Michele G. Sullivan

LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.

This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.

Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.

“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.

By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.

“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.

Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.

When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.

Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.

• Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
• Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
• Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.

Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.

These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”

Dr. Joshi reported no disclosures relevant to his presentation.

[email protected]

LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.

This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.

Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.

“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.

By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.

“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.

Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.

When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.

Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.

• Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
• Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
• Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.

Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.

These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”

Dr. Joshi reported no disclosures relevant to his presentation.

[email protected]

LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.

This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.

Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.

“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.

By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.

“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.

Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.

When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.

Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.

• Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
• Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
• Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.

Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.

These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”

Dr. Joshi reported no disclosures relevant to his presentation.

[email protected]

LAS VEGAS – More than half of patients tested for prescription drug compliance last year misused their medications, often supplementing them with nonprescribed and illicit drugs in dangerous combinations.

sdominick/iStock/Getty Images

Of almost 4 million urine screens examined, 52% were discordant for the screen-ordered drugs, Jeffrey Gudin, MD, said at the annual PAINWeek. Most common was the combination of opioids and benzodiazepines, which accounted for 21% of the discordant samples – and, in 64% of these cases, at least one of the drugs was not prescribed.

“Drug testing is a standard of care in pain management, and it’s the only objective way to know what patients are really taking,” said Dr. Gudin, director of pain and palliative care at Englewood (N.J.) Hospital and Medical Center. “What this tells us is that, if we just ask our patients, half the time they won’t tell you the whole story. More than 50% of the time things don’t match up. To me this is just unbelievable.”

Quest Diagnostics compiled these data, and many more, in its “Health Trends Report: Drug Misuse in America 2018.”

The report examines 3.9 million routine drug screens ordered by primary care and pain physicians during 2011-2017. It not only looks at prescription drug use and misuse but also tracks illicit drugs in both general and substance abuse patient populations. The findings reported at PAINWeek were based on 456,675 screens from 276,953 patients conducted in 2017. These results were included in the Quest Diagnostics medMATCH reports, which indicated what tested drugs were prescribed and whether these drugs were detected in the specimen.

The following were found among the discordant screens identified in 2017:

• 45% were positive for nonprescribed or illicit drugs in addition to all the prescribed drugs.
• 34% did not show all the drugs they had been prescribed, or any other tested drug.
• 22% did not show all the drugs they had been prescribed but were positive for other illicit or nonprescribed drugs.

The tests were ordered as a part of routine care – an important point, Dr. Gudin said in an interview. “These are not ‘gotcha tests,’ ” intended to catch patients unawares. “These are regularly ordered screens that are standard of care in pain management.”

The report found that men and women were equally likely to misuse medications (52% each). There were some age-related differences, with misuse peaking in young adulthood: 60% of 18- to 24-year-olds and 56% of 25- to 45-year-olds. Misuse dropped off in those aged 55-64 years (52%) and in those 65 years and older (43%). But even children showed evidence of medication misuse, with about 41% of samples from children aged 10 years and younger being discordant.

The rates of misuse were about 50% in Medicare and private pay patients, but around 65% in Medicaid patients.

There was some good news: In the general patient population, opioid use was down by 12% from 2016 – the largest annual decrease Quest has noted since 2012. Several factors probably contributed to that decline, including shifts in clinical care and payer reimbursement, as well as regulatory and legislative restrictions.

“This shows that we’re doing better on the pain management front,” Dr. Gudin said. “But in substance use disorder settings, we saw 400% increases for both fentanyl and heroin. The addiction front it out of control.”

More than 27% of all specimens that came from substance abuse treatment centers were positive for nonprescribed fentanyl and 10% were positive for heroin. “We also saw that, in 2016, 45% of those heroin-positive samples had fentanyl in them, and in 2017, 83% did.”

Although not discussed at PAINWeek, the report also noted a rise in gabapentin misuse. The antiepileptic is now the 10th most commonly prescribed drug in the United States, the report noted, with 68 million prescriptions dispensed last year. The report found that 9.5% of tests showed nonprescription gabapentin. In the subset of samples obtained from substance abuse treatment centers, gabapentin misuse increased by 800% from 2016 – the most dramatic increase of any of the tracked drugs.

The combination of gabapentin and opioids is risky, the report noted. Opioid-related deaths are 49% more common among those taking both than those taking opioids only.
 

[email protected]

SOURCE: Gudin J et al. PAINWeek 2018, abstract 44.

LAS VEGAS – More than half of patients tested for prescription drug compliance last year misused their medications, often supplementing them with nonprescribed and illicit drugs in dangerous combinations.

sdominick/iStock/Getty Images

Of almost 4 million urine screens examined, 52% were discordant for the screen-ordered drugs, Jeffrey Gudin, MD, said at the annual PAINWeek. Most common was the combination of opioids and benzodiazepines, which accounted for 21% of the discordant samples – and, in 64% of these cases, at least one of the drugs was not prescribed.

“Drug testing is a standard of care in pain management, and it’s the only objective way to know what patients are really taking,” said Dr. Gudin, director of pain and palliative care at Englewood (N.J.) Hospital and Medical Center. “What this tells us is that, if we just ask our patients, half the time they won’t tell you the whole story. More than 50% of the time things don’t match up. To me this is just unbelievable.”

Quest Diagnostics compiled these data, and many more, in its “Health Trends Report: Drug Misuse in America 2018.”

The report examines 3.9 million routine drug screens ordered by primary care and pain physicians during 2011-2017. It not only looks at prescription drug use and misuse but also tracks illicit drugs in both general and substance abuse patient populations. The findings reported at PAINWeek were based on 456,675 screens from 276,953 patients conducted in 2017. These results were included in the Quest Diagnostics medMATCH reports, which indicated what tested drugs were prescribed and whether these drugs were detected in the specimen.

The following were found among the discordant screens identified in 2017:

• 45% were positive for nonprescribed or illicit drugs in addition to all the prescribed drugs.
• 34% did not show all the drugs they had been prescribed, or any other tested drug.
• 22% did not show all the drugs they had been prescribed but were positive for other illicit or nonprescribed drugs.

The tests were ordered as a part of routine care – an important point, Dr. Gudin said in an interview. “These are not ‘gotcha tests,’ ” intended to catch patients unawares. “These are regularly ordered screens that are standard of care in pain management.”

The report found that men and women were equally likely to misuse medications (52% each). There were some age-related differences, with misuse peaking in young adulthood: 60% of 18- to 24-year-olds and 56% of 25- to 45-year-olds. Misuse dropped off in those aged 55-64 years (52%) and in those 65 years and older (43%). But even children showed evidence of medication misuse, with about 41% of samples from children aged 10 years and younger being discordant.

The rates of misuse were about 50% in Medicare and private pay patients, but around 65% in Medicaid patients.

There was some good news: In the general patient population, opioid use was down by 12% from 2016 – the largest annual decrease Quest has noted since 2012. Several factors probably contributed to that decline, including shifts in clinical care and payer reimbursement, as well as regulatory and legislative restrictions.

“This shows that we’re doing better on the pain management front,” Dr. Gudin said. “But in substance use disorder settings, we saw 400% increases for both fentanyl and heroin. The addiction front it out of control.”

More than 27% of all specimens that came from substance abuse treatment centers were positive for nonprescribed fentanyl and 10% were positive for heroin. “We also saw that, in 2016, 45% of those heroin-positive samples had fentanyl in them, and in 2017, 83% did.”

Although not discussed at PAINWeek, the report also noted a rise in gabapentin misuse. The antiepileptic is now the 10th most commonly prescribed drug in the United States, the report noted, with 68 million prescriptions dispensed last year. The report found that 9.5% of tests showed nonprescription gabapentin. In the subset of samples obtained from substance abuse treatment centers, gabapentin misuse increased by 800% from 2016 – the most dramatic increase of any of the tracked drugs.

The combination of gabapentin and opioids is risky, the report noted. Opioid-related deaths are 49% more common among those taking both than those taking opioids only.
 

[email protected]

SOURCE: Gudin J et al. PAINWeek 2018, abstract 44.

LAS VEGAS – More than half of patients tested for prescription drug compliance last year misused their medications, often supplementing them with nonprescribed and illicit drugs in dangerous combinations.

sdominick/iStock/Getty Images

Of almost 4 million urine screens examined, 52% were discordant for the screen-ordered drugs, Jeffrey Gudin, MD, said at the annual PAINWeek. Most common was the combination of opioids and benzodiazepines, which accounted for 21% of the discordant samples – and, in 64% of these cases, at least one of the drugs was not prescribed.

“Drug testing is a standard of care in pain management, and it’s the only objective way to know what patients are really taking,” said Dr. Gudin, director of pain and palliative care at Englewood (N.J.) Hospital and Medical Center. “What this tells us is that, if we just ask our patients, half the time they won’t tell you the whole story. More than 50% of the time things don’t match up. To me this is just unbelievable.”

Quest Diagnostics compiled these data, and many more, in its “Health Trends Report: Drug Misuse in America 2018.”

The report examines 3.9 million routine drug screens ordered by primary care and pain physicians during 2011-2017. It not only looks at prescription drug use and misuse but also tracks illicit drugs in both general and substance abuse patient populations. The findings reported at PAINWeek were based on 456,675 screens from 276,953 patients conducted in 2017. These results were included in the Quest Diagnostics medMATCH reports, which indicated what tested drugs were prescribed and whether these drugs were detected in the specimen.

The following were found among the discordant screens identified in 2017:

• 45% were positive for nonprescribed or illicit drugs in addition to all the prescribed drugs.
• 34% did not show all the drugs they had been prescribed, or any other tested drug.
• 22% did not show all the drugs they had been prescribed but were positive for other illicit or nonprescribed drugs.

The tests were ordered as a part of routine care – an important point, Dr. Gudin said in an interview. “These are not ‘gotcha tests,’ ” intended to catch patients unawares. “These are regularly ordered screens that are standard of care in pain management.”

The report found that men and women were equally likely to misuse medications (52% each). There were some age-related differences, with misuse peaking in young adulthood: 60% of 18- to 24-year-olds and 56% of 25- to 45-year-olds. Misuse dropped off in those aged 55-64 years (52%) and in those 65 years and older (43%). But even children showed evidence of medication misuse, with about 41% of samples from children aged 10 years and younger being discordant.

The rates of misuse were about 50% in Medicare and private pay patients, but around 65% in Medicaid patients.

There was some good news: In the general patient population, opioid use was down by 12% from 2016 – the largest annual decrease Quest has noted since 2012. Several factors probably contributed to that decline, including shifts in clinical care and payer reimbursement, as well as regulatory and legislative restrictions.

“This shows that we’re doing better on the pain management front,” Dr. Gudin said. “But in substance use disorder settings, we saw 400% increases for both fentanyl and heroin. The addiction front it out of control.”

More than 27% of all specimens that came from substance abuse treatment centers were positive for nonprescribed fentanyl and 10% were positive for heroin. “We also saw that, in 2016, 45% of those heroin-positive samples had fentanyl in them, and in 2017, 83% did.”

Although not discussed at PAINWeek, the report also noted a rise in gabapentin misuse. The antiepileptic is now the 10th most commonly prescribed drug in the United States, the report noted, with 68 million prescriptions dispensed last year. The report found that 9.5% of tests showed nonprescription gabapentin. In the subset of samples obtained from substance abuse treatment centers, gabapentin misuse increased by 800% from 2016 – the most dramatic increase of any of the tracked drugs.

The combination of gabapentin and opioids is risky, the report noted. Opioid-related deaths are 49% more common among those taking both than those taking opioids only.
 

[email protected]

SOURCE: Gudin J et al. PAINWeek 2018, abstract 44.

About one in eight Nigerian women with breast cancer has an inherited mutation of the BRCA1, BRCA2, PALB2, or TP53 gene.

A new analysis of the Nigerian Breast Cancer Study confirmed that these inherited mutations drive about 12% of the country’s breast cancer cases. The findings could pave the way for the first large-scale national breast cancer gene screening program, wrote Olufunmilayo I. Olopade, MD, and her colleagues. The report is in the Journal of Clinical Oncology.

“We suggest that genomic sequencing to identify women at extremely high risk of breast cancer could be a highly innovative approach to tailored risk management and life-saving interventions,” wrote Dr. Olopade, director of the Center for Clinical Cancer Genetics at the University of Chicago, and her colleagues. “Nigeria now has data to prioritize the integration of genetic testing into its cancer control plan. Women with an extremely high risk of breast cancer because of mutations in these genes can be identified inexpensively and unambiguously and offered interventions to reduce cancer risk.”

And, since about half of the sisters and daughters of affected women will carry the same mutation, such a screening program could reach far beyond every index patient identified, the investigators noted.

“If these women at very high risk can be identified either through their relatives with breast cancer or in the general population, resources can be focused particularly on their behalf. For as-yet unaffected women at high genetic risk, these resources would be intensive surveillance for early detection of breast cancer and, after childbearing is completed, the possibility of preventive salpingo-oophorectomy. Integrated population screening for cancer for all women is the goal, but focused outreach to women at extremely high risk represents an especially efficient use of resources and an attainable evidence-based global health approach.”

The Nigerian Breast Cancer Study enrolled 1,136 women with invasive breast cancer from 1998 to 2014. These were compared with 997 women without cancer, matched from the same communities. Genetic sequencing searched for mutations in both known and breast cancer genes.

Cases and controls were a mean of 47 years old; only 6% of cases reported a family history of breast cancer. Of 577 patients with information on tumor stage, 86% (497) were diagnosed at stage III (241) or IV (256).

Among the cases, 167 (14.7%) carried a mutation in a breast cancer risk gene, compared with 1.8% of controls. BRCA1 was the most common mutation, occurring in 7% of patients; these women were 23 times more likely to develop breast cancer than were those without the gene (odds ratio, 23.4). BRCA2 was the next most common, occurring in 4% of cases and conferring a nearly 11-fold increased risk (OR, 10.76). PALB2 occurred in 11 cases (1%) and no controls, and TP53 in four cases (0.4%).

Women with the BRCA1 mutation were diagnosed at a significantly younger age than were other patients (42.6 vs. 47.9 years), as were carriers of the TP53 mutation (32.8 vs. 47.6 years).

Ten other genes (ATM, BARD1, BRIP1, CHEK1, CHEK2, GEN1, NBN, RAD51C, RAD51D, and XRCC2) carried a mutation in at least one patient each. “When limited to mutations in the four high-risk genes, 11%-12% of cases in this study carried a loss-of-function variant.”

Dr. Olopade had no financial disclosures.

[email protected]

SOURCE: Olopade et al. J Clin Oncol. 2018 Aug 21. doi: 10.1200/JCO.2018.78.3977.

About one in eight Nigerian women with breast cancer has an inherited mutation of the BRCA1, BRCA2, PALB2, or TP53 gene.

A new analysis of the Nigerian Breast Cancer Study confirmed that these inherited mutations drive about 12% of the country’s breast cancer cases. The findings could pave the way for the first large-scale national breast cancer gene screening program, wrote Olufunmilayo I. Olopade, MD, and her colleagues. The report is in the Journal of Clinical Oncology.

“We suggest that genomic sequencing to identify women at extremely high risk of breast cancer could be a highly innovative approach to tailored risk management and life-saving interventions,” wrote Dr. Olopade, director of the Center for Clinical Cancer Genetics at the University of Chicago, and her colleagues. “Nigeria now has data to prioritize the integration of genetic testing into its cancer control plan. Women with an extremely high risk of breast cancer because of mutations in these genes can be identified inexpensively and unambiguously and offered interventions to reduce cancer risk.”

And, since about half of the sisters and daughters of affected women will carry the same mutation, such a screening program could reach far beyond every index patient identified, the investigators noted.

“If these women at very high risk can be identified either through their relatives with breast cancer or in the general population, resources can be focused particularly on their behalf. For as-yet unaffected women at high genetic risk, these resources would be intensive surveillance for early detection of breast cancer and, after childbearing is completed, the possibility of preventive salpingo-oophorectomy. Integrated population screening for cancer for all women is the goal, but focused outreach to women at extremely high risk represents an especially efficient use of resources and an attainable evidence-based global health approach.”

The Nigerian Breast Cancer Study enrolled 1,136 women with invasive breast cancer from 1998 to 2014. These were compared with 997 women without cancer, matched from the same communities. Genetic sequencing searched for mutations in both known and breast cancer genes.

Cases and controls were a mean of 47 years old; only 6% of cases reported a family history of breast cancer. Of 577 patients with information on tumor stage, 86% (497) were diagnosed at stage III (241) or IV (256).

Among the cases, 167 (14.7%) carried a mutation in a breast cancer risk gene, compared with 1.8% of controls. BRCA1 was the most common mutation, occurring in 7% of patients; these women were 23 times more likely to develop breast cancer than were those without the gene (odds ratio, 23.4). BRCA2 was the next most common, occurring in 4% of cases and conferring a nearly 11-fold increased risk (OR, 10.76). PALB2 occurred in 11 cases (1%) and no controls, and TP53 in four cases (0.4%).

Women with the BRCA1 mutation were diagnosed at a significantly younger age than were other patients (42.6 vs. 47.9 years), as were carriers of the TP53 mutation (32.8 vs. 47.6 years).

Ten other genes (ATM, BARD1, BRIP1, CHEK1, CHEK2, GEN1, NBN, RAD51C, RAD51D, and XRCC2) carried a mutation in at least one patient each. “When limited to mutations in the four high-risk genes, 11%-12% of cases in this study carried a loss-of-function variant.”

Dr. Olopade had no financial disclosures.

[email protected]

SOURCE: Olopade et al. J Clin Oncol. 2018 Aug 21. doi: 10.1200/JCO.2018.78.3977.

About one in eight Nigerian women with breast cancer has an inherited mutation of the BRCA1, BRCA2, PALB2, or TP53 gene.

A new analysis of the Nigerian Breast Cancer Study confirmed that these inherited mutations drive about 12% of the country’s breast cancer cases. The findings could pave the way for the first large-scale national breast cancer gene screening program, wrote Olufunmilayo I. Olopade, MD, and her colleagues. The report is in the Journal of Clinical Oncology.

“We suggest that genomic sequencing to identify women at extremely high risk of breast cancer could be a highly innovative approach to tailored risk management and life-saving interventions,” wrote Dr. Olopade, director of the Center for Clinical Cancer Genetics at the University of Chicago, and her colleagues. “Nigeria now has data to prioritize the integration of genetic testing into its cancer control plan. Women with an extremely high risk of breast cancer because of mutations in these genes can be identified inexpensively and unambiguously and offered interventions to reduce cancer risk.”

And, since about half of the sisters and daughters of affected women will carry the same mutation, such a screening program could reach far beyond every index patient identified, the investigators noted.

“If these women at very high risk can be identified either through their relatives with breast cancer or in the general population, resources can be focused particularly on their behalf. For as-yet unaffected women at high genetic risk, these resources would be intensive surveillance for early detection of breast cancer and, after childbearing is completed, the possibility of preventive salpingo-oophorectomy. Integrated population screening for cancer for all women is the goal, but focused outreach to women at extremely high risk represents an especially efficient use of resources and an attainable evidence-based global health approach.”

The Nigerian Breast Cancer Study enrolled 1,136 women with invasive breast cancer from 1998 to 2014. These were compared with 997 women without cancer, matched from the same communities. Genetic sequencing searched for mutations in both known and breast cancer genes.

Cases and controls were a mean of 47 years old; only 6% of cases reported a family history of breast cancer. Of 577 patients with information on tumor stage, 86% (497) were diagnosed at stage III (241) or IV (256).

Among the cases, 167 (14.7%) carried a mutation in a breast cancer risk gene, compared with 1.8% of controls. BRCA1 was the most common mutation, occurring in 7% of patients; these women were 23 times more likely to develop breast cancer than were those without the gene (odds ratio, 23.4). BRCA2 was the next most common, occurring in 4% of cases and conferring a nearly 11-fold increased risk (OR, 10.76). PALB2 occurred in 11 cases (1%) and no controls, and TP53 in four cases (0.4%).

Women with the BRCA1 mutation were diagnosed at a significantly younger age than were other patients (42.6 vs. 47.9 years), as were carriers of the TP53 mutation (32.8 vs. 47.6 years).

Ten other genes (ATM, BARD1, BRIP1, CHEK1, CHEK2, GEN1, NBN, RAD51C, RAD51D, and XRCC2) carried a mutation in at least one patient each. “When limited to mutations in the four high-risk genes, 11%-12% of cases in this study carried a loss-of-function variant.”

Dr. Olopade had no financial disclosures.

[email protected]

SOURCE: Olopade et al. J Clin Oncol. 2018 Aug 21. doi: 10.1200/JCO.2018.78.3977.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

[email protected]

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

[email protected]

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

[email protected]

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.

Jupiterimages/Thinkstock

The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.

Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.

The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.

“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”

The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.

The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.

[email protected]

SOURCE: CDC Breastfeeding Report Card
 

More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.

Jupiterimages/Thinkstock

The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.

Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.

The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.

“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”

The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.

The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.

[email protected]

SOURCE: CDC Breastfeeding Report Card
 

More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.

Jupiterimages/Thinkstock

The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.

Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.

The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.

“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”

The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.

The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.

[email protected]

SOURCE: CDC Breastfeeding Report Card
 

About 14% of 1-year-olds with prenatal Zika virus exposure show at least one health problem probably related to the virus, according to a study published in Morbidity and Mortality Weekly Report.

Many of the problems are brain and eye abnormalities, which occurred at 30 times the 0.16% background rate among unexposed babies, Margaret Honein, PhD, and colleagues reported.

In a press briefing, Dr. Honein, chief of the Birth Defects Branch at the National Center on Birth Defects and Developmental Disabilities, described findings from the U.S. Zika Pregnancy and Infant Registry (USZPIR).

“Today’s report is the largest to date with long-term outcomes of babies born to mothers with [lab-confirmed] Zika infections, and the first published data on children 1 year or older from the ongoing surveillance network,” Dr. Honein said. It “clearly shows that the Zika story is not over, especially for the children and families who are affected by it.”

USZPIR is monitoring the outcomes of 7,300 pregnancies with lab-confirmed Zika infection. From these, 4,800 babies were born in the U.S. territories and freely associated states, had reached the age of 1 year by Feb. 1, 2018, and were included in the study.

In addition to clinical outcomes, the investigators looked at how many babies received the recommended evaluations, including neuroimaging, hearing screens, opthalmologic exams, developmental screening, and physical exams.

Almost all (95%) had at least one exam in the first 2 weeks of life; 76% had at least one developmental screening; 60% had postnatal neuroimaging; 48% at least one hearing exam; and 36% at least one eye exam by a specialist, the investigators found.

Findings that many didn’t get all the recommended health screenings are concerning, CDC Director Robert Redfield, MD. said during the briefing. “We are still learning about the full range of long-term health problems these babies could face. We thank clinicians for their continued commitment to conduct all necessary tests and evaluations to ensure appropriate care.”

Zika-associated birth defects occurred 203 babies (14%). Another 136 (9%) had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection, and 20 (1%) had both. Most babies (1,386; 96%) did not have microcephaly detected at birth. But there was some “misclassification” of the condition, the investigators found. “Five infants had microcephaly at birth with brain or eye anomalies identified at birth; 59 had microcephaly at birth with no brain or eye anomalies identified at birth; and 20 infants did not have microcephaly identified at birth but had postnatal identification of microcephaly.”

Neurodevelopmental abnormalities possibly associated with Zika occurred in 136 (9%) of the cohort; 116 (8%) had no Zika-associated birth defects. Among these, half (58) had only possible developmental delay.

Zika transmission appears to be slowing, Lyle Peterson, MD, said during the press briefing, with no cases in the continental U.S. since 2017. That year, there were two cases in Florida and five in Texas. However, it is now endemic in many regions. Everyone should continue to take precautions against mosquito bites, he urged.

The MMWR also included updated guidance for men who are planning a pregnancy with a partner and may have been exposed to Zika.

CDC now recommends that these men wait at least 3 months after onset of Zika symptoms or any possible exposure, including travel to or living in a risk area. Past guidance recommended a 6-month waiting period. The new recommendation reflects emerging data suggesting that the risk of infectious Zika in semen declines during the 3 months after symptom onset.

Men who want to avoid passing Zika through sex should abstain for 3 months, or use a condom every time they have sex, the new recommendation said.

“All other Zika guidance remains unchanged,” the guidelines note. “Men with possible Zika virus exposure whose partner is pregnant should use condoms or the couple should not have sex for the entire pregnancy to reduce the risk of transmission.”

[email protected]

SOURCE: Honein, MA et al. MMWR 2018; 67: 1-10.

About 14% of 1-year-olds with prenatal Zika virus exposure show at least one health problem probably related to the virus, according to a study published in Morbidity and Mortality Weekly Report.

Many of the problems are brain and eye abnormalities, which occurred at 30 times the 0.16% background rate among unexposed babies, Margaret Honein, PhD, and colleagues reported.

In a press briefing, Dr. Honein, chief of the Birth Defects Branch at the National Center on Birth Defects and Developmental Disabilities, described findings from the U.S. Zika Pregnancy and Infant Registry (USZPIR).

“Today’s report is the largest to date with long-term outcomes of babies born to mothers with [lab-confirmed] Zika infections, and the first published data on children 1 year or older from the ongoing surveillance network,” Dr. Honein said. It “clearly shows that the Zika story is not over, especially for the children and families who are affected by it.”

USZPIR is monitoring the outcomes of 7,300 pregnancies with lab-confirmed Zika infection. From these, 4,800 babies were born in the U.S. territories and freely associated states, had reached the age of 1 year by Feb. 1, 2018, and were included in the study.

In addition to clinical outcomes, the investigators looked at how many babies received the recommended evaluations, including neuroimaging, hearing screens, opthalmologic exams, developmental screening, and physical exams.

Almost all (95%) had at least one exam in the first 2 weeks of life; 76% had at least one developmental screening; 60% had postnatal neuroimaging; 48% at least one hearing exam; and 36% at least one eye exam by a specialist, the investigators found.

Findings that many didn’t get all the recommended health screenings are concerning, CDC Director Robert Redfield, MD. said during the briefing. “We are still learning about the full range of long-term health problems these babies could face. We thank clinicians for their continued commitment to conduct all necessary tests and evaluations to ensure appropriate care.”

Zika-associated birth defects occurred 203 babies (14%). Another 136 (9%) had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection, and 20 (1%) had both. Most babies (1,386; 96%) did not have microcephaly detected at birth. But there was some “misclassification” of the condition, the investigators found. “Five infants had microcephaly at birth with brain or eye anomalies identified at birth; 59 had microcephaly at birth with no brain or eye anomalies identified at birth; and 20 infants did not have microcephaly identified at birth but had postnatal identification of microcephaly.”

Neurodevelopmental abnormalities possibly associated with Zika occurred in 136 (9%) of the cohort; 116 (8%) had no Zika-associated birth defects. Among these, half (58) had only possible developmental delay.

Zika transmission appears to be slowing, Lyle Peterson, MD, said during the press briefing, with no cases in the continental U.S. since 2017. That year, there were two cases in Florida and five in Texas. However, it is now endemic in many regions. Everyone should continue to take precautions against mosquito bites, he urged.

The MMWR also included updated guidance for men who are planning a pregnancy with a partner and may have been exposed to Zika.

CDC now recommends that these men wait at least 3 months after onset of Zika symptoms or any possible exposure, including travel to or living in a risk area. Past guidance recommended a 6-month waiting period. The new recommendation reflects emerging data suggesting that the risk of infectious Zika in semen declines during the 3 months after symptom onset.

Men who want to avoid passing Zika through sex should abstain for 3 months, or use a condom every time they have sex, the new recommendation said.

“All other Zika guidance remains unchanged,” the guidelines note. “Men with possible Zika virus exposure whose partner is pregnant should use condoms or the couple should not have sex for the entire pregnancy to reduce the risk of transmission.”

[email protected]

SOURCE: Honein, MA et al. MMWR 2018; 67: 1-10.

About 14% of 1-year-olds with prenatal Zika virus exposure show at least one health problem probably related to the virus, according to a study published in Morbidity and Mortality Weekly Report.

Many of the problems are brain and eye abnormalities, which occurred at 30 times the 0.16% background rate among unexposed babies, Margaret Honein, PhD, and colleagues reported.

In a press briefing, Dr. Honein, chief of the Birth Defects Branch at the National Center on Birth Defects and Developmental Disabilities, described findings from the U.S. Zika Pregnancy and Infant Registry (USZPIR).

“Today’s report is the largest to date with long-term outcomes of babies born to mothers with [lab-confirmed] Zika infections, and the first published data on children 1 year or older from the ongoing surveillance network,” Dr. Honein said. It “clearly shows that the Zika story is not over, especially for the children and families who are affected by it.”

USZPIR is monitoring the outcomes of 7,300 pregnancies with lab-confirmed Zika infection. From these, 4,800 babies were born in the U.S. territories and freely associated states, had reached the age of 1 year by Feb. 1, 2018, and were included in the study.

In addition to clinical outcomes, the investigators looked at how many babies received the recommended evaluations, including neuroimaging, hearing screens, opthalmologic exams, developmental screening, and physical exams.

Almost all (95%) had at least one exam in the first 2 weeks of life; 76% had at least one developmental screening; 60% had postnatal neuroimaging; 48% at least one hearing exam; and 36% at least one eye exam by a specialist, the investigators found.

Findings that many didn’t get all the recommended health screenings are concerning, CDC Director Robert Redfield, MD. said during the briefing. “We are still learning about the full range of long-term health problems these babies could face. We thank clinicians for their continued commitment to conduct all necessary tests and evaluations to ensure appropriate care.”

Zika-associated birth defects occurred 203 babies (14%). Another 136 (9%) had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection, and 20 (1%) had both. Most babies (1,386; 96%) did not have microcephaly detected at birth. But there was some “misclassification” of the condition, the investigators found. “Five infants had microcephaly at birth with brain or eye anomalies identified at birth; 59 had microcephaly at birth with no brain or eye anomalies identified at birth; and 20 infants did not have microcephaly identified at birth but had postnatal identification of microcephaly.”

Neurodevelopmental abnormalities possibly associated with Zika occurred in 136 (9%) of the cohort; 116 (8%) had no Zika-associated birth defects. Among these, half (58) had only possible developmental delay.

Zika transmission appears to be slowing, Lyle Peterson, MD, said during the press briefing, with no cases in the continental U.S. since 2017. That year, there were two cases in Florida and five in Texas. However, it is now endemic in many regions. Everyone should continue to take precautions against mosquito bites, he urged.

The MMWR also included updated guidance for men who are planning a pregnancy with a partner and may have been exposed to Zika.

CDC now recommends that these men wait at least 3 months after onset of Zika symptoms or any possible exposure, including travel to or living in a risk area. Past guidance recommended a 6-month waiting period. The new recommendation reflects emerging data suggesting that the risk of infectious Zika in semen declines during the 3 months after symptom onset.

Men who want to avoid passing Zika through sex should abstain for 3 months, or use a condom every time they have sex, the new recommendation said.

“All other Zika guidance remains unchanged,” the guidelines note. “Men with possible Zika virus exposure whose partner is pregnant should use condoms or the couple should not have sex for the entire pregnancy to reduce the risk of transmission.”

[email protected]

SOURCE: Honein, MA et al. MMWR 2018; 67: 1-10.

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

Patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prone to hospital readmissions that detract from quality of life and dramatically drive up care costs.

Because the two chronic diseases spring from the same root cause and share overlapping symptoms, strategies that improve clinical outcomes in one can also benefit the other, Ravi Kalhan, MD, and R. Kannan Mutharasan, MD, wrote in CHEST Journal (doi: 10.1016/j.chest.2018.06.001).

“Both conditions are characterized by periods of clinical stability punctuated by episodes of exacerbation and are typified by gradual functional decline,” wrote the colleagues, both of Northwestern University, Chicago. “From a patient perspective, both conditions lead to highly overlapping patterns of symptoms, involve complicated medication regimens, and have courses highly sensitive to adherence and lifestyle modification. Therefore, disease management strategies for both conditions can be synergistic.”

The team came up with a “Top 10 list” of practical tips for reducing readmissions in patients with this challenging combination.
 

Diagnose accurately

An acute hospitalization is often the first time these patients pop up on the radar. This is a great time to employ spirometry to accurately diagnose COPD. It’s also appropriate to conduct a chest CT and check right heart size, diameter of the pulmonary artery, and the presence of coronary calcification. The authors noted that relatively little is known about the course of patients with combined asthma and HF in contrast to COPD and HF.

Detect admissions for exacerbations early

Check soon to find out if this is a readmission, get an acute plan going, and don’t wait to implement multidisciplinary interventions. “First, specialist involvement can occur more rapidly, allowing for faster identification of any root causes driving the HF or COPD syndromes, and allowing for more rapid institution of treatment plans to control the acute exacerbation. Second, early identification during hospitalization allows time to deploy multidisciplinary interventions, such as disease management education, social work evaluation, follow-up appointment scheduling, and coordination of home services. These interventions are less effective, and are often not implemented, if initiated toward the end of hospitalization.”

Use specialist management in the hospital

Get experts on board fast. An integrated team means a coordinated treatment plan that’s easier to follow and more effective therapeutically. Specialist care may impact rates of readmission: weight loss with diuretics; discharge doses of guideline-directed medical therapy for heart failure; and higher rates of discharge on long-acting beta-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, and home supplemental oxygen.

Modify the underlying disease substrate

Heart failure is more likely to arise from a correctable pathophysiology, so find it early and treat it thoroughly – especially in younger patients. Ischemic heart disease, valvular heart disease, systemic hypertension, and pulmonary hypertension all have potential to make the HF syndrome more tractable.

Apply and intensify evidence-based therapies

Start in the hospital if possible; if not, begin upon discharge. “The order of application of these therapies can be bewildering, as many strategies for initiation and up-titration of these medications are reasonable. Not only are there long-term outcome benefits for these therapies, evidence suggests early initiation of HF therapies can reduce 30-day readmissions.”

Activate the patient and develop critical health behaviors

Medical regimens for these diseases can be complex, and they must be supported by patient engagement. “Many strategies for engaging patients in care have been tested, including teaching to goal, motivational interviewing, and teach-back methods of activation and engagement. Often these methods are time intensive. Because physician time is increasingly constrained, a team approach is particularly useful.”

Set up feedback loops

“Course correction should the patient decompensate is critically important to maintaining outpatient success. Feedback loops can allow for clinical stabilization before rehospitalization is necessary.” Self-monitoring with individually set benchmarks is critical.

Arrange an early follow-up appointment prior to discharge

About half of Medicare patients with these conditions are readmitted before they’ve even had a postdischarge follow-up appointment. Ideally this should occur within 7 days. The purpose of early follow-up is to identify and address gaps in the discharge plan of care, revise the discharge plan of care to adapt to the outpatient environment, and reinforce critical health behaviors.

Consider and address other comorbidities

Comorbidities are the rule rather than the exception and contribute to many readmissions. Get primary care on the team and enlist their help in managing these issues before they lead to an exacerbation. “Meticulous control – even perfect control were it possible – of cardiopulmonary disease would still leave patients vulnerable to significant risk of readmission from other causes.”

Consider ancillary supportive services at home

Patients may be overwhelmed by the complexity of postdischarge care. Home health assistance can help in getting patients to physical therapy, continuing patient education, and providing a home clinical assessment.

Neither of the authors had any financial disclosures.

[email protected]

Patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prone to hospital readmissions that detract from quality of life and dramatically drive up care costs.

Because the two chronic diseases spring from the same root cause and share overlapping symptoms, strategies that improve clinical outcomes in one can also benefit the other, Ravi Kalhan, MD, and R. Kannan Mutharasan, MD, wrote in CHEST Journal (doi: 10.1016/j.chest.2018.06.001).

“Both conditions are characterized by periods of clinical stability punctuated by episodes of exacerbation and are typified by gradual functional decline,” wrote the colleagues, both of Northwestern University, Chicago. “From a patient perspective, both conditions lead to highly overlapping patterns of symptoms, involve complicated medication regimens, and have courses highly sensitive to adherence and lifestyle modification. Therefore, disease management strategies for both conditions can be synergistic.”

The team came up with a “Top 10 list” of practical tips for reducing readmissions in patients with this challenging combination.
 

Diagnose accurately

An acute hospitalization is often the first time these patients pop up on the radar. This is a great time to employ spirometry to accurately diagnose COPD. It’s also appropriate to conduct a chest CT and check right heart size, diameter of the pulmonary artery, and the presence of coronary calcification. The authors noted that relatively little is known about the course of patients with combined asthma and HF in contrast to COPD and HF.

Detect admissions for exacerbations early

Check soon to find out if this is a readmission, get an acute plan going, and don’t wait to implement multidisciplinary interventions. “First, specialist involvement can occur more rapidly, allowing for faster identification of any root causes driving the HF or COPD syndromes, and allowing for more rapid institution of treatment plans to control the acute exacerbation. Second, early identification during hospitalization allows time to deploy multidisciplinary interventions, such as disease management education, social work evaluation, follow-up appointment scheduling, and coordination of home services. These interventions are less effective, and are often not implemented, if initiated toward the end of hospitalization.”

Use specialist management in the hospital

Get experts on board fast. An integrated team means a coordinated treatment plan that’s easier to follow and more effective therapeutically. Specialist care may impact rates of readmission: weight loss with diuretics; discharge doses of guideline-directed medical therapy for heart failure; and higher rates of discharge on long-acting beta-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, and home supplemental oxygen.

Modify the underlying disease substrate

Heart failure is more likely to arise from a correctable pathophysiology, so find it early and treat it thoroughly – especially in younger patients. Ischemic heart disease, valvular heart disease, systemic hypertension, and pulmonary hypertension all have potential to make the HF syndrome more tractable.

Apply and intensify evidence-based therapies

Start in the hospital if possible; if not, begin upon discharge. “The order of application of these therapies can be bewildering, as many strategies for initiation and up-titration of these medications are reasonable. Not only are there long-term outcome benefits for these therapies, evidence suggests early initiation of HF therapies can reduce 30-day readmissions.”

Activate the patient and develop critical health behaviors

Medical regimens for these diseases can be complex, and they must be supported by patient engagement. “Many strategies for engaging patients in care have been tested, including teaching to goal, motivational interviewing, and teach-back methods of activation and engagement. Often these methods are time intensive. Because physician time is increasingly constrained, a team approach is particularly useful.”

Set up feedback loops

“Course correction should the patient decompensate is critically important to maintaining outpatient success. Feedback loops can allow for clinical stabilization before rehospitalization is necessary.” Self-monitoring with individually set benchmarks is critical.

Arrange an early follow-up appointment prior to discharge

About half of Medicare patients with these conditions are readmitted before they’ve even had a postdischarge follow-up appointment. Ideally this should occur within 7 days. The purpose of early follow-up is to identify and address gaps in the discharge plan of care, revise the discharge plan of care to adapt to the outpatient environment, and reinforce critical health behaviors.

Consider and address other comorbidities

Comorbidities are the rule rather than the exception and contribute to many readmissions. Get primary care on the team and enlist their help in managing these issues before they lead to an exacerbation. “Meticulous control – even perfect control were it possible – of cardiopulmonary disease would still leave patients vulnerable to significant risk of readmission from other causes.”

Consider ancillary supportive services at home

Patients may be overwhelmed by the complexity of postdischarge care. Home health assistance can help in getting patients to physical therapy, continuing patient education, and providing a home clinical assessment.

Neither of the authors had any financial disclosures.

[email protected]

Patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prone to hospital readmissions that detract from quality of life and dramatically drive up care costs.

Because the two chronic diseases spring from the same root cause and share overlapping symptoms, strategies that improve clinical outcomes in one can also benefit the other, Ravi Kalhan, MD, and R. Kannan Mutharasan, MD, wrote in CHEST Journal (doi: 10.1016/j.chest.2018.06.001).

“Both conditions are characterized by periods of clinical stability punctuated by episodes of exacerbation and are typified by gradual functional decline,” wrote the colleagues, both of Northwestern University, Chicago. “From a patient perspective, both conditions lead to highly overlapping patterns of symptoms, involve complicated medication regimens, and have courses highly sensitive to adherence and lifestyle modification. Therefore, disease management strategies for both conditions can be synergistic.”

The team came up with a “Top 10 list” of practical tips for reducing readmissions in patients with this challenging combination.
 

Diagnose accurately

An acute hospitalization is often the first time these patients pop up on the radar. This is a great time to employ spirometry to accurately diagnose COPD. It’s also appropriate to conduct a chest CT and check right heart size, diameter of the pulmonary artery, and the presence of coronary calcification. The authors noted that relatively little is known about the course of patients with combined asthma and HF in contrast to COPD and HF.

Detect admissions for exacerbations early

Check soon to find out if this is a readmission, get an acute plan going, and don’t wait to implement multidisciplinary interventions. “First, specialist involvement can occur more rapidly, allowing for faster identification of any root causes driving the HF or COPD syndromes, and allowing for more rapid institution of treatment plans to control the acute exacerbation. Second, early identification during hospitalization allows time to deploy multidisciplinary interventions, such as disease management education, social work evaluation, follow-up appointment scheduling, and coordination of home services. These interventions are less effective, and are often not implemented, if initiated toward the end of hospitalization.”

Use specialist management in the hospital

Get experts on board fast. An integrated team means a coordinated treatment plan that’s easier to follow and more effective therapeutically. Specialist care may impact rates of readmission: weight loss with diuretics; discharge doses of guideline-directed medical therapy for heart failure; and higher rates of discharge on long-acting beta-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, and home supplemental oxygen.

Modify the underlying disease substrate

Heart failure is more likely to arise from a correctable pathophysiology, so find it early and treat it thoroughly – especially in younger patients. Ischemic heart disease, valvular heart disease, systemic hypertension, and pulmonary hypertension all have potential to make the HF syndrome more tractable.

Apply and intensify evidence-based therapies

Start in the hospital if possible; if not, begin upon discharge. “The order of application of these therapies can be bewildering, as many strategies for initiation and up-titration of these medications are reasonable. Not only are there long-term outcome benefits for these therapies, evidence suggests early initiation of HF therapies can reduce 30-day readmissions.”

Activate the patient and develop critical health behaviors

Medical regimens for these diseases can be complex, and they must be supported by patient engagement. “Many strategies for engaging patients in care have been tested, including teaching to goal, motivational interviewing, and teach-back methods of activation and engagement. Often these methods are time intensive. Because physician time is increasingly constrained, a team approach is particularly useful.”

Set up feedback loops

“Course correction should the patient decompensate is critically important to maintaining outpatient success. Feedback loops can allow for clinical stabilization before rehospitalization is necessary.” Self-monitoring with individually set benchmarks is critical.

Arrange an early follow-up appointment prior to discharge

About half of Medicare patients with these conditions are readmitted before they’ve even had a postdischarge follow-up appointment. Ideally this should occur within 7 days. The purpose of early follow-up is to identify and address gaps in the discharge plan of care, revise the discharge plan of care to adapt to the outpatient environment, and reinforce critical health behaviors.

Consider and address other comorbidities

Comorbidities are the rule rather than the exception and contribute to many readmissions. Get primary care on the team and enlist their help in managing these issues before they lead to an exacerbation. “Meticulous control – even perfect control were it possible – of cardiopulmonary disease would still leave patients vulnerable to significant risk of readmission from other causes.”

Consider ancillary supportive services at home

Patients may be overwhelmed by the complexity of postdischarge care. Home health assistance can help in getting patients to physical therapy, continuing patient education, and providing a home clinical assessment.

Neither of the authors had any financial disclosures.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]