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Predicting response to treatment in AML, MDS
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy. 
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
PEARL score for COPD exacerbations
TITLE: PEARL score predicts COPD readmissions
CLINICAL QUESTION: Which prognostic score is best at predicting 90-day readmission and mortality for patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?
STUDY DESIGN: Prospective study with three separate cohorts: derivation, internal validation, and external validation.
SETTING: Six hospitals in the United Kingdom.
SYNOPSIS: 2,417 patients were included and 936 were readmitted or died within 90 days of index admission. Patients with expected survival for less than 1 year for reasons other than COPD were excluded. The indices retained in the final PEARL score were: Previous admissions for AECOPD of 2 or more (2 points), extended medical research council (MRC) dyspnea score of 4, 5a or 5b (1, 2, or 3 points), age of 80 or older (1 point), clinical diagnoses of right-sided heart failure (1 point) and/or left-sided heart failure on echocardiogram (1 point). Higher scores were associated with a shorter time to death or readmission. The performance of PEARL was superior to all alternative scoring systems. The major limitation to this study is that it did not differentiate between respiratory and other causes of readmission.
BOTTOM LINE: The PEARL score can be calculated for patients hospitalized for AECOPD to predict their 90-day readmission rate and/or mortality risk.
CITATION: Echevarria C, Steer J, Heslop-Marshall K, Stenton SC, Hickey PM, Hughes R, et al. The PEARL score predicts 90-day readmission or death after hospitalization for acute exacerbation of COPD. Thorax. 2017; doi: 10.1136/thoraxjnl-2016-209298.
Dr. Ayoubieh is assistant professor in the division of hospital medicine at the University of New Mexico.
TITLE: PEARL score predicts COPD readmissions
CLINICAL QUESTION: Which prognostic score is best at predicting 90-day readmission and mortality for patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?
STUDY DESIGN: Prospective study with three separate cohorts: derivation, internal validation, and external validation.
SETTING: Six hospitals in the United Kingdom.
SYNOPSIS: 2,417 patients were included and 936 were readmitted or died within 90 days of index admission. Patients with expected survival for less than 1 year for reasons other than COPD were excluded. The indices retained in the final PEARL score were: Previous admissions for AECOPD of 2 or more (2 points), extended medical research council (MRC) dyspnea score of 4, 5a or 5b (1, 2, or 3 points), age of 80 or older (1 point), clinical diagnoses of right-sided heart failure (1 point) and/or left-sided heart failure on echocardiogram (1 point). Higher scores were associated with a shorter time to death or readmission. The performance of PEARL was superior to all alternative scoring systems. The major limitation to this study is that it did not differentiate between respiratory and other causes of readmission.
BOTTOM LINE: The PEARL score can be calculated for patients hospitalized for AECOPD to predict their 90-day readmission rate and/or mortality risk.
CITATION: Echevarria C, Steer J, Heslop-Marshall K, Stenton SC, Hickey PM, Hughes R, et al. The PEARL score predicts 90-day readmission or death after hospitalization for acute exacerbation of COPD. Thorax. 2017; doi: 10.1136/thoraxjnl-2016-209298.
Dr. Ayoubieh is assistant professor in the division of hospital medicine at the University of New Mexico.
TITLE: PEARL score predicts COPD readmissions
CLINICAL QUESTION: Which prognostic score is best at predicting 90-day readmission and mortality for patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?
STUDY DESIGN: Prospective study with three separate cohorts: derivation, internal validation, and external validation.
SETTING: Six hospitals in the United Kingdom.
SYNOPSIS: 2,417 patients were included and 936 were readmitted or died within 90 days of index admission. Patients with expected survival for less than 1 year for reasons other than COPD were excluded. The indices retained in the final PEARL score were: Previous admissions for AECOPD of 2 or more (2 points), extended medical research council (MRC) dyspnea score of 4, 5a or 5b (1, 2, or 3 points), age of 80 or older (1 point), clinical diagnoses of right-sided heart failure (1 point) and/or left-sided heart failure on echocardiogram (1 point). Higher scores were associated with a shorter time to death or readmission. The performance of PEARL was superior to all alternative scoring systems. The major limitation to this study is that it did not differentiate between respiratory and other causes of readmission.
BOTTOM LINE: The PEARL score can be calculated for patients hospitalized for AECOPD to predict their 90-day readmission rate and/or mortality risk.
CITATION: Echevarria C, Steer J, Heslop-Marshall K, Stenton SC, Hickey PM, Hughes R, et al. The PEARL score predicts 90-day readmission or death after hospitalization for acute exacerbation of COPD. Thorax. 2017; doi: 10.1136/thoraxjnl-2016-209298.
Dr. Ayoubieh is assistant professor in the division of hospital medicine at the University of New Mexico.
Tips for managing dermatology procedures in kids
CHICAGO – True complications in pediatric dermatologic surgery probably aren’t that frequent, but no solid data on the topic exist in the medical literature.
“An appropriate and thorough perioperative evaluation and planning may limit complications,” Harper N. Price, MD, said at the World Congress of Pediatric Dermatology.
The first step is to make the child comfortable in the office or operating room (OR) setting; this can include approaching children slowly unless you know them well. “Sit at their level, because coming up very fast and being over ... them is intimidating,” she advised. “Make sure you include the child in the conversation you’re having; it elicits more trust and belief in what’s going to happen. You want to explain what’s going to happen in a friendly manner. I think sometimes we have residents who are new to pediatrics that come in and say, ‘We’re going to cut this out,’ and the next thing you know, the child’s in tears. Describe what the procedure is going to be like in words that they can understand, and whatever you do, do not lie about what’s going to happen.”
Dr. Price also makes it a point to cover surgical trays before they’re wheeled in. “They don’t need to see needles and sharp objects,” she said. “Even afterward, bloody gauze can be scary to kids.” Positioning the patient properly also is important. “We’ll wrap young children up in a swaddle,” she said. “In my opinion, you should not be forcefully restraining an older child. They need to cooperate and it needs to be a safe procedure, otherwise, you should consider doing it in the operating room. I never enlist a parent to hold or restrain a child.”
One key to managing pain during dermatologic procedures in children comes down to anticipation: What kinds of distractions might the child need? What preoperative analgesia will be required? What postoperative pain medications should be used? “We know that certain procedures in children might be more painful, such as nail procedures, ablative laser procedures, and large excisions with extensive undermining,” Dr. Price said. “Pain is subjective and differs from child to child in the way it’s experienced, so you need to consider the child’s age, coping style, and temperament, and what their history of pain is like. We know that inadequate pain control in children has a negative impact and a negative implication on their future health care interventions, as well as their reactions to further pain.”
Parental involvement can sometimes help. “I like a parent to stay in the room if I’m doing a procedure in the office, as long as they agree to stay seated,” she said. “It may make your office staff more anxious, and it may make parents more anxious, too, so it’s something to think about.” There is some evidence that having a parent present during an in-office procedure increases parental satisfaction as well.
In an effort to minimize pain and anxiety before in-office procedures, Dr. Price and her associates at Phoenix Children’s Hospital often use instant ice packs. “They get cold really fast, they’re cheap, and you don’t have to run to a refrigerator to get ice,” she said. Other beneficial measures include topical anesthetics and breathing techniques, such as having the child blow on a pinwheel, blow bubbles, or perform diaphragmatic breathing. Using distractions – stuffed animals, picture books, or video games on a tablet – can also help. “If the child is going to the OR, using preoperative midazolam can help relax the child, especially if they’re having repeated procedures,” Dr. Price said. Oral sucrose solution in infants, especially in young infants, provides about 5-8 minutes of temporary analgesia and can be placed on their pacifier or their tongue, she added, noting that ethyl chloride spray can also be helpful prior to injections.
During the procedure itself, counter-stimulatory methods can be helpful; this can include handheld devices that use a combination of vibration, ice, and distraction methods. “Buffer your lidocaine and don’t inject cold lidocaine; that hurts a lot more,” she recommended. “Inject slowly; inject deep. If you have a painful procedure and you’re in an OR setting where you give Marcaine [bupivacaine], put that in at the end of the procedure for short-term postoperative pain relief.” After the procedure, it’s better not to apologize for causing pain or if the procedure didn’t go well. “Give positive incentives like stickers and stuffed animals, and use a dressing wrap with bright colors,” she said. “We often doctor up stuffed animals in the OR so when [the children] wake up, they have something fun to look at.”
Postoperatively, the best way to prevent pain is to recommend limited physical activity. “Children become active quickly after a procedure, and then they hurt,” Dr. Price said. “For extremity wounds, consider ice and elevation. I like bulky dressings to prevent trauma, to remind the families that they’ve had a procedure done. They can usually keep them on for several days.”
Surgical site infections are uncommon, but if they do occur, it’s usually between postoperative days 4 and 10. “The biggest indicator of an infection in my opinion is pain,” she said. “If they’re having a lot of pain, I would be concerned. Causes may be the presence of bacteria on the skin or mucosa or improper wound care at home.”
The risk factors for surgical site infections in children are not well defined in dermatologic surgery, Dr. Price added, “but we know that if you’re going to be operating in the diaper area, that’s a place where you’re going to have a high risk of infection. Preoperative hair removal – if you shave the scalp before surgery creating small nicks – could [introduce] bacteria. And it’s likely that the overall health of the patient may impact their risk of infection. You want to know the difference between normal wound healing and an infection. Culture it. If you’re worried, you may want to start empiric antibiotics. If you have a severe infection, something with necrosis, fluctuance, or dehiscence, you might want to consider partially opening that wound and letting it drain and heal in by secondary intention.”
Measures to prevent postoperative infections include perioperative counseling to restrict excessive activity to prevent trauma, bleeding, and dehiscence; use of bulky dressings, and explicit wound care instructions. “My nurse calls [the patient’s family] the day after a procedure, and I usually have them come in for a wound check, even if there are no sutures to remove, just to make sure things look OK,” she said.
Suture reactions are another potential complication of dermatologic surgery in children. The incidence is unknown, but suture reactions usually occur around 6 weeks postoperatively and tend to happen more often in older children. “Excessive reactions, while uncommon, can lead to an increased risk of dehiscence, infection, and delayed healing,” Dr. Price said. Small caliber monofilament sutures are less reactive than large caliber, multifilament sutures, she added, while synthetic and nonabsorbable sutures are less reactive than natural materials such as silk and surgical gut. Dr. Price favors using poliglecaprone, polyglactin 910, and polypropylene.
Tips for minimizing suture reactions include the following: Use the smallest caliber suture appropriate for the wound; avoid buried sutures too close to the surface of the skin; use a smaller caliber suture at the end of excisions, where there tends to be less tension; and keep knots small and flat at the apexes of excision. “Manage suture reactions with reassurance,” she said. “The nice thing is that these often heal fine without any delay. When possible, remove the offending suture material. A lot of times, I’ll use sterile forceps. At home, I’ll have [parents] massage the area with warm compresses to try to extrude the suture. But, if you wait long enough, it usually comes out.”
Dr. Price reported having no financial disclosures.
[email protected]
CHICAGO – True complications in pediatric dermatologic surgery probably aren’t that frequent, but no solid data on the topic exist in the medical literature.
“An appropriate and thorough perioperative evaluation and planning may limit complications,” Harper N. Price, MD, said at the World Congress of Pediatric Dermatology.
The first step is to make the child comfortable in the office or operating room (OR) setting; this can include approaching children slowly unless you know them well. “Sit at their level, because coming up very fast and being over ... them is intimidating,” she advised. “Make sure you include the child in the conversation you’re having; it elicits more trust and belief in what’s going to happen. You want to explain what’s going to happen in a friendly manner. I think sometimes we have residents who are new to pediatrics that come in and say, ‘We’re going to cut this out,’ and the next thing you know, the child’s in tears. Describe what the procedure is going to be like in words that they can understand, and whatever you do, do not lie about what’s going to happen.”
Dr. Price also makes it a point to cover surgical trays before they’re wheeled in. “They don’t need to see needles and sharp objects,” she said. “Even afterward, bloody gauze can be scary to kids.” Positioning the patient properly also is important. “We’ll wrap young children up in a swaddle,” she said. “In my opinion, you should not be forcefully restraining an older child. They need to cooperate and it needs to be a safe procedure, otherwise, you should consider doing it in the operating room. I never enlist a parent to hold or restrain a child.”
One key to managing pain during dermatologic procedures in children comes down to anticipation: What kinds of distractions might the child need? What preoperative analgesia will be required? What postoperative pain medications should be used? “We know that certain procedures in children might be more painful, such as nail procedures, ablative laser procedures, and large excisions with extensive undermining,” Dr. Price said. “Pain is subjective and differs from child to child in the way it’s experienced, so you need to consider the child’s age, coping style, and temperament, and what their history of pain is like. We know that inadequate pain control in children has a negative impact and a negative implication on their future health care interventions, as well as their reactions to further pain.”
Parental involvement can sometimes help. “I like a parent to stay in the room if I’m doing a procedure in the office, as long as they agree to stay seated,” she said. “It may make your office staff more anxious, and it may make parents more anxious, too, so it’s something to think about.” There is some evidence that having a parent present during an in-office procedure increases parental satisfaction as well.
In an effort to minimize pain and anxiety before in-office procedures, Dr. Price and her associates at Phoenix Children’s Hospital often use instant ice packs. “They get cold really fast, they’re cheap, and you don’t have to run to a refrigerator to get ice,” she said. Other beneficial measures include topical anesthetics and breathing techniques, such as having the child blow on a pinwheel, blow bubbles, or perform diaphragmatic breathing. Using distractions – stuffed animals, picture books, or video games on a tablet – can also help. “If the child is going to the OR, using preoperative midazolam can help relax the child, especially if they’re having repeated procedures,” Dr. Price said. Oral sucrose solution in infants, especially in young infants, provides about 5-8 minutes of temporary analgesia and can be placed on their pacifier or their tongue, she added, noting that ethyl chloride spray can also be helpful prior to injections.
During the procedure itself, counter-stimulatory methods can be helpful; this can include handheld devices that use a combination of vibration, ice, and distraction methods. “Buffer your lidocaine and don’t inject cold lidocaine; that hurts a lot more,” she recommended. “Inject slowly; inject deep. If you have a painful procedure and you’re in an OR setting where you give Marcaine [bupivacaine], put that in at the end of the procedure for short-term postoperative pain relief.” After the procedure, it’s better not to apologize for causing pain or if the procedure didn’t go well. “Give positive incentives like stickers and stuffed animals, and use a dressing wrap with bright colors,” she said. “We often doctor up stuffed animals in the OR so when [the children] wake up, they have something fun to look at.”
Postoperatively, the best way to prevent pain is to recommend limited physical activity. “Children become active quickly after a procedure, and then they hurt,” Dr. Price said. “For extremity wounds, consider ice and elevation. I like bulky dressings to prevent trauma, to remind the families that they’ve had a procedure done. They can usually keep them on for several days.”
Surgical site infections are uncommon, but if they do occur, it’s usually between postoperative days 4 and 10. “The biggest indicator of an infection in my opinion is pain,” she said. “If they’re having a lot of pain, I would be concerned. Causes may be the presence of bacteria on the skin or mucosa or improper wound care at home.”
The risk factors for surgical site infections in children are not well defined in dermatologic surgery, Dr. Price added, “but we know that if you’re going to be operating in the diaper area, that’s a place where you’re going to have a high risk of infection. Preoperative hair removal – if you shave the scalp before surgery creating small nicks – could [introduce] bacteria. And it’s likely that the overall health of the patient may impact their risk of infection. You want to know the difference between normal wound healing and an infection. Culture it. If you’re worried, you may want to start empiric antibiotics. If you have a severe infection, something with necrosis, fluctuance, or dehiscence, you might want to consider partially opening that wound and letting it drain and heal in by secondary intention.”
Measures to prevent postoperative infections include perioperative counseling to restrict excessive activity to prevent trauma, bleeding, and dehiscence; use of bulky dressings, and explicit wound care instructions. “My nurse calls [the patient’s family] the day after a procedure, and I usually have them come in for a wound check, even if there are no sutures to remove, just to make sure things look OK,” she said.
Suture reactions are another potential complication of dermatologic surgery in children. The incidence is unknown, but suture reactions usually occur around 6 weeks postoperatively and tend to happen more often in older children. “Excessive reactions, while uncommon, can lead to an increased risk of dehiscence, infection, and delayed healing,” Dr. Price said. Small caliber monofilament sutures are less reactive than large caliber, multifilament sutures, she added, while synthetic and nonabsorbable sutures are less reactive than natural materials such as silk and surgical gut. Dr. Price favors using poliglecaprone, polyglactin 910, and polypropylene.
Tips for minimizing suture reactions include the following: Use the smallest caliber suture appropriate for the wound; avoid buried sutures too close to the surface of the skin; use a smaller caliber suture at the end of excisions, where there tends to be less tension; and keep knots small and flat at the apexes of excision. “Manage suture reactions with reassurance,” she said. “The nice thing is that these often heal fine without any delay. When possible, remove the offending suture material. A lot of times, I’ll use sterile forceps. At home, I’ll have [parents] massage the area with warm compresses to try to extrude the suture. But, if you wait long enough, it usually comes out.”
Dr. Price reported having no financial disclosures.
[email protected]
CHICAGO – True complications in pediatric dermatologic surgery probably aren’t that frequent, but no solid data on the topic exist in the medical literature.
“An appropriate and thorough perioperative evaluation and planning may limit complications,” Harper N. Price, MD, said at the World Congress of Pediatric Dermatology.
The first step is to make the child comfortable in the office or operating room (OR) setting; this can include approaching children slowly unless you know them well. “Sit at their level, because coming up very fast and being over ... them is intimidating,” she advised. “Make sure you include the child in the conversation you’re having; it elicits more trust and belief in what’s going to happen. You want to explain what’s going to happen in a friendly manner. I think sometimes we have residents who are new to pediatrics that come in and say, ‘We’re going to cut this out,’ and the next thing you know, the child’s in tears. Describe what the procedure is going to be like in words that they can understand, and whatever you do, do not lie about what’s going to happen.”
Dr. Price also makes it a point to cover surgical trays before they’re wheeled in. “They don’t need to see needles and sharp objects,” she said. “Even afterward, bloody gauze can be scary to kids.” Positioning the patient properly also is important. “We’ll wrap young children up in a swaddle,” she said. “In my opinion, you should not be forcefully restraining an older child. They need to cooperate and it needs to be a safe procedure, otherwise, you should consider doing it in the operating room. I never enlist a parent to hold or restrain a child.”
One key to managing pain during dermatologic procedures in children comes down to anticipation: What kinds of distractions might the child need? What preoperative analgesia will be required? What postoperative pain medications should be used? “We know that certain procedures in children might be more painful, such as nail procedures, ablative laser procedures, and large excisions with extensive undermining,” Dr. Price said. “Pain is subjective and differs from child to child in the way it’s experienced, so you need to consider the child’s age, coping style, and temperament, and what their history of pain is like. We know that inadequate pain control in children has a negative impact and a negative implication on their future health care interventions, as well as their reactions to further pain.”
Parental involvement can sometimes help. “I like a parent to stay in the room if I’m doing a procedure in the office, as long as they agree to stay seated,” she said. “It may make your office staff more anxious, and it may make parents more anxious, too, so it’s something to think about.” There is some evidence that having a parent present during an in-office procedure increases parental satisfaction as well.
In an effort to minimize pain and anxiety before in-office procedures, Dr. Price and her associates at Phoenix Children’s Hospital often use instant ice packs. “They get cold really fast, they’re cheap, and you don’t have to run to a refrigerator to get ice,” she said. Other beneficial measures include topical anesthetics and breathing techniques, such as having the child blow on a pinwheel, blow bubbles, or perform diaphragmatic breathing. Using distractions – stuffed animals, picture books, or video games on a tablet – can also help. “If the child is going to the OR, using preoperative midazolam can help relax the child, especially if they’re having repeated procedures,” Dr. Price said. Oral sucrose solution in infants, especially in young infants, provides about 5-8 minutes of temporary analgesia and can be placed on their pacifier or their tongue, she added, noting that ethyl chloride spray can also be helpful prior to injections.
During the procedure itself, counter-stimulatory methods can be helpful; this can include handheld devices that use a combination of vibration, ice, and distraction methods. “Buffer your lidocaine and don’t inject cold lidocaine; that hurts a lot more,” she recommended. “Inject slowly; inject deep. If you have a painful procedure and you’re in an OR setting where you give Marcaine [bupivacaine], put that in at the end of the procedure for short-term postoperative pain relief.” After the procedure, it’s better not to apologize for causing pain or if the procedure didn’t go well. “Give positive incentives like stickers and stuffed animals, and use a dressing wrap with bright colors,” she said. “We often doctor up stuffed animals in the OR so when [the children] wake up, they have something fun to look at.”
Postoperatively, the best way to prevent pain is to recommend limited physical activity. “Children become active quickly after a procedure, and then they hurt,” Dr. Price said. “For extremity wounds, consider ice and elevation. I like bulky dressings to prevent trauma, to remind the families that they’ve had a procedure done. They can usually keep them on for several days.”
Surgical site infections are uncommon, but if they do occur, it’s usually between postoperative days 4 and 10. “The biggest indicator of an infection in my opinion is pain,” she said. “If they’re having a lot of pain, I would be concerned. Causes may be the presence of bacteria on the skin or mucosa or improper wound care at home.”
The risk factors for surgical site infections in children are not well defined in dermatologic surgery, Dr. Price added, “but we know that if you’re going to be operating in the diaper area, that’s a place where you’re going to have a high risk of infection. Preoperative hair removal – if you shave the scalp before surgery creating small nicks – could [introduce] bacteria. And it’s likely that the overall health of the patient may impact their risk of infection. You want to know the difference between normal wound healing and an infection. Culture it. If you’re worried, you may want to start empiric antibiotics. If you have a severe infection, something with necrosis, fluctuance, or dehiscence, you might want to consider partially opening that wound and letting it drain and heal in by secondary intention.”
Measures to prevent postoperative infections include perioperative counseling to restrict excessive activity to prevent trauma, bleeding, and dehiscence; use of bulky dressings, and explicit wound care instructions. “My nurse calls [the patient’s family] the day after a procedure, and I usually have them come in for a wound check, even if there are no sutures to remove, just to make sure things look OK,” she said.
Suture reactions are another potential complication of dermatologic surgery in children. The incidence is unknown, but suture reactions usually occur around 6 weeks postoperatively and tend to happen more often in older children. “Excessive reactions, while uncommon, can lead to an increased risk of dehiscence, infection, and delayed healing,” Dr. Price said. Small caliber monofilament sutures are less reactive than large caliber, multifilament sutures, she added, while synthetic and nonabsorbable sutures are less reactive than natural materials such as silk and surgical gut. Dr. Price favors using poliglecaprone, polyglactin 910, and polypropylene.
Tips for minimizing suture reactions include the following: Use the smallest caliber suture appropriate for the wound; avoid buried sutures too close to the surface of the skin; use a smaller caliber suture at the end of excisions, where there tends to be less tension; and keep knots small and flat at the apexes of excision. “Manage suture reactions with reassurance,” she said. “The nice thing is that these often heal fine without any delay. When possible, remove the offending suture material. A lot of times, I’ll use sterile forceps. At home, I’ll have [parents] massage the area with warm compresses to try to extrude the suture. But, if you wait long enough, it usually comes out.”
Dr. Price reported having no financial disclosures.
[email protected]
AT WCPD 2017
CDC refocuses Zika testing recommendations in pregnancy
, including those who may have been exposed before pregnancy through travel or sexual contact.
In updated guidance released July 24, the Centers for Disease Control and Prevention cited a combination of factors behind the change in recommendations, including the declining prevalence of Zika virus across the Americas and a high likelihood of false positives associated with the use of a common serologic assay (MMWR Morb Mortal Wkly Rep. ePub 2017 Jul 24. doi: 10.15585/mmwr.mm6629e1).
Positive IgM results can also occur after previous exposure to other flaviviruses besides Zika, Dr. Oduyebo and her colleagues noted.
The CDC now recommends that pregnant women with likely continuing – not previous – exposure to the Zika virus and those with symptoms suggestive of Zika virus disease be tested. Those higher-risk groups should receive nucleic acid testing (NAT).
The new guidance presents two updated testing algorithms, one for each group.
Any pregnant woman with symptoms suggestive of Zika should be tested “as soon as possible through 12 weeks after symptom onset,” the CDC said, with both NAT (serum and urine) and IgM serology testing.
Women with likely ongoing exposure to Zika – such as those living in or traveling to an area of mosquito-borne Zika transmission or those whose partners are living in or traveling to such an area – should be tested up to three times during the pregnancy using NAT serum and urine tests. IgM testing is not recommended for that group.
All pregnant women should be asked about their potential Zika exposures before and during the current pregnancy, the CDC said. That discussion, which covers potential travel and partner exposures along with questions about symptoms, should be repeated at every prenatal visit.
While routine testing of asymptomatic women without ongoing exposure is not recommended, patient preferences, clinical judgment, and a “balanced assessment of risks and expected outcomes” should guide decisions about testing, according to the CDC.
, including those who may have been exposed before pregnancy through travel or sexual contact.
In updated guidance released July 24, the Centers for Disease Control and Prevention cited a combination of factors behind the change in recommendations, including the declining prevalence of Zika virus across the Americas and a high likelihood of false positives associated with the use of a common serologic assay (MMWR Morb Mortal Wkly Rep. ePub 2017 Jul 24. doi: 10.15585/mmwr.mm6629e1).
Positive IgM results can also occur after previous exposure to other flaviviruses besides Zika, Dr. Oduyebo and her colleagues noted.
The CDC now recommends that pregnant women with likely continuing – not previous – exposure to the Zika virus and those with symptoms suggestive of Zika virus disease be tested. Those higher-risk groups should receive nucleic acid testing (NAT).
The new guidance presents two updated testing algorithms, one for each group.
Any pregnant woman with symptoms suggestive of Zika should be tested “as soon as possible through 12 weeks after symptom onset,” the CDC said, with both NAT (serum and urine) and IgM serology testing.
Women with likely ongoing exposure to Zika – such as those living in or traveling to an area of mosquito-borne Zika transmission or those whose partners are living in or traveling to such an area – should be tested up to three times during the pregnancy using NAT serum and urine tests. IgM testing is not recommended for that group.
All pregnant women should be asked about their potential Zika exposures before and during the current pregnancy, the CDC said. That discussion, which covers potential travel and partner exposures along with questions about symptoms, should be repeated at every prenatal visit.
While routine testing of asymptomatic women without ongoing exposure is not recommended, patient preferences, clinical judgment, and a “balanced assessment of risks and expected outcomes” should guide decisions about testing, according to the CDC.
, including those who may have been exposed before pregnancy through travel or sexual contact.
In updated guidance released July 24, the Centers for Disease Control and Prevention cited a combination of factors behind the change in recommendations, including the declining prevalence of Zika virus across the Americas and a high likelihood of false positives associated with the use of a common serologic assay (MMWR Morb Mortal Wkly Rep. ePub 2017 Jul 24. doi: 10.15585/mmwr.mm6629e1).
Positive IgM results can also occur after previous exposure to other flaviviruses besides Zika, Dr. Oduyebo and her colleagues noted.
The CDC now recommends that pregnant women with likely continuing – not previous – exposure to the Zika virus and those with symptoms suggestive of Zika virus disease be tested. Those higher-risk groups should receive nucleic acid testing (NAT).
The new guidance presents two updated testing algorithms, one for each group.
Any pregnant woman with symptoms suggestive of Zika should be tested “as soon as possible through 12 weeks after symptom onset,” the CDC said, with both NAT (serum and urine) and IgM serology testing.
Women with likely ongoing exposure to Zika – such as those living in or traveling to an area of mosquito-borne Zika transmission or those whose partners are living in or traveling to such an area – should be tested up to three times during the pregnancy using NAT serum and urine tests. IgM testing is not recommended for that group.
All pregnant women should be asked about their potential Zika exposures before and during the current pregnancy, the CDC said. That discussion, which covers potential travel and partner exposures along with questions about symptoms, should be repeated at every prenatal visit.
While routine testing of asymptomatic women without ongoing exposure is not recommended, patient preferences, clinical judgment, and a “balanced assessment of risks and expected outcomes” should guide decisions about testing, according to the CDC.
FROM MMWR
Racial differences in dementia risk persist from midlife to oldest old
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: Blacks were 30% more likely to develop dementia than were whites, even after researchers controlled for age, education, and mid- and late-life health–related risk factors.
Data source: The 5-year prospective study comprised more than 2,000 subjects aged 90 years and older.
Disclosures: The presenter had no financial disclosures.
Lupus classification criteria need input from dermatologists
Editor’s note: This commentary relates to the story, “ New classification system for systemic lupus erythematosus moves forward .”
The ACR/EULAR committee that is developing new classification criteria for systemic lupus erythematosus (SLE) has done the field a service by releasing its draft version in a presentation at the recent EULAR meeting. Releasing the draft version facilitates comments before the new classification criteria become finalized.
Many in the derm-rheum field, ourselves included, classify patients with skin-predominant lupus as lupus, but the new draft classification would place a significant percentage of these patients outside of lupus.
The presentation by Dr. Johnson at EULAR stated, “... a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus, but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Abundant data indicate instead that lupus is a spectrum that includes skin-predominant lupus. For example, the histology is identical between discoid lupus erythematosus whether or not there is SLE. Moreover, we and others have published significant rates of progression of cutaneous lupus erythematosus (CLE) to SLE. By not viewing CLE in the lupus spectrum, we have a false sense that the patients won’t progress to SLE, yet many of them do.
Importantly, patients respond similarly to therapies when they have either CLE or SLE, so removing this subset of lupus hurts their inclusion in trials and access to new treatments.
When criteria are devised by one group without input from experts who see a specific subset of the disease, that is also a problem. We went down that path in dermatomyositis and missed a lot of patients with the disease when criteria were devised that said the patient had to have muscle involvement. Those criteria have now finally been revised as the ACR/EULAR myositis criteria.
We and others from the derm-rheum community would be happy to speak with the ACR/EULAR committee about these concerns.
Victoria P. Werth, MD, is professor of medicine and dermatology at the University of Pennsylvania, Philadelphia. Joseph F. Merola, MD, is codirector of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston. Andrew G. Franks, MD, is a clinical professor in the departments of medicine and dermatology at New York University. Benjamin F. Chong, MD, is an assistant professor of dermatology at the University of Texas, Dallas.
Editor’s note: This commentary relates to the story, “ New classification system for systemic lupus erythematosus moves forward .”
The ACR/EULAR committee that is developing new classification criteria for systemic lupus erythematosus (SLE) has done the field a service by releasing its draft version in a presentation at the recent EULAR meeting. Releasing the draft version facilitates comments before the new classification criteria become finalized.
Many in the derm-rheum field, ourselves included, classify patients with skin-predominant lupus as lupus, but the new draft classification would place a significant percentage of these patients outside of lupus.
The presentation by Dr. Johnson at EULAR stated, “... a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus, but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Abundant data indicate instead that lupus is a spectrum that includes skin-predominant lupus. For example, the histology is identical between discoid lupus erythematosus whether or not there is SLE. Moreover, we and others have published significant rates of progression of cutaneous lupus erythematosus (CLE) to SLE. By not viewing CLE in the lupus spectrum, we have a false sense that the patients won’t progress to SLE, yet many of them do.
Importantly, patients respond similarly to therapies when they have either CLE or SLE, so removing this subset of lupus hurts their inclusion in trials and access to new treatments.
When criteria are devised by one group without input from experts who see a specific subset of the disease, that is also a problem. We went down that path in dermatomyositis and missed a lot of patients with the disease when criteria were devised that said the patient had to have muscle involvement. Those criteria have now finally been revised as the ACR/EULAR myositis criteria.
We and others from the derm-rheum community would be happy to speak with the ACR/EULAR committee about these concerns.
Victoria P. Werth, MD, is professor of medicine and dermatology at the University of Pennsylvania, Philadelphia. Joseph F. Merola, MD, is codirector of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston. Andrew G. Franks, MD, is a clinical professor in the departments of medicine and dermatology at New York University. Benjamin F. Chong, MD, is an assistant professor of dermatology at the University of Texas, Dallas.
Editor’s note: This commentary relates to the story, “ New classification system for systemic lupus erythematosus moves forward .”
The ACR/EULAR committee that is developing new classification criteria for systemic lupus erythematosus (SLE) has done the field a service by releasing its draft version in a presentation at the recent EULAR meeting. Releasing the draft version facilitates comments before the new classification criteria become finalized.
Many in the derm-rheum field, ourselves included, classify patients with skin-predominant lupus as lupus, but the new draft classification would place a significant percentage of these patients outside of lupus.
The presentation by Dr. Johnson at EULAR stated, “... a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus, but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Abundant data indicate instead that lupus is a spectrum that includes skin-predominant lupus. For example, the histology is identical between discoid lupus erythematosus whether or not there is SLE. Moreover, we and others have published significant rates of progression of cutaneous lupus erythematosus (CLE) to SLE. By not viewing CLE in the lupus spectrum, we have a false sense that the patients won’t progress to SLE, yet many of them do.
Importantly, patients respond similarly to therapies when they have either CLE or SLE, so removing this subset of lupus hurts their inclusion in trials and access to new treatments.
When criteria are devised by one group without input from experts who see a specific subset of the disease, that is also a problem. We went down that path in dermatomyositis and missed a lot of patients with the disease when criteria were devised that said the patient had to have muscle involvement. Those criteria have now finally been revised as the ACR/EULAR myositis criteria.
We and others from the derm-rheum community would be happy to speak with the ACR/EULAR committee about these concerns.
Victoria P. Werth, MD, is professor of medicine and dermatology at the University of Pennsylvania, Philadelphia. Joseph F. Merola, MD, is codirector of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston. Andrew G. Franks, MD, is a clinical professor in the departments of medicine and dermatology at New York University. Benjamin F. Chong, MD, is an assistant professor of dermatology at the University of Texas, Dallas.
Lupus classification criteria effort is going in the wrong direction
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Hepatitis B elimination: Is it possible?
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Lupus classification criteria effort is going in the wrong direction
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.
Multidisciplinary bundle drives drop in colorectal SSIs
NEW YORK – Facing an “unacceptably high” rate of surgical site infections associated with colorectal surgery at their community hospital, surgeons searched for solutions. They created a perioperative bundle of interventions that ultimately dropped their infection rates enough to achieve the highest ranking in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).
“The Centers for Disease Control and Prevention recommends we use a robust surveillance program to monitor surgical site infection data. The system gives us feedback, and that will [help us] reduce surgical site infection (SSI) risk,” said Christopher Wolff, MD, a PGY4 resident at the Cleveland Clinic Akron General Hospital. “NSQIP and the National Healthcare Safety Network from the CDC are two programs that do just that.”
The effort paid off, with the number of SSIs going from 16 cases in 2013 to 10 cases in 2014 and then 5 cases in 2015. Since the bundle was implemented in the last quarter of 2014, “we’ve seen a consistent downtrend since that point in our total infections, and we kept that in the background of a consistent number of cases.
“We have good outcomes by incidence, but that is not the whole story,” Dr. Wolff said. “With respect to colorectal infections, we are now performing in the ‘exemplary’ category, compared with our peers” according to the ACS NSQIP data. In addition, “we are performing at or below the SIR [standardized infection ratio] or expected number consistently since the implementation.”
The bundle addresses actions in five domains: preoperative, anesthesia, operating room, post–anesthesia care unit, and postoperative floor interventions. Preoperative elements include patient education, use of chlorhexidine wipes before surgery, and antibiotics noted on the chart, for example. Additional features include prewarming preoperatively and maintaining normothermia, requiring all surgeons scrub traditionally instead of “foaming,” use of wound protectors in the OR, and close monitoring of blood glucose in diabetics postoperatively. “There also is education of floor nurses on how to take care of these patients specifically,” Dr. Wolff noted.
To identify these areas for improvement, Dr. Wolff and his colleagues initially reviewed the literature to find individual and bundle elements demonstrated to improve outcomes. Then, a surgeon group “think tank” discussed the possibilities. However, reaching agreement was not easy, Dr. Wolff said. “They had a hard time agreeing on best practices, even within our own specialty. We did finally come to a consensus.
“We took those bundled protocols through to other areas and said ‘here are the things we want you to work on, things we want you to improve.’ That did not necessarily go over so well,” Dr. Wolff said. Because of resistance from their colleagues, they changed strategies. “We brought other people to the table and changed our work groups from being surgeons only to [being] a multidisciplinary team.”
The process took months and months of deliberation. It’s important to have a champion behind the project, said Dr. Wolff. “I have to thank my chairman, Mark C. Horattas, MD, FACS, who had the vision to see this through.
“We implemented tried-and-true measures to reduce surgical site infections. We did so in a team manner and had multidisciplinary buy-in, and that created a culture change in our program over time,” Dr. Wolff said.
This study also shows, Dr. Wolff added, that “a successful multidisciplinary quality improvement program can be implemented in a community hospital setting.”
Going forward, continuous monitoring will identify any areas that need improvement over time. The preoperative bundle also will be integrated into an Enhanced Recovery After Surgery protocol.
The Akron Hospital is now ranked by ACS NSQIP in the top 10% of hospitals for their colorectal SSI rate. “It’s nice to meet someone in the first decile,” session moderator Timothy D. Jackson, MD, FACS, of the University of Toronto said after Dr. Wolff’s presentation. “I’ve never done that before, and I took notes for what to do at my hospital.”
Dr. Wolff had no relevant financial disclosures.
NEW YORK – Facing an “unacceptably high” rate of surgical site infections associated with colorectal surgery at their community hospital, surgeons searched for solutions. They created a perioperative bundle of interventions that ultimately dropped their infection rates enough to achieve the highest ranking in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).
“The Centers for Disease Control and Prevention recommends we use a robust surveillance program to monitor surgical site infection data. The system gives us feedback, and that will [help us] reduce surgical site infection (SSI) risk,” said Christopher Wolff, MD, a PGY4 resident at the Cleveland Clinic Akron General Hospital. “NSQIP and the National Healthcare Safety Network from the CDC are two programs that do just that.”
The effort paid off, with the number of SSIs going from 16 cases in 2013 to 10 cases in 2014 and then 5 cases in 2015. Since the bundle was implemented in the last quarter of 2014, “we’ve seen a consistent downtrend since that point in our total infections, and we kept that in the background of a consistent number of cases.
“We have good outcomes by incidence, but that is not the whole story,” Dr. Wolff said. “With respect to colorectal infections, we are now performing in the ‘exemplary’ category, compared with our peers” according to the ACS NSQIP data. In addition, “we are performing at or below the SIR [standardized infection ratio] or expected number consistently since the implementation.”
The bundle addresses actions in five domains: preoperative, anesthesia, operating room, post–anesthesia care unit, and postoperative floor interventions. Preoperative elements include patient education, use of chlorhexidine wipes before surgery, and antibiotics noted on the chart, for example. Additional features include prewarming preoperatively and maintaining normothermia, requiring all surgeons scrub traditionally instead of “foaming,” use of wound protectors in the OR, and close monitoring of blood glucose in diabetics postoperatively. “There also is education of floor nurses on how to take care of these patients specifically,” Dr. Wolff noted.
To identify these areas for improvement, Dr. Wolff and his colleagues initially reviewed the literature to find individual and bundle elements demonstrated to improve outcomes. Then, a surgeon group “think tank” discussed the possibilities. However, reaching agreement was not easy, Dr. Wolff said. “They had a hard time agreeing on best practices, even within our own specialty. We did finally come to a consensus.
“We took those bundled protocols through to other areas and said ‘here are the things we want you to work on, things we want you to improve.’ That did not necessarily go over so well,” Dr. Wolff said. Because of resistance from their colleagues, they changed strategies. “We brought other people to the table and changed our work groups from being surgeons only to [being] a multidisciplinary team.”
The process took months and months of deliberation. It’s important to have a champion behind the project, said Dr. Wolff. “I have to thank my chairman, Mark C. Horattas, MD, FACS, who had the vision to see this through.
“We implemented tried-and-true measures to reduce surgical site infections. We did so in a team manner and had multidisciplinary buy-in, and that created a culture change in our program over time,” Dr. Wolff said.
This study also shows, Dr. Wolff added, that “a successful multidisciplinary quality improvement program can be implemented in a community hospital setting.”
Going forward, continuous monitoring will identify any areas that need improvement over time. The preoperative bundle also will be integrated into an Enhanced Recovery After Surgery protocol.
The Akron Hospital is now ranked by ACS NSQIP in the top 10% of hospitals for their colorectal SSI rate. “It’s nice to meet someone in the first decile,” session moderator Timothy D. Jackson, MD, FACS, of the University of Toronto said after Dr. Wolff’s presentation. “I’ve never done that before, and I took notes for what to do at my hospital.”
Dr. Wolff had no relevant financial disclosures.
NEW YORK – Facing an “unacceptably high” rate of surgical site infections associated with colorectal surgery at their community hospital, surgeons searched for solutions. They created a perioperative bundle of interventions that ultimately dropped their infection rates enough to achieve the highest ranking in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).
“The Centers for Disease Control and Prevention recommends we use a robust surveillance program to monitor surgical site infection data. The system gives us feedback, and that will [help us] reduce surgical site infection (SSI) risk,” said Christopher Wolff, MD, a PGY4 resident at the Cleveland Clinic Akron General Hospital. “NSQIP and the National Healthcare Safety Network from the CDC are two programs that do just that.”
The effort paid off, with the number of SSIs going from 16 cases in 2013 to 10 cases in 2014 and then 5 cases in 2015. Since the bundle was implemented in the last quarter of 2014, “we’ve seen a consistent downtrend since that point in our total infections, and we kept that in the background of a consistent number of cases.
“We have good outcomes by incidence, but that is not the whole story,” Dr. Wolff said. “With respect to colorectal infections, we are now performing in the ‘exemplary’ category, compared with our peers” according to the ACS NSQIP data. In addition, “we are performing at or below the SIR [standardized infection ratio] or expected number consistently since the implementation.”
The bundle addresses actions in five domains: preoperative, anesthesia, operating room, post–anesthesia care unit, and postoperative floor interventions. Preoperative elements include patient education, use of chlorhexidine wipes before surgery, and antibiotics noted on the chart, for example. Additional features include prewarming preoperatively and maintaining normothermia, requiring all surgeons scrub traditionally instead of “foaming,” use of wound protectors in the OR, and close monitoring of blood glucose in diabetics postoperatively. “There also is education of floor nurses on how to take care of these patients specifically,” Dr. Wolff noted.
To identify these areas for improvement, Dr. Wolff and his colleagues initially reviewed the literature to find individual and bundle elements demonstrated to improve outcomes. Then, a surgeon group “think tank” discussed the possibilities. However, reaching agreement was not easy, Dr. Wolff said. “They had a hard time agreeing on best practices, even within our own specialty. We did finally come to a consensus.
“We took those bundled protocols through to other areas and said ‘here are the things we want you to work on, things we want you to improve.’ That did not necessarily go over so well,” Dr. Wolff said. Because of resistance from their colleagues, they changed strategies. “We brought other people to the table and changed our work groups from being surgeons only to [being] a multidisciplinary team.”
The process took months and months of deliberation. It’s important to have a champion behind the project, said Dr. Wolff. “I have to thank my chairman, Mark C. Horattas, MD, FACS, who had the vision to see this through.
“We implemented tried-and-true measures to reduce surgical site infections. We did so in a team manner and had multidisciplinary buy-in, and that created a culture change in our program over time,” Dr. Wolff said.
This study also shows, Dr. Wolff added, that “a successful multidisciplinary quality improvement program can be implemented in a community hospital setting.”
Going forward, continuous monitoring will identify any areas that need improvement over time. The preoperative bundle also will be integrated into an Enhanced Recovery After Surgery protocol.
The Akron Hospital is now ranked by ACS NSQIP in the top 10% of hospitals for their colorectal SSI rate. “It’s nice to meet someone in the first decile,” session moderator Timothy D. Jackson, MD, FACS, of the University of Toronto said after Dr. Wolff’s presentation. “I’ve never done that before, and I took notes for what to do at my hospital.”
Dr. Wolff had no relevant financial disclosures.
AT THE ACS QUALITY AND SAFETY CONFERENCE
Key clinical point: A multidisciplinary team initiative successfully reduced surgical site infections after colorectal surgery in a community hospital.
Major finding: The number of annual SSIs dropped from 16 in the calendar year before the intervention to 5 afterward.
Data source: Comparison of SSI rates before and after a bundled intervention in late 2014.
Disclosures: Dr. Wolff had no relevant financial disclosures.