Article

Patients with stage II or III gastric cancer are treated with surgical resection and perioperative chemotherapy. Platinum agents have established activity in this disease. Combination chemotherapy FLOT (5-fluorouracil, oxaliplatin, and docetaxel) is now standard perioperative treatment for resectable gastric cancer.¹ The study by Slagter and colleagues evaluated whether cisplatin was noninferior to oxaliplatin when used in the treatment of early-stage gastric cancer. Prior to the incorporation of FLOT into standard treatment practice, patients were treated with ECX (epirubicin, cisplatin, and docetaxel), as per the MAGIC trial.² In the metastatic setting, chemotherapy regimens with either cisplatin or oxaliplatin as a choice of platinum agent have comparable activity against these tumors. Oxaliplatin activity has been shown to be noninferior to cisplatin in the randomized REAL2 trial in metastatic setting.³

The study by Slagter and colleagues is a post hoc analysis of 781 patients with resectable gastric cancer who were enrolled in the CRITICS trial. This analysis demonstrated that chemotherapy regimens containing oxaliplatin and cisplatin had comparable 5-year overall survival rates. Not surprisingly, oxaliplatin was associated with higher neurotoxicity. Based on this analysis, it is likely safe to conclude that, just as in the advanced setting, cisplatin and oxaliplatin have similar activity in early-stage disease.

Mismatch repair protein deficient or microsatellite unstable gastric cancer (MSI-H) represent unique subtypes of gastric cancer, with distinct biologic behaviors and treatment responses. The efficacy of chemotherapy in patients with early-stage MSI-H tumors has been questioned previously. Similar to MSI-H colorectal cancers, the benefit of chemotherapy in resectable MSI-H gastric and esophagogastric junction tumors appears to be less robust than in microsatellite stable (MSS) tumors. In the exploratory analysis of patients with MSI-H tumors enrolled in the perioperative MAGIC trial, patients with MSI-H tumors had better prognosis when treated with surgery alone and potentially experienced detrimental effects from chemotherapy.⁴ The retrospective analysis by Vos and colleagues adds to the body of knowledge about early-stage MSI-H gastric cancers. They evaluated 535 patients with early-stage disease who were treated with surgery alone or surgery plus perioperative therapy between 2000 and 2018. The overall survival in 82 patients with MSI-H tumors was 20% better than in those with MSS disease. This favorable outcome was seen irrespective of whether chemotherapy was given. Though these results suggest that chemotherapy may not be necessary in the treatment of these tumors and there are emerging data regarding the activity of immune checkpoint inhibitors in this setting, these results should definitely be investigated further in prospective studies.⁵ However, in the absence of prospective randomized data, it is difficult to recommend deviating from the established standard of care with FLOT, especially for patients undergoing curative intent treatment.

A study by Yukami and colleagues evaluated whether the presence of liver metastasis, which have been shown to be enriched in immunosuppressive cells in the preclinical setting, had any bearing on the activity of immune checkpoint inhibitors alone or in combination with multi-tyrosine kinase inhibitors. The analysis included 54 patients enrolled in a phase 1b trial  of REGONIVO (regorafenib and nivolumab) and a phase 2 trial of LENPEM (lenvatinib and pembrolizumab). With a median follow up of 14 months, there was no significant difference in the efficacy of the above regimens (overall survival, progression-free survival, and objective response rate) between patients with and without liver metastasis. The promising activity of these combinations is continuing with longer follow-up. The above regimens should be investigated further in larger prospective studies irrespective of metastatic sites.

Additional References

1.           Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1

2.           Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11-20. Doi:  10.1056/NEJMoa055531

3.           Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36-46. Doi: 10.1056/NEJMoa073149

4.           Smyth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762

5.           Andre T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): the GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022;40:244-244. Doi: 10.1200/JCO.2022.40.4_suppl.244

Patients with stage II or III gastric cancer are treated with surgical resection and perioperative chemotherapy. Platinum agents have established activity in this disease. Combination chemotherapy FLOT (5-fluorouracil, oxaliplatin, and docetaxel) is now standard perioperative treatment for resectable gastric cancer.¹ The study by Slagter and colleagues evaluated whether cisplatin was noninferior to oxaliplatin when used in the treatment of early-stage gastric cancer. Prior to the incorporation of FLOT into standard treatment practice, patients were treated with ECX (epirubicin, cisplatin, and docetaxel), as per the MAGIC trial.² In the metastatic setting, chemotherapy regimens with either cisplatin or oxaliplatin as a choice of platinum agent have comparable activity against these tumors. Oxaliplatin activity has been shown to be noninferior to cisplatin in the randomized REAL2 trial in metastatic setting.³

The study by Slagter and colleagues is a post hoc analysis of 781 patients with resectable gastric cancer who were enrolled in the CRITICS trial. This analysis demonstrated that chemotherapy regimens containing oxaliplatin and cisplatin had comparable 5-year overall survival rates. Not surprisingly, oxaliplatin was associated with higher neurotoxicity. Based on this analysis, it is likely safe to conclude that, just as in the advanced setting, cisplatin and oxaliplatin have similar activity in early-stage disease.

Mismatch repair protein deficient or microsatellite unstable gastric cancer (MSI-H) represent unique subtypes of gastric cancer, with distinct biologic behaviors and treatment responses. The efficacy of chemotherapy in patients with early-stage MSI-H tumors has been questioned previously. Similar to MSI-H colorectal cancers, the benefit of chemotherapy in resectable MSI-H gastric and esophagogastric junction tumors appears to be less robust than in microsatellite stable (MSS) tumors. In the exploratory analysis of patients with MSI-H tumors enrolled in the perioperative MAGIC trial, patients with MSI-H tumors had better prognosis when treated with surgery alone and potentially experienced detrimental effects from chemotherapy.⁴ The retrospective analysis by Vos and colleagues adds to the body of knowledge about early-stage MSI-H gastric cancers. They evaluated 535 patients with early-stage disease who were treated with surgery alone or surgery plus perioperative therapy between 2000 and 2018. The overall survival in 82 patients with MSI-H tumors was 20% better than in those with MSS disease. This favorable outcome was seen irrespective of whether chemotherapy was given. Though these results suggest that chemotherapy may not be necessary in the treatment of these tumors and there are emerging data regarding the activity of immune checkpoint inhibitors in this setting, these results should definitely be investigated further in prospective studies.⁵ However, in the absence of prospective randomized data, it is difficult to recommend deviating from the established standard of care with FLOT, especially for patients undergoing curative intent treatment.

A study by Yukami and colleagues evaluated whether the presence of liver metastasis, which have been shown to be enriched in immunosuppressive cells in the preclinical setting, had any bearing on the activity of immune checkpoint inhibitors alone or in combination with multi-tyrosine kinase inhibitors. The analysis included 54 patients enrolled in a phase 1b trial  of REGONIVO (regorafenib and nivolumab) and a phase 2 trial of LENPEM (lenvatinib and pembrolizumab). With a median follow up of 14 months, there was no significant difference in the efficacy of the above regimens (overall survival, progression-free survival, and objective response rate) between patients with and without liver metastasis. The promising activity of these combinations is continuing with longer follow-up. The above regimens should be investigated further in larger prospective studies irrespective of metastatic sites.

Additional References

1.           Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1

2.           Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11-20. Doi:  10.1056/NEJMoa055531

3.           Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36-46. Doi: 10.1056/NEJMoa073149

4.           Smyth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762

5.           Andre T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): the GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022;40:244-244. Doi: 10.1200/JCO.2022.40.4_suppl.244

Patients with stage II or III gastric cancer are treated with surgical resection and perioperative chemotherapy. Platinum agents have established activity in this disease. Combination chemotherapy FLOT (5-fluorouracil, oxaliplatin, and docetaxel) is now standard perioperative treatment for resectable gastric cancer.¹ The study by Slagter and colleagues evaluated whether cisplatin was noninferior to oxaliplatin when used in the treatment of early-stage gastric cancer. Prior to the incorporation of FLOT into standard treatment practice, patients were treated with ECX (epirubicin, cisplatin, and docetaxel), as per the MAGIC trial.² In the metastatic setting, chemotherapy regimens with either cisplatin or oxaliplatin as a choice of platinum agent have comparable activity against these tumors. Oxaliplatin activity has been shown to be noninferior to cisplatin in the randomized REAL2 trial in metastatic setting.³

The study by Slagter and colleagues is a post hoc analysis of 781 patients with resectable gastric cancer who were enrolled in the CRITICS trial. This analysis demonstrated that chemotherapy regimens containing oxaliplatin and cisplatin had comparable 5-year overall survival rates. Not surprisingly, oxaliplatin was associated with higher neurotoxicity. Based on this analysis, it is likely safe to conclude that, just as in the advanced setting, cisplatin and oxaliplatin have similar activity in early-stage disease.

Mismatch repair protein deficient or microsatellite unstable gastric cancer (MSI-H) represent unique subtypes of gastric cancer, with distinct biologic behaviors and treatment responses. The efficacy of chemotherapy in patients with early-stage MSI-H tumors has been questioned previously. Similar to MSI-H colorectal cancers, the benefit of chemotherapy in resectable MSI-H gastric and esophagogastric junction tumors appears to be less robust than in microsatellite stable (MSS) tumors. In the exploratory analysis of patients with MSI-H tumors enrolled in the perioperative MAGIC trial, patients with MSI-H tumors had better prognosis when treated with surgery alone and potentially experienced detrimental effects from chemotherapy.⁴ The retrospective analysis by Vos and colleagues adds to the body of knowledge about early-stage MSI-H gastric cancers. They evaluated 535 patients with early-stage disease who were treated with surgery alone or surgery plus perioperative therapy between 2000 and 2018. The overall survival in 82 patients with MSI-H tumors was 20% better than in those with MSS disease. This favorable outcome was seen irrespective of whether chemotherapy was given. Though these results suggest that chemotherapy may not be necessary in the treatment of these tumors and there are emerging data regarding the activity of immune checkpoint inhibitors in this setting, these results should definitely be investigated further in prospective studies.⁵ However, in the absence of prospective randomized data, it is difficult to recommend deviating from the established standard of care with FLOT, especially for patients undergoing curative intent treatment.

A study by Yukami and colleagues evaluated whether the presence of liver metastasis, which have been shown to be enriched in immunosuppressive cells in the preclinical setting, had any bearing on the activity of immune checkpoint inhibitors alone or in combination with multi-tyrosine kinase inhibitors. The analysis included 54 patients enrolled in a phase 1b trial  of REGONIVO (regorafenib and nivolumab) and a phase 2 trial of LENPEM (lenvatinib and pembrolizumab). With a median follow up of 14 months, there was no significant difference in the efficacy of the above regimens (overall survival, progression-free survival, and objective response rate) between patients with and without liver metastasis. The promising activity of these combinations is continuing with longer follow-up. The above regimens should be investigated further in larger prospective studies irrespective of metastatic sites.

Additional References

1.           Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1

2.           Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11-20. Doi:  10.1056/NEJMoa055531

3.           Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36-46. Doi: 10.1056/NEJMoa073149

4.           Smyth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762

5.           Andre T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): the GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022;40:244-244. Doi: 10.1200/JCO.2022.40.4_suppl.244

Meta-analyses of sodium-glucose cotransporter 2 inhibitor (SGLT2i) outcome trials have shown reductions in all-cause and cardiovascular mortality, but dipeptidyl peptidase 4 inhibitors (DPP4i) have been neutral for these outcomes. In a Taiwanese retrospective cohort study, Chung and colleagues compared 53,264 pairs of propensity-matched patients with type 2 diabetes who were treated with either an SGLT2i or DPP4i. They not only reported relative risk reductions of 34% and 32% for all-cause death and cardiovascular death, respectively, but also a reduction in cancer death of 27% and a reduction in noncancer, noncardiovascular death of 38%. Although limited by its retrospective, observational design, the finding of a benefit of SGLT2i treatment on both cancer death and noncancer, noncardiovascular death would benefit from further research.

In another large Taiwanese retrospective cohort study with propensity matching, Chan and colleagues compared patients treated with SGLT2i, DPP4i, and glucagon-like peptide 1 receptor agonists (GLP-1RA), with a main study outcome of new-onset atrial fibrillation (AF). They noted that SGLT2i treatment was associated with a 10% and 36% lower risk for AF compared with DPP4i and GLP-1RA treatment, respectively. These results are consistent with meta-analyses of SGLT2i outcome trials that have demonstrated reductions in AF with SGLT2i vs placebo. Perhaps it is time to recognize that another clinical benefit of the SGLT2i class is the reduction in risk for AF.

Although GLP-1RA have been linked to an increased risk for gallbladder-related events in many studies, there has been little data suggesting an increased risk with DPP4i. He and colleagues have published a pairwise meta-analysis of 82 randomized clinical trials and found that DPP4i compared with placebo or nonincretin drugs increased the risk for gallbladder or biliary diseases by 1.22-fold, with 11 more events per 10,000 person years. In a network meta-analysis of 184 randomized trials, they also found that DPP4i treatment increased the risk for gallbladder or biliary diseases compared with SGLT2i but not compared with GLP-1RA. This was the first meta-analysis to systematically study the association between DPP4i and gallbladder-related diseases. Although the absolute risk is small, clinicians need to be aware of this link and consider this adverse effect when deciding about the risks vs benefits of DPP4i treatment.

Individuals with obesity and prediabetes are at greater risk for type 2 diabetes. Trials of lifestyle modification and antiobesity agents have shown that restoration to normoglycemia can occur with weight loss. Phase 3A studies of the antiobesity agent semaglutide (2.4 mg/week) included 3375 individuals with prediabetes across three trials. In a post hoc analysis of these patients with prediabetes, Perreault and colleagues found that after 68 weeks of treatment, there was a much higher likelihood of normoglycemia with 2.4 mg/week of semaglutide compared with placebo. Though definite conclusions are limited owing to the post hoc nature of this analysis, these results make it very likely that the ongoing STEP 10 trial of 2.4 mg semaglutide vs placebo (201 participants with obesity and prediabetes) will probably show a significant benefit on the primary outcome of change to normoglycemia.

Meta-analyses of sodium-glucose cotransporter 2 inhibitor (SGLT2i) outcome trials have shown reductions in all-cause and cardiovascular mortality, but dipeptidyl peptidase 4 inhibitors (DPP4i) have been neutral for these outcomes. In a Taiwanese retrospective cohort study, Chung and colleagues compared 53,264 pairs of propensity-matched patients with type 2 diabetes who were treated with either an SGLT2i or DPP4i. They not only reported relative risk reductions of 34% and 32% for all-cause death and cardiovascular death, respectively, but also a reduction in cancer death of 27% and a reduction in noncancer, noncardiovascular death of 38%. Although limited by its retrospective, observational design, the finding of a benefit of SGLT2i treatment on both cancer death and noncancer, noncardiovascular death would benefit from further research.

In another large Taiwanese retrospective cohort study with propensity matching, Chan and colleagues compared patients treated with SGLT2i, DPP4i, and glucagon-like peptide 1 receptor agonists (GLP-1RA), with a main study outcome of new-onset atrial fibrillation (AF). They noted that SGLT2i treatment was associated with a 10% and 36% lower risk for AF compared with DPP4i and GLP-1RA treatment, respectively. These results are consistent with meta-analyses of SGLT2i outcome trials that have demonstrated reductions in AF with SGLT2i vs placebo. Perhaps it is time to recognize that another clinical benefit of the SGLT2i class is the reduction in risk for AF.

Although GLP-1RA have been linked to an increased risk for gallbladder-related events in many studies, there has been little data suggesting an increased risk with DPP4i. He and colleagues have published a pairwise meta-analysis of 82 randomized clinical trials and found that DPP4i compared with placebo or nonincretin drugs increased the risk for gallbladder or biliary diseases by 1.22-fold, with 11 more events per 10,000 person years. In a network meta-analysis of 184 randomized trials, they also found that DPP4i treatment increased the risk for gallbladder or biliary diseases compared with SGLT2i but not compared with GLP-1RA. This was the first meta-analysis to systematically study the association between DPP4i and gallbladder-related diseases. Although the absolute risk is small, clinicians need to be aware of this link and consider this adverse effect when deciding about the risks vs benefits of DPP4i treatment.

Individuals with obesity and prediabetes are at greater risk for type 2 diabetes. Trials of lifestyle modification and antiobesity agents have shown that restoration to normoglycemia can occur with weight loss. Phase 3A studies of the antiobesity agent semaglutide (2.4 mg/week) included 3375 individuals with prediabetes across three trials. In a post hoc analysis of these patients with prediabetes, Perreault and colleagues found that after 68 weeks of treatment, there was a much higher likelihood of normoglycemia with 2.4 mg/week of semaglutide compared with placebo. Though definite conclusions are limited owing to the post hoc nature of this analysis, these results make it very likely that the ongoing STEP 10 trial of 2.4 mg semaglutide vs placebo (201 participants with obesity and prediabetes) will probably show a significant benefit on the primary outcome of change to normoglycemia.

Meta-analyses of sodium-glucose cotransporter 2 inhibitor (SGLT2i) outcome trials have shown reductions in all-cause and cardiovascular mortality, but dipeptidyl peptidase 4 inhibitors (DPP4i) have been neutral for these outcomes. In a Taiwanese retrospective cohort study, Chung and colleagues compared 53,264 pairs of propensity-matched patients with type 2 diabetes who were treated with either an SGLT2i or DPP4i. They not only reported relative risk reductions of 34% and 32% for all-cause death and cardiovascular death, respectively, but also a reduction in cancer death of 27% and a reduction in noncancer, noncardiovascular death of 38%. Although limited by its retrospective, observational design, the finding of a benefit of SGLT2i treatment on both cancer death and noncancer, noncardiovascular death would benefit from further research.

In another large Taiwanese retrospective cohort study with propensity matching, Chan and colleagues compared patients treated with SGLT2i, DPP4i, and glucagon-like peptide 1 receptor agonists (GLP-1RA), with a main study outcome of new-onset atrial fibrillation (AF). They noted that SGLT2i treatment was associated with a 10% and 36% lower risk for AF compared with DPP4i and GLP-1RA treatment, respectively. These results are consistent with meta-analyses of SGLT2i outcome trials that have demonstrated reductions in AF with SGLT2i vs placebo. Perhaps it is time to recognize that another clinical benefit of the SGLT2i class is the reduction in risk for AF.

Although GLP-1RA have been linked to an increased risk for gallbladder-related events in many studies, there has been little data suggesting an increased risk with DPP4i. He and colleagues have published a pairwise meta-analysis of 82 randomized clinical trials and found that DPP4i compared with placebo or nonincretin drugs increased the risk for gallbladder or biliary diseases by 1.22-fold, with 11 more events per 10,000 person years. In a network meta-analysis of 184 randomized trials, they also found that DPP4i treatment increased the risk for gallbladder or biliary diseases compared with SGLT2i but not compared with GLP-1RA. This was the first meta-analysis to systematically study the association between DPP4i and gallbladder-related diseases. Although the absolute risk is small, clinicians need to be aware of this link and consider this adverse effect when deciding about the risks vs benefits of DPP4i treatment.

Individuals with obesity and prediabetes are at greater risk for type 2 diabetes. Trials of lifestyle modification and antiobesity agents have shown that restoration to normoglycemia can occur with weight loss. Phase 3A studies of the antiobesity agent semaglutide (2.4 mg/week) included 3375 individuals with prediabetes across three trials. In a post hoc analysis of these patients with prediabetes, Perreault and colleagues found that after 68 weeks of treatment, there was a much higher likelihood of normoglycemia with 2.4 mg/week of semaglutide compared with placebo. Though definite conclusions are limited owing to the post hoc nature of this analysis, these results make it very likely that the ongoing STEP 10 trial of 2.4 mg semaglutide vs placebo (201 participants with obesity and prediabetes) will probably show a significant benefit on the primary outcome of change to normoglycemia.

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

This month brought us findings from DYNAMIC, a randomized trial of circulating tumor DNA (ctDNA), which aimed to provide guidance on the use of adjuvant chemotherapy in stage II colon cancer. This study has already been touted on oncology Twitter as a massive breakthrough for identifying patients with stage II colon cancer who would benefit from adjuvant chemotherapy. Does the reality live up to the hype? Let's break it down.

Patients with resected stage II colon cancer were eligible for enrollment. Two thirds of patients were randomly assigned to the ctDNA guidance arm, whereas the remaining third had chemotherapy guidance based on clinicopathologic high-risk features (T4, poor differentiation, < 12 lymph nodes in surgical sample, lymphovascular invasion, tumor perforation, or bowel obstruction). Chemotherapy choice was left up to the clinician and could be an oxaliplatin-based doublet or a single-agent fluoropyrimidine. The primary endpoint was recurrence-free survival at 2 years. A key secondary endpoint was chemotherapy treatment frequency by arm. A total of 459 patients were enrolled from 23 Australian centers over 4 years. Approximately 40% of patients were considered to be at high risk for recurrence on the basis of their tumors' clinicopathologic features. Approximately 20% of patients had tumors that were mismatch repair deficient.

There was no difference in 2-year recurrence-free survival between the two arms (93.5% vs 92.4%; 95% CI -4.1 to 6.2). This met criteria for noninferiority. However, chemotherapy administration in the two arms was markedly different. A significantly greater proportion of patients randomly assigned to the standard management arm received chemotherapy (28% vs 15%; relative risk [RR] 1.82; 95% CI 1.25-2.65). However, a significantly greater proportion of patients guided by ctDNA received an oxaliplatin-based doublet (62% vs 10%; RR 2.39; 95% CI 1.62-3.52). Clearly, when clinicians were presented with a positive ctDNA test, they overwhelmingly opted to give an oxaliplatin-based doublet rather than a single-agent fluoropyrimidine. Oxaliplatin's use in stage II colon cancer remains very controversial; it is oxaliplatin that causes most of the long-term toxicity associated with adjuvant chemotherapy for colorectal cancer. Although ctDNA testing might lower the total proportion of patients who received adjuvant treatment, it significantly raised the proportion who received oxaliplatin. I doubt this is a worthy trade-off.

Furthermore, clinicopathologic factors were still highly relevant in patients with ctDNA-negative results. Among ctDNA-negative patients, 3-year recurrence-free survival was higher in patients with clinicopathologic low-risk cancers than in those with high-risk cancers (96.7% vs 85.1%; hazard ratio 3.04; 95% CI 1.26-7.34). This strongly suggests that ctDNA testing is unlikely to replace clinicopathologic high-risk features in the real-world practice of clinical oncology. Rather, ctDNA testing will probably be added to the list of high-risk features, prompting use of more chemotherapy, not less, for stage II colon cancer.

A more useful study, in my opinion, should be performed in stage III colon cancer. Patients with stage III colon cancer receive chemotherapy without exception, although we know from MOSAIC that the absolute benefit of chemotherapy in stage III colon cancer is modest. What proportion of these patients who have a negative ctDNA test might be able to either forgo treatment completely or have treatment with a fluoropyrimidine only? That's something I would be very interested to find out.

This month brought us findings from DYNAMIC, a randomized trial of circulating tumor DNA (ctDNA), which aimed to provide guidance on the use of adjuvant chemotherapy in stage II colon cancer. This study has already been touted on oncology Twitter as a massive breakthrough for identifying patients with stage II colon cancer who would benefit from adjuvant chemotherapy. Does the reality live up to the hype? Let's break it down.

Patients with resected stage II colon cancer were eligible for enrollment. Two thirds of patients were randomly assigned to the ctDNA guidance arm, whereas the remaining third had chemotherapy guidance based on clinicopathologic high-risk features (T4, poor differentiation, < 12 lymph nodes in surgical sample, lymphovascular invasion, tumor perforation, or bowel obstruction). Chemotherapy choice was left up to the clinician and could be an oxaliplatin-based doublet or a single-agent fluoropyrimidine. The primary endpoint was recurrence-free survival at 2 years. A key secondary endpoint was chemotherapy treatment frequency by arm. A total of 459 patients were enrolled from 23 Australian centers over 4 years. Approximately 40% of patients were considered to be at high risk for recurrence on the basis of their tumors' clinicopathologic features. Approximately 20% of patients had tumors that were mismatch repair deficient.

There was no difference in 2-year recurrence-free survival between the two arms (93.5% vs 92.4%; 95% CI -4.1 to 6.2). This met criteria for noninferiority. However, chemotherapy administration in the two arms was markedly different. A significantly greater proportion of patients randomly assigned to the standard management arm received chemotherapy (28% vs 15%; relative risk [RR] 1.82; 95% CI 1.25-2.65). However, a significantly greater proportion of patients guided by ctDNA received an oxaliplatin-based doublet (62% vs 10%; RR 2.39; 95% CI 1.62-3.52). Clearly, when clinicians were presented with a positive ctDNA test, they overwhelmingly opted to give an oxaliplatin-based doublet rather than a single-agent fluoropyrimidine. Oxaliplatin's use in stage II colon cancer remains very controversial; it is oxaliplatin that causes most of the long-term toxicity associated with adjuvant chemotherapy for colorectal cancer. Although ctDNA testing might lower the total proportion of patients who received adjuvant treatment, it significantly raised the proportion who received oxaliplatin. I doubt this is a worthy trade-off.

Furthermore, clinicopathologic factors were still highly relevant in patients with ctDNA-negative results. Among ctDNA-negative patients, 3-year recurrence-free survival was higher in patients with clinicopathologic low-risk cancers than in those with high-risk cancers (96.7% vs 85.1%; hazard ratio 3.04; 95% CI 1.26-7.34). This strongly suggests that ctDNA testing is unlikely to replace clinicopathologic high-risk features in the real-world practice of clinical oncology. Rather, ctDNA testing will probably be added to the list of high-risk features, prompting use of more chemotherapy, not less, for stage II colon cancer.

A more useful study, in my opinion, should be performed in stage III colon cancer. Patients with stage III colon cancer receive chemotherapy without exception, although we know from MOSAIC that the absolute benefit of chemotherapy in stage III colon cancer is modest. What proportion of these patients who have a negative ctDNA test might be able to either forgo treatment completely or have treatment with a fluoropyrimidine only? That's something I would be very interested to find out.

This month brought us findings from DYNAMIC, a randomized trial of circulating tumor DNA (ctDNA), which aimed to provide guidance on the use of adjuvant chemotherapy in stage II colon cancer. This study has already been touted on oncology Twitter as a massive breakthrough for identifying patients with stage II colon cancer who would benefit from adjuvant chemotherapy. Does the reality live up to the hype? Let's break it down.

Patients with resected stage II colon cancer were eligible for enrollment. Two thirds of patients were randomly assigned to the ctDNA guidance arm, whereas the remaining third had chemotherapy guidance based on clinicopathologic high-risk features (T4, poor differentiation, < 12 lymph nodes in surgical sample, lymphovascular invasion, tumor perforation, or bowel obstruction). Chemotherapy choice was left up to the clinician and could be an oxaliplatin-based doublet or a single-agent fluoropyrimidine. The primary endpoint was recurrence-free survival at 2 years. A key secondary endpoint was chemotherapy treatment frequency by arm. A total of 459 patients were enrolled from 23 Australian centers over 4 years. Approximately 40% of patients were considered to be at high risk for recurrence on the basis of their tumors' clinicopathologic features. Approximately 20% of patients had tumors that were mismatch repair deficient.

There was no difference in 2-year recurrence-free survival between the two arms (93.5% vs 92.4%; 95% CI -4.1 to 6.2). This met criteria for noninferiority. However, chemotherapy administration in the two arms was markedly different. A significantly greater proportion of patients randomly assigned to the standard management arm received chemotherapy (28% vs 15%; relative risk [RR] 1.82; 95% CI 1.25-2.65). However, a significantly greater proportion of patients guided by ctDNA received an oxaliplatin-based doublet (62% vs 10%; RR 2.39; 95% CI 1.62-3.52). Clearly, when clinicians were presented with a positive ctDNA test, they overwhelmingly opted to give an oxaliplatin-based doublet rather than a single-agent fluoropyrimidine. Oxaliplatin's use in stage II colon cancer remains very controversial; it is oxaliplatin that causes most of the long-term toxicity associated with adjuvant chemotherapy for colorectal cancer. Although ctDNA testing might lower the total proportion of patients who received adjuvant treatment, it significantly raised the proportion who received oxaliplatin. I doubt this is a worthy trade-off.

Furthermore, clinicopathologic factors were still highly relevant in patients with ctDNA-negative results. Among ctDNA-negative patients, 3-year recurrence-free survival was higher in patients with clinicopathologic low-risk cancers than in those with high-risk cancers (96.7% vs 85.1%; hazard ratio 3.04; 95% CI 1.26-7.34). This strongly suggests that ctDNA testing is unlikely to replace clinicopathologic high-risk features in the real-world practice of clinical oncology. Rather, ctDNA testing will probably be added to the list of high-risk features, prompting use of more chemotherapy, not less, for stage II colon cancer.

A more useful study, in my opinion, should be performed in stage III colon cancer. Patients with stage III colon cancer receive chemotherapy without exception, although we know from MOSAIC that the absolute benefit of chemotherapy in stage III colon cancer is modest. What proportion of these patients who have a negative ctDNA test might be able to either forgo treatment completely or have treatment with a fluoropyrimidine only? That's something I would be very interested to find out.

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.