recent studies documenting inequity in regard to compensation, discrimination around child-rearing, and gender disparities in medical leadership. They also discussed strategies that might improve the future outlook for female physicians.

“As I approach mid-career, I see these issues affecting my career and my colleagues’ careers and I decided we need to be doing more work in this space,” said Dr. Arora.

Fueling the conversation

When asked whether he thinks his research inspired the current conversation around gender inequity in medicine, Anupam Bapu Jena, MD, PhD – lead author of the September 2016 gender pay paper – said that while he did not initiate it, his work “has fueled the conversation.”

“This is an issue that has been going on in the scientific literature for at least 25-30 years,” said Dr. Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy at Harvard Medical School and a physician in the department of medicine at MGH. “I am sure women in medicine have been feeling this since women entered medicine.”

Many female hospitalists hoped that, as a relatively new field, hospital medicine would avoid some of the time-worn challenges women in other specialties faced.

“The birth of hospital medicine held the promise that, as a new field, it would be immune to the ‘old boys’ club mentality that plagues established specialties,” Dr. Farnan and Dr. Arora wrote in their September 2017 Annals article. And yet, they continued, “gender disparities developed in the areas of leadership and academic productivity.”

Being taken seriously

Expectations around gender norms may also affect relationships female doctors have with their patients. In a June 2017 Washington Post editorial, Faye Reiff-Pasarew, MD, describes being objectified as “cute” and “adorable” and not being taken seriously by her patients.⁴

“I’d had a number of interactions with patients that upset me,” said Dr. Reiff-Pasarew, assistant professor of hospital medicine, director of the humanism in medicine program, and unit medical director at Icahn School of Medicine at Mount Sinai in New York City. “Later, I reflected upon them and realized that bias was a systemic problem. There needs to be a conversation amongst the broader medical community about the effect that these biases have on our patients and our practice.”

In her editorial, Dr. Reiff-Pasarew explained that when a female physician is written off as too young or is not recognized as a physician, it can delay necessary care. She also touches on the challenge of earning the trust of hospitalized patients.

“There’s a lot of evidence that the success of medical therapy is influenced by the context in which it is given, beyond mere adherence to a regimen or medication,” Dr. Reiff-Pasarew said, noting that it is a result of “the very powerful placebo effect.

Equal compensation for equal work

Ultimately, it is in the best interest of all physicians, their employers, and their patients to ensure female physicians are satisfied and fulfilled in their professions, said Dr. Jena, and that includes recognizing and rewarding their value.

“What I am trying to argue in my work is for equal pay – equal compensation for equal work,” Dr. Jena said. “Man or woman, it’s a good idea.”

Dr. Jena, who is also a faculty research fellow at the National Bureau of Economic Research, said that when the contributions of a group of people are systematically undervalued, “you run the risk of having those individuals invest less in their career.” In health care, he said, “if fewer women want to go into academic medicine because they know they are underpaid, what impact does it have on new ideas when you eliminate highly successful, intelligent people from a field?”

Dr. Jena and his colleagues authored a February 2017 study in JAMA Internal Medicine that showed hospitalized Medicare patients treated by female internists have lower 30-day mortality and readmissions rates compared with those treated by male internists, including hospitalists. This included millions of hospitalizations and accounted for myriad confounders.⁵

References

1. Jena AB, Olenski AR, Blumenthal DM. Sex differences in physician salary in US public medical schools. JAMA Intern Med. 2016;176(9):1294-1304. doi: 10.1001/jamainternmed.2016.3284.

2. Farnan JM and Arora VM. Gender equality in hospital medicine – are we there yet? Ann Intern Med. 2017;167(6):HO2-HO3. doi: 10.7326/M17-2119.

3. Burden M, Frank MG, Keniston A, et al. Gender disparities in leadership and scholarly productivity of academic hospitalists. J Hosp Med 2015;8;481-5. doi: 10.1002/jhm.2340.

4. Reiff-Pasarew F. I’m a young, female doctor. Calling me ‘sweetie’ won’t help me save your life. Washington Post. Published June 29, 2017. Accessed Dec. 4, 2017.

5. Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs female physicians. JAMA Intern Med. 2017;177(2):206-13. doi: 10.1001/jamainternmed.2016.7875.

It wasn’t something she planned to have happen but about 2 years ago, Vineet Arora, MD, MAPP, MHM, became what she calls an “accidental advocate” for gender parity in medicine.

“I was asked to review a paper around gender pay,” the University of Chicago Medical Center hospitalist said. “It was stunning to me just how different salaries were – between male and female physicians – even when the authors were attempting to control for various factors.”

That paper was published in the Journal of the American Medical Association (JAMA) in September 2016 by researchers at Harvard Medical School and Massachusetts General Hospital (MGH). It found that even after adjustment for age, experience, specialty, faculty rank, research productivity, and clinical revenue, female physicians at 24 public medical schools in 12 states earned nearly $20,000 less per year than their male colleagues.¹

Dr. Arora wrote an editorial to accompany that 2016 paper in JAMA, and in September 2017, she and her colleague at the University of Chicago, Jeanne Farnan, MD, MHPE, coauthored another piece in Annals of Internal Medicine titled, “Inpatient Notes: Gender Equality in Hospital Medicine – Are We There Yet?”²

In the 2017 paper, Dr. Arora and Dr. Farnan assessed recent studies documenting inequity in regard to compensation, discrimination around child-rearing, and gender disparities in medical leadership. They also discussed strategies that might improve the future outlook for female physicians.

“As I approach mid-career, I see these issues affecting my career and my colleagues’ careers and I decided we need to be doing more work in this space,” said Dr. Arora.

Fueling the conversation

When asked whether he thinks his research inspired the current conversation around gender inequity in medicine, Anupam Bapu Jena, MD, PhD – lead author of the September 2016 gender pay paper – said that while he did not initiate it, his work “has fueled the conversation.”

“This is an issue that has been going on in the scientific literature for at least 25-30 years,” said Dr. Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy at Harvard Medical School and a physician in the department of medicine at MGH. “I am sure women in medicine have been feeling this since women entered medicine.”

Many female hospitalists hoped that, as a relatively new field, hospital medicine would avoid some of the time-worn challenges women in other specialties faced.

“The birth of hospital medicine held the promise that, as a new field, it would be immune to the ‘old boys’ club mentality that plagues established specialties,” Dr. Farnan and Dr. Arora wrote in their September 2017 Annals article. And yet, they continued, “gender disparities developed in the areas of leadership and academic productivity.”

Being taken seriously

Expectations around gender norms may also affect relationships female doctors have with their patients. In a June 2017 Washington Post editorial, Faye Reiff-Pasarew, MD, describes being objectified as “cute” and “adorable” and not being taken seriously by her patients.⁴

“I’d had a number of interactions with patients that upset me,” said Dr. Reiff-Pasarew, assistant professor of hospital medicine, director of the humanism in medicine program, and unit medical director at Icahn School of Medicine at Mount Sinai in New York City. “Later, I reflected upon them and realized that bias was a systemic problem. There needs to be a conversation amongst the broader medical community about the effect that these biases have on our patients and our practice.”

In her editorial, Dr. Reiff-Pasarew explained that when a female physician is written off as too young or is not recognized as a physician, it can delay necessary care. She also touches on the challenge of earning the trust of hospitalized patients.

“There’s a lot of evidence that the success of medical therapy is influenced by the context in which it is given, beyond mere adherence to a regimen or medication,” Dr. Reiff-Pasarew said, noting that it is a result of “the very powerful placebo effect.

Equal compensation for equal work

Ultimately, it is in the best interest of all physicians, their employers, and their patients to ensure female physicians are satisfied and fulfilled in their professions, said Dr. Jena, and that includes recognizing and rewarding their value.

“What I am trying to argue in my work is for equal pay – equal compensation for equal work,” Dr. Jena said. “Man or woman, it’s a good idea.”

Dr. Jena, who is also a faculty research fellow at the National Bureau of Economic Research, said that when the contributions of a group of people are systematically undervalued, “you run the risk of having those individuals invest less in their career.” In health care, he said, “if fewer women want to go into academic medicine because they know they are underpaid, what impact does it have on new ideas when you eliminate highly successful, intelligent people from a field?”

Dr. Jena and his colleagues authored a February 2017 study in JAMA Internal Medicine that showed hospitalized Medicare patients treated by female internists have lower 30-day mortality and readmissions rates compared with those treated by male internists, including hospitalists. This included millions of hospitalizations and accounted for myriad confounders.⁵

References

1. Jena AB, Olenski AR, Blumenthal DM. Sex differences in physician salary in US public medical schools. JAMA Intern Med. 2016;176(9):1294-1304. doi: 10.1001/jamainternmed.2016.3284.

2. Farnan JM and Arora VM. Gender equality in hospital medicine – are we there yet? Ann Intern Med. 2017;167(6):HO2-HO3. doi: 10.7326/M17-2119.

3. Burden M, Frank MG, Keniston A, et al. Gender disparities in leadership and scholarly productivity of academic hospitalists. J Hosp Med 2015;8;481-5. doi: 10.1002/jhm.2340.

4. Reiff-Pasarew F. I’m a young, female doctor. Calling me ‘sweetie’ won’t help me save your life. Washington Post. Published June 29, 2017. Accessed Dec. 4, 2017.

5. Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs female physicians. JAMA Intern Med. 2017;177(2):206-13. doi: 10.1001/jamainternmed.2016.7875.

It wasn’t something she planned to have happen but about 2 years ago, Vineet Arora, MD, MAPP, MHM, became what she calls an “accidental advocate” for gender parity in medicine.

“I was asked to review a paper around gender pay,” the University of Chicago Medical Center hospitalist said. “It was stunning to me just how different salaries were – between male and female physicians – even when the authors were attempting to control for various factors.”

That paper was published in the Journal of the American Medical Association (JAMA) in September 2016 by researchers at Harvard Medical School and Massachusetts General Hospital (MGH). It found that even after adjustment for age, experience, specialty, faculty rank, research productivity, and clinical revenue, female physicians at 24 public medical schools in 12 states earned nearly $20,000 less per year than their male colleagues.¹

Dr. Arora wrote an editorial to accompany that 2016 paper in JAMA, and in September 2017, she and her colleague at the University of Chicago, Jeanne Farnan, MD, MHPE, coauthored another piece in Annals of Internal Medicine titled, “Inpatient Notes: Gender Equality in Hospital Medicine – Are We There Yet?”²

In the 2017 paper, Dr. Arora and Dr. Farnan assessed recent studies documenting inequity in regard to compensation, discrimination around child-rearing, and gender disparities in medical leadership. They also discussed strategies that might improve the future outlook for female physicians.

“As I approach mid-career, I see these issues affecting my career and my colleagues’ careers and I decided we need to be doing more work in this space,” said Dr. Arora.

Fueling the conversation

When asked whether he thinks his research inspired the current conversation around gender inequity in medicine, Anupam Bapu Jena, MD, PhD – lead author of the September 2016 gender pay paper – said that while he did not initiate it, his work “has fueled the conversation.”

“This is an issue that has been going on in the scientific literature for at least 25-30 years,” said Dr. Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy at Harvard Medical School and a physician in the department of medicine at MGH. “I am sure women in medicine have been feeling this since women entered medicine.”

Many female hospitalists hoped that, as a relatively new field, hospital medicine would avoid some of the time-worn challenges women in other specialties faced.

“The birth of hospital medicine held the promise that, as a new field, it would be immune to the ‘old boys’ club mentality that plagues established specialties,” Dr. Farnan and Dr. Arora wrote in their September 2017 Annals article. And yet, they continued, “gender disparities developed in the areas of leadership and academic productivity.”

Being taken seriously

Expectations around gender norms may also affect relationships female doctors have with their patients. In a June 2017 Washington Post editorial, Faye Reiff-Pasarew, MD, describes being objectified as “cute” and “adorable” and not being taken seriously by her patients.⁴

“I’d had a number of interactions with patients that upset me,” said Dr. Reiff-Pasarew, assistant professor of hospital medicine, director of the humanism in medicine program, and unit medical director at Icahn School of Medicine at Mount Sinai in New York City. “Later, I reflected upon them and realized that bias was a systemic problem. There needs to be a conversation amongst the broader medical community about the effect that these biases have on our patients and our practice.”

In her editorial, Dr. Reiff-Pasarew explained that when a female physician is written off as too young or is not recognized as a physician, it can delay necessary care. She also touches on the challenge of earning the trust of hospitalized patients.

“There’s a lot of evidence that the success of medical therapy is influenced by the context in which it is given, beyond mere adherence to a regimen or medication,” Dr. Reiff-Pasarew said, noting that it is a result of “the very powerful placebo effect.

Equal compensation for equal work

Ultimately, it is in the best interest of all physicians, their employers, and their patients to ensure female physicians are satisfied and fulfilled in their professions, said Dr. Jena, and that includes recognizing and rewarding their value.

“What I am trying to argue in my work is for equal pay – equal compensation for equal work,” Dr. Jena said. “Man or woman, it’s a good idea.”

Dr. Jena, who is also a faculty research fellow at the National Bureau of Economic Research, said that when the contributions of a group of people are systematically undervalued, “you run the risk of having those individuals invest less in their career.” In health care, he said, “if fewer women want to go into academic medicine because they know they are underpaid, what impact does it have on new ideas when you eliminate highly successful, intelligent people from a field?”

Dr. Jena and his colleagues authored a February 2017 study in JAMA Internal Medicine that showed hospitalized Medicare patients treated by female internists have lower 30-day mortality and readmissions rates compared with those treated by male internists, including hospitalists. This included millions of hospitalizations and accounted for myriad confounders.⁵

References

1. Jena AB, Olenski AR, Blumenthal DM. Sex differences in physician salary in US public medical schools. JAMA Intern Med. 2016;176(9):1294-1304. doi: 10.1001/jamainternmed.2016.3284.

2. Farnan JM and Arora VM. Gender equality in hospital medicine – are we there yet? Ann Intern Med. 2017;167(6):HO2-HO3. doi: 10.7326/M17-2119.

3. Burden M, Frank MG, Keniston A, et al. Gender disparities in leadership and scholarly productivity of academic hospitalists. J Hosp Med 2015;8;481-5. doi: 10.1002/jhm.2340.

4. Reiff-Pasarew F. I’m a young, female doctor. Calling me ‘sweetie’ won’t help me save your life. Washington Post. Published June 29, 2017. Accessed Dec. 4, 2017.

5. Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs female physicians. JAMA Intern Med. 2017;177(2):206-13. doi: 10.1001/jamainternmed.2016.7875.