Doctor and patient

Photo courtesy of NIH

In a small study, patients treated for chronic conditions at safety-net clinics reported lower satisfaction with their care when it involved “high computer use” by clinicians.

Patients were significantly less likely to rate their care as “excellent” if clinicians spent a great deal of time on the computer during visits—silently reviewing data or typing and failing to make consistent eye contact.

Neda Ratanawongsa, MD, of the University of California, San Francisco, and her colleagues conducted this research and described the results in a letter to JAMA Internal Medicine.

The researchers noted that safety-net clinics serve populations with limited health literacy and limited proficiency in English who may experience communication barriers that can contribute to disparities in care and health.

So the team wanted to assess clinician computer use and communication with patients treated for chronic disease in safety-net clinics. The study was conducted over 2 years at an academically affiliated public hospital with a basic electronic health record.

The study included 47 patients who spoke English or Spanish and received primary and subspecialty care. The researchers recorded 71 encounters among 47 patients and 39 clinicians.

Clinician computer use was quantified by the amount of computer data reviewed, typing or clicking the computer mouse, eye contact with patients, and noninteractive pauses.

Compared with patients in clinical encounters with low computer use, patients who had encounters with high computer use were less likely to rate their care as excellent—48% vs 83% (P=0.04).

And clinicians in encounters with high computer use were significantly more likely to engage in more negative rapport building (P<0.01).

The researchers said this study revealed “observable communication differences” according to clinicians’ computer use. They noted that social rapport building can increase patient satisfaction, but concurrent computer use may inhibit authentic engagement.

Doctor and patient

Photo courtesy of NIH

In a small study, patients treated for chronic conditions at safety-net clinics reported lower satisfaction with their care when it involved “high computer use” by clinicians.

Patients were significantly less likely to rate their care as “excellent” if clinicians spent a great deal of time on the computer during visits—silently reviewing data or typing and failing to make consistent eye contact.

Neda Ratanawongsa, MD, of the University of California, San Francisco, and her colleagues conducted this research and described the results in a letter to JAMA Internal Medicine.

The researchers noted that safety-net clinics serve populations with limited health literacy and limited proficiency in English who may experience communication barriers that can contribute to disparities in care and health.

So the team wanted to assess clinician computer use and communication with patients treated for chronic disease in safety-net clinics. The study was conducted over 2 years at an academically affiliated public hospital with a basic electronic health record.

The study included 47 patients who spoke English or Spanish and received primary and subspecialty care. The researchers recorded 71 encounters among 47 patients and 39 clinicians.

Clinician computer use was quantified by the amount of computer data reviewed, typing or clicking the computer mouse, eye contact with patients, and noninteractive pauses.

Compared with patients in clinical encounters with low computer use, patients who had encounters with high computer use were less likely to rate their care as excellent—48% vs 83% (P=0.04).

And clinicians in encounters with high computer use were significantly more likely to engage in more negative rapport building (P<0.01).

The researchers said this study revealed “observable communication differences” according to clinicians’ computer use. They noted that social rapport building can increase patient satisfaction, but concurrent computer use may inhibit authentic engagement.

Doctor and patient

Photo courtesy of NIH

In a small study, patients treated for chronic conditions at safety-net clinics reported lower satisfaction with their care when it involved “high computer use” by clinicians.

Patients were significantly less likely to rate their care as “excellent” if clinicians spent a great deal of time on the computer during visits—silently reviewing data or typing and failing to make consistent eye contact.

Neda Ratanawongsa, MD, of the University of California, San Francisco, and her colleagues conducted this research and described the results in a letter to JAMA Internal Medicine.

The researchers noted that safety-net clinics serve populations with limited health literacy and limited proficiency in English who may experience communication barriers that can contribute to disparities in care and health.

So the team wanted to assess clinician computer use and communication with patients treated for chronic disease in safety-net clinics. The study was conducted over 2 years at an academically affiliated public hospital with a basic electronic health record.

The study included 47 patients who spoke English or Spanish and received primary and subspecialty care. The researchers recorded 71 encounters among 47 patients and 39 clinicians.

Clinician computer use was quantified by the amount of computer data reviewed, typing or clicking the computer mouse, eye contact with patients, and noninteractive pauses.

Compared with patients in clinical encounters with low computer use, patients who had encounters with high computer use were less likely to rate their care as excellent—48% vs 83% (P=0.04).

And clinicians in encounters with high computer use were significantly more likely to engage in more negative rapport building (P<0.01).

The researchers said this study revealed “observable communication differences” according to clinicians’ computer use. They noted that social rapport building can increase patient satisfaction, but concurrent computer use may inhibit authentic engagement.

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

FDA approves first naloxone nasal spray for opioid overdose

BY DEEPAK CHITNIS
Frontline Medical News

The US Food and Drug Administration (FDA) has approved the first nasal spray variant of the opioid-overdose drug naloxone hydrochloride.

Marketed in the United States as Narcan  (Adapt Pharma, a partner of Lightlake Therapeutics, Radnor, Pennsylvania) the nasal spray is known to stop or, in some cases, reverse the effects of opioid overdosing in patients. Narcan is the first naloxone hydrochloride nasal spray approved by the FDA.

“Combating the opioid abuse epidemic is a top priority for the FDA,” Dr Stephen Ostroff, FDA acting commissioner, said in a statement released with the November 18 approval announcement. “While naloxone will not solve the underlying problems of the opioid epidemic, we are speeding to review new formulations that will ultimately save lives that might otherwise be lost to drug addiction and overdose.”¹

The nasal spray itself is available only with a prescription, and is safe for use by both adults and children, according to the FDA.

The spray delivers a dose of 4 mg naloxone in a single 0.1-mL nasal spray, which comes in a ready-to-use, needle-free device, according to Adapt Pharma. Administration of Narcan, which is sprayed into one nostril while the patient is lying on his or her back, does not require special training.

The FDA warned that body aches, diarrhea, tachycardia, fever, piloerection, nausea, nervousness, abdominal cramps, weakness, and increased blood pressure, among other conditions, are all possible side effects of Narcan.

Narcan’s approval is one step of many that must be taken to adequately address and ultimately end the problem of opioid abuse in the US, cautioned Dr Peter Friedmann, an addiction medicine specialist and chief research officer at Baystate Health in Springfield, Massachusetts. He expressed concern regarding the pricing of Narcan, noting that the drug’s affordability is crucial to its success.

“Right now, nasal atomizers with syringes are used off label, and the prices have been going up with increasing demand,” he said. “But [Narcan] is a commercial product based around what is essentially a generic medication, so [I] hope it’s priced at a price point that’s accessible to the great majority of patients and their families who are facing addiction, many of whom don’t have huge means.”

Therapeutic hypothermia after nonshockable-rhythm cardiac arrest

BY MARY ANN MOON
FROM CIRCULATION

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.¹ 

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published, and some clinicians insist the treatment should be reserved for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

In the propensity-matched cohort, the rate of survival-to-hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an odds ratio (OR) of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital cardiac rest; OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr Perman and her associates said.

Andexanet reverses anticoagulant effects of factor Xa inhibitors

BY BIANCA NOGRADY
FROM THE AHA SCIENTIFIC SESSIONS

Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the November 11 issue of the New England Journal of Medicine.¹

In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2 to 5 minutes.

In the patients treated with rivaroxaban, treatment with andexanet reduced antifactor Xa activity by 92%, compared to 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.

Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth. The effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus.¹

“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr Deborah M. Siegal of McMaster University, Hamilton, Ontario, Canada and coauthors wrote.

Continuous no better than interrupted chest compressions

BY MARY ANN MOON
FROM THE AHA SCIENTIFIC SESSIONS

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online November 9 in the New England Journal of Medicine, Dr Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.¹

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome—the rate of survival to hospital discharge—was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said.¹

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.

Answers elusive in quest for better chlamydia treatment

BY BRUCE JANCIN
EXPERT ANALYSIS FROM ICAAC 2015

SAN DIEGO – The hottest topic today in the treatment of sexually transmitted diseases caused by Chlamydia trachomatis is the unresolved question of whether azithromycin is still as effective as doxycycline, the other current guideline-recommended, first-line therapy, Dr Kimberly Workowski said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

“This is important, because doxycycline is administered twice a day for 7 days, and azithromycin is given as a single pill suitable for directly observed therapy,” noted Dr Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 Centers for Disease Control and Prevention STD treatment guidelines.¹

Several recent retrospective case series have suggested azithromycin is less effective, with the biggest efficacy gap being seen in rectal C. trachomatis infections. These nonrandomized studies were further supported by an Australian meta-analysis of six randomized, controlled trials comparing the two antibiotics for the treatment of genital chlamydia. The investigators found roughly 3% greater efficacy for doxycycline, compared with azithromycin, for urogenital chlamydia, and a 7% advantage for doxycycline in treating symptomatic urethral infection in men.

However, the investigators were quick to add the caveat that “the quality of the evidence varies considerably.”²

There’s a pressing need for better data. Dr Workowski and her colleagues on the STD guidelines panel are eagerly awaiting the results of a well-structured randomized trial led by Dr William M. Geisler, professor of medicine at the University of Alabama, Birmingham. The investigators randomized more than 300 chlamydia-infected male and female inmates in youth correctional facilities to guideline-recommended azithromycin at 1 g orally in a single dose or oral doxycycline at 100 mg twice daily for 7 days. The results, which are anticipated soon, should influence clinical practice, Dr Workowski said.

Here’s what else is new in chlamydia:

Pregnancy: For treatment of chlamydia in pregnancy, amoxicillin at 500 mg orally t.i.d. for 7 days has been demoted from a first-line recommended therapy to alternative-regimen status. Now, the sole recommended first-line treatment in pregnancy is oral azithromycin at 1 g orally in a single dose.

“We did this based on in vitro studies showing Chlamydia trachomatis is not well-killed by amoxicillin. Instead, the drug induces persistent viable noninfectious forms which can sometimes reactivate,” Dr Workowski explained.

Delayed-release doxycycline: This FDA-approved drug, known as Doryx, administered as a 200-mg tablet once daily for 7 days, “might be an alternative” to the standard generic doxycycline regimen of 100 mg twice daily for 7 days, according to the current Centers for Disease Control and Prevention guidelines. In a randomized, double-blind trial, the new agent was as effective as twice-daily generic doxycycline in men and women with urogenital C. trachomatis infection, and it had fewer gastrointestinal side effects. Doryx is costlier than the twice-daily alternatives.

Lymphogranuloma venereum: The current guidelines repeat a point made in previous editions, but one Dr Workowski believes remains underappreciated and thus worthy of emphasis: Rectal exposure to C. trachomatis serovars L1, L2, and L3 in men who have sex with men or in women who have rectal sex can cause lymphogranuloma venereum, which takes the form of proctocolitis mimicking inflammatory bowel disease.

Patients suspected of having lymphogranuloma venereum should be started presumptively on the recommended regimen for this STD, which is oral doxycycline at 100 mg b.i.d. for 21 days.

“If you also see painful ulcers or, on anoscopy, mucosal ulcers, you should also treat empirically for herpes simplex until your culture results come back,” she added.

Dr Workowski reported having no financial conflicts of interest.

Catheter-directed thrombolysis trumps systemic for acute pulmonary embolism

BY MITCHEL L. ZOLER
AT CHEST 2015

MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 United States patients.

The review also found evidence that US pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 US clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national US registry of hospitalized patients, Dr Amina Saqib said at the annual meeting of the American College of Chest Physicians.

Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score-matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr Saqib, a researcher at Staten Island (New York) University Hospital.

“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,”
Dr Saqib said.

The US data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.

Dr Saqib and her associates used data collected by the Federal National Inpatient Sample. Among US patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.

The propensity score-adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr Saqib noted.

Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr Saqib said.

Survivors of out-of-hospital cardiac arrest usually had intact brain function

BY AMY KARON
FROM THE AHA SCIENTIFIC SESSIONS

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, North Carolina, and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Procalcitonin assay detects invasive bacterial infection

BY MARY ANN MOON
FROM JAMA PEDIATRICS

The procalcitonin assay was superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infections in very young febrile infants, according to a study published in JAMA Pediatrics.¹

Compared with other biomarker assays, procalcitonin assays allow earlier detection of certain infections in older children. A few small studies have hinted at the usefulness of procalcitonin assays in infants, but to date no large prospective studies have assessed these assays in the youngest infants. For this prospective study, researchers evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a study of 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then, procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, the procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the researchers said.¹

For young febrile infants, combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing offers the potential of avoiding lumbar punctures. These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr Milcent and her associates said.

Out-of-hospital MI survival is best in the Midwest

BY BRUCE JANCIN
AT THE AHA SCIENTIFIC SESSIONS

ORLANDO – Considerable regional variation exists across the United States in outcomes, including survival and hospital charges following out-of-hospital cardiac arrest, Dr Aiham Albaeni reported at the American Heart Association scientific sessions.¹

He presented an analysis of 155,592 adults who survived at least until hospital admission following  non-trauma-related out-of-hospital cardiac arrest (OHCA) during 2002-2012. The data came from the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample, the largest all-payer US inpatient database.

Mortality was lowest among patients whose OHCA occurred in the Midwest. Indeed, taking the Northeast region as the reference point in a multivariate analysis, the adjusted mortality risk was 14% lower in the Midwest and 9% lower in the South. There was no difference in survival rates between the West and Northeast in this analysis adjusted for age, gender, race, primary diagnosis, income, Charlson Comorbidity Index, primary payer, and hospital size and teaching status, reported Dr Albaeni of Johns Hopkins University, Baltimore, Maryland.

Total hospital charges for patients admitted following OHCA were far and away highest in the West, and this increased expenditure didn’t pay off in terms of a survival advantage. The Consumer Price Index–adjusted mean total hospital charges averaged $85,592 per patient in the West, $66,290 in the Northeast, $55,257 in the Midwest, and $54,878 in the South.

Outliers in terms of cost of care—that is, patients admitted with OHCA whose total hospital charges exceeded $109,000 per admission—were 85% more common in the West than the other three regions, he noted.

Hospital length of stay greater than 8 days occurred most often in the Northeast. These lengthier stays were 10% to 12% less common in the other regions.

The explanation for the marked regional differences observed in this study remains unknown.

“These findings call for more efforts to identify a high-quality model of excellence that standardizes health care delivery and improves quality of care in low-performing regions,” said Dr Albaeni.

He reported having no financial conflicts of interest regarding his study.

Modified Valsalva more than doubled conversion rate in supraventricular tachycardia

BY AMY KARON
FROM THE LANCET

A modified version of the Valsalva maneuver more than doubled the rate of conversion from acute supraventricular tachycardia to normal sinus rhythm when compared with the standard maneuver, said authors of a randomized, controlled trial published in the Lancet.

In all, 93 of 214 (43%) emergency department patients with acute supraventricular tachycardia (SVT) achieved cardioversion a minute after treatment with the modified Valsalva maneuver, compared with 37 (17%) of patients treated with standard Valsalva (adjusted odds ratio, 3.7; 95% CI, 2.3-5.8; P < .0001), reported Dr Andrew Appelboam of Royal Devon and Exeter (England) Hospital NHS Foundation Trust and his associates.

Standard Valsalva is safe, but achieves cardioversion for only 5% to 20% of patients with acute SVT. Nonresponders usually receive intravenous adenosine, which causes transient asystole and has other side effects, including a sense of “impending doom” or imminent death, the investigators noted.¹

For the modified Valsalva maneuver, patients underwent standardized strain at 40 mm Hg pressure for 15 seconds while semi-recumbent, but then immediately laid flat while a staff member raised their legs to a 45-degree angle for 15 seconds. They returned to the semi-recumbent position for another 45 seconds before their cardiac rhythm was reassessed. The control group simply remained semirecumbent for 60 seconds after 15 seconds of Valsalva strain.

The adapted technique should achieve the same rate of cardioversion in community practice, and clinicians should repeat it once if it is not initially effective, said the researchers. “As long as individuals can safely undertake a Valsalva strain and be repositioned as described, this maneuver can be used as the routine initial treatment for episodes of supraventricular tachycardia regardless of location,” they said. Patients did not experience serious adverse effects, and transient cardiac events were self-limited and affected similar proportions of both groups, they added.

The National Institute for Health Research funded the study. The researchers declared no competing interests.

Off-label prescriptions link to more adverse events

BY MARY ANN MOON
FROM JAMA INTERNAL MEDICINE

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. Recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events for all 8.5 million residents in the Canadian province of Quebec. There, physicians must provide the indication for every new prescription, the reason for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors reported.

Prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions was analyzed during a 5-year period. Physicians reported off-label use in 17,847 (12%) of these prescriptions, and that off-label use lacked strong scientific evidence in 81% of cases. The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr Tewodros Eguale and his associates reported having no relevant financial disclosures.

Dr Lappin is an assistant professor and an attending physician, department of mergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical College, New York.

FDA approves first naloxone nasal spray for opioid overdose

BY DEEPAK CHITNIS
Frontline Medical News

The US Food and Drug Administration (FDA) has approved the first nasal spray variant of the opioid-overdose drug naloxone hydrochloride.

Marketed in the United States as Narcan  (Adapt Pharma, a partner of Lightlake Therapeutics, Radnor, Pennsylvania) the nasal spray is known to stop or, in some cases, reverse the effects of opioid overdosing in patients. Narcan is the first naloxone hydrochloride nasal spray approved by the FDA.

“Combating the opioid abuse epidemic is a top priority for the FDA,” Dr Stephen Ostroff, FDA acting commissioner, said in a statement released with the November 18 approval announcement. “While naloxone will not solve the underlying problems of the opioid epidemic, we are speeding to review new formulations that will ultimately save lives that might otherwise be lost to drug addiction and overdose.”¹

The nasal spray itself is available only with a prescription, and is safe for use by both adults and children, according to the FDA.

The spray delivers a dose of 4 mg naloxone in a single 0.1-mL nasal spray, which comes in a ready-to-use, needle-free device, according to Adapt Pharma. Administration of Narcan, which is sprayed into one nostril while the patient is lying on his or her back, does not require special training.

The FDA warned that body aches, diarrhea, tachycardia, fever, piloerection, nausea, nervousness, abdominal cramps, weakness, and increased blood pressure, among other conditions, are all possible side effects of Narcan.

Narcan’s approval is one step of many that must be taken to adequately address and ultimately end the problem of opioid abuse in the US, cautioned Dr Peter Friedmann, an addiction medicine specialist and chief research officer at Baystate Health in Springfield, Massachusetts. He expressed concern regarding the pricing of Narcan, noting that the drug’s affordability is crucial to its success.

“Right now, nasal atomizers with syringes are used off label, and the prices have been going up with increasing demand,” he said. “But [Narcan] is a commercial product based around what is essentially a generic medication, so [I] hope it’s priced at a price point that’s accessible to the great majority of patients and their families who are facing addiction, many of whom don’t have huge means.”

Therapeutic hypothermia after nonshockable-rhythm cardiac arrest

BY MARY ANN MOON
FROM CIRCULATION

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.¹ 

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published, and some clinicians insist the treatment should be reserved for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

In the propensity-matched cohort, the rate of survival-to-hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an odds ratio (OR) of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital cardiac rest; OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr Perman and her associates said.

Andexanet reverses anticoagulant effects of factor Xa inhibitors

BY BIANCA NOGRADY
FROM THE AHA SCIENTIFIC SESSIONS

Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the November 11 issue of the New England Journal of Medicine.¹

In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2 to 5 minutes.

In the patients treated with rivaroxaban, treatment with andexanet reduced antifactor Xa activity by 92%, compared to 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.

Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth. The effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus.¹

“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr Deborah M. Siegal of McMaster University, Hamilton, Ontario, Canada and coauthors wrote.

Continuous no better than interrupted chest compressions

BY MARY ANN MOON
FROM THE AHA SCIENTIFIC SESSIONS

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online November 9 in the New England Journal of Medicine, Dr Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.¹

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome—the rate of survival to hospital discharge—was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said.¹

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.

Answers elusive in quest for better chlamydia treatment

BY BRUCE JANCIN
EXPERT ANALYSIS FROM ICAAC 2015

SAN DIEGO – The hottest topic today in the treatment of sexually transmitted diseases caused by Chlamydia trachomatis is the unresolved question of whether azithromycin is still as effective as doxycycline, the other current guideline-recommended, first-line therapy, Dr Kimberly Workowski said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

“This is important, because doxycycline is administered twice a day for 7 days, and azithromycin is given as a single pill suitable for directly observed therapy,” noted Dr Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 Centers for Disease Control and Prevention STD treatment guidelines.¹

Several recent retrospective case series have suggested azithromycin is less effective, with the biggest efficacy gap being seen in rectal C. trachomatis infections. These nonrandomized studies were further supported by an Australian meta-analysis of six randomized, controlled trials comparing the two antibiotics for the treatment of genital chlamydia. The investigators found roughly 3% greater efficacy for doxycycline, compared with azithromycin, for urogenital chlamydia, and a 7% advantage for doxycycline in treating symptomatic urethral infection in men.

However, the investigators were quick to add the caveat that “the quality of the evidence varies considerably.”²

There’s a pressing need for better data. Dr Workowski and her colleagues on the STD guidelines panel are eagerly awaiting the results of a well-structured randomized trial led by Dr William M. Geisler, professor of medicine at the University of Alabama, Birmingham. The investigators randomized more than 300 chlamydia-infected male and female inmates in youth correctional facilities to guideline-recommended azithromycin at 1 g orally in a single dose or oral doxycycline at 100 mg twice daily for 7 days. The results, which are anticipated soon, should influence clinical practice, Dr Workowski said.

Here’s what else is new in chlamydia:

Pregnancy: For treatment of chlamydia in pregnancy, amoxicillin at 500 mg orally t.i.d. for 7 days has been demoted from a first-line recommended therapy to alternative-regimen status. Now, the sole recommended first-line treatment in pregnancy is oral azithromycin at 1 g orally in a single dose.

“We did this based on in vitro studies showing Chlamydia trachomatis is not well-killed by amoxicillin. Instead, the drug induces persistent viable noninfectious forms which can sometimes reactivate,” Dr Workowski explained.

Delayed-release doxycycline: This FDA-approved drug, known as Doryx, administered as a 200-mg tablet once daily for 7 days, “might be an alternative” to the standard generic doxycycline regimen of 100 mg twice daily for 7 days, according to the current Centers for Disease Control and Prevention guidelines. In a randomized, double-blind trial, the new agent was as effective as twice-daily generic doxycycline in men and women with urogenital C. trachomatis infection, and it had fewer gastrointestinal side effects. Doryx is costlier than the twice-daily alternatives.

Lymphogranuloma venereum: The current guidelines repeat a point made in previous editions, but one Dr Workowski believes remains underappreciated and thus worthy of emphasis: Rectal exposure to C. trachomatis serovars L1, L2, and L3 in men who have sex with men or in women who have rectal sex can cause lymphogranuloma venereum, which takes the form of proctocolitis mimicking inflammatory bowel disease.

Patients suspected of having lymphogranuloma venereum should be started presumptively on the recommended regimen for this STD, which is oral doxycycline at 100 mg b.i.d. for 21 days.

“If you also see painful ulcers or, on anoscopy, mucosal ulcers, you should also treat empirically for herpes simplex until your culture results come back,” she added.

Dr Workowski reported having no financial conflicts of interest.

Catheter-directed thrombolysis trumps systemic for acute pulmonary embolism

BY MITCHEL L. ZOLER
AT CHEST 2015

MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 United States patients.

The review also found evidence that US pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 US clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national US registry of hospitalized patients, Dr Amina Saqib said at the annual meeting of the American College of Chest Physicians.

Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score-matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr Saqib, a researcher at Staten Island (New York) University Hospital.

“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,”
Dr Saqib said.

The US data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.

Dr Saqib and her associates used data collected by the Federal National Inpatient Sample. Among US patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.

The propensity score-adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr Saqib noted.

Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr Saqib said.

Survivors of out-of-hospital cardiac arrest usually had intact brain function

BY AMY KARON
FROM THE AHA SCIENTIFIC SESSIONS

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, North Carolina, and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Procalcitonin assay detects invasive bacterial infection

BY MARY ANN MOON
FROM JAMA PEDIATRICS

The procalcitonin assay was superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infections in very young febrile infants, according to a study published in JAMA Pediatrics.¹

Compared with other biomarker assays, procalcitonin assays allow earlier detection of certain infections in older children. A few small studies have hinted at the usefulness of procalcitonin assays in infants, but to date no large prospective studies have assessed these assays in the youngest infants. For this prospective study, researchers evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a study of 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then, procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, the procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the researchers said.¹

For young febrile infants, combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing offers the potential of avoiding lumbar punctures. These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr Milcent and her associates said.

Out-of-hospital MI survival is best in the Midwest

BY BRUCE JANCIN
AT THE AHA SCIENTIFIC SESSIONS

ORLANDO – Considerable regional variation exists across the United States in outcomes, including survival and hospital charges following out-of-hospital cardiac arrest, Dr Aiham Albaeni reported at the American Heart Association scientific sessions.¹

He presented an analysis of 155,592 adults who survived at least until hospital admission following  non-trauma-related out-of-hospital cardiac arrest (OHCA) during 2002-2012. The data came from the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample, the largest all-payer US inpatient database.

Mortality was lowest among patients whose OHCA occurred in the Midwest. Indeed, taking the Northeast region as the reference point in a multivariate analysis, the adjusted mortality risk was 14% lower in the Midwest and 9% lower in the South. There was no difference in survival rates between the West and Northeast in this analysis adjusted for age, gender, race, primary diagnosis, income, Charlson Comorbidity Index, primary payer, and hospital size and teaching status, reported Dr Albaeni of Johns Hopkins University, Baltimore, Maryland.

Total hospital charges for patients admitted following OHCA were far and away highest in the West, and this increased expenditure didn’t pay off in terms of a survival advantage. The Consumer Price Index–adjusted mean total hospital charges averaged $85,592 per patient in the West, $66,290 in the Northeast, $55,257 in the Midwest, and $54,878 in the South.

Outliers in terms of cost of care—that is, patients admitted with OHCA whose total hospital charges exceeded $109,000 per admission—were 85% more common in the West than the other three regions, he noted.

Hospital length of stay greater than 8 days occurred most often in the Northeast. These lengthier stays were 10% to 12% less common in the other regions.

The explanation for the marked regional differences observed in this study remains unknown.

“These findings call for more efforts to identify a high-quality model of excellence that standardizes health care delivery and improves quality of care in low-performing regions,” said Dr Albaeni.

He reported having no financial conflicts of interest regarding his study.

Modified Valsalva more than doubled conversion rate in supraventricular tachycardia

BY AMY KARON
FROM THE LANCET

A modified version of the Valsalva maneuver more than doubled the rate of conversion from acute supraventricular tachycardia to normal sinus rhythm when compared with the standard maneuver, said authors of a randomized, controlled trial published in the Lancet.

In all, 93 of 214 (43%) emergency department patients with acute supraventricular tachycardia (SVT) achieved cardioversion a minute after treatment with the modified Valsalva maneuver, compared with 37 (17%) of patients treated with standard Valsalva (adjusted odds ratio, 3.7; 95% CI, 2.3-5.8; P < .0001), reported Dr Andrew Appelboam of Royal Devon and Exeter (England) Hospital NHS Foundation Trust and his associates.

Standard Valsalva is safe, but achieves cardioversion for only 5% to 20% of patients with acute SVT. Nonresponders usually receive intravenous adenosine, which causes transient asystole and has other side effects, including a sense of “impending doom” or imminent death, the investigators noted.¹

For the modified Valsalva maneuver, patients underwent standardized strain at 40 mm Hg pressure for 15 seconds while semi-recumbent, but then immediately laid flat while a staff member raised their legs to a 45-degree angle for 15 seconds. They returned to the semi-recumbent position for another 45 seconds before their cardiac rhythm was reassessed. The control group simply remained semirecumbent for 60 seconds after 15 seconds of Valsalva strain.

The adapted technique should achieve the same rate of cardioversion in community practice, and clinicians should repeat it once if it is not initially effective, said the researchers. “As long as individuals can safely undertake a Valsalva strain and be repositioned as described, this maneuver can be used as the routine initial treatment for episodes of supraventricular tachycardia regardless of location,” they said. Patients did not experience serious adverse effects, and transient cardiac events were self-limited and affected similar proportions of both groups, they added.

The National Institute for Health Research funded the study. The researchers declared no competing interests.

Off-label prescriptions link to more adverse events

BY MARY ANN MOON
FROM JAMA INTERNAL MEDICINE

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. Recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events for all 8.5 million residents in the Canadian province of Quebec. There, physicians must provide the indication for every new prescription, the reason for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors reported.

Prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions was analyzed during a 5-year period. Physicians reported off-label use in 17,847 (12%) of these prescriptions, and that off-label use lacked strong scientific evidence in 81% of cases. The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr Tewodros Eguale and his associates reported having no relevant financial disclosures.

Dr Lappin is an assistant professor and an attending physician, department of mergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical College, New York.

FDA approves first naloxone nasal spray for opioid overdose

BY DEEPAK CHITNIS
Frontline Medical News

The US Food and Drug Administration (FDA) has approved the first nasal spray variant of the opioid-overdose drug naloxone hydrochloride.

Marketed in the United States as Narcan  (Adapt Pharma, a partner of Lightlake Therapeutics, Radnor, Pennsylvania) the nasal spray is known to stop or, in some cases, reverse the effects of opioid overdosing in patients. Narcan is the first naloxone hydrochloride nasal spray approved by the FDA.

“Combating the opioid abuse epidemic is a top priority for the FDA,” Dr Stephen Ostroff, FDA acting commissioner, said in a statement released with the November 18 approval announcement. “While naloxone will not solve the underlying problems of the opioid epidemic, we are speeding to review new formulations that will ultimately save lives that might otherwise be lost to drug addiction and overdose.”¹

The nasal spray itself is available only with a prescription, and is safe for use by both adults and children, according to the FDA.

The spray delivers a dose of 4 mg naloxone in a single 0.1-mL nasal spray, which comes in a ready-to-use, needle-free device, according to Adapt Pharma. Administration of Narcan, which is sprayed into one nostril while the patient is lying on his or her back, does not require special training.

The FDA warned that body aches, diarrhea, tachycardia, fever, piloerection, nausea, nervousness, abdominal cramps, weakness, and increased blood pressure, among other conditions, are all possible side effects of Narcan.

Narcan’s approval is one step of many that must be taken to adequately address and ultimately end the problem of opioid abuse in the US, cautioned Dr Peter Friedmann, an addiction medicine specialist and chief research officer at Baystate Health in Springfield, Massachusetts. He expressed concern regarding the pricing of Narcan, noting that the drug’s affordability is crucial to its success.

“Right now, nasal atomizers with syringes are used off label, and the prices have been going up with increasing demand,” he said. “But [Narcan] is a commercial product based around what is essentially a generic medication, so [I] hope it’s priced at a price point that’s accessible to the great majority of patients and their families who are facing addiction, many of whom don’t have huge means.”

Therapeutic hypothermia after nonshockable-rhythm cardiac arrest

BY MARY ANN MOON
FROM CIRCULATION

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.¹ 

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published, and some clinicians insist the treatment should be reserved for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

In the propensity-matched cohort, the rate of survival-to-hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an odds ratio (OR) of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital cardiac rest; OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr Perman and her associates said.

Andexanet reverses anticoagulant effects of factor Xa inhibitors

BY BIANCA NOGRADY
FROM THE AHA SCIENTIFIC SESSIONS

Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the November 11 issue of the New England Journal of Medicine.¹

In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2 to 5 minutes.

In the patients treated with rivaroxaban, treatment with andexanet reduced antifactor Xa activity by 92%, compared to 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.

Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth. The effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus.¹

“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr Deborah M. Siegal of McMaster University, Hamilton, Ontario, Canada and coauthors wrote.

Continuous no better than interrupted chest compressions

BY MARY ANN MOON
FROM THE AHA SCIENTIFIC SESSIONS

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online November 9 in the New England Journal of Medicine, Dr Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.¹

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome—the rate of survival to hospital discharge—was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said.¹

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.

Answers elusive in quest for better chlamydia treatment

BY BRUCE JANCIN
EXPERT ANALYSIS FROM ICAAC 2015

SAN DIEGO – The hottest topic today in the treatment of sexually transmitted diseases caused by Chlamydia trachomatis is the unresolved question of whether azithromycin is still as effective as doxycycline, the other current guideline-recommended, first-line therapy, Dr Kimberly Workowski said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

“This is important, because doxycycline is administered twice a day for 7 days, and azithromycin is given as a single pill suitable for directly observed therapy,” noted Dr Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 Centers for Disease Control and Prevention STD treatment guidelines.¹

Several recent retrospective case series have suggested azithromycin is less effective, with the biggest efficacy gap being seen in rectal C. trachomatis infections. These nonrandomized studies were further supported by an Australian meta-analysis of six randomized, controlled trials comparing the two antibiotics for the treatment of genital chlamydia. The investigators found roughly 3% greater efficacy for doxycycline, compared with azithromycin, for urogenital chlamydia, and a 7% advantage for doxycycline in treating symptomatic urethral infection in men.

However, the investigators were quick to add the caveat that “the quality of the evidence varies considerably.”²

There’s a pressing need for better data. Dr Workowski and her colleagues on the STD guidelines panel are eagerly awaiting the results of a well-structured randomized trial led by Dr William M. Geisler, professor of medicine at the University of Alabama, Birmingham. The investigators randomized more than 300 chlamydia-infected male and female inmates in youth correctional facilities to guideline-recommended azithromycin at 1 g orally in a single dose or oral doxycycline at 100 mg twice daily for 7 days. The results, which are anticipated soon, should influence clinical practice, Dr Workowski said.

Here’s what else is new in chlamydia:

Pregnancy: For treatment of chlamydia in pregnancy, amoxicillin at 500 mg orally t.i.d. for 7 days has been demoted from a first-line recommended therapy to alternative-regimen status. Now, the sole recommended first-line treatment in pregnancy is oral azithromycin at 1 g orally in a single dose.

“We did this based on in vitro studies showing Chlamydia trachomatis is not well-killed by amoxicillin. Instead, the drug induces persistent viable noninfectious forms which can sometimes reactivate,” Dr Workowski explained.

Delayed-release doxycycline: This FDA-approved drug, known as Doryx, administered as a 200-mg tablet once daily for 7 days, “might be an alternative” to the standard generic doxycycline regimen of 100 mg twice daily for 7 days, according to the current Centers for Disease Control and Prevention guidelines. In a randomized, double-blind trial, the new agent was as effective as twice-daily generic doxycycline in men and women with urogenital C. trachomatis infection, and it had fewer gastrointestinal side effects. Doryx is costlier than the twice-daily alternatives.

Lymphogranuloma venereum: The current guidelines repeat a point made in previous editions, but one Dr Workowski believes remains underappreciated and thus worthy of emphasis: Rectal exposure to C. trachomatis serovars L1, L2, and L3 in men who have sex with men or in women who have rectal sex can cause lymphogranuloma venereum, which takes the form of proctocolitis mimicking inflammatory bowel disease.

Patients suspected of having lymphogranuloma venereum should be started presumptively on the recommended regimen for this STD, which is oral doxycycline at 100 mg b.i.d. for 21 days.

“If you also see painful ulcers or, on anoscopy, mucosal ulcers, you should also treat empirically for herpes simplex until your culture results come back,” she added.

Dr Workowski reported having no financial conflicts of interest.

Catheter-directed thrombolysis trumps systemic for acute pulmonary embolism

BY MITCHEL L. ZOLER
AT CHEST 2015

MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 United States patients.

The review also found evidence that US pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 US clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national US registry of hospitalized patients, Dr Amina Saqib said at the annual meeting of the American College of Chest Physicians.

Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score-matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr Saqib, a researcher at Staten Island (New York) University Hospital.

“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,”
Dr Saqib said.

The US data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.

Dr Saqib and her associates used data collected by the Federal National Inpatient Sample. Among US patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.

The propensity score-adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr Saqib noted.

Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr Saqib said.

Survivors of out-of-hospital cardiac arrest usually had intact brain function

BY AMY KARON
FROM THE AHA SCIENTIFIC SESSIONS

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, North Carolina, and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Procalcitonin assay detects invasive bacterial infection

BY MARY ANN MOON
FROM JAMA PEDIATRICS

The procalcitonin assay was superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infections in very young febrile infants, according to a study published in JAMA Pediatrics.¹

Compared with other biomarker assays, procalcitonin assays allow earlier detection of certain infections in older children. A few small studies have hinted at the usefulness of procalcitonin assays in infants, but to date no large prospective studies have assessed these assays in the youngest infants. For this prospective study, researchers evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a study of 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then, procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, the procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the researchers said.¹

For young febrile infants, combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing offers the potential of avoiding lumbar punctures. These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr Milcent and her associates said.

Out-of-hospital MI survival is best in the Midwest

BY BRUCE JANCIN
AT THE AHA SCIENTIFIC SESSIONS

ORLANDO – Considerable regional variation exists across the United States in outcomes, including survival and hospital charges following out-of-hospital cardiac arrest, Dr Aiham Albaeni reported at the American Heart Association scientific sessions.¹

He presented an analysis of 155,592 adults who survived at least until hospital admission following  non-trauma-related out-of-hospital cardiac arrest (OHCA) during 2002-2012. The data came from the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample, the largest all-payer US inpatient database.

Mortality was lowest among patients whose OHCA occurred in the Midwest. Indeed, taking the Northeast region as the reference point in a multivariate analysis, the adjusted mortality risk was 14% lower in the Midwest and 9% lower in the South. There was no difference in survival rates between the West and Northeast in this analysis adjusted for age, gender, race, primary diagnosis, income, Charlson Comorbidity Index, primary payer, and hospital size and teaching status, reported Dr Albaeni of Johns Hopkins University, Baltimore, Maryland.

Total hospital charges for patients admitted following OHCA were far and away highest in the West, and this increased expenditure didn’t pay off in terms of a survival advantage. The Consumer Price Index–adjusted mean total hospital charges averaged $85,592 per patient in the West, $66,290 in the Northeast, $55,257 in the Midwest, and $54,878 in the South.

Outliers in terms of cost of care—that is, patients admitted with OHCA whose total hospital charges exceeded $109,000 per admission—were 85% more common in the West than the other three regions, he noted.

Hospital length of stay greater than 8 days occurred most often in the Northeast. These lengthier stays were 10% to 12% less common in the other regions.

The explanation for the marked regional differences observed in this study remains unknown.

“These findings call for more efforts to identify a high-quality model of excellence that standardizes health care delivery and improves quality of care in low-performing regions,” said Dr Albaeni.

He reported having no financial conflicts of interest regarding his study.

Modified Valsalva more than doubled conversion rate in supraventricular tachycardia

BY AMY KARON
FROM THE LANCET

A modified version of the Valsalva maneuver more than doubled the rate of conversion from acute supraventricular tachycardia to normal sinus rhythm when compared with the standard maneuver, said authors of a randomized, controlled trial published in the Lancet.

In all, 93 of 214 (43%) emergency department patients with acute supraventricular tachycardia (SVT) achieved cardioversion a minute after treatment with the modified Valsalva maneuver, compared with 37 (17%) of patients treated with standard Valsalva (adjusted odds ratio, 3.7; 95% CI, 2.3-5.8; P < .0001), reported Dr Andrew Appelboam of Royal Devon and Exeter (England) Hospital NHS Foundation Trust and his associates.

Standard Valsalva is safe, but achieves cardioversion for only 5% to 20% of patients with acute SVT. Nonresponders usually receive intravenous adenosine, which causes transient asystole and has other side effects, including a sense of “impending doom” or imminent death, the investigators noted.¹

For the modified Valsalva maneuver, patients underwent standardized strain at 40 mm Hg pressure for 15 seconds while semi-recumbent, but then immediately laid flat while a staff member raised their legs to a 45-degree angle for 15 seconds. They returned to the semi-recumbent position for another 45 seconds before their cardiac rhythm was reassessed. The control group simply remained semirecumbent for 60 seconds after 15 seconds of Valsalva strain.

The adapted technique should achieve the same rate of cardioversion in community practice, and clinicians should repeat it once if it is not initially effective, said the researchers. “As long as individuals can safely undertake a Valsalva strain and be repositioned as described, this maneuver can be used as the routine initial treatment for episodes of supraventricular tachycardia regardless of location,” they said. Patients did not experience serious adverse effects, and transient cardiac events were self-limited and affected similar proportions of both groups, they added.

The National Institute for Health Research funded the study. The researchers declared no competing interests.

Off-label prescriptions link to more adverse events

BY MARY ANN MOON
FROM JAMA INTERNAL MEDICINE

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. Recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events for all 8.5 million residents in the Canadian province of Quebec. There, physicians must provide the indication for every new prescription, the reason for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors reported.

Prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions was analyzed during a 5-year period. Physicians reported off-label use in 17,847 (12%) of these prescriptions, and that off-label use lacked strong scientific evidence in 81% of cases. The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr Tewodros Eguale and his associates reported having no relevant financial disclosures.

Dr Lappin is an assistant professor and an attending physician, department of mergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical College, New York.

A Pain in the Butt

A 75-year-old man presented to the ED complaining of low back pain radiating to his right buttock and leg. There was no history of trauma or overuse. His medical history was significant for hypertension and benign prostatic hypertrophy. Regarding social history, the patient stated that he had quit smoking 20 years prior and only drank alcohol on occasion. He denied any medication allergies.

On physical examination, the patient’s vital signs were: pulse 98 beats/minute; blood pressure, 132/82 mm Hg; respiratory rate, 18 breaths/minute; and temperature, 99.8°F. The head, eyes, ears, nose, and throat examination, and pulmonary, cardiovascular, and abdominal examinations were all normal. On examination of the lower back, the patient exhibited mild tenderness of the right paraspinal lumbar muscles without midline tenderness. He had normal and equal strength of the lower extremities bilaterally. The patient’s buttocks were not examined during this visit.

The emergency physician (EP) felt the patient’s history and physical examination were consistent with a lumbar radiculopathy, and contacted the patient’s primary care physician (PCP) to communicate his impression. Although the PCP was aware that his patient had recently complained of chills, night sweats, and pain radiating from the hip to the anus, he did not communicate this information to the EP. Unfortunately, the patient also did not relate these complaints to the EP. After the EP’s consultation with the PCP, the patient was prescribed an analgesic, referred to an orthopedic surgeon, and discharged home.

Two days later, the patient returned to the same ED via emergency medical services, this time with altered mental status, fever, and hypotension. He was found to have necrotizing fasciitis of the right buttock. The patient received intravenous fluid resuscitation and broad-spectrum antibiotics, and was taken immediately to the operating room. Unfortunately, he did not survive.

The patient’s estate sued the first EP for failure to visualize and palpate the buttocks area and for failure to diagnose an infection of the right buttocks. The plaintiff further argued that the patient would have survived if he had been properly diagnosed and treated at the initial ED visit. The defense argued the patient received a thorough history and physical examination and that the diagnosis of lumbar radiculopathy was consistent with the patient’s clinical presentation. The defense also argued that the patient never reported any complaints or indication of a buttock infection. The case was settled prior to trial for nearly $600,000.

Discussion

The second important point, examining the area of primary complaint, may sound simple, straightforward, and just plain common sense. However, this can be very challenging in the reality of today’s practice of emergency medicine as EPs are often called upon to perform entire histories and physical examinations on patients in hallway beds. Gone are the days when every patient was undressed and placed in a gown in a private area or room. With the emphasis on maintaining patients with relatively minor complaints “vertical” to improve throughput times, the EP is frequently forced to examine such patients fully clothed. This places the EP at high risk for misdiagnosis or a missed diagnosis. In the same study by Kachalia et al,¹ failure to perform an adequate medical history or physical examination accounted for 42% of all diagnostic errors in the ED. Recognizing the challenge of examining the point of complaint is easy—solving the issue, however, will take all of a hospital’s resources.

Stealing Is Bad for Your Health

A 19-year-old man presented to the ED complaining of left eye pain, foreign body sensation, and tearing. He stated that when he was cleaning his garage approximately 3 hours prior to presentation, a cardboard box had fallen on his head, scattering its contents. Immediately after this occurrence, the patient experienced onset of a foreign body sensation and pain in his left eye. He further noted that he had attempted to irrigate his left eye with tap water, but it did not relieve the pain. After several hours of discomfort, the patient decided to come to the ED. He denied any other injuries or complaints, was in good health, on no medications, and had no known medication allergies. He also denied wearing contacts or corrective lenses.

On physical examination, the patient’s left eye was closed, and he appeared to be somewhat uncomfortable. His vital signs were all normal. His visual acuity was 20/20 in the right eye and 20/60 in the left eye, which was due to tearing and blurriness from the injury. To facilitate the examination, the EP placed two drops of proparacaine hydrochloride ophthalmic solution 0.5% in both of the patient’s eyes, which provided immediate and near total relief of the left eye pain. On fluorescein and slit-lamp examination, the EP found a small foreign body at approximately the seven o’clock position on the cornea, as well as a surrounding abrasion. The corneal anterior chamber was normal. The EP removed the foreign body, prescribed a topical ophthalmic antibiotic cream. and instructed the patient to return to the ED in 24 hours for a recheck. The EP also instructed the patient to take ibuprofen for any associated pain.

While waiting to be discharged, the patient took the vial of proparacaine that had been left on the counter in the room. He did so without informing anyone and without permission. After the nurse returned to the room and gave the patient his discharge instructions, he was released home. Neither the nurse nor the physician realized the patient had stolen the topical anesthetic.

The patient sued the EP for leaving the “miracle” pain-relief medication in the room and thereby facilitating his actions. The plaintiff argued that the immediate and complete pain-relief effects of the medication were too tempting for a nonmedical person to resist, and that the drug should not have been made available to him under any circumstance. The EP argued the patient stole the medication and that any resulting injury was completely the result of the patient’s own actions. The suit was eventually dropped.

Discussion

It is unfortunate that this ever became a malpractice case, since it is clear to any layman that the stealing of medications is inappropriate and illegal; moreover, any damages resulting from that action are completely the responsibility of the transgressor. With that said, a significant amount of time, discomfort, and inconvenience could have been avoided had the nurse or physician simply removed the medication from the room. While I certainly do not think this is required from a medical-legal standpoint, it is a good common-sense practice.

Corneal abrasions and corneal foreign bodies are very uncomfortable, and medications such as nonsteroidal anti-inflammatory drugs or acetaminophen only provide partial pain relief. It is easy to see how a young person, lacking any medical knowledge or the concepts of adverse side effects or toxicity, would be tempted in such a situation. In retrospect, it would probably have been best to have avoided leaving the medication within the patient’s reach in the first place.

With respect to evaluating and treating corneal abrasions, the most commonly used topical ophthalmic anesthetics are proparacaine and tetracaine. When used appropriately and in the hands of trained healthcare workers, these drugs are safe, effective, and exhibit nearly no side effects. However, as this case demonstrates, these drugs can be toxic when abused. The most common toxicities are to the ocular surface and include superficial punctate keratitis, persistent epithelial defects, stromal infiltrates, and corneal edema. More serious injuries can also occur, such as deep corneal infiltrates, ulceration, and eye perforation.¹ The toxic effects associated with these drugs are the reason these medications are never prescribed for home use.

A Pain in the Butt

A 75-year-old man presented to the ED complaining of low back pain radiating to his right buttock and leg. There was no history of trauma or overuse. His medical history was significant for hypertension and benign prostatic hypertrophy. Regarding social history, the patient stated that he had quit smoking 20 years prior and only drank alcohol on occasion. He denied any medication allergies.

On physical examination, the patient’s vital signs were: pulse 98 beats/minute; blood pressure, 132/82 mm Hg; respiratory rate, 18 breaths/minute; and temperature, 99.8°F. The head, eyes, ears, nose, and throat examination, and pulmonary, cardiovascular, and abdominal examinations were all normal. On examination of the lower back, the patient exhibited mild tenderness of the right paraspinal lumbar muscles without midline tenderness. He had normal and equal strength of the lower extremities bilaterally. The patient’s buttocks were not examined during this visit.

The emergency physician (EP) felt the patient’s history and physical examination were consistent with a lumbar radiculopathy, and contacted the patient’s primary care physician (PCP) to communicate his impression. Although the PCP was aware that his patient had recently complained of chills, night sweats, and pain radiating from the hip to the anus, he did not communicate this information to the EP. Unfortunately, the patient also did not relate these complaints to the EP. After the EP’s consultation with the PCP, the patient was prescribed an analgesic, referred to an orthopedic surgeon, and discharged home.

Two days later, the patient returned to the same ED via emergency medical services, this time with altered mental status, fever, and hypotension. He was found to have necrotizing fasciitis of the right buttock. The patient received intravenous fluid resuscitation and broad-spectrum antibiotics, and was taken immediately to the operating room. Unfortunately, he did not survive.

The patient’s estate sued the first EP for failure to visualize and palpate the buttocks area and for failure to diagnose an infection of the right buttocks. The plaintiff further argued that the patient would have survived if he had been properly diagnosed and treated at the initial ED visit. The defense argued the patient received a thorough history and physical examination and that the diagnosis of lumbar radiculopathy was consistent with the patient’s clinical presentation. The defense also argued that the patient never reported any complaints or indication of a buttock infection. The case was settled prior to trial for nearly $600,000.

Discussion

The second important point, examining the area of primary complaint, may sound simple, straightforward, and just plain common sense. However, this can be very challenging in the reality of today’s practice of emergency medicine as EPs are often called upon to perform entire histories and physical examinations on patients in hallway beds. Gone are the days when every patient was undressed and placed in a gown in a private area or room. With the emphasis on maintaining patients with relatively minor complaints “vertical” to improve throughput times, the EP is frequently forced to examine such patients fully clothed. This places the EP at high risk for misdiagnosis or a missed diagnosis. In the same study by Kachalia et al,¹ failure to perform an adequate medical history or physical examination accounted for 42% of all diagnostic errors in the ED. Recognizing the challenge of examining the point of complaint is easy—solving the issue, however, will take all of a hospital’s resources.

Stealing Is Bad for Your Health

A 19-year-old man presented to the ED complaining of left eye pain, foreign body sensation, and tearing. He stated that when he was cleaning his garage approximately 3 hours prior to presentation, a cardboard box had fallen on his head, scattering its contents. Immediately after this occurrence, the patient experienced onset of a foreign body sensation and pain in his left eye. He further noted that he had attempted to irrigate his left eye with tap water, but it did not relieve the pain. After several hours of discomfort, the patient decided to come to the ED. He denied any other injuries or complaints, was in good health, on no medications, and had no known medication allergies. He also denied wearing contacts or corrective lenses.

On physical examination, the patient’s left eye was closed, and he appeared to be somewhat uncomfortable. His vital signs were all normal. His visual acuity was 20/20 in the right eye and 20/60 in the left eye, which was due to tearing and blurriness from the injury. To facilitate the examination, the EP placed two drops of proparacaine hydrochloride ophthalmic solution 0.5% in both of the patient’s eyes, which provided immediate and near total relief of the left eye pain. On fluorescein and slit-lamp examination, the EP found a small foreign body at approximately the seven o’clock position on the cornea, as well as a surrounding abrasion. The corneal anterior chamber was normal. The EP removed the foreign body, prescribed a topical ophthalmic antibiotic cream. and instructed the patient to return to the ED in 24 hours for a recheck. The EP also instructed the patient to take ibuprofen for any associated pain.

While waiting to be discharged, the patient took the vial of proparacaine that had been left on the counter in the room. He did so without informing anyone and without permission. After the nurse returned to the room and gave the patient his discharge instructions, he was released home. Neither the nurse nor the physician realized the patient had stolen the topical anesthetic.

The patient sued the EP for leaving the “miracle” pain-relief medication in the room and thereby facilitating his actions. The plaintiff argued that the immediate and complete pain-relief effects of the medication were too tempting for a nonmedical person to resist, and that the drug should not have been made available to him under any circumstance. The EP argued the patient stole the medication and that any resulting injury was completely the result of the patient’s own actions. The suit was eventually dropped.

Discussion

It is unfortunate that this ever became a malpractice case, since it is clear to any layman that the stealing of medications is inappropriate and illegal; moreover, any damages resulting from that action are completely the responsibility of the transgressor. With that said, a significant amount of time, discomfort, and inconvenience could have been avoided had the nurse or physician simply removed the medication from the room. While I certainly do not think this is required from a medical-legal standpoint, it is a good common-sense practice.

Corneal abrasions and corneal foreign bodies are very uncomfortable, and medications such as nonsteroidal anti-inflammatory drugs or acetaminophen only provide partial pain relief. It is easy to see how a young person, lacking any medical knowledge or the concepts of adverse side effects or toxicity, would be tempted in such a situation. In retrospect, it would probably have been best to have avoided leaving the medication within the patient’s reach in the first place.

With respect to evaluating and treating corneal abrasions, the most commonly used topical ophthalmic anesthetics are proparacaine and tetracaine. When used appropriately and in the hands of trained healthcare workers, these drugs are safe, effective, and exhibit nearly no side effects. However, as this case demonstrates, these drugs can be toxic when abused. The most common toxicities are to the ocular surface and include superficial punctate keratitis, persistent epithelial defects, stromal infiltrates, and corneal edema. More serious injuries can also occur, such as deep corneal infiltrates, ulceration, and eye perforation.¹ The toxic effects associated with these drugs are the reason these medications are never prescribed for home use.

A Pain in the Butt

A 75-year-old man presented to the ED complaining of low back pain radiating to his right buttock and leg. There was no history of trauma or overuse. His medical history was significant for hypertension and benign prostatic hypertrophy. Regarding social history, the patient stated that he had quit smoking 20 years prior and only drank alcohol on occasion. He denied any medication allergies.

On physical examination, the patient’s vital signs were: pulse 98 beats/minute; blood pressure, 132/82 mm Hg; respiratory rate, 18 breaths/minute; and temperature, 99.8°F. The head, eyes, ears, nose, and throat examination, and pulmonary, cardiovascular, and abdominal examinations were all normal. On examination of the lower back, the patient exhibited mild tenderness of the right paraspinal lumbar muscles without midline tenderness. He had normal and equal strength of the lower extremities bilaterally. The patient’s buttocks were not examined during this visit.

The emergency physician (EP) felt the patient’s history and physical examination were consistent with a lumbar radiculopathy, and contacted the patient’s primary care physician (PCP) to communicate his impression. Although the PCP was aware that his patient had recently complained of chills, night sweats, and pain radiating from the hip to the anus, he did not communicate this information to the EP. Unfortunately, the patient also did not relate these complaints to the EP. After the EP’s consultation with the PCP, the patient was prescribed an analgesic, referred to an orthopedic surgeon, and discharged home.

Two days later, the patient returned to the same ED via emergency medical services, this time with altered mental status, fever, and hypotension. He was found to have necrotizing fasciitis of the right buttock. The patient received intravenous fluid resuscitation and broad-spectrum antibiotics, and was taken immediately to the operating room. Unfortunately, he did not survive.

The patient’s estate sued the first EP for failure to visualize and palpate the buttocks area and for failure to diagnose an infection of the right buttocks. The plaintiff further argued that the patient would have survived if he had been properly diagnosed and treated at the initial ED visit. The defense argued the patient received a thorough history and physical examination and that the diagnosis of lumbar radiculopathy was consistent with the patient’s clinical presentation. The defense also argued that the patient never reported any complaints or indication of a buttock infection. The case was settled prior to trial for nearly $600,000.

Discussion

The second important point, examining the area of primary complaint, may sound simple, straightforward, and just plain common sense. However, this can be very challenging in the reality of today’s practice of emergency medicine as EPs are often called upon to perform entire histories and physical examinations on patients in hallway beds. Gone are the days when every patient was undressed and placed in a gown in a private area or room. With the emphasis on maintaining patients with relatively minor complaints “vertical” to improve throughput times, the EP is frequently forced to examine such patients fully clothed. This places the EP at high risk for misdiagnosis or a missed diagnosis. In the same study by Kachalia et al,¹ failure to perform an adequate medical history or physical examination accounted for 42% of all diagnostic errors in the ED. Recognizing the challenge of examining the point of complaint is easy—solving the issue, however, will take all of a hospital’s resources.

Stealing Is Bad for Your Health

A 19-year-old man presented to the ED complaining of left eye pain, foreign body sensation, and tearing. He stated that when he was cleaning his garage approximately 3 hours prior to presentation, a cardboard box had fallen on his head, scattering its contents. Immediately after this occurrence, the patient experienced onset of a foreign body sensation and pain in his left eye. He further noted that he had attempted to irrigate his left eye with tap water, but it did not relieve the pain. After several hours of discomfort, the patient decided to come to the ED. He denied any other injuries or complaints, was in good health, on no medications, and had no known medication allergies. He also denied wearing contacts or corrective lenses.

On physical examination, the patient’s left eye was closed, and he appeared to be somewhat uncomfortable. His vital signs were all normal. His visual acuity was 20/20 in the right eye and 20/60 in the left eye, which was due to tearing and blurriness from the injury. To facilitate the examination, the EP placed two drops of proparacaine hydrochloride ophthalmic solution 0.5% in both of the patient’s eyes, which provided immediate and near total relief of the left eye pain. On fluorescein and slit-lamp examination, the EP found a small foreign body at approximately the seven o’clock position on the cornea, as well as a surrounding abrasion. The corneal anterior chamber was normal. The EP removed the foreign body, prescribed a topical ophthalmic antibiotic cream. and instructed the patient to return to the ED in 24 hours for a recheck. The EP also instructed the patient to take ibuprofen for any associated pain.

While waiting to be discharged, the patient took the vial of proparacaine that had been left on the counter in the room. He did so without informing anyone and without permission. After the nurse returned to the room and gave the patient his discharge instructions, he was released home. Neither the nurse nor the physician realized the patient had stolen the topical anesthetic.

The patient sued the EP for leaving the “miracle” pain-relief medication in the room and thereby facilitating his actions. The plaintiff argued that the immediate and complete pain-relief effects of the medication were too tempting for a nonmedical person to resist, and that the drug should not have been made available to him under any circumstance. The EP argued the patient stole the medication and that any resulting injury was completely the result of the patient’s own actions. The suit was eventually dropped.

Discussion

It is unfortunate that this ever became a malpractice case, since it is clear to any layman that the stealing of medications is inappropriate and illegal; moreover, any damages resulting from that action are completely the responsibility of the transgressor. With that said, a significant amount of time, discomfort, and inconvenience could have been avoided had the nurse or physician simply removed the medication from the room. While I certainly do not think this is required from a medical-legal standpoint, it is a good common-sense practice.

Corneal abrasions and corneal foreign bodies are very uncomfortable, and medications such as nonsteroidal anti-inflammatory drugs or acetaminophen only provide partial pain relief. It is easy to see how a young person, lacking any medical knowledge or the concepts of adverse side effects or toxicity, would be tempted in such a situation. In retrospect, it would probably have been best to have avoided leaving the medication within the patient’s reach in the first place.

With respect to evaluating and treating corneal abrasions, the most commonly used topical ophthalmic anesthetics are proparacaine and tetracaine. When used appropriately and in the hands of trained healthcare workers, these drugs are safe, effective, and exhibit nearly no side effects. However, as this case demonstrates, these drugs can be toxic when abused. The most common toxicities are to the ocular surface and include superficial punctate keratitis, persistent epithelial defects, stromal infiltrates, and corneal edema. More serious injuries can also occur, such as deep corneal infiltrates, ulceration, and eye perforation.¹ The toxic effects associated with these drugs are the reason these medications are never prescribed for home use.

Case

A 37-year-old woman had undergone outpatient tumescent liposuction of her abdominal adipose tissue. Upon initiation of the procedure, she developed acute confusion followed by agitation and hallucinations and was transported by emergency medical services to the nearest hospital. 

Upon arrival to the ED, the patient was mildly agitated. Her initial vital signs were: blood pressure, 122/79 mm Hg; heart rate, 57 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 96.8°F. Oxygen saturation was 100% on room air.

On examination, the patient was awake and oriented, but was restless and perseverating. She described the sensation of “dying and coming back to life.” The patient’s pupils were equal, round, and normally reactive; her skin was neither diaphoretic nor dry; her heart rate and rhythm were normal; and her lungs were clear to auscultation bilaterally. The skin of the patient’s abdomen was pale, cool, and clammy, but otherwise soft with normoactive bowel sounds. An electrocardiogram revealed sinus rhythm with normal QRS and QTc intervals.

What is tumescent liposuction?

The tumescent technique (the word tumescent derived from the Latin word meaning “to swell”) involves the infiltration of a large volume of a dilute solution of lidocaine and epinephrine into the subcutaneous fat until it becomes distended and tense. The administration of this solution allows for the removal of significant adipose tissue with minimal blood loss and without general anesthesia. Advocates of tumescent liposuction argue that this dilution and subcutaneous infiltration alter the pharmacokinetics of lidocaine, providing a safe delivery of large doses of the drug. In addition, a substantial quantity of the infiltrated lidocaine is suctioned out with the fat removal. Klein3 specifically recommends administering a dilution of 1 g lidocaine in 1,000 mL of saline (0.1%) to the patient in aliquots of up to 2 g lidocaine. Such a high dose may approach or surpass 35 mg/kg, far exceeding the recommended lidocaine infiltration dose of 7 mg/kg when mixed with epinephrine.

Several studies have investigated the safety of the tumescent technique and the risk of lidocaine toxicity. In a review of pharmacokinetic studies, patients received between 10.5 and 67.7 mg/kg of lidocaine with a reported maximum serum lidocaine concentration in all patients of only 2.93 mcg/mL (therapeutic, 1-5 mcg/mL).4 However, peak serum lidocaine concentrations may not occur for up to 28 hours following tumescent infiltration.4 Despite the purported safety findings of this and other studies, there are also reports of tumescent anesthesia-associated toxicity and fatalities.5,6

Case Continuation 

The patient’s mental status slowly improved throughout her hospital stay and she was reportedly at baseline by the following morning. Her serum lidocaine concentration drawn at presentation to the ED was 9.7 mcg/mL.

What are the clinical effects of lidocaine toxicity?

The clinical effects of lidocaine overdose are dependent on both the magnitude of the exposure and the rate at which it occurs. The central nervous system (CNS) and heart are the organ systems primarily affected by lidocaine. As a local anesthetic, lidocaine inhibits the action potential formation in electrically excitable cells. This reversible inhibition of the voltage-gated sodium channels prevents the influx of positively charged sodium ions and the resultant depolarization of the cell. Lidocaine, initially or at low concentrations, has a quiescent effect on neurons, which explains its therapeutic use as a local anesthetic.

Similarly, lidocaine initially reduces impulse propagation through the cardiac conduction system and can be used to treat rhythm disturbances. When used for the suppression of cardiac dysrhythmias, the therapeutic serum concentration of lidocaine is 1 to 5 mcg/mL. Subjective symptoms of lidocaine toxicity arising from therapeutic use (primarily when it is used to manage dysrhythmia) include light-headedness, disorientation, confusion, and psychosis, and are associated with serum concentrations of 3 to 6 mcg/mL. As the concentration increases, the clinical effects of lidocaine appear to shift from inhibitory to excitatory. At serum concentrations of 5 to 9 mcg/mL, objective symptoms, such as excitation, tremor, and seizure predominate. As the concentration continues to rise, coma, respiratory depression, cardiovascular (CV) collapse, and death may occur.7

The exact mechanism of this toxicity transition from inhibitory effect of sodium channel blockade to excitatory effect is not well understood. Some suggest a preferential inhibition of inhibitory interneurons in the CNS is responsible.8 Another potential mechanism is a concentration-dependent inhibition of the potassium rectifier channel.9 Inhibition of the efflux of positively charged potassium ions would result in slowing cellular repolarization, leaving the cells in a relatively excitable state. In the CNS, this produces seizures; in the heart, it may result in dysrhythmia. Cardiovascular collapse may occur with very high serum concentrations of lidocaine or following a rapid serum increase—eg, after a large intravenous (IV) bolus dose,7 which can potentially result from an unintentional intravascular injection during tumescent liposuction.

What is the treatment for lidocaine toxicity?

The first step in the treatment of lidocaine-associated CNS toxicity is the discontinuation of the drug. Failure to appropriately recognize the symptoms of early lidocaine toxicity may result in the progression to severe CNS effects and eventual CV collapse. Benzodiazepines should be used as needed for mild symptoms. Seizures should be treated aggressively with benzodiazepines or barbiturates, while ensuring maintenance of oxygenation, ventilation, and perfusion.7

In cases of lidocaine-associated CV toxicity, treatment begins with airway management, oxygen administration, and life support. Potential antidotal treatment of severe local anesthetic-associated CV toxicity involves the rapid administration of IV fat emulsion, or “lipid rescue.” Although best studied for bupivacaine toxicity, the exact mechanism of IV fat emulsion as an antidote is not completely understood. However, in the treatment of local anesthetic toxicity, lipid rescue is believed to offer a “sink” to remove the lipid-soluble anesthetics from their site of action and trap them within the vascular space. Suggested dosing of 20% lipid solution is a bolus of 1.5 mL/kg over a 1-minute period, followed by 0.25mL/kg per minute or 15 mL/kg per hour to run over 30 to 60 minutes.10

Case Conclusion

The patient made a full recovery and was discharged home in normal condition. Her healthcare provider was informed about the complication of the procedure.

Dr Hines is a senior toxicology fellow, department of emergency medicine, New York University School of Medicine. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 37-year-old woman had undergone outpatient tumescent liposuction of her abdominal adipose tissue. Upon initiation of the procedure, she developed acute confusion followed by agitation and hallucinations and was transported by emergency medical services to the nearest hospital. 

Upon arrival to the ED, the patient was mildly agitated. Her initial vital signs were: blood pressure, 122/79 mm Hg; heart rate, 57 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 96.8°F. Oxygen saturation was 100% on room air.

On examination, the patient was awake and oriented, but was restless and perseverating. She described the sensation of “dying and coming back to life.” The patient’s pupils were equal, round, and normally reactive; her skin was neither diaphoretic nor dry; her heart rate and rhythm were normal; and her lungs were clear to auscultation bilaterally. The skin of the patient’s abdomen was pale, cool, and clammy, but otherwise soft with normoactive bowel sounds. An electrocardiogram revealed sinus rhythm with normal QRS and QTc intervals.

What is tumescent liposuction?

The tumescent technique (the word tumescent derived from the Latin word meaning “to swell”) involves the infiltration of a large volume of a dilute solution of lidocaine and epinephrine into the subcutaneous fat until it becomes distended and tense. The administration of this solution allows for the removal of significant adipose tissue with minimal blood loss and without general anesthesia. Advocates of tumescent liposuction argue that this dilution and subcutaneous infiltration alter the pharmacokinetics of lidocaine, providing a safe delivery of large doses of the drug. In addition, a substantial quantity of the infiltrated lidocaine is suctioned out with the fat removal. Klein3 specifically recommends administering a dilution of 1 g lidocaine in 1,000 mL of saline (0.1%) to the patient in aliquots of up to 2 g lidocaine. Such a high dose may approach or surpass 35 mg/kg, far exceeding the recommended lidocaine infiltration dose of 7 mg/kg when mixed with epinephrine.

Several studies have investigated the safety of the tumescent technique and the risk of lidocaine toxicity. In a review of pharmacokinetic studies, patients received between 10.5 and 67.7 mg/kg of lidocaine with a reported maximum serum lidocaine concentration in all patients of only 2.93 mcg/mL (therapeutic, 1-5 mcg/mL).4 However, peak serum lidocaine concentrations may not occur for up to 28 hours following tumescent infiltration.4 Despite the purported safety findings of this and other studies, there are also reports of tumescent anesthesia-associated toxicity and fatalities.5,6

Case Continuation 

The patient’s mental status slowly improved throughout her hospital stay and she was reportedly at baseline by the following morning. Her serum lidocaine concentration drawn at presentation to the ED was 9.7 mcg/mL.

What are the clinical effects of lidocaine toxicity?

The clinical effects of lidocaine overdose are dependent on both the magnitude of the exposure and the rate at which it occurs. The central nervous system (CNS) and heart are the organ systems primarily affected by lidocaine. As a local anesthetic, lidocaine inhibits the action potential formation in electrically excitable cells. This reversible inhibition of the voltage-gated sodium channels prevents the influx of positively charged sodium ions and the resultant depolarization of the cell. Lidocaine, initially or at low concentrations, has a quiescent effect on neurons, which explains its therapeutic use as a local anesthetic.

Similarly, lidocaine initially reduces impulse propagation through the cardiac conduction system and can be used to treat rhythm disturbances. When used for the suppression of cardiac dysrhythmias, the therapeutic serum concentration of lidocaine is 1 to 5 mcg/mL. Subjective symptoms of lidocaine toxicity arising from therapeutic use (primarily when it is used to manage dysrhythmia) include light-headedness, disorientation, confusion, and psychosis, and are associated with serum concentrations of 3 to 6 mcg/mL. As the concentration increases, the clinical effects of lidocaine appear to shift from inhibitory to excitatory. At serum concentrations of 5 to 9 mcg/mL, objective symptoms, such as excitation, tremor, and seizure predominate. As the concentration continues to rise, coma, respiratory depression, cardiovascular (CV) collapse, and death may occur.7

The exact mechanism of this toxicity transition from inhibitory effect of sodium channel blockade to excitatory effect is not well understood. Some suggest a preferential inhibition of inhibitory interneurons in the CNS is responsible.8 Another potential mechanism is a concentration-dependent inhibition of the potassium rectifier channel.9 Inhibition of the efflux of positively charged potassium ions would result in slowing cellular repolarization, leaving the cells in a relatively excitable state. In the CNS, this produces seizures; in the heart, it may result in dysrhythmia. Cardiovascular collapse may occur with very high serum concentrations of lidocaine or following a rapid serum increase—eg, after a large intravenous (IV) bolus dose,7 which can potentially result from an unintentional intravascular injection during tumescent liposuction.

What is the treatment for lidocaine toxicity?

The first step in the treatment of lidocaine-associated CNS toxicity is the discontinuation of the drug. Failure to appropriately recognize the symptoms of early lidocaine toxicity may result in the progression to severe CNS effects and eventual CV collapse. Benzodiazepines should be used as needed for mild symptoms. Seizures should be treated aggressively with benzodiazepines or barbiturates, while ensuring maintenance of oxygenation, ventilation, and perfusion.7

In cases of lidocaine-associated CV toxicity, treatment begins with airway management, oxygen administration, and life support. Potential antidotal treatment of severe local anesthetic-associated CV toxicity involves the rapid administration of IV fat emulsion, or “lipid rescue.” Although best studied for bupivacaine toxicity, the exact mechanism of IV fat emulsion as an antidote is not completely understood. However, in the treatment of local anesthetic toxicity, lipid rescue is believed to offer a “sink” to remove the lipid-soluble anesthetics from their site of action and trap them within the vascular space. Suggested dosing of 20% lipid solution is a bolus of 1.5 mL/kg over a 1-minute period, followed by 0.25mL/kg per minute or 15 mL/kg per hour to run over 30 to 60 minutes.10

Case Conclusion

The patient made a full recovery and was discharged home in normal condition. Her healthcare provider was informed about the complication of the procedure.

Dr Hines is a senior toxicology fellow, department of emergency medicine, New York University School of Medicine. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 37-year-old woman had undergone outpatient tumescent liposuction of her abdominal adipose tissue. Upon initiation of the procedure, she developed acute confusion followed by agitation and hallucinations and was transported by emergency medical services to the nearest hospital. 

Upon arrival to the ED, the patient was mildly agitated. Her initial vital signs were: blood pressure, 122/79 mm Hg; heart rate, 57 beats/minute; respiratory rate, 18 breaths/minute; and temperature, 96.8°F. Oxygen saturation was 100% on room air.

On examination, the patient was awake and oriented, but was restless and perseverating. She described the sensation of “dying and coming back to life.” The patient’s pupils were equal, round, and normally reactive; her skin was neither diaphoretic nor dry; her heart rate and rhythm were normal; and her lungs were clear to auscultation bilaterally. The skin of the patient’s abdomen was pale, cool, and clammy, but otherwise soft with normoactive bowel sounds. An electrocardiogram revealed sinus rhythm with normal QRS and QTc intervals.

What is tumescent liposuction?

The tumescent technique (the word tumescent derived from the Latin word meaning “to swell”) involves the infiltration of a large volume of a dilute solution of lidocaine and epinephrine into the subcutaneous fat until it becomes distended and tense. The administration of this solution allows for the removal of significant adipose tissue with minimal blood loss and without general anesthesia. Advocates of tumescent liposuction argue that this dilution and subcutaneous infiltration alter the pharmacokinetics of lidocaine, providing a safe delivery of large doses of the drug. In addition, a substantial quantity of the infiltrated lidocaine is suctioned out with the fat removal. Klein3 specifically recommends administering a dilution of 1 g lidocaine in 1,000 mL of saline (0.1%) to the patient in aliquots of up to 2 g lidocaine. Such a high dose may approach or surpass 35 mg/kg, far exceeding the recommended lidocaine infiltration dose of 7 mg/kg when mixed with epinephrine.

Several studies have investigated the safety of the tumescent technique and the risk of lidocaine toxicity. In a review of pharmacokinetic studies, patients received between 10.5 and 67.7 mg/kg of lidocaine with a reported maximum serum lidocaine concentration in all patients of only 2.93 mcg/mL (therapeutic, 1-5 mcg/mL).4 However, peak serum lidocaine concentrations may not occur for up to 28 hours following tumescent infiltration.4 Despite the purported safety findings of this and other studies, there are also reports of tumescent anesthesia-associated toxicity and fatalities.5,6

Case Continuation 

The patient’s mental status slowly improved throughout her hospital stay and she was reportedly at baseline by the following morning. Her serum lidocaine concentration drawn at presentation to the ED was 9.7 mcg/mL.

What are the clinical effects of lidocaine toxicity?

The clinical effects of lidocaine overdose are dependent on both the magnitude of the exposure and the rate at which it occurs. The central nervous system (CNS) and heart are the organ systems primarily affected by lidocaine. As a local anesthetic, lidocaine inhibits the action potential formation in electrically excitable cells. This reversible inhibition of the voltage-gated sodium channels prevents the influx of positively charged sodium ions and the resultant depolarization of the cell. Lidocaine, initially or at low concentrations, has a quiescent effect on neurons, which explains its therapeutic use as a local anesthetic.

Similarly, lidocaine initially reduces impulse propagation through the cardiac conduction system and can be used to treat rhythm disturbances. When used for the suppression of cardiac dysrhythmias, the therapeutic serum concentration of lidocaine is 1 to 5 mcg/mL. Subjective symptoms of lidocaine toxicity arising from therapeutic use (primarily when it is used to manage dysrhythmia) include light-headedness, disorientation, confusion, and psychosis, and are associated with serum concentrations of 3 to 6 mcg/mL. As the concentration increases, the clinical effects of lidocaine appear to shift from inhibitory to excitatory. At serum concentrations of 5 to 9 mcg/mL, objective symptoms, such as excitation, tremor, and seizure predominate. As the concentration continues to rise, coma, respiratory depression, cardiovascular (CV) collapse, and death may occur.7

The exact mechanism of this toxicity transition from inhibitory effect of sodium channel blockade to excitatory effect is not well understood. Some suggest a preferential inhibition of inhibitory interneurons in the CNS is responsible.8 Another potential mechanism is a concentration-dependent inhibition of the potassium rectifier channel.9 Inhibition of the efflux of positively charged potassium ions would result in slowing cellular repolarization, leaving the cells in a relatively excitable state. In the CNS, this produces seizures; in the heart, it may result in dysrhythmia. Cardiovascular collapse may occur with very high serum concentrations of lidocaine or following a rapid serum increase—eg, after a large intravenous (IV) bolus dose,7 which can potentially result from an unintentional intravascular injection during tumescent liposuction.

What is the treatment for lidocaine toxicity?

The first step in the treatment of lidocaine-associated CNS toxicity is the discontinuation of the drug. Failure to appropriately recognize the symptoms of early lidocaine toxicity may result in the progression to severe CNS effects and eventual CV collapse. Benzodiazepines should be used as needed for mild symptoms. Seizures should be treated aggressively with benzodiazepines or barbiturates, while ensuring maintenance of oxygenation, ventilation, and perfusion.7

In cases of lidocaine-associated CV toxicity, treatment begins with airway management, oxygen administration, and life support. Potential antidotal treatment of severe local anesthetic-associated CV toxicity involves the rapid administration of IV fat emulsion, or “lipid rescue.” Although best studied for bupivacaine toxicity, the exact mechanism of IV fat emulsion as an antidote is not completely understood. However, in the treatment of local anesthetic toxicity, lipid rescue is believed to offer a “sink” to remove the lipid-soluble anesthetics from their site of action and trap them within the vascular space. Suggested dosing of 20% lipid solution is a bolus of 1.5 mL/kg over a 1-minute period, followed by 0.25mL/kg per minute or 15 mL/kg per hour to run over 30 to 60 minutes.10

Case Conclusion

The patient made a full recovery and was discharged home in normal condition. Her healthcare provider was informed about the complication of the procedure.

Dr Hines is a senior toxicology fellow, department of emergency medicine, New York University School of Medicine. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

THE CASE

A 94-year-old Hispanic man with hypertension, congestive heart failure (CHF), anemia of chronic disease, and end-stage renal disease (ESRD) presented to our facility with weakness and shortness of breath. We diagnosed a CHF exacerbation. Initially, he exhibited some respiratory distress that required observation in the coronary care unit and bi-level positive airway pressure therapy to maintain oxygen saturation. Our patient was then moved to a step-down unit where his primary caregiver, his granddaughter, told the medical team that he was limited at home in some of his instrumental activities of daily living. Specifically, he was unable to prepare meals or manage his finances on his own.

Nephrology was consulted for consideration of hemodialysis (HD) because our patient’s creatinine on admission was 7.2 mg/dL (normal for men is 0.7-1.3 mg/dL) and his estimated glomerular filtration rate (GFR) was 7 mL/min (normal is 90-120 mL/min). The patient’s family was conflicted over whether or not to start HD. Palliative Care was consulted to help establish goals of care.

A decision is made. In light of the patient’s limited functional status and his expressed desire to stay at home with his family and receive limited medical care there, the Nephrology and Palliative Care teams recommended delaying HD despite the patient’s worsening renal function. The patient was discharged home with home care services, and he and the family were instructed to follow up with Nephrology for supportive renal management.

DISCUSSION

The decision to delay HD in patients with ESRD is a difficult one that requires shared decision-making between patients and medical providers. Palliative Care consultation services are often involved in this process.

Recent literature supports an “intent-to-defer” based on an evaluation of the patient’s functionality. This represents a paradigm shift from the previous “intent-to-start-early” treatment strategy. In fact, rather than starting early, the Canadian Society of Nephrology recommends delaying initiation of HD in patients with a GFR <15 mL/min.¹ Close monitoring of these patients by both a primary care physician and nephrologist is essential.

When considering initiation of HD, it’s important to look at the overall benefit of this intervention in light of the patient’s mortality risk and quality of life. Many patients who receive HD—especially the elderly—report that it takes more than 6 hours to recover following a dialysis treatment.²

Not surprisingly, depression is common in elderly HD patients. Compared to their younger cohorts, older HD patients have a 62% increased risk of developing depression.³ Also, patients who are considered frail and are receiving HD have more than 3 times the mortality risk within one year than those who are not (hazard ratio=3.42; 95% confidence interval, 2.45-4.76).⁴ (The researchers’ definition of frailty included poor self-reported physical function, exhaustion/fatigue, low physical activity, and undernutrition.⁴)

Functional status. Although a patient’s age should not be a limiting factor for HD referral, functional status should be considered. Patients with limited functionality and significant dependence have an increased risk of death during the first year of HD.⁵

Palliative approach gains acceptance. It is becoming more accepted within the nephrology community to consider a palliative approach to patients with ESRD. Organizations such as the Renal Physicians Association recommend effective prognostication, early advanced care planning, forgoing HD in patients with a poor prognosis, and involving Palliative Care early in the decision-making process.⁶ Aligning the patient’s goals of care with the appropriate treatment method—particularly in patients with comorbid conditions—is an important practice when caring for those with limited life expectancy and functionality.⁷

THE TAKEAWAY

Intent-to-defer HD may be a preferred strategy when caring for many patients with ESRD. Taking into consideration a patient’s comorbidities and functional status, while considering mortality risk and quality of life are essential. Involving palliative care and nephrology specialists can help patients and families understand HD and make an educated decision regarding when to start it.

THE CASE

A 94-year-old Hispanic man with hypertension, congestive heart failure (CHF), anemia of chronic disease, and end-stage renal disease (ESRD) presented to our facility with weakness and shortness of breath. We diagnosed a CHF exacerbation. Initially, he exhibited some respiratory distress that required observation in the coronary care unit and bi-level positive airway pressure therapy to maintain oxygen saturation. Our patient was then moved to a step-down unit where his primary caregiver, his granddaughter, told the medical team that he was limited at home in some of his instrumental activities of daily living. Specifically, he was unable to prepare meals or manage his finances on his own.

Nephrology was consulted for consideration of hemodialysis (HD) because our patient’s creatinine on admission was 7.2 mg/dL (normal for men is 0.7-1.3 mg/dL) and his estimated glomerular filtration rate (GFR) was 7 mL/min (normal is 90-120 mL/min). The patient’s family was conflicted over whether or not to start HD. Palliative Care was consulted to help establish goals of care.

A decision is made. In light of the patient’s limited functional status and his expressed desire to stay at home with his family and receive limited medical care there, the Nephrology and Palliative Care teams recommended delaying HD despite the patient’s worsening renal function. The patient was discharged home with home care services, and he and the family were instructed to follow up with Nephrology for supportive renal management.

DISCUSSION

The decision to delay HD in patients with ESRD is a difficult one that requires shared decision-making between patients and medical providers. Palliative Care consultation services are often involved in this process.

Recent literature supports an “intent-to-defer” based on an evaluation of the patient’s functionality. This represents a paradigm shift from the previous “intent-to-start-early” treatment strategy. In fact, rather than starting early, the Canadian Society of Nephrology recommends delaying initiation of HD in patients with a GFR <15 mL/min.¹ Close monitoring of these patients by both a primary care physician and nephrologist is essential.

When considering initiation of HD, it’s important to look at the overall benefit of this intervention in light of the patient’s mortality risk and quality of life. Many patients who receive HD—especially the elderly—report that it takes more than 6 hours to recover following a dialysis treatment.²

Not surprisingly, depression is common in elderly HD patients. Compared to their younger cohorts, older HD patients have a 62% increased risk of developing depression.³ Also, patients who are considered frail and are receiving HD have more than 3 times the mortality risk within one year than those who are not (hazard ratio=3.42; 95% confidence interval, 2.45-4.76).⁴ (The researchers’ definition of frailty included poor self-reported physical function, exhaustion/fatigue, low physical activity, and undernutrition.⁴)

Functional status. Although a patient’s age should not be a limiting factor for HD referral, functional status should be considered. Patients with limited functionality and significant dependence have an increased risk of death during the first year of HD.⁵

Palliative approach gains acceptance. It is becoming more accepted within the nephrology community to consider a palliative approach to patients with ESRD. Organizations such as the Renal Physicians Association recommend effective prognostication, early advanced care planning, forgoing HD in patients with a poor prognosis, and involving Palliative Care early in the decision-making process.⁶ Aligning the patient’s goals of care with the appropriate treatment method—particularly in patients with comorbid conditions—is an important practice when caring for those with limited life expectancy and functionality.⁷

THE TAKEAWAY

Intent-to-defer HD may be a preferred strategy when caring for many patients with ESRD. Taking into consideration a patient’s comorbidities and functional status, while considering mortality risk and quality of life are essential. Involving palliative care and nephrology specialists can help patients and families understand HD and make an educated decision regarding when to start it.

THE CASE

A 94-year-old Hispanic man with hypertension, congestive heart failure (CHF), anemia of chronic disease, and end-stage renal disease (ESRD) presented to our facility with weakness and shortness of breath. We diagnosed a CHF exacerbation. Initially, he exhibited some respiratory distress that required observation in the coronary care unit and bi-level positive airway pressure therapy to maintain oxygen saturation. Our patient was then moved to a step-down unit where his primary caregiver, his granddaughter, told the medical team that he was limited at home in some of his instrumental activities of daily living. Specifically, he was unable to prepare meals or manage his finances on his own.

Nephrology was consulted for consideration of hemodialysis (HD) because our patient’s creatinine on admission was 7.2 mg/dL (normal for men is 0.7-1.3 mg/dL) and his estimated glomerular filtration rate (GFR) was 7 mL/min (normal is 90-120 mL/min). The patient’s family was conflicted over whether or not to start HD. Palliative Care was consulted to help establish goals of care.

A decision is made. In light of the patient’s limited functional status and his expressed desire to stay at home with his family and receive limited medical care there, the Nephrology and Palliative Care teams recommended delaying HD despite the patient’s worsening renal function. The patient was discharged home with home care services, and he and the family were instructed to follow up with Nephrology for supportive renal management.

DISCUSSION

The decision to delay HD in patients with ESRD is a difficult one that requires shared decision-making between patients and medical providers. Palliative Care consultation services are often involved in this process.

Recent literature supports an “intent-to-defer” based on an evaluation of the patient’s functionality. This represents a paradigm shift from the previous “intent-to-start-early” treatment strategy. In fact, rather than starting early, the Canadian Society of Nephrology recommends delaying initiation of HD in patients with a GFR <15 mL/min.¹ Close monitoring of these patients by both a primary care physician and nephrologist is essential.

When considering initiation of HD, it’s important to look at the overall benefit of this intervention in light of the patient’s mortality risk and quality of life. Many patients who receive HD—especially the elderly—report that it takes more than 6 hours to recover following a dialysis treatment.²

Not surprisingly, depression is common in elderly HD patients. Compared to their younger cohorts, older HD patients have a 62% increased risk of developing depression.³ Also, patients who are considered frail and are receiving HD have more than 3 times the mortality risk within one year than those who are not (hazard ratio=3.42; 95% confidence interval, 2.45-4.76).⁴ (The researchers’ definition of frailty included poor self-reported physical function, exhaustion/fatigue, low physical activity, and undernutrition.⁴)

Functional status. Although a patient’s age should not be a limiting factor for HD referral, functional status should be considered. Patients with limited functionality and significant dependence have an increased risk of death during the first year of HD.⁵

Palliative approach gains acceptance. It is becoming more accepted within the nephrology community to consider a palliative approach to patients with ESRD. Organizations such as the Renal Physicians Association recommend effective prognostication, early advanced care planning, forgoing HD in patients with a poor prognosis, and involving Palliative Care early in the decision-making process.⁶ Aligning the patient’s goals of care with the appropriate treatment method—particularly in patients with comorbid conditions—is an important practice when caring for those with limited life expectancy and functionality.⁷

THE TAKEAWAY

Intent-to-defer HD may be a preferred strategy when caring for many patients with ESRD. Taking into consideration a patient’s comorbidities and functional status, while considering mortality risk and quality of life are essential. Involving palliative care and nephrology specialists can help patients and families understand HD and make an educated decision regarding when to start it.

THE CASE

A 49-year-old Mexican immigrant woman was admitted to the hospital with a 5-month history of fatigue and a 30-pound unintentional weight loss. She was also experiencing arthralgia, swelling, and stiffness in her hands and feet that was worse in the morning. The patient, who was obese and suffered from type 2 diabetes and hypertension, said that at the onset of her illness 5 months earlier, she’d experienced approximately 2 weeks of night sweats and a few days of fever.

A month before being admitted to the hospital, she’d been seen in our southern New Mexico family medicine office. Her recent history of fever, joint symptoms, and weight loss raised concerns of an insidious infection, a new-onset rheumatologic condition, or an occult malignancy.

Initial lab tests revealed leukopenia (white blood cell count, 3200/mcL), microcytic anemia (hemoglobin, 9.4 g/dL), and an elevated erythrocyte sedimentation rate of 30 mm/hr (normal range, 0-20 mm/hr). A rheumatoid factor test was negative, and her thyroid, kidney, and liver function tests were all normal.

More testing… The patient frequently traveled between New Mexico and her hometown of Chihuahua, Mexico, but there had been no recent changes in her diet or environmental exposures. She denied drinking any unpasteurized milk in Chihuahua. But based on her travel history, we ordered enzyme-linked immunosorbent assay (ELISA) antibody titers for Brucella, immunoglobulin G, and immunoglobulin M, which all came back negative. Additionally, we ordered an abdominal and pelvic ultrasound and a chest x-ray that were nondiagnostic. Given the patient’s weight loss and anemia, we referred her to a gastroenterologist for upper and lower gastrointestinal endoscopic evaluations. Unfortunately, the patient was uninsured and did not go to see the gastroenterologist.

A month after seeing us, our patient’s fatigue, lack of appetite, and joint pain became debilitating and she was admitted to the hospital for further evaluation, including a consultation with an oncologist.

THE DIAGNOSIS

During our patient’s 6-day hospital stay, a bone scintigraphy showed a focus of uptake in her left parietal bone and computed tomography scans of her chest, abdomen, and pelvis revealed a left thyroid nodule, as well as multiple noncalcified pulmonary nodules. Blood cultures were also obtained.

Despite the initial negative antibody tests, the blood cultures drawn in the hospital revealed the presence of Brucella melitensis, and we diagnosed brucellosis in this patient.

DISCUSSION

Brucella melitensis is one of the 4 recognized, land-based species of the Brucella genus that can cause disease in humans. Goats, sheep, and camels are natural hosts of B melitensis and consumption of their unpasteurized, infected milk and milk products (especially soft cheeses, ice cream, milk, and butter) leads to human disease. (Once hospitalized, our patient admitted to frequently eating unpasteurized goat cheese from Chihuahua. The only other person in her household that ate the cheese was her 26-year-old daughter, who was also experiencing similar symptoms.)

Brucellosis can also result from inhaling infected, aerosolized material; therefore, individuals whose occupations involve close work with host animals or work in laboratories with the bacteria have an increased risk of infection.¹ Due to the risk of acquiring the infection via inhalation, brucellosis is considered a bioterrorism threat.² Additionally, there have been reports of human-to-human transmission via sexual intercourse, transplacental infection, blood and bone marrow transfusion, and breastfeeding.³

B melitensis is the cause of the majority of Brucella-related illnesses in the world, though symptoms of infection are similar among the different Brucella species. The pathogen can affect almost all organ systems after the initial 2- to 4-week incubation period. Symptoms of brucellosis can be highly variable, although fever is consistently present.¹ Other red flags include arthritis (usually affecting the peripheral joints, the sacroiliac joints, and the lower spine), epididymo-orchitis, and hepatitis resulting in transaminase elevation. Abscess formation can be seen in the liver, spleen, and other organs.

Less common but more ominous complications include central nervous system infections and abscesses, endocarditis, and pulmonary infections. Endocarditis and the resulting aortic valve involvement is the major cause of mortality.¹Brucella­-related uveitis, thyroiditis, nephritis, vasculitis, and acalculous cholecystitis have also been reported.^4-9

Rare in the United States. Pasteurization of dairy products and mass vaccination of livestock make Brucella infection rare in the United States. While there have only been 80 to 139 cases of brucellosis reported per year in the United States since 1993, it remains a persistent threat. International travel is common from the United States to the Middle East and other parts of the world where brucellosis is endemic.

Additionally, infection of livestock with Brucella remains widespread in Mexico and the consumption of unpasteurized Mexican dairy products from goats and sheep remains a high-risk activity for acquiring the disease.¹⁰ Consequently, Texas and California account for more than half of the brucellosis diagnoses in the United States. However, in 2010, cases were reported in 25 other states and the District of Columbia.¹¹

Texas and California account for more than half of the brucellosis diagnoses in the United States.

Repeat serology tests are preferred for confirming the Dx

It is interesting that our patient’s initial Brucella serology by ELISA was negative, because it was ordered months after her initial symptoms. Antibodies should be seen within a month of symptom onset. The Centers for Disease Control and Prevention (CDC) recommends taking 2 serum samples to establish a serologic diagnosis of brucellosis. The first should be drawn within 7 days of symptom onset and the second should be taken 2 to 4 weeks later. A greater than 4-fold rise in the antibody titer confirms the diagnosis. While ELISA is an acceptable serologic test, the CDC recommends using a serum tube agglutination test called the Brucella microagglutination test (BMAT).¹² Repeat serology was not performed on our patient because the diagnosis had been confirmed by blood culture.

A combination of antibiotics is the recommended treatment

Treatment of brucellosis should include a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin 600 mg/d for an all-oral regimen.¹³ Doxycycline 100 mg twice a day is preferred due to fewer gastrointestinal adverse effects than tetracycline. Relapse is not uncommon (10%) and usually occurs within one year of completing the antibiotics.⁸ However, there is a case report of a patient having reactivated brucellosis manifested as acalculous cholecystitis 28 years after completing antibiotics.⁸

Our patient was started on oral doxycycline 100 mg twice a day and oral rifampin 600 mg/d for 6 weeks. Within days of starting the antibiotics, her joint symptoms and fatigue rapidly abated and her appetite returned. Follow-up radiological testing was not performed after her initial hospital studies due to her lack of financial resources.

The patient’s daughter had also been experiencing night sweats, chills, malaise, anorexia, joint pains, weight loss, and alopecia over the previous 2 months. Her blood cultures were positive for B melitensis as well, and she was started on the same antibiotic regimen as her mother. The daughter was also seen in our clinic by another physician and improved quickly within a week of starting treatment.

Both our patient and her daughter remained symptom-free 6 years after treatment.

THE TAKEAWAY

Brucellosis is rare in the United States, but international travel to endemic areas is commonplace and consumption of unpasteurized Mexican dairy products from goats and sheep is widespread. Brucellosis has a wide range of symptoms, but a prompt diagnosis by an ELISA or BMAT serologic test and appropriate treatment can avoid morbidity and mortality. Treatment includes a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin.

THE CASE

A 49-year-old Mexican immigrant woman was admitted to the hospital with a 5-month history of fatigue and a 30-pound unintentional weight loss. She was also experiencing arthralgia, swelling, and stiffness in her hands and feet that was worse in the morning. The patient, who was obese and suffered from type 2 diabetes and hypertension, said that at the onset of her illness 5 months earlier, she’d experienced approximately 2 weeks of night sweats and a few days of fever.

A month before being admitted to the hospital, she’d been seen in our southern New Mexico family medicine office. Her recent history of fever, joint symptoms, and weight loss raised concerns of an insidious infection, a new-onset rheumatologic condition, or an occult malignancy.

Initial lab tests revealed leukopenia (white blood cell count, 3200/mcL), microcytic anemia (hemoglobin, 9.4 g/dL), and an elevated erythrocyte sedimentation rate of 30 mm/hr (normal range, 0-20 mm/hr). A rheumatoid factor test was negative, and her thyroid, kidney, and liver function tests were all normal.

More testing… The patient frequently traveled between New Mexico and her hometown of Chihuahua, Mexico, but there had been no recent changes in her diet or environmental exposures. She denied drinking any unpasteurized milk in Chihuahua. But based on her travel history, we ordered enzyme-linked immunosorbent assay (ELISA) antibody titers for Brucella, immunoglobulin G, and immunoglobulin M, which all came back negative. Additionally, we ordered an abdominal and pelvic ultrasound and a chest x-ray that were nondiagnostic. Given the patient’s weight loss and anemia, we referred her to a gastroenterologist for upper and lower gastrointestinal endoscopic evaluations. Unfortunately, the patient was uninsured and did not go to see the gastroenterologist.

A month after seeing us, our patient’s fatigue, lack of appetite, and joint pain became debilitating and she was admitted to the hospital for further evaluation, including a consultation with an oncologist.

THE DIAGNOSIS

During our patient’s 6-day hospital stay, a bone scintigraphy showed a focus of uptake in her left parietal bone and computed tomography scans of her chest, abdomen, and pelvis revealed a left thyroid nodule, as well as multiple noncalcified pulmonary nodules. Blood cultures were also obtained.

Despite the initial negative antibody tests, the blood cultures drawn in the hospital revealed the presence of Brucella melitensis, and we diagnosed brucellosis in this patient.

DISCUSSION

Brucella melitensis is one of the 4 recognized, land-based species of the Brucella genus that can cause disease in humans. Goats, sheep, and camels are natural hosts of B melitensis and consumption of their unpasteurized, infected milk and milk products (especially soft cheeses, ice cream, milk, and butter) leads to human disease. (Once hospitalized, our patient admitted to frequently eating unpasteurized goat cheese from Chihuahua. The only other person in her household that ate the cheese was her 26-year-old daughter, who was also experiencing similar symptoms.)

Brucellosis can also result from inhaling infected, aerosolized material; therefore, individuals whose occupations involve close work with host animals or work in laboratories with the bacteria have an increased risk of infection.¹ Due to the risk of acquiring the infection via inhalation, brucellosis is considered a bioterrorism threat.² Additionally, there have been reports of human-to-human transmission via sexual intercourse, transplacental infection, blood and bone marrow transfusion, and breastfeeding.³

B melitensis is the cause of the majority of Brucella-related illnesses in the world, though symptoms of infection are similar among the different Brucella species. The pathogen can affect almost all organ systems after the initial 2- to 4-week incubation period. Symptoms of brucellosis can be highly variable, although fever is consistently present.¹ Other red flags include arthritis (usually affecting the peripheral joints, the sacroiliac joints, and the lower spine), epididymo-orchitis, and hepatitis resulting in transaminase elevation. Abscess formation can be seen in the liver, spleen, and other organs.

Less common but more ominous complications include central nervous system infections and abscesses, endocarditis, and pulmonary infections. Endocarditis and the resulting aortic valve involvement is the major cause of mortality.¹Brucella­-related uveitis, thyroiditis, nephritis, vasculitis, and acalculous cholecystitis have also been reported.^4-9

Rare in the United States. Pasteurization of dairy products and mass vaccination of livestock make Brucella infection rare in the United States. While there have only been 80 to 139 cases of brucellosis reported per year in the United States since 1993, it remains a persistent threat. International travel is common from the United States to the Middle East and other parts of the world where brucellosis is endemic.

Additionally, infection of livestock with Brucella remains widespread in Mexico and the consumption of unpasteurized Mexican dairy products from goats and sheep remains a high-risk activity for acquiring the disease.¹⁰ Consequently, Texas and California account for more than half of the brucellosis diagnoses in the United States. However, in 2010, cases were reported in 25 other states and the District of Columbia.¹¹

Texas and California account for more than half of the brucellosis diagnoses in the United States.

Repeat serology tests are preferred for confirming the Dx

It is interesting that our patient’s initial Brucella serology by ELISA was negative, because it was ordered months after her initial symptoms. Antibodies should be seen within a month of symptom onset. The Centers for Disease Control and Prevention (CDC) recommends taking 2 serum samples to establish a serologic diagnosis of brucellosis. The first should be drawn within 7 days of symptom onset and the second should be taken 2 to 4 weeks later. A greater than 4-fold rise in the antibody titer confirms the diagnosis. While ELISA is an acceptable serologic test, the CDC recommends using a serum tube agglutination test called the Brucella microagglutination test (BMAT).¹² Repeat serology was not performed on our patient because the diagnosis had been confirmed by blood culture.

A combination of antibiotics is the recommended treatment

Treatment of brucellosis should include a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin 600 mg/d for an all-oral regimen.¹³ Doxycycline 100 mg twice a day is preferred due to fewer gastrointestinal adverse effects than tetracycline. Relapse is not uncommon (10%) and usually occurs within one year of completing the antibiotics.⁸ However, there is a case report of a patient having reactivated brucellosis manifested as acalculous cholecystitis 28 years after completing antibiotics.⁸

Our patient was started on oral doxycycline 100 mg twice a day and oral rifampin 600 mg/d for 6 weeks. Within days of starting the antibiotics, her joint symptoms and fatigue rapidly abated and her appetite returned. Follow-up radiological testing was not performed after her initial hospital studies due to her lack of financial resources.

The patient’s daughter had also been experiencing night sweats, chills, malaise, anorexia, joint pains, weight loss, and alopecia over the previous 2 months. Her blood cultures were positive for B melitensis as well, and she was started on the same antibiotic regimen as her mother. The daughter was also seen in our clinic by another physician and improved quickly within a week of starting treatment.

Both our patient and her daughter remained symptom-free 6 years after treatment.

THE TAKEAWAY

Brucellosis is rare in the United States, but international travel to endemic areas is commonplace and consumption of unpasteurized Mexican dairy products from goats and sheep is widespread. Brucellosis has a wide range of symptoms, but a prompt diagnosis by an ELISA or BMAT serologic test and appropriate treatment can avoid morbidity and mortality. Treatment includes a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin.

THE CASE

A 49-year-old Mexican immigrant woman was admitted to the hospital with a 5-month history of fatigue and a 30-pound unintentional weight loss. She was also experiencing arthralgia, swelling, and stiffness in her hands and feet that was worse in the morning. The patient, who was obese and suffered from type 2 diabetes and hypertension, said that at the onset of her illness 5 months earlier, she’d experienced approximately 2 weeks of night sweats and a few days of fever.

A month before being admitted to the hospital, she’d been seen in our southern New Mexico family medicine office. Her recent history of fever, joint symptoms, and weight loss raised concerns of an insidious infection, a new-onset rheumatologic condition, or an occult malignancy.

Initial lab tests revealed leukopenia (white blood cell count, 3200/mcL), microcytic anemia (hemoglobin, 9.4 g/dL), and an elevated erythrocyte sedimentation rate of 30 mm/hr (normal range, 0-20 mm/hr). A rheumatoid factor test was negative, and her thyroid, kidney, and liver function tests were all normal.

More testing… The patient frequently traveled between New Mexico and her hometown of Chihuahua, Mexico, but there had been no recent changes in her diet or environmental exposures. She denied drinking any unpasteurized milk in Chihuahua. But based on her travel history, we ordered enzyme-linked immunosorbent assay (ELISA) antibody titers for Brucella, immunoglobulin G, and immunoglobulin M, which all came back negative. Additionally, we ordered an abdominal and pelvic ultrasound and a chest x-ray that were nondiagnostic. Given the patient’s weight loss and anemia, we referred her to a gastroenterologist for upper and lower gastrointestinal endoscopic evaluations. Unfortunately, the patient was uninsured and did not go to see the gastroenterologist.

A month after seeing us, our patient’s fatigue, lack of appetite, and joint pain became debilitating and she was admitted to the hospital for further evaluation, including a consultation with an oncologist.

THE DIAGNOSIS

During our patient’s 6-day hospital stay, a bone scintigraphy showed a focus of uptake in her left parietal bone and computed tomography scans of her chest, abdomen, and pelvis revealed a left thyroid nodule, as well as multiple noncalcified pulmonary nodules. Blood cultures were also obtained.

Despite the initial negative antibody tests, the blood cultures drawn in the hospital revealed the presence of Brucella melitensis, and we diagnosed brucellosis in this patient.

DISCUSSION

Brucella melitensis is one of the 4 recognized, land-based species of the Brucella genus that can cause disease in humans. Goats, sheep, and camels are natural hosts of B melitensis and consumption of their unpasteurized, infected milk and milk products (especially soft cheeses, ice cream, milk, and butter) leads to human disease. (Once hospitalized, our patient admitted to frequently eating unpasteurized goat cheese from Chihuahua. The only other person in her household that ate the cheese was her 26-year-old daughter, who was also experiencing similar symptoms.)

Brucellosis can also result from inhaling infected, aerosolized material; therefore, individuals whose occupations involve close work with host animals or work in laboratories with the bacteria have an increased risk of infection.¹ Due to the risk of acquiring the infection via inhalation, brucellosis is considered a bioterrorism threat.² Additionally, there have been reports of human-to-human transmission via sexual intercourse, transplacental infection, blood and bone marrow transfusion, and breastfeeding.³

B melitensis is the cause of the majority of Brucella-related illnesses in the world, though symptoms of infection are similar among the different Brucella species. The pathogen can affect almost all organ systems after the initial 2- to 4-week incubation period. Symptoms of brucellosis can be highly variable, although fever is consistently present.¹ Other red flags include arthritis (usually affecting the peripheral joints, the sacroiliac joints, and the lower spine), epididymo-orchitis, and hepatitis resulting in transaminase elevation. Abscess formation can be seen in the liver, spleen, and other organs.

Less common but more ominous complications include central nervous system infections and abscesses, endocarditis, and pulmonary infections. Endocarditis and the resulting aortic valve involvement is the major cause of mortality.¹Brucella­-related uveitis, thyroiditis, nephritis, vasculitis, and acalculous cholecystitis have also been reported.^4-9

Rare in the United States. Pasteurization of dairy products and mass vaccination of livestock make Brucella infection rare in the United States. While there have only been 80 to 139 cases of brucellosis reported per year in the United States since 1993, it remains a persistent threat. International travel is common from the United States to the Middle East and other parts of the world where brucellosis is endemic.

Additionally, infection of livestock with Brucella remains widespread in Mexico and the consumption of unpasteurized Mexican dairy products from goats and sheep remains a high-risk activity for acquiring the disease.¹⁰ Consequently, Texas and California account for more than half of the brucellosis diagnoses in the United States. However, in 2010, cases were reported in 25 other states and the District of Columbia.¹¹

Texas and California account for more than half of the brucellosis diagnoses in the United States.

Repeat serology tests are preferred for confirming the Dx

It is interesting that our patient’s initial Brucella serology by ELISA was negative, because it was ordered months after her initial symptoms. Antibodies should be seen within a month of symptom onset. The Centers for Disease Control and Prevention (CDC) recommends taking 2 serum samples to establish a serologic diagnosis of brucellosis. The first should be drawn within 7 days of symptom onset and the second should be taken 2 to 4 weeks later. A greater than 4-fold rise in the antibody titer confirms the diagnosis. While ELISA is an acceptable serologic test, the CDC recommends using a serum tube agglutination test called the Brucella microagglutination test (BMAT).¹² Repeat serology was not performed on our patient because the diagnosis had been confirmed by blood culture.

A combination of antibiotics is the recommended treatment

Treatment of brucellosis should include a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin 600 mg/d for an all-oral regimen.¹³ Doxycycline 100 mg twice a day is preferred due to fewer gastrointestinal adverse effects than tetracycline. Relapse is not uncommon (10%) and usually occurs within one year of completing the antibiotics.⁸ However, there is a case report of a patient having reactivated brucellosis manifested as acalculous cholecystitis 28 years after completing antibiotics.⁸

Our patient was started on oral doxycycline 100 mg twice a day and oral rifampin 600 mg/d for 6 weeks. Within days of starting the antibiotics, her joint symptoms and fatigue rapidly abated and her appetite returned. Follow-up radiological testing was not performed after her initial hospital studies due to her lack of financial resources.

The patient’s daughter had also been experiencing night sweats, chills, malaise, anorexia, joint pains, weight loss, and alopecia over the previous 2 months. Her blood cultures were positive for B melitensis as well, and she was started on the same antibiotic regimen as her mother. The daughter was also seen in our clinic by another physician and improved quickly within a week of starting treatment.

Both our patient and her daughter remained symptom-free 6 years after treatment.

THE TAKEAWAY

Brucellosis is rare in the United States, but international travel to endemic areas is commonplace and consumption of unpasteurized Mexican dairy products from goats and sheep is widespread. Brucellosis has a wide range of symptoms, but a prompt diagnosis by an ELISA or BMAT serologic test and appropriate treatment can avoid morbidity and mortality. Treatment includes a tetracycline for at least 6 weeks in combination with an aminoglycoside or rifampin.

While some physicians prefer a narrower clinic focus, the wide variety and complexity of the care provided by family physicians is precisely what drew many of us to the specialty. We enjoy caring for patients of all ages who see us for the diagnosis and treatment of acute illnesses, management of chronic diseases, preventive care, and behavioral and mental health concerns.

The quantity, variety, and complexity of the care we provide has been well-documented in the literature. In a study performed by the Wisconsin Research Network,¹ 29 family physicians reported addressing an average of 3.05 problems per patient during 572 office visits. A chart review confirmed physician self-report: 2.82 problems were recorded on average for each visit. For patients older than age 65, an average of 3.88 problems were addressed at each visit. For patients with diabetes, the average was 4.60.

Using data from the 2000 National Ambulatory Medical Care Survey, Katerndahl et al² estimated the complexity of patient encounters in family practice, cardiology, and psychiatry. They used a formula that took into account the per-patient number of reasons for each visit, diagnoses, and body systems examined, and the variability and diversity of each of these factors. After adjusting the results for length of visit, they found the complexity of care provided per hour by family physicians was 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

The topics in this issue are a terrific illustration of the breadth of family medicine. Peripheral neuropathy, which we see almost daily, is difficult to diagnose and treat. Prolotherapy is an up-and-coming dextrose injection therapy for tendinopathies and joint pain that shows promise, and patients are likely to start asking us about it. Home apnea monitors are used frequently for newborns—but how effective are they, and when can you tell parents to discontinue their use?

The complexity of care provided per hour by family physicians is 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

It seems that vaccine recommendations change every year, and this issue’s Practice Alert covers the latest on meningococcal immunization. This month’s PURL answers the question: Do we really need to “bridge” patients with atrial fibrillation from warfarin to low molecular weight heparin immediately before and after a surgical procedure?

The authors and editors of The Journal of Family Practice constantly strive to bring you the most up-to-date information to support your work as a master of the complexity of primary care practice.

While some physicians prefer a narrower clinic focus, the wide variety and complexity of the care provided by family physicians is precisely what drew many of us to the specialty. We enjoy caring for patients of all ages who see us for the diagnosis and treatment of acute illnesses, management of chronic diseases, preventive care, and behavioral and mental health concerns.

The quantity, variety, and complexity of the care we provide has been well-documented in the literature. In a study performed by the Wisconsin Research Network,¹ 29 family physicians reported addressing an average of 3.05 problems per patient during 572 office visits. A chart review confirmed physician self-report: 2.82 problems were recorded on average for each visit. For patients older than age 65, an average of 3.88 problems were addressed at each visit. For patients with diabetes, the average was 4.60.

Using data from the 2000 National Ambulatory Medical Care Survey, Katerndahl et al² estimated the complexity of patient encounters in family practice, cardiology, and psychiatry. They used a formula that took into account the per-patient number of reasons for each visit, diagnoses, and body systems examined, and the variability and diversity of each of these factors. After adjusting the results for length of visit, they found the complexity of care provided per hour by family physicians was 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

The topics in this issue are a terrific illustration of the breadth of family medicine. Peripheral neuropathy, which we see almost daily, is difficult to diagnose and treat. Prolotherapy is an up-and-coming dextrose injection therapy for tendinopathies and joint pain that shows promise, and patients are likely to start asking us about it. Home apnea monitors are used frequently for newborns—but how effective are they, and when can you tell parents to discontinue their use?

The complexity of care provided per hour by family physicians is 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

It seems that vaccine recommendations change every year, and this issue’s Practice Alert covers the latest on meningococcal immunization. This month’s PURL answers the question: Do we really need to “bridge” patients with atrial fibrillation from warfarin to low molecular weight heparin immediately before and after a surgical procedure?

The authors and editors of The Journal of Family Practice constantly strive to bring you the most up-to-date information to support your work as a master of the complexity of primary care practice.

While some physicians prefer a narrower clinic focus, the wide variety and complexity of the care provided by family physicians is precisely what drew many of us to the specialty. We enjoy caring for patients of all ages who see us for the diagnosis and treatment of acute illnesses, management of chronic diseases, preventive care, and behavioral and mental health concerns.

The quantity, variety, and complexity of the care we provide has been well-documented in the literature. In a study performed by the Wisconsin Research Network,¹ 29 family physicians reported addressing an average of 3.05 problems per patient during 572 office visits. A chart review confirmed physician self-report: 2.82 problems were recorded on average for each visit. For patients older than age 65, an average of 3.88 problems were addressed at each visit. For patients with diabetes, the average was 4.60.

Using data from the 2000 National Ambulatory Medical Care Survey, Katerndahl et al² estimated the complexity of patient encounters in family practice, cardiology, and psychiatry. They used a formula that took into account the per-patient number of reasons for each visit, diagnoses, and body systems examined, and the variability and diversity of each of these factors. After adjusting the results for length of visit, they found the complexity of care provided per hour by family physicians was 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

The topics in this issue are a terrific illustration of the breadth of family medicine. Peripheral neuropathy, which we see almost daily, is difficult to diagnose and treat. Prolotherapy is an up-and-coming dextrose injection therapy for tendinopathies and joint pain that shows promise, and patients are likely to start asking us about it. Home apnea monitors are used frequently for newborns—but how effective are they, and when can you tell parents to discontinue their use?

The complexity of care provided per hour by family physicians is 33% higher than that of cardiologists and 5 times higher than that of psychiatrists.

It seems that vaccine recommendations change every year, and this issue’s Practice Alert covers the latest on meningococcal immunization. This month’s PURL answers the question: Do we really need to “bridge” patients with atrial fibrillation from warfarin to low molecular weight heparin immediately before and after a surgical procedure?

The authors and editors of The Journal of Family Practice constantly strive to bring you the most up-to-date information to support your work as a master of the complexity of primary care practice.