User login
New HIV antiretroviral guidelines embrace PrEP, early ART
The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.
In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)
The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.
Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.
In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.
For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.
For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).
On Twitter @richpizzi
The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.
In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)
The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.
Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.
In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.
For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.
For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).
On Twitter @richpizzi
The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.
In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)
The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.
Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.
In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.
For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.
For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).
On Twitter @richpizzi
FROM JAMA
Is a Persistent Vacuum Phenomenon a Sign of Pseudarthrosis After Posterolateral Spinal Fusion?
The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).3 Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,4 ankylosing spondylitis,5,6 and lumbar spinal fusion.7
To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.
We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.
Materials and Methods
After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.
CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.8 Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.
Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.
Descriptive and inferential statistical tests were performed as applicable. Pearson χ2 test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.
Results
Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.
On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).
Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.
At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.
Discussion
The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson1 in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.2 The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.9 CT is more sensitive than radiography in detecting the VP; Lardé and colleagues3 found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.10 In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues11 found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,12 in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.
We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures4 and ankylosing spondylitis.5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues4 found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel5 first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues6 identified the intervertebral VP on CT in 7 patients. Edwards and colleagues7 studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues13 identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.
This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,14 even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.11 Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.
Conclusion
The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.
1. Knutsson F. The vacuum phenomenon in the intervertebral discs. Acta Radiol. 1942;23:173-179.
2. Resnick D, Niwayama G, Guerra J Jr, Vint V, Usselman J. Spinal vacuum phenomenon: anatomical study and review. Radiology. 1981;139(2):341-348.
3. Lardé D, Mathieu D, Frija J, Gaston A, Vasile N. Spinal vacuum phenomenon: CT diagnosis and significance. J Comput Assist Tomogr. 1982;6(4):671-676.
4. Stallenberg B, Madani A, Burny F, Gevenois PA. The vacuum phenomenon: a CT sign of nonunited fracture. AJR Am J Roentgenol. 2001;176(5):1161-1164.
5. Martel W. Spinal pseudarthrosis: a complication of ankylosing spondylitis. Arthritis Rheum. 1978;21(4):485-490.
6. Chan FL, Ho EK, Chau EM. Spinal pseudarthrosis complicating ankylosing spondylitis: comparison of CT and conventional tomography. AJR Am J Roentgenol. 1988;150(3):611-614.
7. Edwards CE, Antonoiades SB, Ford L, Crabster E. CT vacuum disc sign: a highly specific predictor of lumbar nonunion. Poster presented at: 41st Annual Meeting of the Scoliosis Research Society; September 2006; Monterey, CA.
8. Carreon LY, Djurasovic M, Glassman SD, Sailer P. Diagnostic accuracy and reliability of fine-cut CT scans with reconstructions to determine the status of an instrumented posterolateral fusion with surgical exploration as reference standard. Spine. 2007;32(8):892-895.
9. Goobar JE, Pate D, Resnick D, Sartoris DJ. Radiography of the hyperextended lumbar spine: an effective technique for the demonstration of discal vacuum phenomena. Can Assoc Radiol J. 1987;38(4):271-274.
10. Grenier N, Grossman RI, Schiebler ML, Yeager BA, Goldberg HI, Kressel HY. Degenerative lumbar disk disease: pitfalls and usefulness of MR imaging in detection of vacuum phenomenon. Radiology. 1987;164(3):861-865.
11. Wang HJ, Chen BB, Yu CW, Hsu CY, Shih TT. Alteration of disc vacuum contents during prolonged supine positioning: evaluation with MR Image. Spine. 2007;32(23):2610-2615.
12. D’Anastasi M, Birkenmaier C, Schmidt GP, Wegener B, Reiser MF, Baur-Melnyk A. Correlation between vacuum phenomenon on CT and fluid on MRI in degenerative disks. AJR Am J Roentgenol. 2011;197(5):1182-1189.
13. Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol. 2005;26(7):1634-1640.
14. Selby MD, Clark SR, Hall DJ, Freeman BJ. Radiologic assessment of spinal fusion. J Am Acad Orthop Surg. 2012;20(11):694-703.
15. Kanayama M, Hashimoto T, Shigenobu K, Yamane S, Bauer TW, Togawa D. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine. 2006;31(10):1067-1074.
The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).3 Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,4 ankylosing spondylitis,5,6 and lumbar spinal fusion.7
To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.
We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.
Materials and Methods
After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.
CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.8 Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.
Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.
Descriptive and inferential statistical tests were performed as applicable. Pearson χ2 test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.
Results
Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.
On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).
Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.
At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.
Discussion
The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson1 in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.2 The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.9 CT is more sensitive than radiography in detecting the VP; Lardé and colleagues3 found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.10 In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues11 found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,12 in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.
We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures4 and ankylosing spondylitis.5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues4 found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel5 first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues6 identified the intervertebral VP on CT in 7 patients. Edwards and colleagues7 studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues13 identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.
This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,14 even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.11 Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.
Conclusion
The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.
The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).3 Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,4 ankylosing spondylitis,5,6 and lumbar spinal fusion.7
To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.
We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.
Materials and Methods
After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.
CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.8 Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.
Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.
Descriptive and inferential statistical tests were performed as applicable. Pearson χ2 test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.
Results
Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.
On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).
Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.
At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.
Discussion
The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson1 in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.2 The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.9 CT is more sensitive than radiography in detecting the VP; Lardé and colleagues3 found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.10 In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues11 found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,12 in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.
We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures4 and ankylosing spondylitis.5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues4 found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel5 first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues6 identified the intervertebral VP on CT in 7 patients. Edwards and colleagues7 studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues13 identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.
This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,14 even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.11 Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.
Conclusion
The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.
1. Knutsson F. The vacuum phenomenon in the intervertebral discs. Acta Radiol. 1942;23:173-179.
2. Resnick D, Niwayama G, Guerra J Jr, Vint V, Usselman J. Spinal vacuum phenomenon: anatomical study and review. Radiology. 1981;139(2):341-348.
3. Lardé D, Mathieu D, Frija J, Gaston A, Vasile N. Spinal vacuum phenomenon: CT diagnosis and significance. J Comput Assist Tomogr. 1982;6(4):671-676.
4. Stallenberg B, Madani A, Burny F, Gevenois PA. The vacuum phenomenon: a CT sign of nonunited fracture. AJR Am J Roentgenol. 2001;176(5):1161-1164.
5. Martel W. Spinal pseudarthrosis: a complication of ankylosing spondylitis. Arthritis Rheum. 1978;21(4):485-490.
6. Chan FL, Ho EK, Chau EM. Spinal pseudarthrosis complicating ankylosing spondylitis: comparison of CT and conventional tomography. AJR Am J Roentgenol. 1988;150(3):611-614.
7. Edwards CE, Antonoiades SB, Ford L, Crabster E. CT vacuum disc sign: a highly specific predictor of lumbar nonunion. Poster presented at: 41st Annual Meeting of the Scoliosis Research Society; September 2006; Monterey, CA.
8. Carreon LY, Djurasovic M, Glassman SD, Sailer P. Diagnostic accuracy and reliability of fine-cut CT scans with reconstructions to determine the status of an instrumented posterolateral fusion with surgical exploration as reference standard. Spine. 2007;32(8):892-895.
9. Goobar JE, Pate D, Resnick D, Sartoris DJ. Radiography of the hyperextended lumbar spine: an effective technique for the demonstration of discal vacuum phenomena. Can Assoc Radiol J. 1987;38(4):271-274.
10. Grenier N, Grossman RI, Schiebler ML, Yeager BA, Goldberg HI, Kressel HY. Degenerative lumbar disk disease: pitfalls and usefulness of MR imaging in detection of vacuum phenomenon. Radiology. 1987;164(3):861-865.
11. Wang HJ, Chen BB, Yu CW, Hsu CY, Shih TT. Alteration of disc vacuum contents during prolonged supine positioning: evaluation with MR Image. Spine. 2007;32(23):2610-2615.
12. D’Anastasi M, Birkenmaier C, Schmidt GP, Wegener B, Reiser MF, Baur-Melnyk A. Correlation between vacuum phenomenon on CT and fluid on MRI in degenerative disks. AJR Am J Roentgenol. 2011;197(5):1182-1189.
13. Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol. 2005;26(7):1634-1640.
14. Selby MD, Clark SR, Hall DJ, Freeman BJ. Radiologic assessment of spinal fusion. J Am Acad Orthop Surg. 2012;20(11):694-703.
15. Kanayama M, Hashimoto T, Shigenobu K, Yamane S, Bauer TW, Togawa D. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine. 2006;31(10):1067-1074.
1. Knutsson F. The vacuum phenomenon in the intervertebral discs. Acta Radiol. 1942;23:173-179.
2. Resnick D, Niwayama G, Guerra J Jr, Vint V, Usselman J. Spinal vacuum phenomenon: anatomical study and review. Radiology. 1981;139(2):341-348.
3. Lardé D, Mathieu D, Frija J, Gaston A, Vasile N. Spinal vacuum phenomenon: CT diagnosis and significance. J Comput Assist Tomogr. 1982;6(4):671-676.
4. Stallenberg B, Madani A, Burny F, Gevenois PA. The vacuum phenomenon: a CT sign of nonunited fracture. AJR Am J Roentgenol. 2001;176(5):1161-1164.
5. Martel W. Spinal pseudarthrosis: a complication of ankylosing spondylitis. Arthritis Rheum. 1978;21(4):485-490.
6. Chan FL, Ho EK, Chau EM. Spinal pseudarthrosis complicating ankylosing spondylitis: comparison of CT and conventional tomography. AJR Am J Roentgenol. 1988;150(3):611-614.
7. Edwards CE, Antonoiades SB, Ford L, Crabster E. CT vacuum disc sign: a highly specific predictor of lumbar nonunion. Poster presented at: 41st Annual Meeting of the Scoliosis Research Society; September 2006; Monterey, CA.
8. Carreon LY, Djurasovic M, Glassman SD, Sailer P. Diagnostic accuracy and reliability of fine-cut CT scans with reconstructions to determine the status of an instrumented posterolateral fusion with surgical exploration as reference standard. Spine. 2007;32(8):892-895.
9. Goobar JE, Pate D, Resnick D, Sartoris DJ. Radiography of the hyperextended lumbar spine: an effective technique for the demonstration of discal vacuum phenomena. Can Assoc Radiol J. 1987;38(4):271-274.
10. Grenier N, Grossman RI, Schiebler ML, Yeager BA, Goldberg HI, Kressel HY. Degenerative lumbar disk disease: pitfalls and usefulness of MR imaging in detection of vacuum phenomenon. Radiology. 1987;164(3):861-865.
11. Wang HJ, Chen BB, Yu CW, Hsu CY, Shih TT. Alteration of disc vacuum contents during prolonged supine positioning: evaluation with MR Image. Spine. 2007;32(23):2610-2615.
12. D’Anastasi M, Birkenmaier C, Schmidt GP, Wegener B, Reiser MF, Baur-Melnyk A. Correlation between vacuum phenomenon on CT and fluid on MRI in degenerative disks. AJR Am J Roentgenol. 2011;197(5):1182-1189.
13. Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol. 2005;26(7):1634-1640.
14. Selby MD, Clark SR, Hall DJ, Freeman BJ. Radiologic assessment of spinal fusion. J Am Acad Orthop Surg. 2012;20(11):694-703.
15. Kanayama M, Hashimoto T, Shigenobu K, Yamane S, Bauer TW, Togawa D. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine. 2006;31(10):1067-1074.
Driving skills already affected with mild cognitive impairment
TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.
The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.
“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”
The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).
Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.
Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.
Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.
When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.
Differences in brain activation revealed
The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.
On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”
The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”
Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.
“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”
During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.
“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”
Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”
Ms. Hird had no financial disclosures.
On Twitter @alz_gal
TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.
The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.
“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”
The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).
Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.
Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.
Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.
When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.
Differences in brain activation revealed
The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.
On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”
The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”
Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.
“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”
During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.
“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”
Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”
Ms. Hird had no financial disclosures.
On Twitter @alz_gal
TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.
The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.
“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”
The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).
Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.
Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.
Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.
When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.
Differences in brain activation revealed
The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.
On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”
The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”
Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.
“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”
During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.
“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”
Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”
Ms. Hird had no financial disclosures.
On Twitter @alz_gal
AT AAIC 2016
Key clinical point: Patients with mild cognitive impairment may already be unsafe drivers.
Major finding: Patients with multidomain MCI made significantly more driving errors than did healthy controls (mean of 14 vs. 2.7 errors).
Data source: The studies comprised 40 patients with MCI and 36 age-matched cognitively healthy controls.
Disclosures: Megan Hird had no financial disclosures.
Using Aminocaproic Acid to Reduce Blood Loss After Primary Unilateral Total Knee Arthroplasty
During total knee arthroplasty (TKA), traditionally a thigh tourniquet is used to minimize blood loss. Although intraoperative blood loss is negligible, postoperative blood loss can be extensive, and patients often require blood transfusions. Transfusions expose patients to clinical risks and increase costs. Well-documented transfusion complications include allergic reaction, transfusion-related acute lung injury, transfusion-associated circulatory overload, venous thromboembolism, graft vs host disease, bloodborne infections, and immunomodulation.1 Although measures are taken to reduce these risks, the costs associated with transfusions continue to escalate.2
Postoperative bleeding is attributed to fibrinolytic system activation. The antifibrinolytic agent aminocaproic acid (ACA), a synthetic analogue of the amino acid lysine, acts by competitively blocking the lysine-binding site of plasminogen, inhibiting fibrinolysis.3 Multiple studies have shown that ACA and a similar drug, tranexamic acid, can reduce postoperative blood loss when used intravenously in unilateral TKA.4,5 However, more studies are needed to evaluate antifibrinolytic agents with comparative controls using standardized procedures and documented outcome measures. In addition, the majority of studies have used tranexamic acid rather than ACA, despite the lower cost and similar efficacy of ACA.1,4 ACA is an inexpensive medication with a low risk profile, making it an attractive alternative to historical post-TKA management (which has a higher rate of blood transfusions) and a viable replacement in protocols already implementing tranexamic acid, the more expensive antifibrinolytic.5,6 It has been proposed that ACA use reduces equipment (drain) costs, blood transfusion costs, exposure to complications of blood loss, and transfusion reactions and reduces or eliminates the need for costly medications, such as erythropoiesis-stimulating agents.
Kagoma and colleagues5 reported that antifibrinolytic agents may reduce bleeding by at least 300 mL and may reduce the need for transfusions by 50% or eliminate this need altogether. Other antifibrinolytic agents have been studied in unilateral TKA, with results showing decreased drainage and improved postoperative hemoglobin (Hb) levels.6
We conducted a study to evaluate the effectiveness of a single intraoperative dose of ACA in reducing postoperative blood loss and the need for blood transfusions with increased preservation of postoperative Hb levels.
Methods
In October 2011, Dr. Anderson initiated an intraoperative intravenous (IV) ACA protocol for primary unilateral TKA. Given the decreased drain output immediately observed, and patients’ increased postoperative Hb levels, a retrospective study was proposed. After obtaining full Institutional Review Board approval for the study, we retrospectively reviewed the medical charts of 50 consecutive patients who underwent primary unilateral TKA—the last 25 who had the surgery before the IV ACA protocol was initiated (control group) and the first 25 who were given the IV ACA medication during the surgery (antifibrinolytic group). Inclusion criteria were primary unilateral TKA, no bleeding dyscrasia, no history of anaphylactic response to antifibrinolytic agents, no history of deep vein thrombosis, and normal preoperative coagulation parameters, international normalized ratio (INR), and partial thromboplastin time. Exclusion criteria included lateral corner release, lateral retinacular release, combined extensive deep and superficial medial collateral ligament releases, and cardiac or peripheral stent in place.
Each surgery—a standard primary unilateral TKA with an intramedullary femoral component and an extramedullary tibial component—was performed by Dr. Anderson. Each component was cemented. Each patient underwent a posterior cruciate ligament release and/or a deep medial collateral ligament release. A well-padded thigh tourniquet was inflated before surgical incision, and it remained inflated until all postoperative surgical dressings were applied. Each patient in the antifibrinolytic group was given a 10-g dose of IV ACA at the start of implant cementation; the dose was administered over 10 minutes and was completely infused before tourniquet deflation. For each patient in the control group, a suction drain (Constavac, Stryker) was used. As postoperative drainage was so insignificant in the first 12 antifibrinolytic cases, use of the drain was then discontinued.
All patients received standard postoperative deep vein thrombosis prophylaxis in the form of warfarin in accordance with existing practice. Warfarin was given once a day starting the night of surgery and was continued until discharge based on daily INR values with an agreed-on target of 2.0. Thigh-high compression stockings and calf sequential compression devices were used in all cases. No patient in either group predonated blood or was given erythropoietin injections before or after surgery. Postoperative allogeneic transfusions were given to patients who were clinically symptomatic or short of breath; patients with hypotension uncorrectable with IV volume supplementation and an Hb level under 9.0 g/dL; and patients with an Hb level under 7.0 g/dL regardless of symptoms. All patients were monitored for postoperative adverse events and complications.
Postoperative blood loss (drain output), Hb levels on postoperative days 1 and 2 (POD-1, POD-2), blood transfusion amounts, and complications were recorded for all patients. Group means were compared with 2-sample t tests for independent samples. Data are reported as group means and SDs. All significance tests were 2-tailed, and statistical significance was set at P < .05.
Results
Fifty patients enrolled in the study: 25 in the control group and 25 in the antifibrinolytic group. Table 1 compares the main characteristics of the 2 groups. No significant differences were found between these groups for any of the characteristics considered.
There was significantly (P < .0001) more postoperative drainage in the control group: Mean drain output was 410.9 mL for the control group and 155.0 mL for the antifibrinolytic group (Table 2). Patients in the antifibrinolytic group did not receive any blood transfusions, whereas 40% of patients in the control group received transfusions (P = .022). On average, the transfused patients received 0.4 unit of packed red blood cells.
Although there was no statistically significant difference in POD-1 or POD-2 Hb levels between the antifibrinolytic and control groups, the antifibrinolytic group trended higher on POD-1 (11.1 g vs 10.7 g; P = .108) and POD-2 (11.5 g vs 10.2 g; P = .117) (Table 3). Mean Hb level was 8.1 g for control patients transfused on POD-1 and 7.9 g for control patients transfused on POD-2. For control patients who were not transfused, mean Hb level was 10.7 g on POD-1 and 10.2 g on POD-2.
There were no adverse events (eg, anaphylaxis, hypersensitivity) in either group, and there was no difference in incision drainage or returns to operating room between the groups.
Discussion
In TKA, a tourniquet is used to minimize intraoperative blood loss; postoperative bleeding, however, is often extensive. Both surgery and tourniquet use are reported to enhance local fibrinolytic activity within the limb.8 The synthetic antifibrinolytic ACA reduces blood loss by clot stabilization rather than by promotion of clot formation.8
In the present study, a single intraoperative dose of IV ACA administered in primary unilateral TKA significantly reduced postoperative wound drainage and eliminated the need for postoperative allogeneic blood transfusions. In addition, patients who received ACA had higher Hb levels on POD-1 and POD-2. These results are similar to those of other clinical trials in which external blood losses were measured.4-7 The postoperative drain output differences (~250 mL) in our study are clinically relevant, as they indicate significant reductions in postoperative blood loss with the implementation of an antifibrinolytic operative protocol.
In a study by Ponnusamy and colleagues,1 blood transfusion after orthopedic surgery accounted for 10% of all packed red blood cell transfusions, but use varied widely. National TKA transfusion rates vary from 4.3% to 63.8% among surgeons and hospitals.9 This evidence calls for standardization and critical review of practices to ensure more efficient use of blood products, effectively protecting patients from unneeded complications and reducing hospital costs. Mounting evidence supporting the efficacy of ACA in reducing perioperative blood loss and lowering postoperative blood transfusion rates points toward including antifibrinolytic therapy in standard TKA protocols. In our study, 40% of control patients and no antifibrinolytic patients required a transfusion—a stark contrast.
Although our antifibrinolytic group’s postoperative Hb levels were not statistically significantly higher, their being elevated illustrates the protective effect of intraoperative use of antifibrinolytics in TKA. This elevation in Hb levels is especially valid given the similarity of the antifibrinolytic and control patients’ preoperative Hb levels (P = .871) (Table 1). Other studies have shown similar upward trends in postoperative Hb levels, many of which were statistically significant.5-8,10
Conclusion
This study showed that a single intraoperative 10-g dose of IV ACA significantly reduced perioperative blood loss and lowered blood transfusion rates in TKA. In addition, postoperative Hb levels were higher in the patients who received ACA than in patients who did not receive an antifibrinolytic. The positive effects of ACA were obtained without adverse events or complications, making use of this antifibrinolytic a relevant addition to TKA protocols.
1. Ponnusamy KE, Kim TJ, Khanuja HS. Perioperative blood transfusions in orthopaedic surgery. J Bone Joint Surg Am. 2014;96(21):1836-1844.
2. Spahn DR, Casutt M. Eliminating blood transfusions: new aspects and perspectives. Anesthesiology. 2000;93(1):242-255.
3. Van Aelbrouck C, Englberger L, Faraoni D. Review of the fibrinolytic system: comparison of different antifibrinolytics used during cardiopulmonary bypass. Recent Pat Cardiovasc Drug Discov. 2012;7(3):175-179.
4. Sepah YJ, Umer M, Ahmad T, Nasim F, Chaudhry MU, Umar M. Use of tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement. J Orthop Surg Res. 2011;6:22.
5. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009;123(5):687-696.
6. Zufferey P, Merquiol F, Laporte S, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105(5):1034-1046.
7. Camarasa MA, Ollé G, Serra-Prat M, et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth. 2006;96(5):576-582.
8. Orpen NM, Little C, Walker G, Crawfurd EJ. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee. 2006;13(2):106-110.
9. Chen AF, Klatt BA, Yazer MH, Waters JH. Blood utilization after primary total joint arthroplasty in a large hospital network. HSS J. 2013;9(2):123-128.
10. Aguilera X, Martinez-Zapata MJ, Bosch A, et al. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am. 2013;95(22):2001-2007.
During total knee arthroplasty (TKA), traditionally a thigh tourniquet is used to minimize blood loss. Although intraoperative blood loss is negligible, postoperative blood loss can be extensive, and patients often require blood transfusions. Transfusions expose patients to clinical risks and increase costs. Well-documented transfusion complications include allergic reaction, transfusion-related acute lung injury, transfusion-associated circulatory overload, venous thromboembolism, graft vs host disease, bloodborne infections, and immunomodulation.1 Although measures are taken to reduce these risks, the costs associated with transfusions continue to escalate.2
Postoperative bleeding is attributed to fibrinolytic system activation. The antifibrinolytic agent aminocaproic acid (ACA), a synthetic analogue of the amino acid lysine, acts by competitively blocking the lysine-binding site of plasminogen, inhibiting fibrinolysis.3 Multiple studies have shown that ACA and a similar drug, tranexamic acid, can reduce postoperative blood loss when used intravenously in unilateral TKA.4,5 However, more studies are needed to evaluate antifibrinolytic agents with comparative controls using standardized procedures and documented outcome measures. In addition, the majority of studies have used tranexamic acid rather than ACA, despite the lower cost and similar efficacy of ACA.1,4 ACA is an inexpensive medication with a low risk profile, making it an attractive alternative to historical post-TKA management (which has a higher rate of blood transfusions) and a viable replacement in protocols already implementing tranexamic acid, the more expensive antifibrinolytic.5,6 It has been proposed that ACA use reduces equipment (drain) costs, blood transfusion costs, exposure to complications of blood loss, and transfusion reactions and reduces or eliminates the need for costly medications, such as erythropoiesis-stimulating agents.
Kagoma and colleagues5 reported that antifibrinolytic agents may reduce bleeding by at least 300 mL and may reduce the need for transfusions by 50% or eliminate this need altogether. Other antifibrinolytic agents have been studied in unilateral TKA, with results showing decreased drainage and improved postoperative hemoglobin (Hb) levels.6
We conducted a study to evaluate the effectiveness of a single intraoperative dose of ACA in reducing postoperative blood loss and the need for blood transfusions with increased preservation of postoperative Hb levels.
Methods
In October 2011, Dr. Anderson initiated an intraoperative intravenous (IV) ACA protocol for primary unilateral TKA. Given the decreased drain output immediately observed, and patients’ increased postoperative Hb levels, a retrospective study was proposed. After obtaining full Institutional Review Board approval for the study, we retrospectively reviewed the medical charts of 50 consecutive patients who underwent primary unilateral TKA—the last 25 who had the surgery before the IV ACA protocol was initiated (control group) and the first 25 who were given the IV ACA medication during the surgery (antifibrinolytic group). Inclusion criteria were primary unilateral TKA, no bleeding dyscrasia, no history of anaphylactic response to antifibrinolytic agents, no history of deep vein thrombosis, and normal preoperative coagulation parameters, international normalized ratio (INR), and partial thromboplastin time. Exclusion criteria included lateral corner release, lateral retinacular release, combined extensive deep and superficial medial collateral ligament releases, and cardiac or peripheral stent in place.
Each surgery—a standard primary unilateral TKA with an intramedullary femoral component and an extramedullary tibial component—was performed by Dr. Anderson. Each component was cemented. Each patient underwent a posterior cruciate ligament release and/or a deep medial collateral ligament release. A well-padded thigh tourniquet was inflated before surgical incision, and it remained inflated until all postoperative surgical dressings were applied. Each patient in the antifibrinolytic group was given a 10-g dose of IV ACA at the start of implant cementation; the dose was administered over 10 minutes and was completely infused before tourniquet deflation. For each patient in the control group, a suction drain (Constavac, Stryker) was used. As postoperative drainage was so insignificant in the first 12 antifibrinolytic cases, use of the drain was then discontinued.
All patients received standard postoperative deep vein thrombosis prophylaxis in the form of warfarin in accordance with existing practice. Warfarin was given once a day starting the night of surgery and was continued until discharge based on daily INR values with an agreed-on target of 2.0. Thigh-high compression stockings and calf sequential compression devices were used in all cases. No patient in either group predonated blood or was given erythropoietin injections before or after surgery. Postoperative allogeneic transfusions were given to patients who were clinically symptomatic or short of breath; patients with hypotension uncorrectable with IV volume supplementation and an Hb level under 9.0 g/dL; and patients with an Hb level under 7.0 g/dL regardless of symptoms. All patients were monitored for postoperative adverse events and complications.
Postoperative blood loss (drain output), Hb levels on postoperative days 1 and 2 (POD-1, POD-2), blood transfusion amounts, and complications were recorded for all patients. Group means were compared with 2-sample t tests for independent samples. Data are reported as group means and SDs. All significance tests were 2-tailed, and statistical significance was set at P < .05.
Results
Fifty patients enrolled in the study: 25 in the control group and 25 in the antifibrinolytic group. Table 1 compares the main characteristics of the 2 groups. No significant differences were found between these groups for any of the characteristics considered.
There was significantly (P < .0001) more postoperative drainage in the control group: Mean drain output was 410.9 mL for the control group and 155.0 mL for the antifibrinolytic group (Table 2). Patients in the antifibrinolytic group did not receive any blood transfusions, whereas 40% of patients in the control group received transfusions (P = .022). On average, the transfused patients received 0.4 unit of packed red blood cells.
Although there was no statistically significant difference in POD-1 or POD-2 Hb levels between the antifibrinolytic and control groups, the antifibrinolytic group trended higher on POD-1 (11.1 g vs 10.7 g; P = .108) and POD-2 (11.5 g vs 10.2 g; P = .117) (Table 3). Mean Hb level was 8.1 g for control patients transfused on POD-1 and 7.9 g for control patients transfused on POD-2. For control patients who were not transfused, mean Hb level was 10.7 g on POD-1 and 10.2 g on POD-2.
There were no adverse events (eg, anaphylaxis, hypersensitivity) in either group, and there was no difference in incision drainage or returns to operating room between the groups.
Discussion
In TKA, a tourniquet is used to minimize intraoperative blood loss; postoperative bleeding, however, is often extensive. Both surgery and tourniquet use are reported to enhance local fibrinolytic activity within the limb.8 The synthetic antifibrinolytic ACA reduces blood loss by clot stabilization rather than by promotion of clot formation.8
In the present study, a single intraoperative dose of IV ACA administered in primary unilateral TKA significantly reduced postoperative wound drainage and eliminated the need for postoperative allogeneic blood transfusions. In addition, patients who received ACA had higher Hb levels on POD-1 and POD-2. These results are similar to those of other clinical trials in which external blood losses were measured.4-7 The postoperative drain output differences (~250 mL) in our study are clinically relevant, as they indicate significant reductions in postoperative blood loss with the implementation of an antifibrinolytic operative protocol.
In a study by Ponnusamy and colleagues,1 blood transfusion after orthopedic surgery accounted for 10% of all packed red blood cell transfusions, but use varied widely. National TKA transfusion rates vary from 4.3% to 63.8% among surgeons and hospitals.9 This evidence calls for standardization and critical review of practices to ensure more efficient use of blood products, effectively protecting patients from unneeded complications and reducing hospital costs. Mounting evidence supporting the efficacy of ACA in reducing perioperative blood loss and lowering postoperative blood transfusion rates points toward including antifibrinolytic therapy in standard TKA protocols. In our study, 40% of control patients and no antifibrinolytic patients required a transfusion—a stark contrast.
Although our antifibrinolytic group’s postoperative Hb levels were not statistically significantly higher, their being elevated illustrates the protective effect of intraoperative use of antifibrinolytics in TKA. This elevation in Hb levels is especially valid given the similarity of the antifibrinolytic and control patients’ preoperative Hb levels (P = .871) (Table 1). Other studies have shown similar upward trends in postoperative Hb levels, many of which were statistically significant.5-8,10
Conclusion
This study showed that a single intraoperative 10-g dose of IV ACA significantly reduced perioperative blood loss and lowered blood transfusion rates in TKA. In addition, postoperative Hb levels were higher in the patients who received ACA than in patients who did not receive an antifibrinolytic. The positive effects of ACA were obtained without adverse events or complications, making use of this antifibrinolytic a relevant addition to TKA protocols.
During total knee arthroplasty (TKA), traditionally a thigh tourniquet is used to minimize blood loss. Although intraoperative blood loss is negligible, postoperative blood loss can be extensive, and patients often require blood transfusions. Transfusions expose patients to clinical risks and increase costs. Well-documented transfusion complications include allergic reaction, transfusion-related acute lung injury, transfusion-associated circulatory overload, venous thromboembolism, graft vs host disease, bloodborne infections, and immunomodulation.1 Although measures are taken to reduce these risks, the costs associated with transfusions continue to escalate.2
Postoperative bleeding is attributed to fibrinolytic system activation. The antifibrinolytic agent aminocaproic acid (ACA), a synthetic analogue of the amino acid lysine, acts by competitively blocking the lysine-binding site of plasminogen, inhibiting fibrinolysis.3 Multiple studies have shown that ACA and a similar drug, tranexamic acid, can reduce postoperative blood loss when used intravenously in unilateral TKA.4,5 However, more studies are needed to evaluate antifibrinolytic agents with comparative controls using standardized procedures and documented outcome measures. In addition, the majority of studies have used tranexamic acid rather than ACA, despite the lower cost and similar efficacy of ACA.1,4 ACA is an inexpensive medication with a low risk profile, making it an attractive alternative to historical post-TKA management (which has a higher rate of blood transfusions) and a viable replacement in protocols already implementing tranexamic acid, the more expensive antifibrinolytic.5,6 It has been proposed that ACA use reduces equipment (drain) costs, blood transfusion costs, exposure to complications of blood loss, and transfusion reactions and reduces or eliminates the need for costly medications, such as erythropoiesis-stimulating agents.
Kagoma and colleagues5 reported that antifibrinolytic agents may reduce bleeding by at least 300 mL and may reduce the need for transfusions by 50% or eliminate this need altogether. Other antifibrinolytic agents have been studied in unilateral TKA, with results showing decreased drainage and improved postoperative hemoglobin (Hb) levels.6
We conducted a study to evaluate the effectiveness of a single intraoperative dose of ACA in reducing postoperative blood loss and the need for blood transfusions with increased preservation of postoperative Hb levels.
Methods
In October 2011, Dr. Anderson initiated an intraoperative intravenous (IV) ACA protocol for primary unilateral TKA. Given the decreased drain output immediately observed, and patients’ increased postoperative Hb levels, a retrospective study was proposed. After obtaining full Institutional Review Board approval for the study, we retrospectively reviewed the medical charts of 50 consecutive patients who underwent primary unilateral TKA—the last 25 who had the surgery before the IV ACA protocol was initiated (control group) and the first 25 who were given the IV ACA medication during the surgery (antifibrinolytic group). Inclusion criteria were primary unilateral TKA, no bleeding dyscrasia, no history of anaphylactic response to antifibrinolytic agents, no history of deep vein thrombosis, and normal preoperative coagulation parameters, international normalized ratio (INR), and partial thromboplastin time. Exclusion criteria included lateral corner release, lateral retinacular release, combined extensive deep and superficial medial collateral ligament releases, and cardiac or peripheral stent in place.
Each surgery—a standard primary unilateral TKA with an intramedullary femoral component and an extramedullary tibial component—was performed by Dr. Anderson. Each component was cemented. Each patient underwent a posterior cruciate ligament release and/or a deep medial collateral ligament release. A well-padded thigh tourniquet was inflated before surgical incision, and it remained inflated until all postoperative surgical dressings were applied. Each patient in the antifibrinolytic group was given a 10-g dose of IV ACA at the start of implant cementation; the dose was administered over 10 minutes and was completely infused before tourniquet deflation. For each patient in the control group, a suction drain (Constavac, Stryker) was used. As postoperative drainage was so insignificant in the first 12 antifibrinolytic cases, use of the drain was then discontinued.
All patients received standard postoperative deep vein thrombosis prophylaxis in the form of warfarin in accordance with existing practice. Warfarin was given once a day starting the night of surgery and was continued until discharge based on daily INR values with an agreed-on target of 2.0. Thigh-high compression stockings and calf sequential compression devices were used in all cases. No patient in either group predonated blood or was given erythropoietin injections before or after surgery. Postoperative allogeneic transfusions were given to patients who were clinically symptomatic or short of breath; patients with hypotension uncorrectable with IV volume supplementation and an Hb level under 9.0 g/dL; and patients with an Hb level under 7.0 g/dL regardless of symptoms. All patients were monitored for postoperative adverse events and complications.
Postoperative blood loss (drain output), Hb levels on postoperative days 1 and 2 (POD-1, POD-2), blood transfusion amounts, and complications were recorded for all patients. Group means were compared with 2-sample t tests for independent samples. Data are reported as group means and SDs. All significance tests were 2-tailed, and statistical significance was set at P < .05.
Results
Fifty patients enrolled in the study: 25 in the control group and 25 in the antifibrinolytic group. Table 1 compares the main characteristics of the 2 groups. No significant differences were found between these groups for any of the characteristics considered.
There was significantly (P < .0001) more postoperative drainage in the control group: Mean drain output was 410.9 mL for the control group and 155.0 mL for the antifibrinolytic group (Table 2). Patients in the antifibrinolytic group did not receive any blood transfusions, whereas 40% of patients in the control group received transfusions (P = .022). On average, the transfused patients received 0.4 unit of packed red blood cells.
Although there was no statistically significant difference in POD-1 or POD-2 Hb levels between the antifibrinolytic and control groups, the antifibrinolytic group trended higher on POD-1 (11.1 g vs 10.7 g; P = .108) and POD-2 (11.5 g vs 10.2 g; P = .117) (Table 3). Mean Hb level was 8.1 g for control patients transfused on POD-1 and 7.9 g for control patients transfused on POD-2. For control patients who were not transfused, mean Hb level was 10.7 g on POD-1 and 10.2 g on POD-2.
There were no adverse events (eg, anaphylaxis, hypersensitivity) in either group, and there was no difference in incision drainage or returns to operating room between the groups.
Discussion
In TKA, a tourniquet is used to minimize intraoperative blood loss; postoperative bleeding, however, is often extensive. Both surgery and tourniquet use are reported to enhance local fibrinolytic activity within the limb.8 The synthetic antifibrinolytic ACA reduces blood loss by clot stabilization rather than by promotion of clot formation.8
In the present study, a single intraoperative dose of IV ACA administered in primary unilateral TKA significantly reduced postoperative wound drainage and eliminated the need for postoperative allogeneic blood transfusions. In addition, patients who received ACA had higher Hb levels on POD-1 and POD-2. These results are similar to those of other clinical trials in which external blood losses were measured.4-7 The postoperative drain output differences (~250 mL) in our study are clinically relevant, as they indicate significant reductions in postoperative blood loss with the implementation of an antifibrinolytic operative protocol.
In a study by Ponnusamy and colleagues,1 blood transfusion after orthopedic surgery accounted for 10% of all packed red blood cell transfusions, but use varied widely. National TKA transfusion rates vary from 4.3% to 63.8% among surgeons and hospitals.9 This evidence calls for standardization and critical review of practices to ensure more efficient use of blood products, effectively protecting patients from unneeded complications and reducing hospital costs. Mounting evidence supporting the efficacy of ACA in reducing perioperative blood loss and lowering postoperative blood transfusion rates points toward including antifibrinolytic therapy in standard TKA protocols. In our study, 40% of control patients and no antifibrinolytic patients required a transfusion—a stark contrast.
Although our antifibrinolytic group’s postoperative Hb levels were not statistically significantly higher, their being elevated illustrates the protective effect of intraoperative use of antifibrinolytics in TKA. This elevation in Hb levels is especially valid given the similarity of the antifibrinolytic and control patients’ preoperative Hb levels (P = .871) (Table 1). Other studies have shown similar upward trends in postoperative Hb levels, many of which were statistically significant.5-8,10
Conclusion
This study showed that a single intraoperative 10-g dose of IV ACA significantly reduced perioperative blood loss and lowered blood transfusion rates in TKA. In addition, postoperative Hb levels were higher in the patients who received ACA than in patients who did not receive an antifibrinolytic. The positive effects of ACA were obtained without adverse events or complications, making use of this antifibrinolytic a relevant addition to TKA protocols.
1. Ponnusamy KE, Kim TJ, Khanuja HS. Perioperative blood transfusions in orthopaedic surgery. J Bone Joint Surg Am. 2014;96(21):1836-1844.
2. Spahn DR, Casutt M. Eliminating blood transfusions: new aspects and perspectives. Anesthesiology. 2000;93(1):242-255.
3. Van Aelbrouck C, Englberger L, Faraoni D. Review of the fibrinolytic system: comparison of different antifibrinolytics used during cardiopulmonary bypass. Recent Pat Cardiovasc Drug Discov. 2012;7(3):175-179.
4. Sepah YJ, Umer M, Ahmad T, Nasim F, Chaudhry MU, Umar M. Use of tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement. J Orthop Surg Res. 2011;6:22.
5. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009;123(5):687-696.
6. Zufferey P, Merquiol F, Laporte S, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105(5):1034-1046.
7. Camarasa MA, Ollé G, Serra-Prat M, et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth. 2006;96(5):576-582.
8. Orpen NM, Little C, Walker G, Crawfurd EJ. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee. 2006;13(2):106-110.
9. Chen AF, Klatt BA, Yazer MH, Waters JH. Blood utilization after primary total joint arthroplasty in a large hospital network. HSS J. 2013;9(2):123-128.
10. Aguilera X, Martinez-Zapata MJ, Bosch A, et al. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am. 2013;95(22):2001-2007.
1. Ponnusamy KE, Kim TJ, Khanuja HS. Perioperative blood transfusions in orthopaedic surgery. J Bone Joint Surg Am. 2014;96(21):1836-1844.
2. Spahn DR, Casutt M. Eliminating blood transfusions: new aspects and perspectives. Anesthesiology. 2000;93(1):242-255.
3. Van Aelbrouck C, Englberger L, Faraoni D. Review of the fibrinolytic system: comparison of different antifibrinolytics used during cardiopulmonary bypass. Recent Pat Cardiovasc Drug Discov. 2012;7(3):175-179.
4. Sepah YJ, Umer M, Ahmad T, Nasim F, Chaudhry MU, Umar M. Use of tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement. J Orthop Surg Res. 2011;6:22.
5. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009;123(5):687-696.
6. Zufferey P, Merquiol F, Laporte S, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105(5):1034-1046.
7. Camarasa MA, Ollé G, Serra-Prat M, et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth. 2006;96(5):576-582.
8. Orpen NM, Little C, Walker G, Crawfurd EJ. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee. 2006;13(2):106-110.
9. Chen AF, Klatt BA, Yazer MH, Waters JH. Blood utilization after primary total joint arthroplasty in a large hospital network. HSS J. 2013;9(2):123-128.
10. Aguilera X, Martinez-Zapata MJ, Bosch A, et al. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am. 2013;95(22):2001-2007.
Study compares sterile vs. nonsterile gloves for outpatient derm procedures
The use of sterile or nonsterile gloves during outpatient dermatologic and dental procedures resulted in similar rates of postoperative surgical site infections (SSIs), results from a large systematic review and meta-analysis demonstrated.
“During the past few decades, the use of surgical gloves has become standard practice to prevent postoperative wound infections or surgical site infection,” researchers led by Dr. Jerry Brewer wrote in a study published online Aug. 3, 2016 in JAMA Dermatology. “However, whether the use of sterile vs. non-sterile gloves makes a difference in the development of postoperative SSIs in the setting of cutaneous and minor outpatient surgical procedures remains unclear.”
In an effort to examine that question, Dr. Brewer of the division of dermatologic surgery at Mayo Clinic, Rochester, Minn., and his associates conducted a systematic review and meta-analysis of randomized clinical trials and comparative studies with information on sterile vs. non-sterile gloves in outpatient surgical procedures (JAMA Dermatol. 2016 Aug. 3. doi: 10.1001/jamadermatol.2016.1965). Patients in the studies underwent outpatient cutaneous or mucosal surgical procedures, including Mohs micrographic surgery, repair of a laceration, standard excisions, and tooth extractions.
The final meta-analysis included 11,071 patients from 13 studies. Of these, 6,040 underwent procedures with sterile gloves and 5,031 underwent procedures with nonsterile gloves. The researchers reported that a total of 228 patients (2.1%) had a postoperative SSI, including 107 in the nonsterile glove group (2.1%), and 121 in the sterile glove group (2%). The overall relative risk for an SSI with nonsterile glove use was 1.06.
In an interview, Dr. Brewer estimated that sterile gloves cost anywhere from $0.27 to $1.29 per pair, compared with about 8 cents per pair for clean nonsterile gloves. “This cost difference may not seem like much, but if you think about all the surgeries that are done on a regular basis across the country, that’s a huge difference in cost,” he said.
The authors acknowledged certain limitations of the study, including the potential for selection bias, since many of the studies included in the meta-analysis were observational. They also noted that findings from some previous studies on the topic run counter to theirs (see Dermatol. Surg. 2010; 36[10]:1529-36 and J. Hosp. Infect. 2007;65[3]:258-63 ). “Although the broad use of nonsterile clean gloves may be justified, caution is advised in generalizing this justification to more advanced outpatient surgical procedures that may not pertain to the information summarized in this review and meta-analysis,” they concluded. “Future study could include whether duration of surgery and complexity of the repair influence postoperative SSI development in the setting of sterile vs. nonsterile gloves.”
The researchers reported having no financial disclosures.
The use of sterile or nonsterile gloves during outpatient dermatologic and dental procedures resulted in similar rates of postoperative surgical site infections (SSIs), results from a large systematic review and meta-analysis demonstrated.
“During the past few decades, the use of surgical gloves has become standard practice to prevent postoperative wound infections or surgical site infection,” researchers led by Dr. Jerry Brewer wrote in a study published online Aug. 3, 2016 in JAMA Dermatology. “However, whether the use of sterile vs. non-sterile gloves makes a difference in the development of postoperative SSIs in the setting of cutaneous and minor outpatient surgical procedures remains unclear.”
In an effort to examine that question, Dr. Brewer of the division of dermatologic surgery at Mayo Clinic, Rochester, Minn., and his associates conducted a systematic review and meta-analysis of randomized clinical trials and comparative studies with information on sterile vs. non-sterile gloves in outpatient surgical procedures (JAMA Dermatol. 2016 Aug. 3. doi: 10.1001/jamadermatol.2016.1965). Patients in the studies underwent outpatient cutaneous or mucosal surgical procedures, including Mohs micrographic surgery, repair of a laceration, standard excisions, and tooth extractions.
The final meta-analysis included 11,071 patients from 13 studies. Of these, 6,040 underwent procedures with sterile gloves and 5,031 underwent procedures with nonsterile gloves. The researchers reported that a total of 228 patients (2.1%) had a postoperative SSI, including 107 in the nonsterile glove group (2.1%), and 121 in the sterile glove group (2%). The overall relative risk for an SSI with nonsterile glove use was 1.06.
In an interview, Dr. Brewer estimated that sterile gloves cost anywhere from $0.27 to $1.29 per pair, compared with about 8 cents per pair for clean nonsterile gloves. “This cost difference may not seem like much, but if you think about all the surgeries that are done on a regular basis across the country, that’s a huge difference in cost,” he said.
The authors acknowledged certain limitations of the study, including the potential for selection bias, since many of the studies included in the meta-analysis were observational. They also noted that findings from some previous studies on the topic run counter to theirs (see Dermatol. Surg. 2010; 36[10]:1529-36 and J. Hosp. Infect. 2007;65[3]:258-63 ). “Although the broad use of nonsterile clean gloves may be justified, caution is advised in generalizing this justification to more advanced outpatient surgical procedures that may not pertain to the information summarized in this review and meta-analysis,” they concluded. “Future study could include whether duration of surgery and complexity of the repair influence postoperative SSI development in the setting of sterile vs. nonsterile gloves.”
The researchers reported having no financial disclosures.
The use of sterile or nonsterile gloves during outpatient dermatologic and dental procedures resulted in similar rates of postoperative surgical site infections (SSIs), results from a large systematic review and meta-analysis demonstrated.
“During the past few decades, the use of surgical gloves has become standard practice to prevent postoperative wound infections or surgical site infection,” researchers led by Dr. Jerry Brewer wrote in a study published online Aug. 3, 2016 in JAMA Dermatology. “However, whether the use of sterile vs. non-sterile gloves makes a difference in the development of postoperative SSIs in the setting of cutaneous and minor outpatient surgical procedures remains unclear.”
In an effort to examine that question, Dr. Brewer of the division of dermatologic surgery at Mayo Clinic, Rochester, Minn., and his associates conducted a systematic review and meta-analysis of randomized clinical trials and comparative studies with information on sterile vs. non-sterile gloves in outpatient surgical procedures (JAMA Dermatol. 2016 Aug. 3. doi: 10.1001/jamadermatol.2016.1965). Patients in the studies underwent outpatient cutaneous or mucosal surgical procedures, including Mohs micrographic surgery, repair of a laceration, standard excisions, and tooth extractions.
The final meta-analysis included 11,071 patients from 13 studies. Of these, 6,040 underwent procedures with sterile gloves and 5,031 underwent procedures with nonsterile gloves. The researchers reported that a total of 228 patients (2.1%) had a postoperative SSI, including 107 in the nonsterile glove group (2.1%), and 121 in the sterile glove group (2%). The overall relative risk for an SSI with nonsterile glove use was 1.06.
In an interview, Dr. Brewer estimated that sterile gloves cost anywhere from $0.27 to $1.29 per pair, compared with about 8 cents per pair for clean nonsterile gloves. “This cost difference may not seem like much, but if you think about all the surgeries that are done on a regular basis across the country, that’s a huge difference in cost,” he said.
The authors acknowledged certain limitations of the study, including the potential for selection bias, since many of the studies included in the meta-analysis were observational. They also noted that findings from some previous studies on the topic run counter to theirs (see Dermatol. Surg. 2010; 36[10]:1529-36 and J. Hosp. Infect. 2007;65[3]:258-63 ). “Although the broad use of nonsterile clean gloves may be justified, caution is advised in generalizing this justification to more advanced outpatient surgical procedures that may not pertain to the information summarized in this review and meta-analysis,” they concluded. “Future study could include whether duration of surgery and complexity of the repair influence postoperative SSI development in the setting of sterile vs. nonsterile gloves.”
The researchers reported having no financial disclosures.
FROM JAMA DERMATOLOGY
Key clinical point: No difference was observed in the rate of postoperative SSIs between outpatient surgical procedures performed with sterile versus nonsterile gloves.
Major finding: Overall, 2.1% of patients had a postoperative SSI, including 2.1% in the nonsterile glove group and 2% in the sterile glove group.
Data source: A meta-analysis that included 11,071 patients from 13 studies with information on sterile vs. nonsterile gloves in outpatient surgical procedures.
Disclosures: The researchers reported having no financial disclosures.
Extended-release naltrexone helps alcohol-dependent HIV-positive prisoners transition to community
DURBAN, SOUTH AFRICA – Extended-release naltrexone provides clinically meaningful benefits in HIV-infected prisoners with alcohol use disorder and multiple comorbid conditions as they transition back into the community, according to the findings of a double-blind randomized clinical trial.
“I think it’s important to know that a very effective medication, which has not previously been given to this population, was accepted by this group. It may be a feasible conduit to care as they transition to the community, even among those with severe psychosocial disparities like homelessness and mental illness,” Sandra A. Springer, MD, said in presenting the study findings at the 21st International AIDS Conference.
Extended-release naltrexone (Vivitrol) is a mu-opioid receptor antagonist approved for the treatment of alcohol use disorder, where it has been shown to decrease consumption. But prior to her study, the once-monthly injectable drug hadn’t been studied in alcohol-dependent prisoners living with HIV who are transitioning from jail or prison into the community, noted Dr. Springer, an infectious disease specialist at Yale University in New Haven, Conn.
This is a large, important, and seriously neglected patient population, she observed. The United States has the highest incarceration rate in the world. The prevalence of HIV infection is at least three times greater in U.S. criminal justice settings than in the general population. Alcohol use disorders are eightfold more common. Release from prison or jail in affected individuals often is complicated by relapse to alcohol use, which in turn is associated with poor HIV treatment outcomes.
Dr. Springer reported on 100 HIV-positive adult prisoners with alcohol use disorder diagnosed by DSM-IV criteria who were randomized double-blind two-to-one to 6 monthly 380-mg intramuscular injections of extended-release naltrexone or placebo, with the first dose given 3-7 days prior to release. Participants were required to have no baseline clinical evidence of cirrhosis or very high liver enzyme levels.
Half of participants had chronic hepatitis C. Eighty-seven percent of subjects scored 20 or higher on the Alcohol Use Disorders Identification test, indicating alcohol dependence. On the Mini International Neuropsychiatric Interview, 15% of participants met criteria for major depressive disorder, 16% for bipolar disorder, 59% for cocaine use disorder, 16% for narcotic use disorder, and 16% for cannabis use disorder. Most of the subjects were homeless or had an unstable housing situation.
Alcohol outcomes were assessed monthly during the 6-month trial. Not surprisingly, the better the treatment adherence, the better the outcomes. During the 90 days before incarceration, patients self-reported that 70% of those days were heavy drinking days, defined in men as having five or more drinks per day and in women as four or more. Their average consumption on those heavy drinking days was 28 drinks per day. In contrast, patients who accepted four or more extended-release naltrexone injections during 180 days of follow-up after release from custody drank heavily on just 7.6% of days, with an average of 8.6 drinks per day on those heavy drinking days. Subjects who received four or more placebo injections drank heavily on 11.6% of days, consuming an average of 12 drinks per heavy drinking day.
The time to first heavy drinking day was longer in patients who accepted 4-6 monthly injections of extended-release naltrexone than in those with 4-6 placebo injections. However, the difference achieved statistical significance only in the younger subgroup of participants aged 21-29 years. In that subgroup, the average time to the first heavy drinking day was 24.1 days, compared with 9.5 days with placebo.
On a composite alcohol consumption index comprised of time to first heavy drinking day after release, mean number of drinks per drinking day, change from before to after incarceration in average number of drinks per drinking day, alcohol craving score, and total number of drinking days, subjects who received four or more extended-release naltrexone injections had a significantly more favorable result, with a mean score of 3.15, compared with 2.93 in patients who took four or more placebo injections.
Moreover, consistent use of extended-release naltrexone was associated with significantly lower HIV viral load counts, compared with placebo-treated controls.
Treatment with extended-release naltrexone was safe. No serious side effects occurred, even in patients with comorbid hepatitis C who were on antiretroviral therapy. The most common side effects were the same as in seen in studies of the drug in other populations: mild to moderate nausea, headache, decreased appetite, fatigue, and dizziness.
Elsewhere at AIDS 2016, Chris Beyrer, MD, president of the International AIDS Society, included prisoners on his list of the populations most vulnerable to HIV because of discriminatory laws and policies in many parts of the world. Others on the list were transgender people, sex workers, men who have sex with men, and injection drug users.
“We’ll never be able to end AIDS without addressing the needs of these most vulnerable individuals and communities, and yet we know in 2016 far too many are being left behind,” said Dr. Beyrer, professor of epidemiology at Johns Hopkins University, Baltimore.
Transgender individuals, for example, are 49 times more likely to have HIV infection than other adults. Injection drug users and men who have sex with men are each 24-fold more likely to become HIV infected than the general population. Sex workers are 10 times more likely to acquire HIV infection than others in their reproductive years. And prisoners have a fivefold greater prevalence of HIV.
“In 2014 these vulnerable groups accounted for more than one-third of all new HIV infections. That’s an extraordinary proportion of HIV,” he observed. “This truly is the undone work of the HIV response. If there’s any silver lining in this cloud, it’s this: We’re talking about a relatively small number of people who are at high risk of infection relative to the world’s population. And that means that turning this around doesn’t require massive new commitments to very large populations. What it does require is an honest acknowledgment of where the epidemic is hitting hardest and directing resources to that need.”
Unfortunately, screening and treatment programs are rarely tailored to reach these highly vulnerable groups effectively, he added.
Dr. Beyrer was a contributor to a special issue of the Lancet devoted to HIV infection among prisoners published with the AIDS 2016 conference.
Dr. Springer’s study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse. She reported having no financial conflicts of interest.
DURBAN, SOUTH AFRICA – Extended-release naltrexone provides clinically meaningful benefits in HIV-infected prisoners with alcohol use disorder and multiple comorbid conditions as they transition back into the community, according to the findings of a double-blind randomized clinical trial.
“I think it’s important to know that a very effective medication, which has not previously been given to this population, was accepted by this group. It may be a feasible conduit to care as they transition to the community, even among those with severe psychosocial disparities like homelessness and mental illness,” Sandra A. Springer, MD, said in presenting the study findings at the 21st International AIDS Conference.
Extended-release naltrexone (Vivitrol) is a mu-opioid receptor antagonist approved for the treatment of alcohol use disorder, where it has been shown to decrease consumption. But prior to her study, the once-monthly injectable drug hadn’t been studied in alcohol-dependent prisoners living with HIV who are transitioning from jail or prison into the community, noted Dr. Springer, an infectious disease specialist at Yale University in New Haven, Conn.
This is a large, important, and seriously neglected patient population, she observed. The United States has the highest incarceration rate in the world. The prevalence of HIV infection is at least three times greater in U.S. criminal justice settings than in the general population. Alcohol use disorders are eightfold more common. Release from prison or jail in affected individuals often is complicated by relapse to alcohol use, which in turn is associated with poor HIV treatment outcomes.
Dr. Springer reported on 100 HIV-positive adult prisoners with alcohol use disorder diagnosed by DSM-IV criteria who were randomized double-blind two-to-one to 6 monthly 380-mg intramuscular injections of extended-release naltrexone or placebo, with the first dose given 3-7 days prior to release. Participants were required to have no baseline clinical evidence of cirrhosis or very high liver enzyme levels.
Half of participants had chronic hepatitis C. Eighty-seven percent of subjects scored 20 or higher on the Alcohol Use Disorders Identification test, indicating alcohol dependence. On the Mini International Neuropsychiatric Interview, 15% of participants met criteria for major depressive disorder, 16% for bipolar disorder, 59% for cocaine use disorder, 16% for narcotic use disorder, and 16% for cannabis use disorder. Most of the subjects were homeless or had an unstable housing situation.
Alcohol outcomes were assessed monthly during the 6-month trial. Not surprisingly, the better the treatment adherence, the better the outcomes. During the 90 days before incarceration, patients self-reported that 70% of those days were heavy drinking days, defined in men as having five or more drinks per day and in women as four or more. Their average consumption on those heavy drinking days was 28 drinks per day. In contrast, patients who accepted four or more extended-release naltrexone injections during 180 days of follow-up after release from custody drank heavily on just 7.6% of days, with an average of 8.6 drinks per day on those heavy drinking days. Subjects who received four or more placebo injections drank heavily on 11.6% of days, consuming an average of 12 drinks per heavy drinking day.
The time to first heavy drinking day was longer in patients who accepted 4-6 monthly injections of extended-release naltrexone than in those with 4-6 placebo injections. However, the difference achieved statistical significance only in the younger subgroup of participants aged 21-29 years. In that subgroup, the average time to the first heavy drinking day was 24.1 days, compared with 9.5 days with placebo.
On a composite alcohol consumption index comprised of time to first heavy drinking day after release, mean number of drinks per drinking day, change from before to after incarceration in average number of drinks per drinking day, alcohol craving score, and total number of drinking days, subjects who received four or more extended-release naltrexone injections had a significantly more favorable result, with a mean score of 3.15, compared with 2.93 in patients who took four or more placebo injections.
Moreover, consistent use of extended-release naltrexone was associated with significantly lower HIV viral load counts, compared with placebo-treated controls.
Treatment with extended-release naltrexone was safe. No serious side effects occurred, even in patients with comorbid hepatitis C who were on antiretroviral therapy. The most common side effects were the same as in seen in studies of the drug in other populations: mild to moderate nausea, headache, decreased appetite, fatigue, and dizziness.
Elsewhere at AIDS 2016, Chris Beyrer, MD, president of the International AIDS Society, included prisoners on his list of the populations most vulnerable to HIV because of discriminatory laws and policies in many parts of the world. Others on the list were transgender people, sex workers, men who have sex with men, and injection drug users.
“We’ll never be able to end AIDS without addressing the needs of these most vulnerable individuals and communities, and yet we know in 2016 far too many are being left behind,” said Dr. Beyrer, professor of epidemiology at Johns Hopkins University, Baltimore.
Transgender individuals, for example, are 49 times more likely to have HIV infection than other adults. Injection drug users and men who have sex with men are each 24-fold more likely to become HIV infected than the general population. Sex workers are 10 times more likely to acquire HIV infection than others in their reproductive years. And prisoners have a fivefold greater prevalence of HIV.
“In 2014 these vulnerable groups accounted for more than one-third of all new HIV infections. That’s an extraordinary proportion of HIV,” he observed. “This truly is the undone work of the HIV response. If there’s any silver lining in this cloud, it’s this: We’re talking about a relatively small number of people who are at high risk of infection relative to the world’s population. And that means that turning this around doesn’t require massive new commitments to very large populations. What it does require is an honest acknowledgment of where the epidemic is hitting hardest and directing resources to that need.”
Unfortunately, screening and treatment programs are rarely tailored to reach these highly vulnerable groups effectively, he added.
Dr. Beyrer was a contributor to a special issue of the Lancet devoted to HIV infection among prisoners published with the AIDS 2016 conference.
Dr. Springer’s study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse. She reported having no financial conflicts of interest.
DURBAN, SOUTH AFRICA – Extended-release naltrexone provides clinically meaningful benefits in HIV-infected prisoners with alcohol use disorder and multiple comorbid conditions as they transition back into the community, according to the findings of a double-blind randomized clinical trial.
“I think it’s important to know that a very effective medication, which has not previously been given to this population, was accepted by this group. It may be a feasible conduit to care as they transition to the community, even among those with severe psychosocial disparities like homelessness and mental illness,” Sandra A. Springer, MD, said in presenting the study findings at the 21st International AIDS Conference.
Extended-release naltrexone (Vivitrol) is a mu-opioid receptor antagonist approved for the treatment of alcohol use disorder, where it has been shown to decrease consumption. But prior to her study, the once-monthly injectable drug hadn’t been studied in alcohol-dependent prisoners living with HIV who are transitioning from jail or prison into the community, noted Dr. Springer, an infectious disease specialist at Yale University in New Haven, Conn.
This is a large, important, and seriously neglected patient population, she observed. The United States has the highest incarceration rate in the world. The prevalence of HIV infection is at least three times greater in U.S. criminal justice settings than in the general population. Alcohol use disorders are eightfold more common. Release from prison or jail in affected individuals often is complicated by relapse to alcohol use, which in turn is associated with poor HIV treatment outcomes.
Dr. Springer reported on 100 HIV-positive adult prisoners with alcohol use disorder diagnosed by DSM-IV criteria who were randomized double-blind two-to-one to 6 monthly 380-mg intramuscular injections of extended-release naltrexone or placebo, with the first dose given 3-7 days prior to release. Participants were required to have no baseline clinical evidence of cirrhosis or very high liver enzyme levels.
Half of participants had chronic hepatitis C. Eighty-seven percent of subjects scored 20 or higher on the Alcohol Use Disorders Identification test, indicating alcohol dependence. On the Mini International Neuropsychiatric Interview, 15% of participants met criteria for major depressive disorder, 16% for bipolar disorder, 59% for cocaine use disorder, 16% for narcotic use disorder, and 16% for cannabis use disorder. Most of the subjects were homeless or had an unstable housing situation.
Alcohol outcomes were assessed monthly during the 6-month trial. Not surprisingly, the better the treatment adherence, the better the outcomes. During the 90 days before incarceration, patients self-reported that 70% of those days were heavy drinking days, defined in men as having five or more drinks per day and in women as four or more. Their average consumption on those heavy drinking days was 28 drinks per day. In contrast, patients who accepted four or more extended-release naltrexone injections during 180 days of follow-up after release from custody drank heavily on just 7.6% of days, with an average of 8.6 drinks per day on those heavy drinking days. Subjects who received four or more placebo injections drank heavily on 11.6% of days, consuming an average of 12 drinks per heavy drinking day.
The time to first heavy drinking day was longer in patients who accepted 4-6 monthly injections of extended-release naltrexone than in those with 4-6 placebo injections. However, the difference achieved statistical significance only in the younger subgroup of participants aged 21-29 years. In that subgroup, the average time to the first heavy drinking day was 24.1 days, compared with 9.5 days with placebo.
On a composite alcohol consumption index comprised of time to first heavy drinking day after release, mean number of drinks per drinking day, change from before to after incarceration in average number of drinks per drinking day, alcohol craving score, and total number of drinking days, subjects who received four or more extended-release naltrexone injections had a significantly more favorable result, with a mean score of 3.15, compared with 2.93 in patients who took four or more placebo injections.
Moreover, consistent use of extended-release naltrexone was associated with significantly lower HIV viral load counts, compared with placebo-treated controls.
Treatment with extended-release naltrexone was safe. No serious side effects occurred, even in patients with comorbid hepatitis C who were on antiretroviral therapy. The most common side effects were the same as in seen in studies of the drug in other populations: mild to moderate nausea, headache, decreased appetite, fatigue, and dizziness.
Elsewhere at AIDS 2016, Chris Beyrer, MD, president of the International AIDS Society, included prisoners on his list of the populations most vulnerable to HIV because of discriminatory laws and policies in many parts of the world. Others on the list were transgender people, sex workers, men who have sex with men, and injection drug users.
“We’ll never be able to end AIDS without addressing the needs of these most vulnerable individuals and communities, and yet we know in 2016 far too many are being left behind,” said Dr. Beyrer, professor of epidemiology at Johns Hopkins University, Baltimore.
Transgender individuals, for example, are 49 times more likely to have HIV infection than other adults. Injection drug users and men who have sex with men are each 24-fold more likely to become HIV infected than the general population. Sex workers are 10 times more likely to acquire HIV infection than others in their reproductive years. And prisoners have a fivefold greater prevalence of HIV.
“In 2014 these vulnerable groups accounted for more than one-third of all new HIV infections. That’s an extraordinary proportion of HIV,” he observed. “This truly is the undone work of the HIV response. If there’s any silver lining in this cloud, it’s this: We’re talking about a relatively small number of people who are at high risk of infection relative to the world’s population. And that means that turning this around doesn’t require massive new commitments to very large populations. What it does require is an honest acknowledgment of where the epidemic is hitting hardest and directing resources to that need.”
Unfortunately, screening and treatment programs are rarely tailored to reach these highly vulnerable groups effectively, he added.
Dr. Beyrer was a contributor to a special issue of the Lancet devoted to HIV infection among prisoners published with the AIDS 2016 conference.
Dr. Springer’s study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse. She reported having no financial conflicts of interest.
AT AIDS 2016
Key clinical point: Extended-release naltrexone helps HIV-infected prisoners with alcohol use disorder in transitioning to the community.
Major finding: The mean time to the first heavy drinking day among 21- to 29-year-old HIV-infected prisoners with an alcohol use disorder was 24.1 days following release from prison or jail in those on extended-release naltrexone versus 9.5 days with placebo.
Data source: This randomized, double-blind clinical trial included 100 HIV-positive prisoners with alcohol use disorder who were released into the community. Two-thirds received six monthly injections of extended-release naltrexone, the rest placebo.
Disclosures: The study was funded by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. The presenter reported having no financial conflicts of interest.
FDA grants fast track status to volixibat
The Food and Drug Administration has granted fast track status to volixibat, an investigational treatment manufactured by Shire.
“The FDA’s fast track is a process designed to facilitate the development, and expedite the review, of drugs to treat serious conditions and fill an unmet medical need,” the Dublin-based pharmaceutical company explained in a statement. “However, it does not guarantee that the FDA will ultimately approve [volixibat] for NASH [nonalcoholic steatohepatitis] or the timing of any such approval.”
Volixibat, also known as SHP626, is meant to treat NASH with liver fibrosis in adult patients via an apical sodium-dependent bile acid transporter inhibitor, which is a protein that recycles bile acids from the intestine and into the liver. This orally administered, once-daily treatment would be the first ever treatment available for NASH.
“This fast track designation is further recognition of the critical need to develop new, effective therapeutic options for patients with this serious condition,” said Philip J. Vickers, PhD, head of research and development for Shire, in a statement.
Preclinical and phase I studies have already been completed, the results of which contributed to the FDA granting volixibat fast track status. A randomized, placebo-controlled, double-blind phase II trial is set to get underway shortly at centers in the United States, Canada, and the United Kingdom, which will examine safety, tolerability, and efficacy of a three-dose volixibat regimen administered over the course of 48 weeks.
The Food and Drug Administration has granted fast track status to volixibat, an investigational treatment manufactured by Shire.
“The FDA’s fast track is a process designed to facilitate the development, and expedite the review, of drugs to treat serious conditions and fill an unmet medical need,” the Dublin-based pharmaceutical company explained in a statement. “However, it does not guarantee that the FDA will ultimately approve [volixibat] for NASH [nonalcoholic steatohepatitis] or the timing of any such approval.”
Volixibat, also known as SHP626, is meant to treat NASH with liver fibrosis in adult patients via an apical sodium-dependent bile acid transporter inhibitor, which is a protein that recycles bile acids from the intestine and into the liver. This orally administered, once-daily treatment would be the first ever treatment available for NASH.
“This fast track designation is further recognition of the critical need to develop new, effective therapeutic options for patients with this serious condition,” said Philip J. Vickers, PhD, head of research and development for Shire, in a statement.
Preclinical and phase I studies have already been completed, the results of which contributed to the FDA granting volixibat fast track status. A randomized, placebo-controlled, double-blind phase II trial is set to get underway shortly at centers in the United States, Canada, and the United Kingdom, which will examine safety, tolerability, and efficacy of a three-dose volixibat regimen administered over the course of 48 weeks.
The Food and Drug Administration has granted fast track status to volixibat, an investigational treatment manufactured by Shire.
“The FDA’s fast track is a process designed to facilitate the development, and expedite the review, of drugs to treat serious conditions and fill an unmet medical need,” the Dublin-based pharmaceutical company explained in a statement. “However, it does not guarantee that the FDA will ultimately approve [volixibat] for NASH [nonalcoholic steatohepatitis] or the timing of any such approval.”
Volixibat, also known as SHP626, is meant to treat NASH with liver fibrosis in adult patients via an apical sodium-dependent bile acid transporter inhibitor, which is a protein that recycles bile acids from the intestine and into the liver. This orally administered, once-daily treatment would be the first ever treatment available for NASH.
“This fast track designation is further recognition of the critical need to develop new, effective therapeutic options for patients with this serious condition,” said Philip J. Vickers, PhD, head of research and development for Shire, in a statement.
Preclinical and phase I studies have already been completed, the results of which contributed to the FDA granting volixibat fast track status. A randomized, placebo-controlled, double-blind phase II trial is set to get underway shortly at centers in the United States, Canada, and the United Kingdom, which will examine safety, tolerability, and efficacy of a three-dose volixibat regimen administered over the course of 48 weeks.
Studies highlight diagnostic and treatment challenges in hidradenitis suppurativa
SCOTTSDALE, ARIZ. – Patients with hidradenitis suppurativa (HS) may be misdiagnosed when they see providers who are not dermatologists – as is usually the case during the initial years of their disease, according to a large analysis of medical claims data.
The findings highlight the need for visual diagnostic aids and specific guidelines for treating HS that target nondermatologists, Melissa Butt, MPH, of Penn State Hershey (Pa.) Medical Center, said during an interview at the annual meeting of the Society for Investigative Dermatology. She presented the findings during a poster session at the meeting.
HS is a chronic inflammatory disease of the hair follicles that affects 0.5%-4% of people in the United States. In past studies, up to 12 years elapsed between disease onset and diagnosis, in part because patients often cannot readily access dermatologists, Ms. Butt said. To better understand patterns of health care use during the years leading up to HS diagnosis, she and her colleagues used MarketScan data to identify 1,733 patients with HS-specific medical care claims filed in 2012 and 2013. Then they looked back at medical claims for these patients during 2008 through 2011, before the patients were diagnosed with HS. The cohort averaged 37 years of age (standard deviation, 15 years), and 73% were female.
Among 239,892 claims filed before patients were diagnosed with HS, 11,381 (4.7%) included codes for other diseases of the skin and subcutaneous tissues, Ms. Butt said. Dermatologists filed only 31% of these skin-specific claims, while 69% were filed by other providers, such as family practitioners, internists, emergency department physicians, and acute care hospitalists.
Notably, about two-thirds of the skin-specific diagnostic codes could have represented a misdiagnosis of HS. These codes included conditions such as abscesses, carbuncles, local infections, ulcers, and diseases of the sebaceous glands.
The fact that 78% of visits occurred in offices and other outpatient settings further underscores the need to improve the detection and care of HS in these environments, Ms. Butt said. Given current national shortages of dermatologists, visual HS diagnostic aids and “detailed, multistep clinical practice guidelines” for nondermatologists could help improve care of HS while patients wait to see the specialists, she added.
A second poster presented at the meeting provided results of a study on the use and impact of antibiotics in the treatment of HS. Alexander Fischer of Johns Hopkins University, Baltimore, and his associates studied antibiotic prescriptions and bacterial cultures from the lesions of 239 patients with HS who were treated at Johns Hopkins medical facilities between 2010 and 2015. Not only were 51% of HS patients on antibiotics at the time of culture, but these patients’ lesions were significantly more likely to contain antibiotic-resistant bacteria than were those of patients not on antibiotics.
Strikingly, Proteus species were isolated from nearly half of patients on trimethoprim-sulfamethoxazole (TMP/SMX), and 88% of colonies were resistant to TMP/SMX, while only 13% of cultures from untreated patients grew Proteus (P less than .001) and all were TMP/SMX-susceptible (P less than .001). Likewise, 100% of methicillin-resistant Staphylococcus aureus (MRSA) strains from patients prescribed ciprofloxacin were resistant to it, compared with a 10% background rate of ciprofloxacin resistance among MRSA from patients not taking antibiotics (P = .04). In addition, the proportion of other S. aureus strains that were clindamycin-resistant was higher when patients were taking this antibiotic than when they were not (63% versus 17%; P = .03).
The results “raise questions” about whether antibiotics should be used in HS patients who are not clearly benefiting from them, according to the researchers.
The authors of both studies reported no funding sources and had no disclosures.
SCOTTSDALE, ARIZ. – Patients with hidradenitis suppurativa (HS) may be misdiagnosed when they see providers who are not dermatologists – as is usually the case during the initial years of their disease, according to a large analysis of medical claims data.
The findings highlight the need for visual diagnostic aids and specific guidelines for treating HS that target nondermatologists, Melissa Butt, MPH, of Penn State Hershey (Pa.) Medical Center, said during an interview at the annual meeting of the Society for Investigative Dermatology. She presented the findings during a poster session at the meeting.
HS is a chronic inflammatory disease of the hair follicles that affects 0.5%-4% of people in the United States. In past studies, up to 12 years elapsed between disease onset and diagnosis, in part because patients often cannot readily access dermatologists, Ms. Butt said. To better understand patterns of health care use during the years leading up to HS diagnosis, she and her colleagues used MarketScan data to identify 1,733 patients with HS-specific medical care claims filed in 2012 and 2013. Then they looked back at medical claims for these patients during 2008 through 2011, before the patients were diagnosed with HS. The cohort averaged 37 years of age (standard deviation, 15 years), and 73% were female.
Among 239,892 claims filed before patients were diagnosed with HS, 11,381 (4.7%) included codes for other diseases of the skin and subcutaneous tissues, Ms. Butt said. Dermatologists filed only 31% of these skin-specific claims, while 69% were filed by other providers, such as family practitioners, internists, emergency department physicians, and acute care hospitalists.
Notably, about two-thirds of the skin-specific diagnostic codes could have represented a misdiagnosis of HS. These codes included conditions such as abscesses, carbuncles, local infections, ulcers, and diseases of the sebaceous glands.
The fact that 78% of visits occurred in offices and other outpatient settings further underscores the need to improve the detection and care of HS in these environments, Ms. Butt said. Given current national shortages of dermatologists, visual HS diagnostic aids and “detailed, multistep clinical practice guidelines” for nondermatologists could help improve care of HS while patients wait to see the specialists, she added.
A second poster presented at the meeting provided results of a study on the use and impact of antibiotics in the treatment of HS. Alexander Fischer of Johns Hopkins University, Baltimore, and his associates studied antibiotic prescriptions and bacterial cultures from the lesions of 239 patients with HS who were treated at Johns Hopkins medical facilities between 2010 and 2015. Not only were 51% of HS patients on antibiotics at the time of culture, but these patients’ lesions were significantly more likely to contain antibiotic-resistant bacteria than were those of patients not on antibiotics.
Strikingly, Proteus species were isolated from nearly half of patients on trimethoprim-sulfamethoxazole (TMP/SMX), and 88% of colonies were resistant to TMP/SMX, while only 13% of cultures from untreated patients grew Proteus (P less than .001) and all were TMP/SMX-susceptible (P less than .001). Likewise, 100% of methicillin-resistant Staphylococcus aureus (MRSA) strains from patients prescribed ciprofloxacin were resistant to it, compared with a 10% background rate of ciprofloxacin resistance among MRSA from patients not taking antibiotics (P = .04). In addition, the proportion of other S. aureus strains that were clindamycin-resistant was higher when patients were taking this antibiotic than when they were not (63% versus 17%; P = .03).
The results “raise questions” about whether antibiotics should be used in HS patients who are not clearly benefiting from them, according to the researchers.
The authors of both studies reported no funding sources and had no disclosures.
SCOTTSDALE, ARIZ. – Patients with hidradenitis suppurativa (HS) may be misdiagnosed when they see providers who are not dermatologists – as is usually the case during the initial years of their disease, according to a large analysis of medical claims data.
The findings highlight the need for visual diagnostic aids and specific guidelines for treating HS that target nondermatologists, Melissa Butt, MPH, of Penn State Hershey (Pa.) Medical Center, said during an interview at the annual meeting of the Society for Investigative Dermatology. She presented the findings during a poster session at the meeting.
HS is a chronic inflammatory disease of the hair follicles that affects 0.5%-4% of people in the United States. In past studies, up to 12 years elapsed between disease onset and diagnosis, in part because patients often cannot readily access dermatologists, Ms. Butt said. To better understand patterns of health care use during the years leading up to HS diagnosis, she and her colleagues used MarketScan data to identify 1,733 patients with HS-specific medical care claims filed in 2012 and 2013. Then they looked back at medical claims for these patients during 2008 through 2011, before the patients were diagnosed with HS. The cohort averaged 37 years of age (standard deviation, 15 years), and 73% were female.
Among 239,892 claims filed before patients were diagnosed with HS, 11,381 (4.7%) included codes for other diseases of the skin and subcutaneous tissues, Ms. Butt said. Dermatologists filed only 31% of these skin-specific claims, while 69% were filed by other providers, such as family practitioners, internists, emergency department physicians, and acute care hospitalists.
Notably, about two-thirds of the skin-specific diagnostic codes could have represented a misdiagnosis of HS. These codes included conditions such as abscesses, carbuncles, local infections, ulcers, and diseases of the sebaceous glands.
The fact that 78% of visits occurred in offices and other outpatient settings further underscores the need to improve the detection and care of HS in these environments, Ms. Butt said. Given current national shortages of dermatologists, visual HS diagnostic aids and “detailed, multistep clinical practice guidelines” for nondermatologists could help improve care of HS while patients wait to see the specialists, she added.
A second poster presented at the meeting provided results of a study on the use and impact of antibiotics in the treatment of HS. Alexander Fischer of Johns Hopkins University, Baltimore, and his associates studied antibiotic prescriptions and bacterial cultures from the lesions of 239 patients with HS who were treated at Johns Hopkins medical facilities between 2010 and 2015. Not only were 51% of HS patients on antibiotics at the time of culture, but these patients’ lesions were significantly more likely to contain antibiotic-resistant bacteria than were those of patients not on antibiotics.
Strikingly, Proteus species were isolated from nearly half of patients on trimethoprim-sulfamethoxazole (TMP/SMX), and 88% of colonies were resistant to TMP/SMX, while only 13% of cultures from untreated patients grew Proteus (P less than .001) and all were TMP/SMX-susceptible (P less than .001). Likewise, 100% of methicillin-resistant Staphylococcus aureus (MRSA) strains from patients prescribed ciprofloxacin were resistant to it, compared with a 10% background rate of ciprofloxacin resistance among MRSA from patients not taking antibiotics (P = .04). In addition, the proportion of other S. aureus strains that were clindamycin-resistant was higher when patients were taking this antibiotic than when they were not (63% versus 17%; P = .03).
The results “raise questions” about whether antibiotics should be used in HS patients who are not clearly benefiting from them, according to the researchers.
The authors of both studies reported no funding sources and had no disclosures.
AT THE 2016 SID ANNUAL MEETING
Key clinical point: Two studies underscored current challenges in diagnosing and treating hidradenitis suppurativa (HS).
Major finding: HS was usually diagnosed in outpatient settings by nondermatologists who often initially filed claims for carbuncles, ulcers, and other conditions that are confused with HS. In a separate study, antibiotic-resistant bacteria were significantly more prevalent in the lesions of HS patients who were receiving antibiotics than in patients who were not taking antibiotics.
Data source: A medical claims analysis of 1,733 patients with HS, and a study of antibiotic prescriptions and bacterial cultures from 239 patients with HS.
Disclosures: The authors of both studies reported no funding sources and had no disclosures.
Are Periodic Endoscopies Useful for Patients Under 40?
Endoscopies do not necessarily help catch early gastric cancer in young people, say researchers from Severance Hospital, Seoul, and Hanyang University, Guri, both in Korea.
In countries such as Korea and Japan, where the researchers say Helicobacter pylori is endemic and gastric cancer is prevalent, screening for gastric cancer is recommended for people aged ≥ 40 years. In a previous study, they found that biennial endoscopies increased the diagnosis of gastric neoplasms, including gastric cancer and adenoma, at an early stage in people aged ≥ 40 years. Noting that disease-free status and overall survival of younger patients with gastric cancer are dependent on the cancer’s stage at diagnosis, as is the case with middle-aged patients, they wanted to find out whether earlier periodic endoscopies would be useful.
Related:Clarifying the Links Between Gallbladder Disease and Cancer
In their study, 101 patients underwent screening endoscopy within 24 months after receiving their gastric cancer diagnosis. Another 463 had not had an endoscopy within 2 years. Overall, 65% to 68% had early gastric cancer, but the researchers found no significant difference between the 2 groups. However, the proportion of lesions that were treated with endoscopic submucosal dissection (ESD) differed according to the interval: 9.8% for ≤ 24 and 4.5% for ≥ 24 months.
The only factor associated with early gastric cancer was gastrointestinal symptoms at the time of diagnosis.
Related: How Much Is Too Much Cancer Screening?
Performing an earlier endoscopy detected gastric cancer at a smaller size (23.8 mm in the ≤ 24-month group vs 30.5 mm in the ≥ 24-month group), which could facilitate treatment with ESD, the researchers say. They suggest that although not necessarily influencing early diagnosis, periodic endoscopies may help increase the proportion of lesions treated with ESD.
Source:
Park CH, Kim EH, Chung H, et al. PLoS One. 2016;11(7):e0159759.
doi: 10.1371/journal.pone.0159759.
Endoscopies do not necessarily help catch early gastric cancer in young people, say researchers from Severance Hospital, Seoul, and Hanyang University, Guri, both in Korea.
In countries such as Korea and Japan, where the researchers say Helicobacter pylori is endemic and gastric cancer is prevalent, screening for gastric cancer is recommended for people aged ≥ 40 years. In a previous study, they found that biennial endoscopies increased the diagnosis of gastric neoplasms, including gastric cancer and adenoma, at an early stage in people aged ≥ 40 years. Noting that disease-free status and overall survival of younger patients with gastric cancer are dependent on the cancer’s stage at diagnosis, as is the case with middle-aged patients, they wanted to find out whether earlier periodic endoscopies would be useful.
Related:Clarifying the Links Between Gallbladder Disease and Cancer
In their study, 101 patients underwent screening endoscopy within 24 months after receiving their gastric cancer diagnosis. Another 463 had not had an endoscopy within 2 years. Overall, 65% to 68% had early gastric cancer, but the researchers found no significant difference between the 2 groups. However, the proportion of lesions that were treated with endoscopic submucosal dissection (ESD) differed according to the interval: 9.8% for ≤ 24 and 4.5% for ≥ 24 months.
The only factor associated with early gastric cancer was gastrointestinal symptoms at the time of diagnosis.
Related: How Much Is Too Much Cancer Screening?
Performing an earlier endoscopy detected gastric cancer at a smaller size (23.8 mm in the ≤ 24-month group vs 30.5 mm in the ≥ 24-month group), which could facilitate treatment with ESD, the researchers say. They suggest that although not necessarily influencing early diagnosis, periodic endoscopies may help increase the proportion of lesions treated with ESD.
Source:
Park CH, Kim EH, Chung H, et al. PLoS One. 2016;11(7):e0159759.
doi: 10.1371/journal.pone.0159759.
Endoscopies do not necessarily help catch early gastric cancer in young people, say researchers from Severance Hospital, Seoul, and Hanyang University, Guri, both in Korea.
In countries such as Korea and Japan, where the researchers say Helicobacter pylori is endemic and gastric cancer is prevalent, screening for gastric cancer is recommended for people aged ≥ 40 years. In a previous study, they found that biennial endoscopies increased the diagnosis of gastric neoplasms, including gastric cancer and adenoma, at an early stage in people aged ≥ 40 years. Noting that disease-free status and overall survival of younger patients with gastric cancer are dependent on the cancer’s stage at diagnosis, as is the case with middle-aged patients, they wanted to find out whether earlier periodic endoscopies would be useful.
Related:Clarifying the Links Between Gallbladder Disease and Cancer
In their study, 101 patients underwent screening endoscopy within 24 months after receiving their gastric cancer diagnosis. Another 463 had not had an endoscopy within 2 years. Overall, 65% to 68% had early gastric cancer, but the researchers found no significant difference between the 2 groups. However, the proportion of lesions that were treated with endoscopic submucosal dissection (ESD) differed according to the interval: 9.8% for ≤ 24 and 4.5% for ≥ 24 months.
The only factor associated with early gastric cancer was gastrointestinal symptoms at the time of diagnosis.
Related: How Much Is Too Much Cancer Screening?
Performing an earlier endoscopy detected gastric cancer at a smaller size (23.8 mm in the ≤ 24-month group vs 30.5 mm in the ≥ 24-month group), which could facilitate treatment with ESD, the researchers say. They suggest that although not necessarily influencing early diagnosis, periodic endoscopies may help increase the proportion of lesions treated with ESD.
Source:
Park CH, Kim EH, Chung H, et al. PLoS One. 2016;11(7):e0159759.
doi: 10.1371/journal.pone.0159759.
Emergency Imaging: Shortness of breath
A 79-year-old woman presented to the ED with acute shortness of breath. Of note, she had been recently discharged from our hospital after an open reduction and internal fixation of an intertrochanteric fracture of the right hip. The patient’s postoperative course was uncomplicated, and she was discharged home after a brief inpatient stay.
On physical examination, the patient was diaphoretic and tachypneic; oxygen saturation was 68% on room air, but increased to 100% saturation with supplemental oxygen through a nonrebreather mask. Radiographs from the patient’s inpatient hospital stay (Figure 1a) as well as ED visit (Figure 1b) were reviewed; representative images are shown above.
What is the diagnosis? What additional imaging tests may be useful to confirm the diagnosis?
Answer
The radiographs taken at the time of the patient’s discharge were normal. The radiograph of the chest obtained in the ED, however, demonstrated a distinct cut-off of the right mainstem bronchus, referred to as a bronchial cut-off sign (white arrow, Figure 2), with a rounded density projecting over the right mainstem bronchus (white asterisk, Figure 2). These radiographic appearances suggested the presence of an aspirated foreign body.
A computed tomography (CT) scan of the chest with contrast was performed to further evaluate the radiographic opacity and to exclude pulmonary embolism (PE), as this patient was at risk for such. The CT scan revealed no evidence of PE but confirmed the diagnosis of an aspirated foreign body. A high-density tablet (black asterisk, Figure 3) was noted to be completely occluding the right mainstem bronchus (white arrow, Figure 3) with resultant mild hyperinflation of the right lung. Upon further questioning, the patient stated that she had choked on a calcium tablet earlier in the day, but thought that the pill had finally “gone down.”
Since aspiration of foreign bodies is far more common in children,1,2 the diagnosis often is not considered in adults who present with acute onset of shortness of breath. In adults, the most significant predisposing factor to aspiration is alcoholism. However, foreign body aspiration may arise in various clinical scenarios, including in patients with structural abnormalities, in those with neuromuscular disease, and in the postoperative setting. The most common aspirated foreign bodies are food and broken tooth fragments/periodontal devices (eg, periodontal splint).2
Presentation is varied and depends upon the nature and volume of the aspirated foreign body, which may contribute to the airway obstruction or an inflammatory bronchopneumonia. The posterior segment of the upper lobes and the superior segments of the lower lobes are the most commonly involved sites, with the right lung preferentially involved over the left lung.3
The diagnosis of foreign body aspiration begins with an appropriate clinical history. Given our patient’s recent orthopedic surgery, PE was an understandable diagnostic consideration. As with any patient acutely short of breath, radiographs are the initial diagnostic imaging study of choice. An abrupt truncation of a bronchus on radiography suggests obstruction related to a mucous plugging, cancer, or foreign body aspiration. Other findings of foreign body aspiration include segmental/lobar hyperinflation and/or atelectasis.3 In many scenarios, the aspirated foreign body may not be radiodense, which limits the utility and diagnostic accuracy of radiography. Computed tomography improves diagnostic precision and time to diagnosis by directly visualizing the airway lumen and improving visualization of radiolucent objects.4
Treatment for obstructive aspiration depends upon the location and nature of the aspirated object. However, bedside bronchoscopy and extraction of the foreign object is the mainstay of treatment, and is how this patient was treated. Rapid diagnosis and treatment is key to alleviating obstruction and preventing potential complications of hemoptysis and infection.
1. Marom EM, McAdams HP, Erasmus JJ, Goodman PC. The many faces of pulmonary aspiration. AJR Am J Roentgenol. 1999;172(1):121-128.
2. McGuirt WF, Holmes KD, Feehs R, Browne JD. Tracheobronchial foreign bodies. Laryngoscope. 1988;98(6 Pt 1):615-618.
3. Franquet T, Giménez A, Rosón N, Torrubia S, Sabaté JM, Pérez C. Aspiration diseases: Findings, pitfalls, and differential diagnosis. Radiographics. 2000;20(3):673-685.
4. Newton JP, Abel RW, Lloyd CH, Yemm R. The use of computed tomography in the detection of radiolucent denture base material in the chest. J Oral Rehabil. 1987;14(2):193-202.
A 79-year-old woman presented to the ED with acute shortness of breath. Of note, she had been recently discharged from our hospital after an open reduction and internal fixation of an intertrochanteric fracture of the right hip. The patient’s postoperative course was uncomplicated, and she was discharged home after a brief inpatient stay.
On physical examination, the patient was diaphoretic and tachypneic; oxygen saturation was 68% on room air, but increased to 100% saturation with supplemental oxygen through a nonrebreather mask. Radiographs from the patient’s inpatient hospital stay (Figure 1a) as well as ED visit (Figure 1b) were reviewed; representative images are shown above.
What is the diagnosis? What additional imaging tests may be useful to confirm the diagnosis?
Answer
The radiographs taken at the time of the patient’s discharge were normal. The radiograph of the chest obtained in the ED, however, demonstrated a distinct cut-off of the right mainstem bronchus, referred to as a bronchial cut-off sign (white arrow, Figure 2), with a rounded density projecting over the right mainstem bronchus (white asterisk, Figure 2). These radiographic appearances suggested the presence of an aspirated foreign body.
A computed tomography (CT) scan of the chest with contrast was performed to further evaluate the radiographic opacity and to exclude pulmonary embolism (PE), as this patient was at risk for such. The CT scan revealed no evidence of PE but confirmed the diagnosis of an aspirated foreign body. A high-density tablet (black asterisk, Figure 3) was noted to be completely occluding the right mainstem bronchus (white arrow, Figure 3) with resultant mild hyperinflation of the right lung. Upon further questioning, the patient stated that she had choked on a calcium tablet earlier in the day, but thought that the pill had finally “gone down.”
Since aspiration of foreign bodies is far more common in children,1,2 the diagnosis often is not considered in adults who present with acute onset of shortness of breath. In adults, the most significant predisposing factor to aspiration is alcoholism. However, foreign body aspiration may arise in various clinical scenarios, including in patients with structural abnormalities, in those with neuromuscular disease, and in the postoperative setting. The most common aspirated foreign bodies are food and broken tooth fragments/periodontal devices (eg, periodontal splint).2
Presentation is varied and depends upon the nature and volume of the aspirated foreign body, which may contribute to the airway obstruction or an inflammatory bronchopneumonia. The posterior segment of the upper lobes and the superior segments of the lower lobes are the most commonly involved sites, with the right lung preferentially involved over the left lung.3
The diagnosis of foreign body aspiration begins with an appropriate clinical history. Given our patient’s recent orthopedic surgery, PE was an understandable diagnostic consideration. As with any patient acutely short of breath, radiographs are the initial diagnostic imaging study of choice. An abrupt truncation of a bronchus on radiography suggests obstruction related to a mucous plugging, cancer, or foreign body aspiration. Other findings of foreign body aspiration include segmental/lobar hyperinflation and/or atelectasis.3 In many scenarios, the aspirated foreign body may not be radiodense, which limits the utility and diagnostic accuracy of radiography. Computed tomography improves diagnostic precision and time to diagnosis by directly visualizing the airway lumen and improving visualization of radiolucent objects.4
Treatment for obstructive aspiration depends upon the location and nature of the aspirated object. However, bedside bronchoscopy and extraction of the foreign object is the mainstay of treatment, and is how this patient was treated. Rapid diagnosis and treatment is key to alleviating obstruction and preventing potential complications of hemoptysis and infection.
A 79-year-old woman presented to the ED with acute shortness of breath. Of note, she had been recently discharged from our hospital after an open reduction and internal fixation of an intertrochanteric fracture of the right hip. The patient’s postoperative course was uncomplicated, and she was discharged home after a brief inpatient stay.
On physical examination, the patient was diaphoretic and tachypneic; oxygen saturation was 68% on room air, but increased to 100% saturation with supplemental oxygen through a nonrebreather mask. Radiographs from the patient’s inpatient hospital stay (Figure 1a) as well as ED visit (Figure 1b) were reviewed; representative images are shown above.
What is the diagnosis? What additional imaging tests may be useful to confirm the diagnosis?
Answer
The radiographs taken at the time of the patient’s discharge were normal. The radiograph of the chest obtained in the ED, however, demonstrated a distinct cut-off of the right mainstem bronchus, referred to as a bronchial cut-off sign (white arrow, Figure 2), with a rounded density projecting over the right mainstem bronchus (white asterisk, Figure 2). These radiographic appearances suggested the presence of an aspirated foreign body.
A computed tomography (CT) scan of the chest with contrast was performed to further evaluate the radiographic opacity and to exclude pulmonary embolism (PE), as this patient was at risk for such. The CT scan revealed no evidence of PE but confirmed the diagnosis of an aspirated foreign body. A high-density tablet (black asterisk, Figure 3) was noted to be completely occluding the right mainstem bronchus (white arrow, Figure 3) with resultant mild hyperinflation of the right lung. Upon further questioning, the patient stated that she had choked on a calcium tablet earlier in the day, but thought that the pill had finally “gone down.”
Since aspiration of foreign bodies is far more common in children,1,2 the diagnosis often is not considered in adults who present with acute onset of shortness of breath. In adults, the most significant predisposing factor to aspiration is alcoholism. However, foreign body aspiration may arise in various clinical scenarios, including in patients with structural abnormalities, in those with neuromuscular disease, and in the postoperative setting. The most common aspirated foreign bodies are food and broken tooth fragments/periodontal devices (eg, periodontal splint).2
Presentation is varied and depends upon the nature and volume of the aspirated foreign body, which may contribute to the airway obstruction or an inflammatory bronchopneumonia. The posterior segment of the upper lobes and the superior segments of the lower lobes are the most commonly involved sites, with the right lung preferentially involved over the left lung.3
The diagnosis of foreign body aspiration begins with an appropriate clinical history. Given our patient’s recent orthopedic surgery, PE was an understandable diagnostic consideration. As with any patient acutely short of breath, radiographs are the initial diagnostic imaging study of choice. An abrupt truncation of a bronchus on radiography suggests obstruction related to a mucous plugging, cancer, or foreign body aspiration. Other findings of foreign body aspiration include segmental/lobar hyperinflation and/or atelectasis.3 In many scenarios, the aspirated foreign body may not be radiodense, which limits the utility and diagnostic accuracy of radiography. Computed tomography improves diagnostic precision and time to diagnosis by directly visualizing the airway lumen and improving visualization of radiolucent objects.4
Treatment for obstructive aspiration depends upon the location and nature of the aspirated object. However, bedside bronchoscopy and extraction of the foreign object is the mainstay of treatment, and is how this patient was treated. Rapid diagnosis and treatment is key to alleviating obstruction and preventing potential complications of hemoptysis and infection.
1. Marom EM, McAdams HP, Erasmus JJ, Goodman PC. The many faces of pulmonary aspiration. AJR Am J Roentgenol. 1999;172(1):121-128.
2. McGuirt WF, Holmes KD, Feehs R, Browne JD. Tracheobronchial foreign bodies. Laryngoscope. 1988;98(6 Pt 1):615-618.
3. Franquet T, Giménez A, Rosón N, Torrubia S, Sabaté JM, Pérez C. Aspiration diseases: Findings, pitfalls, and differential diagnosis. Radiographics. 2000;20(3):673-685.
4. Newton JP, Abel RW, Lloyd CH, Yemm R. The use of computed tomography in the detection of radiolucent denture base material in the chest. J Oral Rehabil. 1987;14(2):193-202.
1. Marom EM, McAdams HP, Erasmus JJ, Goodman PC. The many faces of pulmonary aspiration. AJR Am J Roentgenol. 1999;172(1):121-128.
2. McGuirt WF, Holmes KD, Feehs R, Browne JD. Tracheobronchial foreign bodies. Laryngoscope. 1988;98(6 Pt 1):615-618.
3. Franquet T, Giménez A, Rosón N, Torrubia S, Sabaté JM, Pérez C. Aspiration diseases: Findings, pitfalls, and differential diagnosis. Radiographics. 2000;20(3):673-685.
4. Newton JP, Abel RW, Lloyd CH, Yemm R. The use of computed tomography in the detection of radiolucent denture base material in the chest. J Oral Rehabil. 1987;14(2):193-202.
