Doug Brunk

SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.

A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Doug Brunk/Frontline Medical News

In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm³ and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.

The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m². Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m² vs. 32 kg/m²), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).

Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm³, and 4 had an ANC below 500 cells/mm³. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm³. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.

“Once the ANC falls below 2,500 cells/mm³, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”

The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.

A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Doug Brunk/Frontline Medical News

In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm³ and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.

The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m². Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m² vs. 32 kg/m²), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).

Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm³, and 4 had an ANC below 500 cells/mm³. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm³. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.

“Once the ANC falls below 2,500 cells/mm³, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”

The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.

A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Doug Brunk/Frontline Medical News

In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm³ and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.

The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m². Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m² vs. 32 kg/m²), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).

Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm³, and 4 had an ANC below 500 cells/mm³. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm³. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.

“Once the ANC falls below 2,500 cells/mm³, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”

The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.

“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”

Doug Brunk/Frontline Medical News

In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.

The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.

A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).

Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).

“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”

While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.

The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.

“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”

Doug Brunk/Frontline Medical News

In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.

The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.

A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).

Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).

“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”

While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.

The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.

“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”

Doug Brunk/Frontline Medical News

In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.

The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.

A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).

Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).

“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”

While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.

The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – According to Dr. Joseph P. McEvoy, early recognition and treatment of first-episode psychosis affords the best opportunity for a positive outcome.

“In the United States, we do a very poor job detecting psychosis early,” Dr. McEvoy, professor and I. Clark Case Chair in Psychotic Disorders at the Medical College of Georgia, Augusta, said at the annual U.S. Psychiatric and Mental Health Congress.

“The sooner you identify them and get them into treatment the better they do in the long run. Treatment of these folks cannot be done by the smartest, best, most decent, overworked person doing 15-minute medication checks. It just can’t happen. You need a team,” he said.

Current estimates suggest that only 20%-40% of people who meet clinical high-risk criteria for a first episode of psychosis (FEP) convert to psychosis within 2-4 years. A challenge for clinicians, he continued, is that the criteria for identifying individuals at risk for FEP have a low predictive value, which raises concern about unnecessary and potentially harmful interventions. “Any interventions we would want to try now for somebody we’re worried about should have a very low burden of toxicity: antipsychotic medications at very low doses, cognitive-behavioral therapy to reduce or delay the onset of psychosis, and the use of long-chain polyunsaturated fatty acids,” he said.

In a study led by Dr. McEvoy, researchers used a lipidomics platform to measure individual lipid species in 20 drug-naive patients with a first episode of schizophrenia, 20 patients with chronic schizophrenia who had not adhered to prescribed medications, and 29 controls without schizophrenia (PloS One. 2013;8[7]:e68717). They found that, compared with controls, patients with a first episode of schizophrenia demonstrated significant downregulation of several n3 polyunsaturated fatty acids, including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes.

In a separate trial, 81 individuals at high risk of psychotic disorder received 1.2 g/day omega-3 fatty acid or placebo for 12 weeks, followed by a 40-week monitoring period (Arch Gen Psych. 2010;67[2]:146-54). At the end of the 1-year study, 5% of 2 of 41 individuals (5%), in the omega-3 group and 11 of 40 (28%) in the placebo group had transitioned to psychotic disorder (P = .007). “There are several groups around the world that are trying to replicate this,” Dr. McEvoy said. “But can you imagine if we can draw a blood test, identify an 11-year-old with a 70%-plus likelihood of getting a psychotic disorder later, and affect them favorably, protect them with something as simple as long chain fatty acids? I hope so.”

Study after study shows that the shorter the duration of untreated psychosis, the greater the response to antipsychotic treatment. “At the time of treatment initiation, shorter duration of untreated psychosis is associated with reduced severity of negative symptoms such as a motivation and impaired communication,” said Dr. McEvoy, who is also director of public psychiatry at East Central Regional Hospital in Augusta. “Negative symptoms may be the way that the duration of untreated psychosis trumps future function. If you’ve got big negative symptoms, who’s going to hire you? Who’s going to date you? It’s a powerful prognostic factor, and there are probably ways you can modify it.”

Intervening sometime during the first 3 months of untreated psychosis is ideal, he said, “but once you get out past a year, you are in serious trouble. After that time, the likelihood of the person working, having a social life, going back to being a ‘regular person’ is really going down.”

In Scandinavia, researchers used a combination of easy-access detection teams and a massive information campaign about the signs and symptoms of psychosis. It reduced the duration of untreated psychosis in first-episode schizophrenia from 16 to 5 weeks (Schizophr Bull. 2008;34[3]:466-72). Youth at risk for psychosis prioritize getting a job, education that will lead to a job, independent living, and a social life. Or, as Dr. McEvoy put it, “the three C’s: a cell phone, a car, and a condo.” In fact, a combined employment and education program for people with a first episode of psychosis led to higher rates of employment and class completion, compared with usual services (Psychiatr Rehabil J. 2012;35[6]:421-7).

In Dr. McEvoy’s opinion, family members are “grossly underused” in attempts to help FEP patients. “We have more than 30 years of evidence that family intervention clearly reduces relapse rates and enhances medication compliance,” he said. “The burden of care may be reduced by psychosocial interventions, but the specific effects of interventions for caregivers themselves are not usually reported or are seen as secondary outcomes. Caregiver-focused interventions appear to improve the experience of caring and the quality of life of those caring for people with severe mental illness, and these benefits may be gained in first-episode psychosis.”

Current evidence indicates that low-dose antipsychotic treatment during the FEP is associated with symptomatic and functional improvement. “We have a variety of drugs that have one common feature: They sit on dopamine receptors in the limbic system and they protect them from storm,” Dr. McEvoy said. “If we give [patients] too much of these drugs, they get side effects they don’t need. First-episode psychosis patients are discriminating consumers. If you give them drugs that jack up their prolactin or make them sleep 18 hours a day, they’re unhappy.” He favors a “succeed first” strategy with very lose dose first-generation antipsychotics such as haloperidol, perphenazine, or loxapine. “Selection of antipsychotic medications that do not produce extrapyramidal side effects, weight gain/metabolic side effects, sedation, or sexual dysfunction at reasonable doses is now possible,” he said.

According to results from up to 10 years of follow-up in patients who experienced FEP, 60%-70% will achieve remission (defined as key positive and negative features rated mild or less) at some point, but the numbers for sustained remission are substantially lower. In addition, 10%-20% of patients will achieve recovery (defined as good social and occupational functioning in the community) at some point, but the numbers for sustained recovery are lower. Relapse rates are high, even with continued treatment. For example, among patients enrolled in an FEP program in Spain, 21% relapsed by the end of year 1, 41% by the end of year 2, and 65% by the end of year 3 (J Psychiatr Res. 2012;46[8]:1099-1105). And in an FEP program in New York, 5 years after initial recovery, the cumulative first relapse rate was 82%. Discontinuing antipsychotic drug therapy increased the risk of relapse by almost fivefold (Arch Gen Psychiatry 1999;56[3]:241-7).

A novel study led by Jean Addington, Ph.D., of the University of Calgary (Alta.), underscores the importance of early treatment of FEP patients. The researchers enrolled 404 individuals with FEP who presented for treatment at 34 nonacademic medical centers in 21 states (Psychiatr Serv. 2015;66[7]:753-6). The mean duration of untreated psychosis was 74 weeks. “This is like someone coming to you a year-and-a-half after developing untreated hypertension, with changes in the vascular system, the kidneys, and the heart,” said Dr. McEvoy, who was not involved with the study. “You can’t reverse some of these changes.”

Correlates of longer duration of untreated psychosis included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings.

Dr. McEvoy disclosed that he has received research grants from Alkermes, Avanir Pharmaceuticals, Ameritox, Auspex Pharmaceuticals, and Otsuka Pharmaceutical. He also is a member of the advisory boards for FORUM Pharmaceuticals, Otsuka, and Lundbeck.

[email protected]

SAN DIEGO – According to Dr. Joseph P. McEvoy, early recognition and treatment of first-episode psychosis affords the best opportunity for a positive outcome.

“In the United States, we do a very poor job detecting psychosis early,” Dr. McEvoy, professor and I. Clark Case Chair in Psychotic Disorders at the Medical College of Georgia, Augusta, said at the annual U.S. Psychiatric and Mental Health Congress.

“The sooner you identify them and get them into treatment the better they do in the long run. Treatment of these folks cannot be done by the smartest, best, most decent, overworked person doing 15-minute medication checks. It just can’t happen. You need a team,” he said.

Current estimates suggest that only 20%-40% of people who meet clinical high-risk criteria for a first episode of psychosis (FEP) convert to psychosis within 2-4 years. A challenge for clinicians, he continued, is that the criteria for identifying individuals at risk for FEP have a low predictive value, which raises concern about unnecessary and potentially harmful interventions. “Any interventions we would want to try now for somebody we’re worried about should have a very low burden of toxicity: antipsychotic medications at very low doses, cognitive-behavioral therapy to reduce or delay the onset of psychosis, and the use of long-chain polyunsaturated fatty acids,” he said.

In a study led by Dr. McEvoy, researchers used a lipidomics platform to measure individual lipid species in 20 drug-naive patients with a first episode of schizophrenia, 20 patients with chronic schizophrenia who had not adhered to prescribed medications, and 29 controls without schizophrenia (PloS One. 2013;8[7]:e68717). They found that, compared with controls, patients with a first episode of schizophrenia demonstrated significant downregulation of several n3 polyunsaturated fatty acids, including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes.

In a separate trial, 81 individuals at high risk of psychotic disorder received 1.2 g/day omega-3 fatty acid or placebo for 12 weeks, followed by a 40-week monitoring period (Arch Gen Psych. 2010;67[2]:146-54). At the end of the 1-year study, 5% of 2 of 41 individuals (5%), in the omega-3 group and 11 of 40 (28%) in the placebo group had transitioned to psychotic disorder (P = .007). “There are several groups around the world that are trying to replicate this,” Dr. McEvoy said. “But can you imagine if we can draw a blood test, identify an 11-year-old with a 70%-plus likelihood of getting a psychotic disorder later, and affect them favorably, protect them with something as simple as long chain fatty acids? I hope so.”

Study after study shows that the shorter the duration of untreated psychosis, the greater the response to antipsychotic treatment. “At the time of treatment initiation, shorter duration of untreated psychosis is associated with reduced severity of negative symptoms such as a motivation and impaired communication,” said Dr. McEvoy, who is also director of public psychiatry at East Central Regional Hospital in Augusta. “Negative symptoms may be the way that the duration of untreated psychosis trumps future function. If you’ve got big negative symptoms, who’s going to hire you? Who’s going to date you? It’s a powerful prognostic factor, and there are probably ways you can modify it.”

Intervening sometime during the first 3 months of untreated psychosis is ideal, he said, “but once you get out past a year, you are in serious trouble. After that time, the likelihood of the person working, having a social life, going back to being a ‘regular person’ is really going down.”

In Scandinavia, researchers used a combination of easy-access detection teams and a massive information campaign about the signs and symptoms of psychosis. It reduced the duration of untreated psychosis in first-episode schizophrenia from 16 to 5 weeks (Schizophr Bull. 2008;34[3]:466-72). Youth at risk for psychosis prioritize getting a job, education that will lead to a job, independent living, and a social life. Or, as Dr. McEvoy put it, “the three C’s: a cell phone, a car, and a condo.” In fact, a combined employment and education program for people with a first episode of psychosis led to higher rates of employment and class completion, compared with usual services (Psychiatr Rehabil J. 2012;35[6]:421-7).

In Dr. McEvoy’s opinion, family members are “grossly underused” in attempts to help FEP patients. “We have more than 30 years of evidence that family intervention clearly reduces relapse rates and enhances medication compliance,” he said. “The burden of care may be reduced by psychosocial interventions, but the specific effects of interventions for caregivers themselves are not usually reported or are seen as secondary outcomes. Caregiver-focused interventions appear to improve the experience of caring and the quality of life of those caring for people with severe mental illness, and these benefits may be gained in first-episode psychosis.”

Current evidence indicates that low-dose antipsychotic treatment during the FEP is associated with symptomatic and functional improvement. “We have a variety of drugs that have one common feature: They sit on dopamine receptors in the limbic system and they protect them from storm,” Dr. McEvoy said. “If we give [patients] too much of these drugs, they get side effects they don’t need. First-episode psychosis patients are discriminating consumers. If you give them drugs that jack up their prolactin or make them sleep 18 hours a day, they’re unhappy.” He favors a “succeed first” strategy with very lose dose first-generation antipsychotics such as haloperidol, perphenazine, or loxapine. “Selection of antipsychotic medications that do not produce extrapyramidal side effects, weight gain/metabolic side effects, sedation, or sexual dysfunction at reasonable doses is now possible,” he said.

According to results from up to 10 years of follow-up in patients who experienced FEP, 60%-70% will achieve remission (defined as key positive and negative features rated mild or less) at some point, but the numbers for sustained remission are substantially lower. In addition, 10%-20% of patients will achieve recovery (defined as good social and occupational functioning in the community) at some point, but the numbers for sustained recovery are lower. Relapse rates are high, even with continued treatment. For example, among patients enrolled in an FEP program in Spain, 21% relapsed by the end of year 1, 41% by the end of year 2, and 65% by the end of year 3 (J Psychiatr Res. 2012;46[8]:1099-1105). And in an FEP program in New York, 5 years after initial recovery, the cumulative first relapse rate was 82%. Discontinuing antipsychotic drug therapy increased the risk of relapse by almost fivefold (Arch Gen Psychiatry 1999;56[3]:241-7).

A novel study led by Jean Addington, Ph.D., of the University of Calgary (Alta.), underscores the importance of early treatment of FEP patients. The researchers enrolled 404 individuals with FEP who presented for treatment at 34 nonacademic medical centers in 21 states (Psychiatr Serv. 2015;66[7]:753-6). The mean duration of untreated psychosis was 74 weeks. “This is like someone coming to you a year-and-a-half after developing untreated hypertension, with changes in the vascular system, the kidneys, and the heart,” said Dr. McEvoy, who was not involved with the study. “You can’t reverse some of these changes.”

Correlates of longer duration of untreated psychosis included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings.

Dr. McEvoy disclosed that he has received research grants from Alkermes, Avanir Pharmaceuticals, Ameritox, Auspex Pharmaceuticals, and Otsuka Pharmaceutical. He also is a member of the advisory boards for FORUM Pharmaceuticals, Otsuka, and Lundbeck.

[email protected]

SAN DIEGO – According to Dr. Joseph P. McEvoy, early recognition and treatment of first-episode psychosis affords the best opportunity for a positive outcome.

“In the United States, we do a very poor job detecting psychosis early,” Dr. McEvoy, professor and I. Clark Case Chair in Psychotic Disorders at the Medical College of Georgia, Augusta, said at the annual U.S. Psychiatric and Mental Health Congress.

“The sooner you identify them and get them into treatment the better they do in the long run. Treatment of these folks cannot be done by the smartest, best, most decent, overworked person doing 15-minute medication checks. It just can’t happen. You need a team,” he said.

Current estimates suggest that only 20%-40% of people who meet clinical high-risk criteria for a first episode of psychosis (FEP) convert to psychosis within 2-4 years. A challenge for clinicians, he continued, is that the criteria for identifying individuals at risk for FEP have a low predictive value, which raises concern about unnecessary and potentially harmful interventions. “Any interventions we would want to try now for somebody we’re worried about should have a very low burden of toxicity: antipsychotic medications at very low doses, cognitive-behavioral therapy to reduce or delay the onset of psychosis, and the use of long-chain polyunsaturated fatty acids,” he said.

In a study led by Dr. McEvoy, researchers used a lipidomics platform to measure individual lipid species in 20 drug-naive patients with a first episode of schizophrenia, 20 patients with chronic schizophrenia who had not adhered to prescribed medications, and 29 controls without schizophrenia (PloS One. 2013;8[7]:e68717). They found that, compared with controls, patients with a first episode of schizophrenia demonstrated significant downregulation of several n3 polyunsaturated fatty acids, including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes.

In a separate trial, 81 individuals at high risk of psychotic disorder received 1.2 g/day omega-3 fatty acid or placebo for 12 weeks, followed by a 40-week monitoring period (Arch Gen Psych. 2010;67[2]:146-54). At the end of the 1-year study, 5% of 2 of 41 individuals (5%), in the omega-3 group and 11 of 40 (28%) in the placebo group had transitioned to psychotic disorder (P = .007). “There are several groups around the world that are trying to replicate this,” Dr. McEvoy said. “But can you imagine if we can draw a blood test, identify an 11-year-old with a 70%-plus likelihood of getting a psychotic disorder later, and affect them favorably, protect them with something as simple as long chain fatty acids? I hope so.”

Study after study shows that the shorter the duration of untreated psychosis, the greater the response to antipsychotic treatment. “At the time of treatment initiation, shorter duration of untreated psychosis is associated with reduced severity of negative symptoms such as a motivation and impaired communication,” said Dr. McEvoy, who is also director of public psychiatry at East Central Regional Hospital in Augusta. “Negative symptoms may be the way that the duration of untreated psychosis trumps future function. If you’ve got big negative symptoms, who’s going to hire you? Who’s going to date you? It’s a powerful prognostic factor, and there are probably ways you can modify it.”

Intervening sometime during the first 3 months of untreated psychosis is ideal, he said, “but once you get out past a year, you are in serious trouble. After that time, the likelihood of the person working, having a social life, going back to being a ‘regular person’ is really going down.”

In Scandinavia, researchers used a combination of easy-access detection teams and a massive information campaign about the signs and symptoms of psychosis. It reduced the duration of untreated psychosis in first-episode schizophrenia from 16 to 5 weeks (Schizophr Bull. 2008;34[3]:466-72). Youth at risk for psychosis prioritize getting a job, education that will lead to a job, independent living, and a social life. Or, as Dr. McEvoy put it, “the three C’s: a cell phone, a car, and a condo.” In fact, a combined employment and education program for people with a first episode of psychosis led to higher rates of employment and class completion, compared with usual services (Psychiatr Rehabil J. 2012;35[6]:421-7).

In Dr. McEvoy’s opinion, family members are “grossly underused” in attempts to help FEP patients. “We have more than 30 years of evidence that family intervention clearly reduces relapse rates and enhances medication compliance,” he said. “The burden of care may be reduced by psychosocial interventions, but the specific effects of interventions for caregivers themselves are not usually reported or are seen as secondary outcomes. Caregiver-focused interventions appear to improve the experience of caring and the quality of life of those caring for people with severe mental illness, and these benefits may be gained in first-episode psychosis.”

Current evidence indicates that low-dose antipsychotic treatment during the FEP is associated with symptomatic and functional improvement. “We have a variety of drugs that have one common feature: They sit on dopamine receptors in the limbic system and they protect them from storm,” Dr. McEvoy said. “If we give [patients] too much of these drugs, they get side effects they don’t need. First-episode psychosis patients are discriminating consumers. If you give them drugs that jack up their prolactin or make them sleep 18 hours a day, they’re unhappy.” He favors a “succeed first” strategy with very lose dose first-generation antipsychotics such as haloperidol, perphenazine, or loxapine. “Selection of antipsychotic medications that do not produce extrapyramidal side effects, weight gain/metabolic side effects, sedation, or sexual dysfunction at reasonable doses is now possible,” he said.

According to results from up to 10 years of follow-up in patients who experienced FEP, 60%-70% will achieve remission (defined as key positive and negative features rated mild or less) at some point, but the numbers for sustained remission are substantially lower. In addition, 10%-20% of patients will achieve recovery (defined as good social and occupational functioning in the community) at some point, but the numbers for sustained recovery are lower. Relapse rates are high, even with continued treatment. For example, among patients enrolled in an FEP program in Spain, 21% relapsed by the end of year 1, 41% by the end of year 2, and 65% by the end of year 3 (J Psychiatr Res. 2012;46[8]:1099-1105). And in an FEP program in New York, 5 years after initial recovery, the cumulative first relapse rate was 82%. Discontinuing antipsychotic drug therapy increased the risk of relapse by almost fivefold (Arch Gen Psychiatry 1999;56[3]:241-7).

A novel study led by Jean Addington, Ph.D., of the University of Calgary (Alta.), underscores the importance of early treatment of FEP patients. The researchers enrolled 404 individuals with FEP who presented for treatment at 34 nonacademic medical centers in 21 states (Psychiatr Serv. 2015;66[7]:753-6). The mean duration of untreated psychosis was 74 weeks. “This is like someone coming to you a year-and-a-half after developing untreated hypertension, with changes in the vascular system, the kidneys, and the heart,” said Dr. McEvoy, who was not involved with the study. “You can’t reverse some of these changes.”

Correlates of longer duration of untreated psychosis included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings.

Dr. McEvoy disclosed that he has received research grants from Alkermes, Avanir Pharmaceuticals, Ameritox, Auspex Pharmaceuticals, and Otsuka Pharmaceutical. He also is a member of the advisory boards for FORUM Pharmaceuticals, Otsuka, and Lundbeck.

[email protected]

SAN DIEGO – The incidence of septicemia due to antibiotic-resistant bacteria (referred to as the ESKAPE pathogens) increased in United States hospitals between 2008 and 2012, yet length of stay and in-hospital mortality both decreased over the same time period.

“We don’t know what’s going on here,” lead study author Dana R. Bowers, Pharm.D., said in an interview at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “No new drugs [for septicemia] came out during that time frame. Maybe we’re getting better at identifying these patients and treating them earlier; maybe that’s impacting mortality.”

Doug Brunk/Frontline Medical News

According to the Infectious Diseases Society of America, ESKAPE pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. “Septicemia caused by these pathogens is particularly concerning because of their propensity for antimicrobial resistance, limited treatment options, and elevated risk of death,” the researchers wrote in their abstract. “However, the burden of ESKAPE septicemia in the United States is relatively unknown.”

In an effort to provide national estimates for ESKAPE septicemia incidence over 5 years and to identify trends related to in-hospital mortality and hospital length of stay, Dr. Bowers, a clinical specialist in infectious diseases at Kingman (Ariz.) Regional Medical Center and her associates retrospectively evaluated the Nationwide Inpatient Sample between 2008 and 2012.

They used clinical classification software to identify patients with septicemia who were at least 18 years of age, and followed the International Classification of Diseases, Ninth Revision, Clinical Modification to identify codes for E. faecium [EF], Staphylococcus aureus [MRSA], Klebsiella pneumonia [KP], Acinetobacter baumannii [AB], Pseudomonas aeruginosa [PA] and Enterobacter spp. [EB].

In all, 7,668,636 patients acquired septicemia during the study period. Of these, 951,677 acquired septicemia due to ESKAPE pathogens. Patients in this cohort had a median age of 67 years, 47% were women, and 66% were white.

The researchers observed that the incidence for septicemia caused by ESKAPE pathogens increased over the time period, especially for MRSA (from 3.8 per 10,000 hospital discharges in 2008 to 14.6 per 10,000 discharges in 2012) and EF (from 6.2 per 10,000 discharges in 2008 to 10.4 per 10,000 discharges in 2012). They also observed a slight decline in median LOS for patients with MRSA (from 11 days in 2008 to 10 days in 2012), PA (from 10 days in 2008 to 9 days in 2012), as well as among those with KP/AB/EB (from 9 days in 2008 to 7 days in 2012).

In-hospital mortality declined over the study period among all pathogen groups and was greatest for those with KP/AB/EB septicemia (from 16.3% in 2008 to 12.1% in 2012).

The researchers concluded that additional research is needed to assess the clinical impact of these findings at the population level. They reported having no financial disclosures.

[email protected]

SAN DIEGO – The incidence of septicemia due to antibiotic-resistant bacteria (referred to as the ESKAPE pathogens) increased in United States hospitals between 2008 and 2012, yet length of stay and in-hospital mortality both decreased over the same time period.

“We don’t know what’s going on here,” lead study author Dana R. Bowers, Pharm.D., said in an interview at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “No new drugs [for septicemia] came out during that time frame. Maybe we’re getting better at identifying these patients and treating them earlier; maybe that’s impacting mortality.”

Doug Brunk/Frontline Medical News

According to the Infectious Diseases Society of America, ESKAPE pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. “Septicemia caused by these pathogens is particularly concerning because of their propensity for antimicrobial resistance, limited treatment options, and elevated risk of death,” the researchers wrote in their abstract. “However, the burden of ESKAPE septicemia in the United States is relatively unknown.”

In an effort to provide national estimates for ESKAPE septicemia incidence over 5 years and to identify trends related to in-hospital mortality and hospital length of stay, Dr. Bowers, a clinical specialist in infectious diseases at Kingman (Ariz.) Regional Medical Center and her associates retrospectively evaluated the Nationwide Inpatient Sample between 2008 and 2012.

They used clinical classification software to identify patients with septicemia who were at least 18 years of age, and followed the International Classification of Diseases, Ninth Revision, Clinical Modification to identify codes for E. faecium [EF], Staphylococcus aureus [MRSA], Klebsiella pneumonia [KP], Acinetobacter baumannii [AB], Pseudomonas aeruginosa [PA] and Enterobacter spp. [EB].

In all, 7,668,636 patients acquired septicemia during the study period. Of these, 951,677 acquired septicemia due to ESKAPE pathogens. Patients in this cohort had a median age of 67 years, 47% were women, and 66% were white.

The researchers observed that the incidence for septicemia caused by ESKAPE pathogens increased over the time period, especially for MRSA (from 3.8 per 10,000 hospital discharges in 2008 to 14.6 per 10,000 discharges in 2012) and EF (from 6.2 per 10,000 discharges in 2008 to 10.4 per 10,000 discharges in 2012). They also observed a slight decline in median LOS for patients with MRSA (from 11 days in 2008 to 10 days in 2012), PA (from 10 days in 2008 to 9 days in 2012), as well as among those with KP/AB/EB (from 9 days in 2008 to 7 days in 2012).

In-hospital mortality declined over the study period among all pathogen groups and was greatest for those with KP/AB/EB septicemia (from 16.3% in 2008 to 12.1% in 2012).

The researchers concluded that additional research is needed to assess the clinical impact of these findings at the population level. They reported having no financial disclosures.

[email protected]

SAN DIEGO – The incidence of septicemia due to antibiotic-resistant bacteria (referred to as the ESKAPE pathogens) increased in United States hospitals between 2008 and 2012, yet length of stay and in-hospital mortality both decreased over the same time period.

“We don’t know what’s going on here,” lead study author Dana R. Bowers, Pharm.D., said in an interview at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “No new drugs [for septicemia] came out during that time frame. Maybe we’re getting better at identifying these patients and treating them earlier; maybe that’s impacting mortality.”

Doug Brunk/Frontline Medical News

According to the Infectious Diseases Society of America, ESKAPE pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. “Septicemia caused by these pathogens is particularly concerning because of their propensity for antimicrobial resistance, limited treatment options, and elevated risk of death,” the researchers wrote in their abstract. “However, the burden of ESKAPE septicemia in the United States is relatively unknown.”

In an effort to provide national estimates for ESKAPE septicemia incidence over 5 years and to identify trends related to in-hospital mortality and hospital length of stay, Dr. Bowers, a clinical specialist in infectious diseases at Kingman (Ariz.) Regional Medical Center and her associates retrospectively evaluated the Nationwide Inpatient Sample between 2008 and 2012.

They used clinical classification software to identify patients with septicemia who were at least 18 years of age, and followed the International Classification of Diseases, Ninth Revision, Clinical Modification to identify codes for E. faecium [EF], Staphylococcus aureus [MRSA], Klebsiella pneumonia [KP], Acinetobacter baumannii [AB], Pseudomonas aeruginosa [PA] and Enterobacter spp. [EB].

In all, 7,668,636 patients acquired septicemia during the study period. Of these, 951,677 acquired septicemia due to ESKAPE pathogens. Patients in this cohort had a median age of 67 years, 47% were women, and 66% were white.

The researchers observed that the incidence for septicemia caused by ESKAPE pathogens increased over the time period, especially for MRSA (from 3.8 per 10,000 hospital discharges in 2008 to 14.6 per 10,000 discharges in 2012) and EF (from 6.2 per 10,000 discharges in 2008 to 10.4 per 10,000 discharges in 2012). They also observed a slight decline in median LOS for patients with MRSA (from 11 days in 2008 to 10 days in 2012), PA (from 10 days in 2008 to 9 days in 2012), as well as among those with KP/AB/EB (from 9 days in 2008 to 7 days in 2012).

In-hospital mortality declined over the study period among all pathogen groups and was greatest for those with KP/AB/EB septicemia (from 16.3% in 2008 to 12.1% in 2012).

The researchers concluded that additional research is needed to assess the clinical impact of these findings at the population level. They reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with vancomycin-resistant Enterococcus bloodstream infections, delay of treatment with linezolid or daptomycin for three days or more increased the morality risk by 39%, a nationwide retrospective cohort study demonstrated.

In addition, propensity score matching revealed that treatment with linezolid was associated with an increased mortality, compared with daptomycin.

“Based on these findings, we believe daptomycin should be the treatment of choice for patients with vancomycin-resistant Enterococcus (VRE) bacteremia and that early initiation is associated with improved survival,” lead study author Nicholas S. Britt, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Prior to the current study, linezolid and daptomycin were considered equivalent in terms of clinical outcomes for vancomycin-resistant Enterococcal (VRE) bacteremia, said Dr. Britt, of Barnes-Jewish Hospital/Washington University Medical Center, St. Louis, Mo. “However, the studies that had compared these agents were small and may not have had enough patients enrolled to find an outcomes difference between the two agents if one existed.”

In an effort to evaluate the effect of time to treatment with linezolid or daptomycin on 30-day mortality and to compare clinical outcomes between linezolid and daptomycin while accounting for time to treatment and potential treatment selection bias, the researchers conducted a nationwide retrospective cohort study of hospitalized Veterans Affairs patients treated with linezolid or daptomycin for VRE BSI between 2004 and 2014. They included all adult patients with at least one blood culture positive for VRE who were treated with at least one dose of linezolid or daptomycin. Classification and regression tree (CART) analysis was performed to identify the most significant time to treatment breakpoint for the primary outcome, which was 30-day mortality. To account for treatment selection bias, propensity scores were derived and 1:1 matching was performed.

A total of 851 patients were evaluated: 426 in the linezolid group and 425 in the daptomycin group. CART analysis demonstrated a significant time to treatment breakpoint for 30-day mortality of 80 hours or more (RR 1.39; P less than .001). After propensity score matching, treatment with linezolid was significantly associated with 30-day mortality (RR 1.16; P =.018). This association persisted in propensity score adjusted binomial regression (adjusted RR, 1.25; P =.014) and Cox regression (hazard ratio 1.73; P less than .001). There was no difference between the two agents in terms of adverse effects.

“In this evaluation, we found that every hour delay in initiation of anti-VRE therapy was associated with an increased risk of death,” Dr. Britt said. “Delays in therapy of greater than 3 days were associated with the greatest risk of mortality, but overall, the sooner anti-VRE therapy was initiated, the better the patients did.” He went on to note that some debate exists among clinicians “as far as the virulence of VRE and the true impact of VRE bacteremia on patient outcomes. We were surprised that the time to treatment effect was so pronounced and that this effect persisted independent of other patient factors.”

Dr. Britt acknowledged certain limitations of the study, including the potential for bias due to its retrospective design. “However, attempts at clinical trials comparing these two agents have failed in the past due to poor enrollment,” he said. “Other potential limitations are with regard to generalizability to non-VA patient populations. This study featured a relatively low number of stem cell and solid organ transplant recipients and further research in these populations are warranted.”

The study was funded in part by the National Institutes of Health and the Department of Veterans Affairs. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with vancomycin-resistant Enterococcus bloodstream infections, delay of treatment with linezolid or daptomycin for three days or more increased the morality risk by 39%, a nationwide retrospective cohort study demonstrated.

In addition, propensity score matching revealed that treatment with linezolid was associated with an increased mortality, compared with daptomycin.

“Based on these findings, we believe daptomycin should be the treatment of choice for patients with vancomycin-resistant Enterococcus (VRE) bacteremia and that early initiation is associated with improved survival,” lead study author Nicholas S. Britt, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Prior to the current study, linezolid and daptomycin were considered equivalent in terms of clinical outcomes for vancomycin-resistant Enterococcal (VRE) bacteremia, said Dr. Britt, of Barnes-Jewish Hospital/Washington University Medical Center, St. Louis, Mo. “However, the studies that had compared these agents were small and may not have had enough patients enrolled to find an outcomes difference between the two agents if one existed.”

In an effort to evaluate the effect of time to treatment with linezolid or daptomycin on 30-day mortality and to compare clinical outcomes between linezolid and daptomycin while accounting for time to treatment and potential treatment selection bias, the researchers conducted a nationwide retrospective cohort study of hospitalized Veterans Affairs patients treated with linezolid or daptomycin for VRE BSI between 2004 and 2014. They included all adult patients with at least one blood culture positive for VRE who were treated with at least one dose of linezolid or daptomycin. Classification and regression tree (CART) analysis was performed to identify the most significant time to treatment breakpoint for the primary outcome, which was 30-day mortality. To account for treatment selection bias, propensity scores were derived and 1:1 matching was performed.

A total of 851 patients were evaluated: 426 in the linezolid group and 425 in the daptomycin group. CART analysis demonstrated a significant time to treatment breakpoint for 30-day mortality of 80 hours or more (RR 1.39; P less than .001). After propensity score matching, treatment with linezolid was significantly associated with 30-day mortality (RR 1.16; P =.018). This association persisted in propensity score adjusted binomial regression (adjusted RR, 1.25; P =.014) and Cox regression (hazard ratio 1.73; P less than .001). There was no difference between the two agents in terms of adverse effects.

“In this evaluation, we found that every hour delay in initiation of anti-VRE therapy was associated with an increased risk of death,” Dr. Britt said. “Delays in therapy of greater than 3 days were associated with the greatest risk of mortality, but overall, the sooner anti-VRE therapy was initiated, the better the patients did.” He went on to note that some debate exists among clinicians “as far as the virulence of VRE and the true impact of VRE bacteremia on patient outcomes. We were surprised that the time to treatment effect was so pronounced and that this effect persisted independent of other patient factors.”

Dr. Britt acknowledged certain limitations of the study, including the potential for bias due to its retrospective design. “However, attempts at clinical trials comparing these two agents have failed in the past due to poor enrollment,” he said. “Other potential limitations are with regard to generalizability to non-VA patient populations. This study featured a relatively low number of stem cell and solid organ transplant recipients and further research in these populations are warranted.”

The study was funded in part by the National Institutes of Health and the Department of Veterans Affairs. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with vancomycin-resistant Enterococcus bloodstream infections, delay of treatment with linezolid or daptomycin for three days or more increased the morality risk by 39%, a nationwide retrospective cohort study demonstrated.

In addition, propensity score matching revealed that treatment with linezolid was associated with an increased mortality, compared with daptomycin.

“Based on these findings, we believe daptomycin should be the treatment of choice for patients with vancomycin-resistant Enterococcus (VRE) bacteremia and that early initiation is associated with improved survival,” lead study author Nicholas S. Britt, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Prior to the current study, linezolid and daptomycin were considered equivalent in terms of clinical outcomes for vancomycin-resistant Enterococcal (VRE) bacteremia, said Dr. Britt, of Barnes-Jewish Hospital/Washington University Medical Center, St. Louis, Mo. “However, the studies that had compared these agents were small and may not have had enough patients enrolled to find an outcomes difference between the two agents if one existed.”

In an effort to evaluate the effect of time to treatment with linezolid or daptomycin on 30-day mortality and to compare clinical outcomes between linezolid and daptomycin while accounting for time to treatment and potential treatment selection bias, the researchers conducted a nationwide retrospective cohort study of hospitalized Veterans Affairs patients treated with linezolid or daptomycin for VRE BSI between 2004 and 2014. They included all adult patients with at least one blood culture positive for VRE who were treated with at least one dose of linezolid or daptomycin. Classification and regression tree (CART) analysis was performed to identify the most significant time to treatment breakpoint for the primary outcome, which was 30-day mortality. To account for treatment selection bias, propensity scores were derived and 1:1 matching was performed.

A total of 851 patients were evaluated: 426 in the linezolid group and 425 in the daptomycin group. CART analysis demonstrated a significant time to treatment breakpoint for 30-day mortality of 80 hours or more (RR 1.39; P less than .001). After propensity score matching, treatment with linezolid was significantly associated with 30-day mortality (RR 1.16; P =.018). This association persisted in propensity score adjusted binomial regression (adjusted RR, 1.25; P =.014) and Cox regression (hazard ratio 1.73; P less than .001). There was no difference between the two agents in terms of adverse effects.

“In this evaluation, we found that every hour delay in initiation of anti-VRE therapy was associated with an increased risk of death,” Dr. Britt said. “Delays in therapy of greater than 3 days were associated with the greatest risk of mortality, but overall, the sooner anti-VRE therapy was initiated, the better the patients did.” He went on to note that some debate exists among clinicians “as far as the virulence of VRE and the true impact of VRE bacteremia on patient outcomes. We were surprised that the time to treatment effect was so pronounced and that this effect persisted independent of other patient factors.”

Dr. Britt acknowledged certain limitations of the study, including the potential for bias due to its retrospective design. “However, attempts at clinical trials comparing these two agents have failed in the past due to poor enrollment,” he said. “Other potential limitations are with regard to generalizability to non-VA patient populations. This study featured a relatively low number of stem cell and solid organ transplant recipients and further research in these populations are warranted.”

The study was funded in part by the National Institutes of Health and the Department of Veterans Affairs. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients hospitalized for gram-negative bacteremia who weighed more than 70 kg had improved 30-day mortality, compared with those who weighed 70 kg or less, results from a single-center study showed.

“This study is a first step to determine the impact of low body weight on mortality in patients with bloodstream infections due to gram negative pathogens,” Ronald G. Hall II, Pharm.D., MSCS, said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “It should reinforce that clinicians need to aggressively treat patients who weigh less than 70 kg due to the increased risk of death. However, more data are needed to confirm this finding and determine the causes of this association.”

For the study, Dr. Hall, of the Texas Tech University Health Sciences Center School of Pharmacy, Dallas, and his associates retrospectively evaluated 324 patients admitted to a community teaching hospital for gram-negative bacteremia who received at least two days of empiric antibiotic therapy. They used univariate and multivariable logistic regression analysis to compare the 30-day mortality of patients with a total body weight of 70 kg or less with those weighing more than 70 kg.

Of the 324 patients, 184 (57%) weighed more than 70 kg. The 30-day mortality rate was 16.3% for patients who weighed 70 kg or less, compared with 10.5% for their counterparts who weighed more than 70 kg. This difference did not reach statistical significance on univariate analysis (odds ratio 0.67 for the higher body weight patients), but it did reach statistical significance on multivariable analysis (OR .43 for the higher body weight patients). Other factors that remained significant in the multivariable model were a cancer diagnosis (OR 2.55) and a Pitt bacteremia score of 4 or greater (OR 16.83).

“This study is the first, to our knowledge, to evaluate the impact of low total body weight on mortality in patients with bloodstream infections due to gram-negative pathogens,” Dr. Hall said. “Other investigators have found similar results previously evaluating the impact of underweight patients using body mass index (BMI). However, BMI uses both height and weight, with height being taken into a greater account (kg/m²) which may be misleading on the impact of weight.”

He acknowledged certain limitations of the study, including its single-center design. “A larger cohort will help improve our confidence in this finding by being able to control for more potential confounding variables,” he said.

Dr. Hall disclosed that he is a scientific advisor for Genentech. The other researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients hospitalized for gram-negative bacteremia who weighed more than 70 kg had improved 30-day mortality, compared with those who weighed 70 kg or less, results from a single-center study showed.

“This study is a first step to determine the impact of low body weight on mortality in patients with bloodstream infections due to gram negative pathogens,” Ronald G. Hall II, Pharm.D., MSCS, said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “It should reinforce that clinicians need to aggressively treat patients who weigh less than 70 kg due to the increased risk of death. However, more data are needed to confirm this finding and determine the causes of this association.”

For the study, Dr. Hall, of the Texas Tech University Health Sciences Center School of Pharmacy, Dallas, and his associates retrospectively evaluated 324 patients admitted to a community teaching hospital for gram-negative bacteremia who received at least two days of empiric antibiotic therapy. They used univariate and multivariable logistic regression analysis to compare the 30-day mortality of patients with a total body weight of 70 kg or less with those weighing more than 70 kg.

Of the 324 patients, 184 (57%) weighed more than 70 kg. The 30-day mortality rate was 16.3% for patients who weighed 70 kg or less, compared with 10.5% for their counterparts who weighed more than 70 kg. This difference did not reach statistical significance on univariate analysis (odds ratio 0.67 for the higher body weight patients), but it did reach statistical significance on multivariable analysis (OR .43 for the higher body weight patients). Other factors that remained significant in the multivariable model were a cancer diagnosis (OR 2.55) and a Pitt bacteremia score of 4 or greater (OR 16.83).

“This study is the first, to our knowledge, to evaluate the impact of low total body weight on mortality in patients with bloodstream infections due to gram-negative pathogens,” Dr. Hall said. “Other investigators have found similar results previously evaluating the impact of underweight patients using body mass index (BMI). However, BMI uses both height and weight, with height being taken into a greater account (kg/m²) which may be misleading on the impact of weight.”

He acknowledged certain limitations of the study, including its single-center design. “A larger cohort will help improve our confidence in this finding by being able to control for more potential confounding variables,” he said.

Dr. Hall disclosed that he is a scientific advisor for Genentech. The other researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients hospitalized for gram-negative bacteremia who weighed more than 70 kg had improved 30-day mortality, compared with those who weighed 70 kg or less, results from a single-center study showed.

“This study is a first step to determine the impact of low body weight on mortality in patients with bloodstream infections due to gram negative pathogens,” Ronald G. Hall II, Pharm.D., MSCS, said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “It should reinforce that clinicians need to aggressively treat patients who weigh less than 70 kg due to the increased risk of death. However, more data are needed to confirm this finding and determine the causes of this association.”

For the study, Dr. Hall, of the Texas Tech University Health Sciences Center School of Pharmacy, Dallas, and his associates retrospectively evaluated 324 patients admitted to a community teaching hospital for gram-negative bacteremia who received at least two days of empiric antibiotic therapy. They used univariate and multivariable logistic regression analysis to compare the 30-day mortality of patients with a total body weight of 70 kg or less with those weighing more than 70 kg.

Of the 324 patients, 184 (57%) weighed more than 70 kg. The 30-day mortality rate was 16.3% for patients who weighed 70 kg or less, compared with 10.5% for their counterparts who weighed more than 70 kg. This difference did not reach statistical significance on univariate analysis (odds ratio 0.67 for the higher body weight patients), but it did reach statistical significance on multivariable analysis (OR .43 for the higher body weight patients). Other factors that remained significant in the multivariable model were a cancer diagnosis (OR 2.55) and a Pitt bacteremia score of 4 or greater (OR 16.83).

“This study is the first, to our knowledge, to evaluate the impact of low total body weight on mortality in patients with bloodstream infections due to gram-negative pathogens,” Dr. Hall said. “Other investigators have found similar results previously evaluating the impact of underweight patients using body mass index (BMI). However, BMI uses both height and weight, with height being taken into a greater account (kg/m²) which may be misleading on the impact of weight.”

He acknowledged certain limitations of the study, including its single-center design. “A larger cohort will help improve our confidence in this finding by being able to control for more potential confounding variables,” he said.

Dr. Hall disclosed that he is a scientific advisor for Genentech. The other researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – The longer patients have sepsis, the more likely they are to die while in the hospital, a retrospective, single-center study showed.

However, lower respiratory tract infection, methicillin-resistant Staphylococcus aureus infection, Charlson score, and time to first antibiotic dose were not significantly associated with increased odds for mortality.

“Sepsis is a life-threatening acute condition that is commonly associated with inpatient mortality,” lead study author Joseph J. Carreno, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “To date, numerous interventions have evaluated the impact of interventions on sepsis-related mortality. However, few have examined duration of sepsis as a predictor of mortality.”

An earlier analysis conducted by Dr. Carreno and his associates at the Albany (N.Y.) College of Pharmacy and Health Sciences found that the duration of sepsis may be reduced through the use of multimodal interventions implemented by interdisciplinary teams.

For the current study, the researchers set out to evaluate the relationship between time to sepsis resolution and inpatient mortality by reviewing the records of 248 patients with documented sepsis who received antimicrobial therapy at Albany Medical Center Hospital. They defined time to sepsis resolution as time in days from blood culture to first date with fewer than two signs of systemic inflammatory response syndrome.

The mean age of the patients was 63 years, 67% were male, and 31% initially were admitted to the intensive care unit. The most prevalent sources of infection were genitourinary (24%), lower respiratory tract (17%), and endovascular (17%), while the most prevalent organisms isolated were coagulase-negative Staphylococcus (20%), Escherichia coli (18%), Streptococcus (15%), and methicillin-sensitive S. aureus (8%).

In all, 21 patients (9%) died. On multivariable analysis, the only significant risk factors for inpatient mortality were time (in days) to sepsis resolution (odds ratio, 1.13) and being initially admitted to the ICU (OR, 5.21).

“What was most surprising to me was the steady increase in mortality that was seen with each day of unresolved sepsis,” Dr. Carreno commented. “We hypothesized that there would be an association between time to sepsis resolution and mortality, but we thought that there would be a natural cut point rather than a steady increase in risk.”

Others factors such as lower respiratory tract infection, Charlson score, methicillin-resistant S. aureus infection, and time to first antibiotic dose didn’t have a significant association with increased odds for mortality.

“In our study, prolonged duration of sepsis was an early predictor of inpatient mortality,” he concluded. “Hence, patients’ response to therapy should be evaluated early in therapy. Our study supports recommendations from the Food and Drug Administration’s new guidance for clinical trials and the Centers for Disease Control and Prevention’s antibiotic ‘time out’ concept.”

Dr. Carreno reported having no financial disclosures.

[email protected]

SAN DIEGO – The longer patients have sepsis, the more likely they are to die while in the hospital, a retrospective, single-center study showed.

However, lower respiratory tract infection, methicillin-resistant Staphylococcus aureus infection, Charlson score, and time to first antibiotic dose were not significantly associated with increased odds for mortality.

“Sepsis is a life-threatening acute condition that is commonly associated with inpatient mortality,” lead study author Joseph J. Carreno, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “To date, numerous interventions have evaluated the impact of interventions on sepsis-related mortality. However, few have examined duration of sepsis as a predictor of mortality.”

An earlier analysis conducted by Dr. Carreno and his associates at the Albany (N.Y.) College of Pharmacy and Health Sciences found that the duration of sepsis may be reduced through the use of multimodal interventions implemented by interdisciplinary teams.

For the current study, the researchers set out to evaluate the relationship between time to sepsis resolution and inpatient mortality by reviewing the records of 248 patients with documented sepsis who received antimicrobial therapy at Albany Medical Center Hospital. They defined time to sepsis resolution as time in days from blood culture to first date with fewer than two signs of systemic inflammatory response syndrome.

The mean age of the patients was 63 years, 67% were male, and 31% initially were admitted to the intensive care unit. The most prevalent sources of infection were genitourinary (24%), lower respiratory tract (17%), and endovascular (17%), while the most prevalent organisms isolated were coagulase-negative Staphylococcus (20%), Escherichia coli (18%), Streptococcus (15%), and methicillin-sensitive S. aureus (8%).

In all, 21 patients (9%) died. On multivariable analysis, the only significant risk factors for inpatient mortality were time (in days) to sepsis resolution (odds ratio, 1.13) and being initially admitted to the ICU (OR, 5.21).

“What was most surprising to me was the steady increase in mortality that was seen with each day of unresolved sepsis,” Dr. Carreno commented. “We hypothesized that there would be an association between time to sepsis resolution and mortality, but we thought that there would be a natural cut point rather than a steady increase in risk.”

Others factors such as lower respiratory tract infection, Charlson score, methicillin-resistant S. aureus infection, and time to first antibiotic dose didn’t have a significant association with increased odds for mortality.

“In our study, prolonged duration of sepsis was an early predictor of inpatient mortality,” he concluded. “Hence, patients’ response to therapy should be evaluated early in therapy. Our study supports recommendations from the Food and Drug Administration’s new guidance for clinical trials and the Centers for Disease Control and Prevention’s antibiotic ‘time out’ concept.”

Dr. Carreno reported having no financial disclosures.

[email protected]

SAN DIEGO – The longer patients have sepsis, the more likely they are to die while in the hospital, a retrospective, single-center study showed.

However, lower respiratory tract infection, methicillin-resistant Staphylococcus aureus infection, Charlson score, and time to first antibiotic dose were not significantly associated with increased odds for mortality.

“Sepsis is a life-threatening acute condition that is commonly associated with inpatient mortality,” lead study author Joseph J. Carreno, Pharm.D., said in an interview in advance of the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “To date, numerous interventions have evaluated the impact of interventions on sepsis-related mortality. However, few have examined duration of sepsis as a predictor of mortality.”

An earlier analysis conducted by Dr. Carreno and his associates at the Albany (N.Y.) College of Pharmacy and Health Sciences found that the duration of sepsis may be reduced through the use of multimodal interventions implemented by interdisciplinary teams.

For the current study, the researchers set out to evaluate the relationship between time to sepsis resolution and inpatient mortality by reviewing the records of 248 patients with documented sepsis who received antimicrobial therapy at Albany Medical Center Hospital. They defined time to sepsis resolution as time in days from blood culture to first date with fewer than two signs of systemic inflammatory response syndrome.

The mean age of the patients was 63 years, 67% were male, and 31% initially were admitted to the intensive care unit. The most prevalent sources of infection were genitourinary (24%), lower respiratory tract (17%), and endovascular (17%), while the most prevalent organisms isolated were coagulase-negative Staphylococcus (20%), Escherichia coli (18%), Streptococcus (15%), and methicillin-sensitive S. aureus (8%).

In all, 21 patients (9%) died. On multivariable analysis, the only significant risk factors for inpatient mortality were time (in days) to sepsis resolution (odds ratio, 1.13) and being initially admitted to the ICU (OR, 5.21).

“What was most surprising to me was the steady increase in mortality that was seen with each day of unresolved sepsis,” Dr. Carreno commented. “We hypothesized that there would be an association between time to sepsis resolution and mortality, but we thought that there would be a natural cut point rather than a steady increase in risk.”

Others factors such as lower respiratory tract infection, Charlson score, methicillin-resistant S. aureus infection, and time to first antibiotic dose didn’t have a significant association with increased odds for mortality.

“In our study, prolonged duration of sepsis was an early predictor of inpatient mortality,” he concluded. “Hence, patients’ response to therapy should be evaluated early in therapy. Our study supports recommendations from the Food and Drug Administration’s new guidance for clinical trials and the Centers for Disease Control and Prevention’s antibiotic ‘time out’ concept.”

Dr. Carreno reported having no financial disclosures.

[email protected]

SAN DIEGO – According to Dr. Dilip V. Jeste, aging presents mankind with a paradox: Physical health may decline, but psychosocial functioning often improves with age, even in people with serious illnesses.

In a longitudinal study conducted for more than 2 decades by Dr. Jeste and his associates at the University of California, San Diego, researchers are following more than 1,400 community-based middle-aged and older adults with schizophrenia and 300-plus healthy controls with comprehensive clinical, neuropsychological, and functional evaluations. To date, they have observed accelerated physical aging among patients with schizophrenia, compared with controls, with a high morbidity and a lifespan shorter by 20 years, tied in most cases to heart disease and other afflictions common in older age. (Schizophr Bull. 2011;37[3]:451-5. doi:1093/schbul/sbr026).

They also have observed mild cognitive deficits at baseline, but a normal rate of age-associated impairment, as well as improving mental health, a reduction in psychotic symptoms, substance abuse, psychotic relapses, and increased treatment adherence, “because they have learned from experience that when they stop treatment, they have a relapse, and may become suicidal, agitated, and in need of hospitalization,” Dr. Jeste, a distinguished professor of psychiatry and neurosciences at UCSD, said at the annual U.S. Psychiatric and Mental Health Congress. “They don’t want that. Older people with schizophrenia get hospitalized not because of their psychosis, but because of the physical problems.”

More recently, he and his associates have been using biomarkers of aging to longitudinally study 140 outpatients with schizophrenia and 120 healthy controls aged 26-65 years. Data from the full sample have not yet been published, but the mean age of study participants was 50 years and 52% were male. Compared with controls, patients with schizophrenia had worse scores on psychopathology, physical functioning, and cognitive performance, “which is what you would expect.”

However, the researchers also observed shorter telomeres in some patients with schizophrenia. A telomere is a segment of DNA at the end of chromosomes. “Every time a cell divides, the telomere becomes shorter,” explained Dr. Jeste, who also is director of UCSD’s Stein Institute for Research on Aging. “After multiple cell divisions, the telomere disappears, and the cell dies.” The researchers found that women controls had significantly longer telomeres, compared with male controls (unpublished data). “That is consistent with the fact that women live longer than men,” he said. “That’s not surprising. What was surprising is that we did not see this gender difference in patients with schizophrenia. That means that women with schizophrenia have shorter telomeres than women controls. At this time, we don’t know what to make of this finding, but we will pursue it.”

The researchers also observed that the more severe the Calgary Depression Scale scores among patients, the shorter their telomeres, suggesting potential seriousness of depression in schizophrenia.

In an earlier study of 145 community-based middle-aged and older persons with schizophrenia, predictors of sustained remission were having social support, being (or having been) married at least once, greater cognitive/personality reserve, and early initiation of treatment, but not age or duration of illness (Am J Psychiatry. 2004;161[8]1490-3). “It’s worth keeping in mind that even older people with schizophrenia can have sustained remission,” Dr. Jeste said. He cited the late John Nash, Ph.D., – the Nobel Prize winning mathematician whose life story was the subject of the movie “A Beautiful Mind”– as someone who can function “at a very high level in spite of a serious illness like schizophrenia.”

This also occurs in adults with HIV and cancer, he continued. A “substantial proportion” of these patients demonstrate high ratings on mental well-being, despite worse physical health and more stressors (J Clin Psychiatry. 2013 May;74[5]:e417-23. doi: 10.4088/JCP.12m08100), (Psychooncology. 2015 Feb;24[2]:241-4. doi: 10.1002/pon.3600) and (Schizophr Res. 2014 Oct;159[1]:151-6. doi: 10.1016/j.schres.2014.07.02). Predictors of well-being in these patients include high levels of resilience and optimism, and low levels of depression and perceived stress.

These same “successful aging” traits were observed in a longitudinal study of a randomly selected community-based sample of 2,100 San Diego County residents aged 21-100. Known as the SAGE study, Dr. Jeste and his associates set out to test hypotheses regarding different domains of successful aging: physical, cognitive, and psychosocial. They found that aging is associated with declining levels of physical function yet improving mental health. Moreover, the study participants reported being more satisfied with life as they advance in age. The most significant correlates to self-reported well-being, happiness, and satisfaction in life were high levels of resilience and optimism, and low levels of depression and perceived stress (Am J Psychiatry. 2013 Feb;170[2]:188-96. doi: 10.1176/appi.ajp.2012.12030386).

“People think that as we get older we become more depressed, pessimistic, and negative,” Dr. Jeste said. “That’s not true. In our study we found no decrease in optimism bias with aging.”

Other published research supports this notion. A meta-analysis of 83 studies found a significantly positive association between optimism and better cardiovascular and cancer outcomes, better physiological markers such as immune function, better pregnancy-related outcomes, less pain, and improved mortality (Ann Behav Med. 2009 Jun;37[3]:239-56. doi: 10.1007/s12160-009-9111-x). Another meta-analysis of 148 studies involving more than 300,000 subjects found a 50% increased likelihood of survival for individuals with stronger social relationships (PLoS Med. 2010;7[7]:31000361).

Dr. Jeste went on to discuss a growing interest in the association of wisdom with aging. He defined wisdom as “a complex, multidimensional trait involving integration of several components that is useful to society and self.” Common components include social decision-making, emotional regulation, prosocial behaviors such as compassion, insight, tolerance of divergent views, and decisiveness amid uncertainty. To date, he said, studies in the medical literature have found no automatic increase in wisdom with age, but some older people show higher levels of specific components of wisdom, including better social reasoning and experience-based decision-making, and “positivity,” which Dr. Jeste defined as “having fewer negative emotions, better emotional regulation, positive biases in memory, and less regret.”

In the opinion of Dr. Jeste, such findings in medical research warrant a greater emphasis on positive aspects of health such as well-being, successful aging, and behavioral strategies for prevention – a concept known as “positive psychiatry.” “Enhancing positive psychological traits such as optimism, resilience, social engagement, and wisdom should become a key component of any medical treatment,” he said. For example, current strategies for successful aging in people with schizophrenia include optimal pharmacotherapy and psychosocial interventions, “but they are not enough,” he said. “Calorie restriction and physical exercise are critical, because we know that many of our patients are obese, partly because of sedentary habits and partly because of the medication.”

In an interview, Dr. Carl C. Bell, a psychiatrist at Jackson Park Hospital in Chicago, said the concepts behind positive psychiatry are long overdue. “Psychiatry needs to come out of the dark ages and realize that we psychiatrists should not only focus on patients’ psychopathology but also their psychoresilience, psychocreativity, and psychohealth,” Dr. Bell said. “The glass is neither half-empty nor half-full; it is both. Until we realize that wisdom, we are doing our patients a disservice.”

The practice of psychiatry “should go beyond prescribing medication” concluded Dr. Jeste, who is the principal coeditor of “Positive Psychiatry: A Clinical Handbook” (Arlington, Va.: American Psychiatric Publishing, 2015). “We need to get interested in patients’ lifestyle. We need to ask them about their level of physical activity, diet and nutrition, cognitive activity, sleep habits, socialization, and what they do for recreation and leisure.”

Dr. Jeste reported having no financial disclosures.

[email protected]

SAN DIEGO – According to Dr. Dilip V. Jeste, aging presents mankind with a paradox: Physical health may decline, but psychosocial functioning often improves with age, even in people with serious illnesses.

In a longitudinal study conducted for more than 2 decades by Dr. Jeste and his associates at the University of California, San Diego, researchers are following more than 1,400 community-based middle-aged and older adults with schizophrenia and 300-plus healthy controls with comprehensive clinical, neuropsychological, and functional evaluations. To date, they have observed accelerated physical aging among patients with schizophrenia, compared with controls, with a high morbidity and a lifespan shorter by 20 years, tied in most cases to heart disease and other afflictions common in older age. (Schizophr Bull. 2011;37[3]:451-5. doi:1093/schbul/sbr026).

They also have observed mild cognitive deficits at baseline, but a normal rate of age-associated impairment, as well as improving mental health, a reduction in psychotic symptoms, substance abuse, psychotic relapses, and increased treatment adherence, “because they have learned from experience that when they stop treatment, they have a relapse, and may become suicidal, agitated, and in need of hospitalization,” Dr. Jeste, a distinguished professor of psychiatry and neurosciences at UCSD, said at the annual U.S. Psychiatric and Mental Health Congress. “They don’t want that. Older people with schizophrenia get hospitalized not because of their psychosis, but because of the physical problems.”

More recently, he and his associates have been using biomarkers of aging to longitudinally study 140 outpatients with schizophrenia and 120 healthy controls aged 26-65 years. Data from the full sample have not yet been published, but the mean age of study participants was 50 years and 52% were male. Compared with controls, patients with schizophrenia had worse scores on psychopathology, physical functioning, and cognitive performance, “which is what you would expect.”

However, the researchers also observed shorter telomeres in some patients with schizophrenia. A telomere is a segment of DNA at the end of chromosomes. “Every time a cell divides, the telomere becomes shorter,” explained Dr. Jeste, who also is director of UCSD’s Stein Institute for Research on Aging. “After multiple cell divisions, the telomere disappears, and the cell dies.” The researchers found that women controls had significantly longer telomeres, compared with male controls (unpublished data). “That is consistent with the fact that women live longer than men,” he said. “That’s not surprising. What was surprising is that we did not see this gender difference in patients with schizophrenia. That means that women with schizophrenia have shorter telomeres than women controls. At this time, we don’t know what to make of this finding, but we will pursue it.”

The researchers also observed that the more severe the Calgary Depression Scale scores among patients, the shorter their telomeres, suggesting potential seriousness of depression in schizophrenia.

In an earlier study of 145 community-based middle-aged and older persons with schizophrenia, predictors of sustained remission were having social support, being (or having been) married at least once, greater cognitive/personality reserve, and early initiation of treatment, but not age or duration of illness (Am J Psychiatry. 2004;161[8]1490-3). “It’s worth keeping in mind that even older people with schizophrenia can have sustained remission,” Dr. Jeste said. He cited the late John Nash, Ph.D., – the Nobel Prize winning mathematician whose life story was the subject of the movie “A Beautiful Mind”– as someone who can function “at a very high level in spite of a serious illness like schizophrenia.”

This also occurs in adults with HIV and cancer, he continued. A “substantial proportion” of these patients demonstrate high ratings on mental well-being, despite worse physical health and more stressors (J Clin Psychiatry. 2013 May;74[5]:e417-23. doi: 10.4088/JCP.12m08100), (Psychooncology. 2015 Feb;24[2]:241-4. doi: 10.1002/pon.3600) and (Schizophr Res. 2014 Oct;159[1]:151-6. doi: 10.1016/j.schres.2014.07.02). Predictors of well-being in these patients include high levels of resilience and optimism, and low levels of depression and perceived stress.

These same “successful aging” traits were observed in a longitudinal study of a randomly selected community-based sample of 2,100 San Diego County residents aged 21-100. Known as the SAGE study, Dr. Jeste and his associates set out to test hypotheses regarding different domains of successful aging: physical, cognitive, and psychosocial. They found that aging is associated with declining levels of physical function yet improving mental health. Moreover, the study participants reported being more satisfied with life as they advance in age. The most significant correlates to self-reported well-being, happiness, and satisfaction in life were high levels of resilience and optimism, and low levels of depression and perceived stress (Am J Psychiatry. 2013 Feb;170[2]:188-96. doi: 10.1176/appi.ajp.2012.12030386).

“People think that as we get older we become more depressed, pessimistic, and negative,” Dr. Jeste said. “That’s not true. In our study we found no decrease in optimism bias with aging.”

Other published research supports this notion. A meta-analysis of 83 studies found a significantly positive association between optimism and better cardiovascular and cancer outcomes, better physiological markers such as immune function, better pregnancy-related outcomes, less pain, and improved mortality (Ann Behav Med. 2009 Jun;37[3]:239-56. doi: 10.1007/s12160-009-9111-x). Another meta-analysis of 148 studies involving more than 300,000 subjects found a 50% increased likelihood of survival for individuals with stronger social relationships (PLoS Med. 2010;7[7]:31000361).

Dr. Jeste went on to discuss a growing interest in the association of wisdom with aging. He defined wisdom as “a complex, multidimensional trait involving integration of several components that is useful to society and self.” Common components include social decision-making, emotional regulation, prosocial behaviors such as compassion, insight, tolerance of divergent views, and decisiveness amid uncertainty. To date, he said, studies in the medical literature have found no automatic increase in wisdom with age, but some older people show higher levels of specific components of wisdom, including better social reasoning and experience-based decision-making, and “positivity,” which Dr. Jeste defined as “having fewer negative emotions, better emotional regulation, positive biases in memory, and less regret.”

In the opinion of Dr. Jeste, such findings in medical research warrant a greater emphasis on positive aspects of health such as well-being, successful aging, and behavioral strategies for prevention – a concept known as “positive psychiatry.” “Enhancing positive psychological traits such as optimism, resilience, social engagement, and wisdom should become a key component of any medical treatment,” he said. For example, current strategies for successful aging in people with schizophrenia include optimal pharmacotherapy and psychosocial interventions, “but they are not enough,” he said. “Calorie restriction and physical exercise are critical, because we know that many of our patients are obese, partly because of sedentary habits and partly because of the medication.”

In an interview, Dr. Carl C. Bell, a psychiatrist at Jackson Park Hospital in Chicago, said the concepts behind positive psychiatry are long overdue. “Psychiatry needs to come out of the dark ages and realize that we psychiatrists should not only focus on patients’ psychopathology but also their psychoresilience, psychocreativity, and psychohealth,” Dr. Bell said. “The glass is neither half-empty nor half-full; it is both. Until we realize that wisdom, we are doing our patients a disservice.”

The practice of psychiatry “should go beyond prescribing medication” concluded Dr. Jeste, who is the principal coeditor of “Positive Psychiatry: A Clinical Handbook” (Arlington, Va.: American Psychiatric Publishing, 2015). “We need to get interested in patients’ lifestyle. We need to ask them about their level of physical activity, diet and nutrition, cognitive activity, sleep habits, socialization, and what they do for recreation and leisure.”

Dr. Jeste reported having no financial disclosures.

[email protected]

SAN DIEGO – According to Dr. Dilip V. Jeste, aging presents mankind with a paradox: Physical health may decline, but psychosocial functioning often improves with age, even in people with serious illnesses.

In a longitudinal study conducted for more than 2 decades by Dr. Jeste and his associates at the University of California, San Diego, researchers are following more than 1,400 community-based middle-aged and older adults with schizophrenia and 300-plus healthy controls with comprehensive clinical, neuropsychological, and functional evaluations. To date, they have observed accelerated physical aging among patients with schizophrenia, compared with controls, with a high morbidity and a lifespan shorter by 20 years, tied in most cases to heart disease and other afflictions common in older age. (Schizophr Bull. 2011;37[3]:451-5. doi:1093/schbul/sbr026).

They also have observed mild cognitive deficits at baseline, but a normal rate of age-associated impairment, as well as improving mental health, a reduction in psychotic symptoms, substance abuse, psychotic relapses, and increased treatment adherence, “because they have learned from experience that when they stop treatment, they have a relapse, and may become suicidal, agitated, and in need of hospitalization,” Dr. Jeste, a distinguished professor of psychiatry and neurosciences at UCSD, said at the annual U.S. Psychiatric and Mental Health Congress. “They don’t want that. Older people with schizophrenia get hospitalized not because of their psychosis, but because of the physical problems.”

More recently, he and his associates have been using biomarkers of aging to longitudinally study 140 outpatients with schizophrenia and 120 healthy controls aged 26-65 years. Data from the full sample have not yet been published, but the mean age of study participants was 50 years and 52% were male. Compared with controls, patients with schizophrenia had worse scores on psychopathology, physical functioning, and cognitive performance, “which is what you would expect.”

However, the researchers also observed shorter telomeres in some patients with schizophrenia. A telomere is a segment of DNA at the end of chromosomes. “Every time a cell divides, the telomere becomes shorter,” explained Dr. Jeste, who also is director of UCSD’s Stein Institute for Research on Aging. “After multiple cell divisions, the telomere disappears, and the cell dies.” The researchers found that women controls had significantly longer telomeres, compared with male controls (unpublished data). “That is consistent with the fact that women live longer than men,” he said. “That’s not surprising. What was surprising is that we did not see this gender difference in patients with schizophrenia. That means that women with schizophrenia have shorter telomeres than women controls. At this time, we don’t know what to make of this finding, but we will pursue it.”

The researchers also observed that the more severe the Calgary Depression Scale scores among patients, the shorter their telomeres, suggesting potential seriousness of depression in schizophrenia.

In an earlier study of 145 community-based middle-aged and older persons with schizophrenia, predictors of sustained remission were having social support, being (or having been) married at least once, greater cognitive/personality reserve, and early initiation of treatment, but not age or duration of illness (Am J Psychiatry. 2004;161[8]1490-3). “It’s worth keeping in mind that even older people with schizophrenia can have sustained remission,” Dr. Jeste said. He cited the late John Nash, Ph.D., – the Nobel Prize winning mathematician whose life story was the subject of the movie “A Beautiful Mind”– as someone who can function “at a very high level in spite of a serious illness like schizophrenia.”

This also occurs in adults with HIV and cancer, he continued. A “substantial proportion” of these patients demonstrate high ratings on mental well-being, despite worse physical health and more stressors (J Clin Psychiatry. 2013 May;74[5]:e417-23. doi: 10.4088/JCP.12m08100), (Psychooncology. 2015 Feb;24[2]:241-4. doi: 10.1002/pon.3600) and (Schizophr Res. 2014 Oct;159[1]:151-6. doi: 10.1016/j.schres.2014.07.02). Predictors of well-being in these patients include high levels of resilience and optimism, and low levels of depression and perceived stress.

These same “successful aging” traits were observed in a longitudinal study of a randomly selected community-based sample of 2,100 San Diego County residents aged 21-100. Known as the SAGE study, Dr. Jeste and his associates set out to test hypotheses regarding different domains of successful aging: physical, cognitive, and psychosocial. They found that aging is associated with declining levels of physical function yet improving mental health. Moreover, the study participants reported being more satisfied with life as they advance in age. The most significant correlates to self-reported well-being, happiness, and satisfaction in life were high levels of resilience and optimism, and low levels of depression and perceived stress (Am J Psychiatry. 2013 Feb;170[2]:188-96. doi: 10.1176/appi.ajp.2012.12030386).

“People think that as we get older we become more depressed, pessimistic, and negative,” Dr. Jeste said. “That’s not true. In our study we found no decrease in optimism bias with aging.”

Other published research supports this notion. A meta-analysis of 83 studies found a significantly positive association between optimism and better cardiovascular and cancer outcomes, better physiological markers such as immune function, better pregnancy-related outcomes, less pain, and improved mortality (Ann Behav Med. 2009 Jun;37[3]:239-56. doi: 10.1007/s12160-009-9111-x). Another meta-analysis of 148 studies involving more than 300,000 subjects found a 50% increased likelihood of survival for individuals with stronger social relationships (PLoS Med. 2010;7[7]:31000361).

Dr. Jeste went on to discuss a growing interest in the association of wisdom with aging. He defined wisdom as “a complex, multidimensional trait involving integration of several components that is useful to society and self.” Common components include social decision-making, emotional regulation, prosocial behaviors such as compassion, insight, tolerance of divergent views, and decisiveness amid uncertainty. To date, he said, studies in the medical literature have found no automatic increase in wisdom with age, but some older people show higher levels of specific components of wisdom, including better social reasoning and experience-based decision-making, and “positivity,” which Dr. Jeste defined as “having fewer negative emotions, better emotional regulation, positive biases in memory, and less regret.”

In the opinion of Dr. Jeste, such findings in medical research warrant a greater emphasis on positive aspects of health such as well-being, successful aging, and behavioral strategies for prevention – a concept known as “positive psychiatry.” “Enhancing positive psychological traits such as optimism, resilience, social engagement, and wisdom should become a key component of any medical treatment,” he said. For example, current strategies for successful aging in people with schizophrenia include optimal pharmacotherapy and psychosocial interventions, “but they are not enough,” he said. “Calorie restriction and physical exercise are critical, because we know that many of our patients are obese, partly because of sedentary habits and partly because of the medication.”

In an interview, Dr. Carl C. Bell, a psychiatrist at Jackson Park Hospital in Chicago, said the concepts behind positive psychiatry are long overdue. “Psychiatry needs to come out of the dark ages and realize that we psychiatrists should not only focus on patients’ psychopathology but also their psychoresilience, psychocreativity, and psychohealth,” Dr. Bell said. “The glass is neither half-empty nor half-full; it is both. Until we realize that wisdom, we are doing our patients a disservice.”

The practice of psychiatry “should go beyond prescribing medication” concluded Dr. Jeste, who is the principal coeditor of “Positive Psychiatry: A Clinical Handbook” (Arlington, Va.: American Psychiatric Publishing, 2015). “We need to get interested in patients’ lifestyle. We need to ask them about their level of physical activity, diet and nutrition, cognitive activity, sleep habits, socialization, and what they do for recreation and leisure.”

Dr. Jeste reported having no financial disclosures.

[email protected]

PARK CITY, UTAH – When you ask clinicians why they elect to reexcise dysplastic nevi, you’re likely to get a variety of answers, according to Dr. Douglas Grossman.

“Sometimes they have no reason all,” Dr. Grossman, professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “Sometimes the answer is ‘to prevent recurrence.’ Sometimes it’s to ensure complete removal of the lesion, to confirm the diagnosis, to rule out melanoma, or for ‘therapeutic’ purposes.”

Dysplastic nevus margins are often positive, “because the melanocytes in these lesions tend to extend up to 2 mm beyond clinical margins,” Dr. Grossman said. “I always try to remove the entire clinical lesion as well as 1-2 mm around the lesion to avoid positive margins.”

A survey of 101 Chicago Dermatological Society members found wide variation in clinical practice concerning how clinicians manage dysplastic nevi if the margins are clear vs. positive, and based on the degree of atypia (Arch Dermatol. 2012;148[2]:259-60). The greatest quantitative shift in decision making (from observe to reexcise) was seen for dysplastic nevi with moderate dysplasia. Specifically, the decision to reexcise dysplastic nevi with moderate dysplasia ranged from 9% (for clear margins) to 81% (for positive margins) of respondents. “The margin status is driving the management,” said Dr. Grossman, who was not involved with the study.

In his opinion, two “unspoken fears” are also impacting the way clinicians treat dysplastic nevi. The first is that the nevus will recur in the scar years later and be indistinguishable from melanoma – the so-called pseudomelanoma phenomenon. The second fear is that residual nevus cells left behind will transform to melanoma. Evidence for these two possibilities, however, is lacking, Dr. Grossman said. According to a large study of pseudomelanoma phenomena, recurrence was rare and easily distinguishable from cases of melanoma with regression (Modern Pathol. 2009;22:611-7). “Almost all of them had recurred within a year, so if a nevus is going to recur, it’s usually going to recur within that first year,” he said.

As for the issue of recurrence, Dr. Grossman led a research team that evaluated 271 nevus biopsy sites in 115 patients (J Am Acad Dermatol. 2010;62[4]:591-6). At greater than 2 years of follow-up they observed a recurrence rate of 3.6% for dysplastic nevi, compared with 3.3% for nondysplastic nevi, “which is similar,” he said. In terms of melanoma development, one study of 28 incompletely removed dysplastic nevi found that no melanomas developed during 5 years of follow-up (Am J Dermatopathol. 1985;7 Suppl:93-7).

Dr. Grossman referenced four cases in the medical literature in which the diagnosis was changed upon reexcision from dysplastic nevus to melanoma. “The question here is whether the initial biopsy or the reexcision was the correct diagnosis,” he said. “Development of melanoma at the site of a previously biopsied dysplastic nevus is exceedingly rare, and has not been described beyond a few case reports. The most likely explanation for how this could occur would be sampling error. If you have a melanoma arising at the site, maybe it was melanoma to start with, and the diagnosis was missed on the original biopsy. It could also be the case of pseudomelanoma phenomenon where it’s a nevus to start with but it comes back looking more atypical, so it’s incorrectly diagnosed as melanoma. A final possibility, which is the least likely, is that the few nevus cells left behind transformed into melanoma.”

According to a recent consensus statement from the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group, mild/moderate dysplastic nevi with clear margins do not need reexcision (JAMA Dermatol. 2015;151[2]:212-8). The working group also recommends that mild dysplastic nevi with positive margins may be safely observed and that observation for moderately dysplastic nevi with positive margins “may be a reasonable option.”

Dr. Grossman reported having no financial disclosures.

PARK CITY, UTAH – When you ask clinicians why they elect to reexcise dysplastic nevi, you’re likely to get a variety of answers, according to Dr. Douglas Grossman.

“Sometimes they have no reason all,” Dr. Grossman, professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “Sometimes the answer is ‘to prevent recurrence.’ Sometimes it’s to ensure complete removal of the lesion, to confirm the diagnosis, to rule out melanoma, or for ‘therapeutic’ purposes.”

Dysplastic nevus margins are often positive, “because the melanocytes in these lesions tend to extend up to 2 mm beyond clinical margins,” Dr. Grossman said. “I always try to remove the entire clinical lesion as well as 1-2 mm around the lesion to avoid positive margins.”

A survey of 101 Chicago Dermatological Society members found wide variation in clinical practice concerning how clinicians manage dysplastic nevi if the margins are clear vs. positive, and based on the degree of atypia (Arch Dermatol. 2012;148[2]:259-60). The greatest quantitative shift in decision making (from observe to reexcise) was seen for dysplastic nevi with moderate dysplasia. Specifically, the decision to reexcise dysplastic nevi with moderate dysplasia ranged from 9% (for clear margins) to 81% (for positive margins) of respondents. “The margin status is driving the management,” said Dr. Grossman, who was not involved with the study.

In his opinion, two “unspoken fears” are also impacting the way clinicians treat dysplastic nevi. The first is that the nevus will recur in the scar years later and be indistinguishable from melanoma – the so-called pseudomelanoma phenomenon. The second fear is that residual nevus cells left behind will transform to melanoma. Evidence for these two possibilities, however, is lacking, Dr. Grossman said. According to a large study of pseudomelanoma phenomena, recurrence was rare and easily distinguishable from cases of melanoma with regression (Modern Pathol. 2009;22:611-7). “Almost all of them had recurred within a year, so if a nevus is going to recur, it’s usually going to recur within that first year,” he said.

As for the issue of recurrence, Dr. Grossman led a research team that evaluated 271 nevus biopsy sites in 115 patients (J Am Acad Dermatol. 2010;62[4]:591-6). At greater than 2 years of follow-up they observed a recurrence rate of 3.6% for dysplastic nevi, compared with 3.3% for nondysplastic nevi, “which is similar,” he said. In terms of melanoma development, one study of 28 incompletely removed dysplastic nevi found that no melanomas developed during 5 years of follow-up (Am J Dermatopathol. 1985;7 Suppl:93-7).

Dr. Grossman referenced four cases in the medical literature in which the diagnosis was changed upon reexcision from dysplastic nevus to melanoma. “The question here is whether the initial biopsy or the reexcision was the correct diagnosis,” he said. “Development of melanoma at the site of a previously biopsied dysplastic nevus is exceedingly rare, and has not been described beyond a few case reports. The most likely explanation for how this could occur would be sampling error. If you have a melanoma arising at the site, maybe it was melanoma to start with, and the diagnosis was missed on the original biopsy. It could also be the case of pseudomelanoma phenomenon where it’s a nevus to start with but it comes back looking more atypical, so it’s incorrectly diagnosed as melanoma. A final possibility, which is the least likely, is that the few nevus cells left behind transformed into melanoma.”

According to a recent consensus statement from the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group, mild/moderate dysplastic nevi with clear margins do not need reexcision (JAMA Dermatol. 2015;151[2]:212-8). The working group also recommends that mild dysplastic nevi with positive margins may be safely observed and that observation for moderately dysplastic nevi with positive margins “may be a reasonable option.”

Dr. Grossman reported having no financial disclosures.

PARK CITY, UTAH – When you ask clinicians why they elect to reexcise dysplastic nevi, you’re likely to get a variety of answers, according to Dr. Douglas Grossman.

“Sometimes they have no reason all,” Dr. Grossman, professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “Sometimes the answer is ‘to prevent recurrence.’ Sometimes it’s to ensure complete removal of the lesion, to confirm the diagnosis, to rule out melanoma, or for ‘therapeutic’ purposes.”

Dysplastic nevus margins are often positive, “because the melanocytes in these lesions tend to extend up to 2 mm beyond clinical margins,” Dr. Grossman said. “I always try to remove the entire clinical lesion as well as 1-2 mm around the lesion to avoid positive margins.”

A survey of 101 Chicago Dermatological Society members found wide variation in clinical practice concerning how clinicians manage dysplastic nevi if the margins are clear vs. positive, and based on the degree of atypia (Arch Dermatol. 2012;148[2]:259-60). The greatest quantitative shift in decision making (from observe to reexcise) was seen for dysplastic nevi with moderate dysplasia. Specifically, the decision to reexcise dysplastic nevi with moderate dysplasia ranged from 9% (for clear margins) to 81% (for positive margins) of respondents. “The margin status is driving the management,” said Dr. Grossman, who was not involved with the study.

In his opinion, two “unspoken fears” are also impacting the way clinicians treat dysplastic nevi. The first is that the nevus will recur in the scar years later and be indistinguishable from melanoma – the so-called pseudomelanoma phenomenon. The second fear is that residual nevus cells left behind will transform to melanoma. Evidence for these two possibilities, however, is lacking, Dr. Grossman said. According to a large study of pseudomelanoma phenomena, recurrence was rare and easily distinguishable from cases of melanoma with regression (Modern Pathol. 2009;22:611-7). “Almost all of them had recurred within a year, so if a nevus is going to recur, it’s usually going to recur within that first year,” he said.

As for the issue of recurrence, Dr. Grossman led a research team that evaluated 271 nevus biopsy sites in 115 patients (J Am Acad Dermatol. 2010;62[4]:591-6). At greater than 2 years of follow-up they observed a recurrence rate of 3.6% for dysplastic nevi, compared with 3.3% for nondysplastic nevi, “which is similar,” he said. In terms of melanoma development, one study of 28 incompletely removed dysplastic nevi found that no melanomas developed during 5 years of follow-up (Am J Dermatopathol. 1985;7 Suppl:93-7).

Dr. Grossman referenced four cases in the medical literature in which the diagnosis was changed upon reexcision from dysplastic nevus to melanoma. “The question here is whether the initial biopsy or the reexcision was the correct diagnosis,” he said. “Development of melanoma at the site of a previously biopsied dysplastic nevus is exceedingly rare, and has not been described beyond a few case reports. The most likely explanation for how this could occur would be sampling error. If you have a melanoma arising at the site, maybe it was melanoma to start with, and the diagnosis was missed on the original biopsy. It could also be the case of pseudomelanoma phenomenon where it’s a nevus to start with but it comes back looking more atypical, so it’s incorrectly diagnosed as melanoma. A final possibility, which is the least likely, is that the few nevus cells left behind transformed into melanoma.”

According to a recent consensus statement from the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group, mild/moderate dysplastic nevi with clear margins do not need reexcision (JAMA Dermatol. 2015;151[2]:212-8). The working group also recommends that mild dysplastic nevi with positive margins may be safely observed and that observation for moderately dysplastic nevi with positive margins “may be a reasonable option.”

Dr. Grossman reported having no financial disclosures.