Americans spend billions of dollars out-of-pocket on complementary health care, according to an analysis of data from the 2012 National Health Interview Survey conducted by the National Center for Complementary and Integrative Health (NCCIH) and the CDC.

Of the more than $30 billion spent by consumers, nearly $15 billion went to visits to chiropractors, acupuncturists, massage therapists, and other complementary practitioners—almost 30% of what Americans spent on out-of-pocket services by conventional physicians. The mean annual out-of-pocket expenditure for practitioner visits was $433. This analysis also included the first-ever data on spending for children: almost $2 billion.

Related: Complementary Therapp-y

Americans also spent billions on natural product supplements for an annual mean of $368 or about one-fourth of what they spent on prescription drugs.

Income level made little difference in expenditure. People with family incomes of < $25,000 averaged $314 for visits to complementary practitioners, vs $518 for those with incomes of more than $100,000.

The fact that so many people spent money on complementary approaches is “an indication that users believe enough in the value of these approaches to pay for them,” said Richard Nahin, PhD, lead author of the analysis and lead epidemiologist for National Center for Complementary and Integrative Health, which conducted the analysis.

Related: Complementary and Alternative Medicine for Chronic Musculoskeletal Pain

It’s also the reason that it’s “extremely important for us to provide the public with evidence-based information to help inform decisions,” said Josephine Briggs, MD, director of NCCIH. “This underscores the importance of conducting rigorous research to know whether the products and practices being used are safe and effective.”

Americans spend billions of dollars out-of-pocket on complementary health care, according to an analysis of data from the 2012 National Health Interview Survey conducted by the National Center for Complementary and Integrative Health (NCCIH) and the CDC.

Of the more than $30 billion spent by consumers, nearly $15 billion went to visits to chiropractors, acupuncturists, massage therapists, and other complementary practitioners—almost 30% of what Americans spent on out-of-pocket services by conventional physicians. The mean annual out-of-pocket expenditure for practitioner visits was $433. This analysis also included the first-ever data on spending for children: almost $2 billion.

Related: Complementary Therapp-y

Americans also spent billions on natural product supplements for an annual mean of $368 or about one-fourth of what they spent on prescription drugs.

Income level made little difference in expenditure. People with family incomes of < $25,000 averaged $314 for visits to complementary practitioners, vs $518 for those with incomes of more than $100,000.

The fact that so many people spent money on complementary approaches is “an indication that users believe enough in the value of these approaches to pay for them,” said Richard Nahin, PhD, lead author of the analysis and lead epidemiologist for National Center for Complementary and Integrative Health, which conducted the analysis.

Related: Complementary and Alternative Medicine for Chronic Musculoskeletal Pain

It’s also the reason that it’s “extremely important for us to provide the public with evidence-based information to help inform decisions,” said Josephine Briggs, MD, director of NCCIH. “This underscores the importance of conducting rigorous research to know whether the products and practices being used are safe and effective.”

Americans spend billions of dollars out-of-pocket on complementary health care, according to an analysis of data from the 2012 National Health Interview Survey conducted by the National Center for Complementary and Integrative Health (NCCIH) and the CDC.

Of the more than $30 billion spent by consumers, nearly $15 billion went to visits to chiropractors, acupuncturists, massage therapists, and other complementary practitioners—almost 30% of what Americans spent on out-of-pocket services by conventional physicians. The mean annual out-of-pocket expenditure for practitioner visits was $433. This analysis also included the first-ever data on spending for children: almost $2 billion.

Related: Complementary Therapp-y

Americans also spent billions on natural product supplements for an annual mean of $368 or about one-fourth of what they spent on prescription drugs.

Income level made little difference in expenditure. People with family incomes of < $25,000 averaged $314 for visits to complementary practitioners, vs $518 for those with incomes of more than $100,000.

The fact that so many people spent money on complementary approaches is “an indication that users believe enough in the value of these approaches to pay for them,” said Richard Nahin, PhD, lead author of the analysis and lead epidemiologist for National Center for Complementary and Integrative Health, which conducted the analysis.

Related: Complementary and Alternative Medicine for Chronic Musculoskeletal Pain

It’s also the reason that it’s “extremely important for us to provide the public with evidence-based information to help inform decisions,” said Josephine Briggs, MD, director of NCCIH. “This underscores the importance of conducting rigorous research to know whether the products and practices being used are safe and effective.”

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.

CML cells

Image by Difu Wu

Two preclinical studies published in Cancer Discovery suggest that EZH2 inhibitors might enhance the efficacy of treatment with tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

One study showed that CML leukemic stem cells (LSCs) are dependent upon EZH2.

The other study revealed that epigenetic reprogramming sensitizes CML LSCs to combined treatment with an EZH2 inhibitor and a TKI.

EZH2 dependence

In the first study, in vitro experiments revealed that LSCs have an overabundance of EZH2. In fact, the researchers found that EZH2 helps LSCs survive and give rise to full-fledged CML cells.

Experiments in mice showed that inactivating EZH2 through gene-editing techniques caused LSCs to die, halting CML at its source.

“The stem cells’ dependence on EZH2 suggests they will be especially vulnerable to drugs that target the protein,” said study author Stuart Orkin, MD, of Boston Children’s Hospital in Massachusetts.

“Our findings suggest inhibition of EZH2 should be considered as a way to eradicate CML when used in combination with current targeted therapies. It offers a promising approach to shortening the duration of therapy in order to achieve a cure. If successful, the cost savings of such an approach could also be significant.”

Combination treatment

The second study supports the idea that combining EZH2 inhibitors and TKIs could benefit patients with CML.

Mary T. Scott, of the University of Glasgow in the UK, and her colleagues found that EZH2 and H3K27me3 reprogramming is important for LSC survival and renders the cells sensitive to combined treatment with an EZH2 inhibitor and a TKI.

The researchers treated CML CD34+ cells, normal CD34+ cells, and LSCs with the EZH2 inhibitor GSK343 and the TKI dasatinib, both alone and in combination. The team said that GSK343 selectively targeted the loss of H3K27me3 in the presence of dasatinib.

In addition, combination treatment led to a significant reduction in cell viability (even in “TKI-persistent” cells), an increase in apoptosis, and a reduction in colony-forming cell and granulocyte/erythroid/macrophage/megakaryocyte outputs, when compared to dasatinib alone.

The researchers also evaluated a TKI and an EZH2 inhibitor in a mouse model of CML. The mice received nilotinib and EPZ-6438, both alone and in combination, for either 14 days or 25 days.

After 14 days of treatment, mice that received the combination had significant reductions in levels of leukemic (Ph+) human CD45+ cells, CD45+CD34+ progenitor cells, and primitive CD45+CD34+CD38− stem cells in the bone marrow, when compared to mice that received nilotinib alone.

After 25 days of treatment, mice that received the combination had near-complete elimination of CD45+CD34+ progenitor cells and a greater than 70% reduction of CD45+CD34+CD38− cells, when compared to mice that received nilotinib alone.

The researchers said these results demonstrate a clear rationale for combining TKI treatment with an EZH2 inhibitor, as an EZH2 inhibitor can target primitive CML cells not eradicated by a TKI alone.

CML cells

Image by Difu Wu

Two preclinical studies published in Cancer Discovery suggest that EZH2 inhibitors might enhance the efficacy of treatment with tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

One study showed that CML leukemic stem cells (LSCs) are dependent upon EZH2.

The other study revealed that epigenetic reprogramming sensitizes CML LSCs to combined treatment with an EZH2 inhibitor and a TKI.

EZH2 dependence

In the first study, in vitro experiments revealed that LSCs have an overabundance of EZH2. In fact, the researchers found that EZH2 helps LSCs survive and give rise to full-fledged CML cells.

Experiments in mice showed that inactivating EZH2 through gene-editing techniques caused LSCs to die, halting CML at its source.

“The stem cells’ dependence on EZH2 suggests they will be especially vulnerable to drugs that target the protein,” said study author Stuart Orkin, MD, of Boston Children’s Hospital in Massachusetts.

“Our findings suggest inhibition of EZH2 should be considered as a way to eradicate CML when used in combination with current targeted therapies. It offers a promising approach to shortening the duration of therapy in order to achieve a cure. If successful, the cost savings of such an approach could also be significant.”

Combination treatment

The second study supports the idea that combining EZH2 inhibitors and TKIs could benefit patients with CML.

Mary T. Scott, of the University of Glasgow in the UK, and her colleagues found that EZH2 and H3K27me3 reprogramming is important for LSC survival and renders the cells sensitive to combined treatment with an EZH2 inhibitor and a TKI.

The researchers treated CML CD34+ cells, normal CD34+ cells, and LSCs with the EZH2 inhibitor GSK343 and the TKI dasatinib, both alone and in combination. The team said that GSK343 selectively targeted the loss of H3K27me3 in the presence of dasatinib.

In addition, combination treatment led to a significant reduction in cell viability (even in “TKI-persistent” cells), an increase in apoptosis, and a reduction in colony-forming cell and granulocyte/erythroid/macrophage/megakaryocyte outputs, when compared to dasatinib alone.

The researchers also evaluated a TKI and an EZH2 inhibitor in a mouse model of CML. The mice received nilotinib and EPZ-6438, both alone and in combination, for either 14 days or 25 days.

After 14 days of treatment, mice that received the combination had significant reductions in levels of leukemic (Ph+) human CD45+ cells, CD45+CD34+ progenitor cells, and primitive CD45+CD34+CD38− stem cells in the bone marrow, when compared to mice that received nilotinib alone.

After 25 days of treatment, mice that received the combination had near-complete elimination of CD45+CD34+ progenitor cells and a greater than 70% reduction of CD45+CD34+CD38− cells, when compared to mice that received nilotinib alone.

The researchers said these results demonstrate a clear rationale for combining TKI treatment with an EZH2 inhibitor, as an EZH2 inhibitor can target primitive CML cells not eradicated by a TKI alone.

CML cells

Image by Difu Wu

Two preclinical studies published in Cancer Discovery suggest that EZH2 inhibitors might enhance the efficacy of treatment with tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

One study showed that CML leukemic stem cells (LSCs) are dependent upon EZH2.

The other study revealed that epigenetic reprogramming sensitizes CML LSCs to combined treatment with an EZH2 inhibitor and a TKI.

EZH2 dependence

In the first study, in vitro experiments revealed that LSCs have an overabundance of EZH2. In fact, the researchers found that EZH2 helps LSCs survive and give rise to full-fledged CML cells.

Experiments in mice showed that inactivating EZH2 through gene-editing techniques caused LSCs to die, halting CML at its source.

“The stem cells’ dependence on EZH2 suggests they will be especially vulnerable to drugs that target the protein,” said study author Stuart Orkin, MD, of Boston Children’s Hospital in Massachusetts.

“Our findings suggest inhibition of EZH2 should be considered as a way to eradicate CML when used in combination with current targeted therapies. It offers a promising approach to shortening the duration of therapy in order to achieve a cure. If successful, the cost savings of such an approach could also be significant.”

Combination treatment

The second study supports the idea that combining EZH2 inhibitors and TKIs could benefit patients with CML.

Mary T. Scott, of the University of Glasgow in the UK, and her colleagues found that EZH2 and H3K27me3 reprogramming is important for LSC survival and renders the cells sensitive to combined treatment with an EZH2 inhibitor and a TKI.

The researchers treated CML CD34+ cells, normal CD34+ cells, and LSCs with the EZH2 inhibitor GSK343 and the TKI dasatinib, both alone and in combination. The team said that GSK343 selectively targeted the loss of H3K27me3 in the presence of dasatinib.

In addition, combination treatment led to a significant reduction in cell viability (even in “TKI-persistent” cells), an increase in apoptosis, and a reduction in colony-forming cell and granulocyte/erythroid/macrophage/megakaryocyte outputs, when compared to dasatinib alone.

The researchers also evaluated a TKI and an EZH2 inhibitor in a mouse model of CML. The mice received nilotinib and EPZ-6438, both alone and in combination, for either 14 days or 25 days.

After 14 days of treatment, mice that received the combination had significant reductions in levels of leukemic (Ph+) human CD45+ cells, CD45+CD34+ progenitor cells, and primitive CD45+CD34+CD38− stem cells in the bone marrow, when compared to mice that received nilotinib alone.

After 25 days of treatment, mice that received the combination had near-complete elimination of CD45+CD34+ progenitor cells and a greater than 70% reduction of CD45+CD34+CD38− cells, when compared to mice that received nilotinib alone.

The researchers said these results demonstrate a clear rationale for combining TKI treatment with an EZH2 inhibitor, as an EZH2 inhibitor can target primitive CML cells not eradicated by a TKI alone.

Doctor using a smartphone

Photo by Daniel Sone

HEIDELBERG, GERMANY—Scientists have developed a smartphone application called HemaApp that can be used to measure hemoglobin levels and screen for anemia non-invasively.

HemaApp uses illumination sources from a smartphone, in combination with other light sources, and algorithms that analyze the color of a patient’s blood to estimate hemoglobin levels.

In a trial of 31 patients, HemaApp’s results compared favorably to an approved medical device that measures hemoglobin non-invasively.

Researchers described HemaApp in a paper presented at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016).

“In developing countries, community health workers have so much specialized equipment to monitor different conditions that they literally have whole bags full of devices,” said study author Edward Wang, a doctoral student at the University of Washington in Seattle.

“We are trying to make these screening tools work on one ubiquitous platform—a smartphone.”

How the app works

By shining light from the phone’s camera flash through the patient’s finger, HemaApp analyzes the color of the patient’s blood to estimate hemoglobin concentrations.

HemaApp bombards the finger with different wavelengths of light and infrared energy and creates a series of videos. By analyzing how colors are absorbed and reflected across those wavelengths, it can detect concentrations of hemoglobin and other blood components like plasma.

To ensure that the app works on different skin tones and body masses, the researchers developed processing algorithms that use the patient’s pulse to distinguish between the properties of the patient’s blood and the physical characteristics of his or her finger.

Testing

The researchers tested HemaApp on 31 subjects, including healthy students and staff at the University of Washington, inpatients at a children’s cancer and transfusion clinic, and inpatients at an adult cancer and bone marrow transplant clinic.

The subjects ranged in age from 6 to 77. Their hemoglobin levels ranged from 8 to 16 g/dL, and they had skin tones ranging from pale to dark.

The researchers compared results with HemaApp to results obtained via a complete blood count (CBC) and via the Masimo Pronto 7, a device that non-invasively measures hemoglobin by clipping a sensor onto a person’s finger.

The team tested HemaApp under 3 different scenarios—using the smartphone camera’s flash alone, in combination with a common incandescent lightbulb, and with a low-cost LED lighting attachment.

The additional illumination sources tap into other parts of the electromagnetic spectrum that have useful absorption properties but that aren’t currently found on all smartphone cameras.

“New phones are beginning to have more advanced infrared and multi-color LED capabilities,” said study author Shwetak Patel, PhD, of the University of Washington.

“But what we found is that even if your phone doesn’t have all that, you can put your finger near an external light source like a common lightbulb and boost the accuracy rates.”

Results

HemaApp’s hemoglobin measurements using a smartphone camera alone had a 69% correlation to results with the CBC. The app had a 74% correlation with the CBC when used with an incandescent light bulb and an 82% correlation when used with the LED lights.

In comparison, the Masimo Pronto 7’s measurements had an 81% correlation to the CBC.

When used to screen for anemia, HemaApp had higher sensitivity than the Masimo Pronto but lower specificity.

The app’s sensitivity was 79% using just the phone camera and 86% when used with the incandescent light bulb or LED lights, whereas Masimo Pronto’s sensitivity was 69%.

The app’s specificity was 71% when using just the phone or the incandescent light bulb and 77% with the LED lights, whereas Masimo Pronto’s specificity was 88%.

Next steps

The researchers said HemaApp is not intended to replace blood tests, which remain the most accurate way to measure hemoglobin. But the early test results suggest HemaApp can be an effective and affordable initial screening tool to determine whether further blood testing is warranted.

“Anemia is one of the most common problems affecting adults and children worldwide,” said study author Doug Hawkins, MD, of Seattle Children’s Hospital.

“The ability to screen quickly with a smartphone-based test could be a huge improvement to delivering care in limited-resource environments.”

Next research steps include wider national and international testing of HemaApp, collecting more data to improve accuracy rates, and using smartphones to try to detect abnormal hemoglobin properties that could help screen for sickle cell disease and other blood disorders.

“We’re just starting to scratch the surface here,” Dr Patel said. “There’s a lot that we want to tackle in using phones for non-invasively screening disease.”

Doctor using a smartphone

Photo by Daniel Sone

HEIDELBERG, GERMANY—Scientists have developed a smartphone application called HemaApp that can be used to measure hemoglobin levels and screen for anemia non-invasively.

HemaApp uses illumination sources from a smartphone, in combination with other light sources, and algorithms that analyze the color of a patient’s blood to estimate hemoglobin levels.

In a trial of 31 patients, HemaApp’s results compared favorably to an approved medical device that measures hemoglobin non-invasively.

Researchers described HemaApp in a paper presented at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016).

“In developing countries, community health workers have so much specialized equipment to monitor different conditions that they literally have whole bags full of devices,” said study author Edward Wang, a doctoral student at the University of Washington in Seattle.

“We are trying to make these screening tools work on one ubiquitous platform—a smartphone.”

How the app works

By shining light from the phone’s camera flash through the patient’s finger, HemaApp analyzes the color of the patient’s blood to estimate hemoglobin concentrations.

HemaApp bombards the finger with different wavelengths of light and infrared energy and creates a series of videos. By analyzing how colors are absorbed and reflected across those wavelengths, it can detect concentrations of hemoglobin and other blood components like plasma.

To ensure that the app works on different skin tones and body masses, the researchers developed processing algorithms that use the patient’s pulse to distinguish between the properties of the patient’s blood and the physical characteristics of his or her finger.

Testing

The researchers tested HemaApp on 31 subjects, including healthy students and staff at the University of Washington, inpatients at a children’s cancer and transfusion clinic, and inpatients at an adult cancer and bone marrow transplant clinic.

The subjects ranged in age from 6 to 77. Their hemoglobin levels ranged from 8 to 16 g/dL, and they had skin tones ranging from pale to dark.

The researchers compared results with HemaApp to results obtained via a complete blood count (CBC) and via the Masimo Pronto 7, a device that non-invasively measures hemoglobin by clipping a sensor onto a person’s finger.

The team tested HemaApp under 3 different scenarios—using the smartphone camera’s flash alone, in combination with a common incandescent lightbulb, and with a low-cost LED lighting attachment.

The additional illumination sources tap into other parts of the electromagnetic spectrum that have useful absorption properties but that aren’t currently found on all smartphone cameras.

“New phones are beginning to have more advanced infrared and multi-color LED capabilities,” said study author Shwetak Patel, PhD, of the University of Washington.

“But what we found is that even if your phone doesn’t have all that, you can put your finger near an external light source like a common lightbulb and boost the accuracy rates.”

Results

HemaApp’s hemoglobin measurements using a smartphone camera alone had a 69% correlation to results with the CBC. The app had a 74% correlation with the CBC when used with an incandescent light bulb and an 82% correlation when used with the LED lights.

In comparison, the Masimo Pronto 7’s measurements had an 81% correlation to the CBC.

When used to screen for anemia, HemaApp had higher sensitivity than the Masimo Pronto but lower specificity.

The app’s sensitivity was 79% using just the phone camera and 86% when used with the incandescent light bulb or LED lights, whereas Masimo Pronto’s sensitivity was 69%.

The app’s specificity was 71% when using just the phone or the incandescent light bulb and 77% with the LED lights, whereas Masimo Pronto’s specificity was 88%.

Next steps

The researchers said HemaApp is not intended to replace blood tests, which remain the most accurate way to measure hemoglobin. But the early test results suggest HemaApp can be an effective and affordable initial screening tool to determine whether further blood testing is warranted.

“Anemia is one of the most common problems affecting adults and children worldwide,” said study author Doug Hawkins, MD, of Seattle Children’s Hospital.

“The ability to screen quickly with a smartphone-based test could be a huge improvement to delivering care in limited-resource environments.”

Next research steps include wider national and international testing of HemaApp, collecting more data to improve accuracy rates, and using smartphones to try to detect abnormal hemoglobin properties that could help screen for sickle cell disease and other blood disorders.

“We’re just starting to scratch the surface here,” Dr Patel said. “There’s a lot that we want to tackle in using phones for non-invasively screening disease.”

Doctor using a smartphone

Photo by Daniel Sone

HEIDELBERG, GERMANY—Scientists have developed a smartphone application called HemaApp that can be used to measure hemoglobin levels and screen for anemia non-invasively.

HemaApp uses illumination sources from a smartphone, in combination with other light sources, and algorithms that analyze the color of a patient’s blood to estimate hemoglobin levels.

In a trial of 31 patients, HemaApp’s results compared favorably to an approved medical device that measures hemoglobin non-invasively.

Researchers described HemaApp in a paper presented at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016).

“In developing countries, community health workers have so much specialized equipment to monitor different conditions that they literally have whole bags full of devices,” said study author Edward Wang, a doctoral student at the University of Washington in Seattle.

“We are trying to make these screening tools work on one ubiquitous platform—a smartphone.”

How the app works

By shining light from the phone’s camera flash through the patient’s finger, HemaApp analyzes the color of the patient’s blood to estimate hemoglobin concentrations.

HemaApp bombards the finger with different wavelengths of light and infrared energy and creates a series of videos. By analyzing how colors are absorbed and reflected across those wavelengths, it can detect concentrations of hemoglobin and other blood components like plasma.

To ensure that the app works on different skin tones and body masses, the researchers developed processing algorithms that use the patient’s pulse to distinguish between the properties of the patient’s blood and the physical characteristics of his or her finger.

Testing

The researchers tested HemaApp on 31 subjects, including healthy students and staff at the University of Washington, inpatients at a children’s cancer and transfusion clinic, and inpatients at an adult cancer and bone marrow transplant clinic.

The subjects ranged in age from 6 to 77. Their hemoglobin levels ranged from 8 to 16 g/dL, and they had skin tones ranging from pale to dark.

The researchers compared results with HemaApp to results obtained via a complete blood count (CBC) and via the Masimo Pronto 7, a device that non-invasively measures hemoglobin by clipping a sensor onto a person’s finger.

The team tested HemaApp under 3 different scenarios—using the smartphone camera’s flash alone, in combination with a common incandescent lightbulb, and with a low-cost LED lighting attachment.

The additional illumination sources tap into other parts of the electromagnetic spectrum that have useful absorption properties but that aren’t currently found on all smartphone cameras.

“New phones are beginning to have more advanced infrared and multi-color LED capabilities,” said study author Shwetak Patel, PhD, of the University of Washington.

“But what we found is that even if your phone doesn’t have all that, you can put your finger near an external light source like a common lightbulb and boost the accuracy rates.”

Results

HemaApp’s hemoglobin measurements using a smartphone camera alone had a 69% correlation to results with the CBC. The app had a 74% correlation with the CBC when used with an incandescent light bulb and an 82% correlation when used with the LED lights.

In comparison, the Masimo Pronto 7’s measurements had an 81% correlation to the CBC.

When used to screen for anemia, HemaApp had higher sensitivity than the Masimo Pronto but lower specificity.

The app’s sensitivity was 79% using just the phone camera and 86% when used with the incandescent light bulb or LED lights, whereas Masimo Pronto’s sensitivity was 69%.

The app’s specificity was 71% when using just the phone or the incandescent light bulb and 77% with the LED lights, whereas Masimo Pronto’s specificity was 88%.

Next steps

The researchers said HemaApp is not intended to replace blood tests, which remain the most accurate way to measure hemoglobin. But the early test results suggest HemaApp can be an effective and affordable initial screening tool to determine whether further blood testing is warranted.

“Anemia is one of the most common problems affecting adults and children worldwide,” said study author Doug Hawkins, MD, of Seattle Children’s Hospital.

“The ability to screen quickly with a smartphone-based test could be a huge improvement to delivering care in limited-resource environments.”

Next research steps include wider national and international testing of HemaApp, collecting more data to improve accuracy rates, and using smartphones to try to detect abnormal hemoglobin properties that could help screen for sickle cell disease and other blood disorders.

“We’re just starting to scratch the surface here,” Dr Patel said. “There’s a lot that we want to tackle in using phones for non-invasively screening disease.”

Pregnant woman

Photo by Nina Matthews

A new study suggests that treating pregnant women according to the results of malaria tests does not lower the risk of adverse pregnancy outcomes when compared to treating all women prophylactically.

In fact, the screen-and-treat approach, in which women received dihydroartemisinin-piperaquine (DP) only if they tested positive for malaria, was associated with higher fetal loss and more malaria at delivery than the prophylactic approach, in which women just received treatment with sulfadoxine-pyrimethamine (SP).

This is in spite of the fact that the study was conducted in an area of high SP resistance.

Feiko ter Kuile, MD, PhD, of the Liverpool School of Tropical Medicine in the UK, and his colleagues conducted this study and detailed the results in PLOS Medicine.

During pregnancy, undetected infection with malaria parasites can lead to maternal anemia, low birthweight, and fetal loss.

Therefore, in areas where malaria is endemic, the World Health Organization recommends treating pregnant women with SP. However, in some areas, more than 90% of Plasmodium parasites are resistant to SP.

In the current study, researchers compared this standard of care to a screening approach where pregnant women were tested for malaria using rapid diagnostic tests and treated with DP only if they tested positive for the parasite.

The study included 1873 HIV-negative pregnant women treated at 3 sites in Malawi, Africa. All of the women had 3 or 4 scheduled visits in the second and third trimester, 4 to 6 weeks apart.

The women were randomized to receive SP at each visit (n=921) or to be screened for malaria at every visit and treated with DP if they tested positive (n=923).

The prevalence of malaria at delivery was higher in the screening-DP group than in the SP group—48.7% and 40.8%, respectively (relative risk=1.19; P=0.007).

And fetal loss was higher in the screening-DP group than the SP group—2.6% and 1.3%, respectively (relative risk=2.06; P=0.046).

However, the risk of live adverse birth outcomes was similar between the screening-DP and SP groups—29.9% and 28.8%, respectively (relative risk=1.04, P=0.625).

The researchers said these results suggest that intermittent malaria screening and treatment with DP is not a viable strategy to replace intermittent preventive therapy with SP in malaria-endemic areas in sub-Saharan Africa, despite the high levels of resistance to SP.

Pregnant woman

Photo by Nina Matthews

A new study suggests that treating pregnant women according to the results of malaria tests does not lower the risk of adverse pregnancy outcomes when compared to treating all women prophylactically.

In fact, the screen-and-treat approach, in which women received dihydroartemisinin-piperaquine (DP) only if they tested positive for malaria, was associated with higher fetal loss and more malaria at delivery than the prophylactic approach, in which women just received treatment with sulfadoxine-pyrimethamine (SP).

This is in spite of the fact that the study was conducted in an area of high SP resistance.

Feiko ter Kuile, MD, PhD, of the Liverpool School of Tropical Medicine in the UK, and his colleagues conducted this study and detailed the results in PLOS Medicine.

During pregnancy, undetected infection with malaria parasites can lead to maternal anemia, low birthweight, and fetal loss.

Therefore, in areas where malaria is endemic, the World Health Organization recommends treating pregnant women with SP. However, in some areas, more than 90% of Plasmodium parasites are resistant to SP.

In the current study, researchers compared this standard of care to a screening approach where pregnant women were tested for malaria using rapid diagnostic tests and treated with DP only if they tested positive for the parasite.

The study included 1873 HIV-negative pregnant women treated at 3 sites in Malawi, Africa. All of the women had 3 or 4 scheduled visits in the second and third trimester, 4 to 6 weeks apart.

The women were randomized to receive SP at each visit (n=921) or to be screened for malaria at every visit and treated with DP if they tested positive (n=923).

The prevalence of malaria at delivery was higher in the screening-DP group than in the SP group—48.7% and 40.8%, respectively (relative risk=1.19; P=0.007).

And fetal loss was higher in the screening-DP group than the SP group—2.6% and 1.3%, respectively (relative risk=2.06; P=0.046).

However, the risk of live adverse birth outcomes was similar between the screening-DP and SP groups—29.9% and 28.8%, respectively (relative risk=1.04, P=0.625).

The researchers said these results suggest that intermittent malaria screening and treatment with DP is not a viable strategy to replace intermittent preventive therapy with SP in malaria-endemic areas in sub-Saharan Africa, despite the high levels of resistance to SP.

Pregnant woman

Photo by Nina Matthews

A new study suggests that treating pregnant women according to the results of malaria tests does not lower the risk of adverse pregnancy outcomes when compared to treating all women prophylactically.

In fact, the screen-and-treat approach, in which women received dihydroartemisinin-piperaquine (DP) only if they tested positive for malaria, was associated with higher fetal loss and more malaria at delivery than the prophylactic approach, in which women just received treatment with sulfadoxine-pyrimethamine (SP).

This is in spite of the fact that the study was conducted in an area of high SP resistance.

Feiko ter Kuile, MD, PhD, of the Liverpool School of Tropical Medicine in the UK, and his colleagues conducted this study and detailed the results in PLOS Medicine.

During pregnancy, undetected infection with malaria parasites can lead to maternal anemia, low birthweight, and fetal loss.

Therefore, in areas where malaria is endemic, the World Health Organization recommends treating pregnant women with SP. However, in some areas, more than 90% of Plasmodium parasites are resistant to SP.

In the current study, researchers compared this standard of care to a screening approach where pregnant women were tested for malaria using rapid diagnostic tests and treated with DP only if they tested positive for the parasite.

The study included 1873 HIV-negative pregnant women treated at 3 sites in Malawi, Africa. All of the women had 3 or 4 scheduled visits in the second and third trimester, 4 to 6 weeks apart.

The women were randomized to receive SP at each visit (n=921) or to be screened for malaria at every visit and treated with DP if they tested positive (n=923).

The prevalence of malaria at delivery was higher in the screening-DP group than in the SP group—48.7% and 40.8%, respectively (relative risk=1.19; P=0.007).

And fetal loss was higher in the screening-DP group than the SP group—2.6% and 1.3%, respectively (relative risk=2.06; P=0.046).

However, the risk of live adverse birth outcomes was similar between the screening-DP and SP groups—29.9% and 28.8%, respectively (relative risk=1.04, P=0.625).

The researchers said these results suggest that intermittent malaria screening and treatment with DP is not a viable strategy to replace intermittent preventive therapy with SP in malaria-endemic areas in sub-Saharan Africa, despite the high levels of resistance to SP.

The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.

At 28 weeks, HbA_1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA_1c levels under 7.0%, outpacing those on the solo treatments.

Michele Sullivan/Frontline Medical News

Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.

In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA_1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.

Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m². Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.

At 28 weeks, baseline HbA_1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.

Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA_1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).

Specifically, the percentage of patients with an HbA_1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.

The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.

Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.

This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.

In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA_1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.

The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.

The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.

At 28 weeks, HbA_1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA_1c levels under 7.0%, outpacing those on the solo treatments.

Michele Sullivan/Frontline Medical News

Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.

In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA_1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.

Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m². Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.

At 28 weeks, baseline HbA_1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.

Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA_1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).

Specifically, the percentage of patients with an HbA_1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.

The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.

Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.

This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.

In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA_1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.

The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.

The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.

At 28 weeks, HbA_1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA_1c levels under 7.0%, outpacing those on the solo treatments.

Michele Sullivan/Frontline Medical News

Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.

In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA_1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.

Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m². Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.

At 28 weeks, baseline HbA_1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.

Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA_1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).

Specifically, the percentage of patients with an HbA_1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.

The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.

Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.

This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.

In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA_1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.

The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

[email protected]

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

[email protected]

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

[email protected]

Minimal residual disease negativity following treatment for newly diagnosed multiple myeloma is associated with long-term survival, according to findings from a meta-analysis of relevant data.

The findings suggest that assessment for minimal residual disease (MRD) should be included as an end point in clinical trials of multiple myeloma, Nikhil C. Munshi, MD, of Harvard Medical School, Boston, and his colleagues reported online Sept. 15 in JAMA Oncology.

Dana-Farber Cancer Institute

“This large cohort meta-analysis confirms that MRD status has prognostic value and is a valid surrogate marker for both PFS [progression-free survival] and OS [overall survival] in patients with multiple myeloma, including those who had achieved a CR [complete response],” the researchers wrote, noting that all of the studies confirmed the impact of MRD status on outcome, indicating that the predictive value of MRD status was independent of the type of treatment used.

Of 1,273 patients from 14 studies that looked at the impact of MRD status on PFS, 660 were MRD-negative and 613 were MRD-positive. Of 1,100 patients from 12 studies that looked at the impact of MRD on OS, 599 were MRD-negative, and 501 were MRD-positive. MRD-negative vs. -positive status was associated with better PFS and OS (hazard ratio, 0.41 and 0.57, respectively).

“Median PFS was 54 months for MRD-negative patients and 26 months for MRD-positive patients; median OS was 98 and 82 months, respectively,” the researchers wrote (JAMA Oncol. 2016 Sep 15. doi: 10.1001/jamaoncol.2016.3160).

Further, to evaluate the impact of MRD status on PFS and OS in patients who achieved conventional CR, they analyzed data from five studies looking at PFS in 396 MRD-negative and 178 MRD-positive patients, and 6 studies looking at OS in 430 MRD-negative and 186 MRD-positive patients. In patients achieving CR, the presence of MRD predicted shorter PFS (HR, 0.44) and shorter OS (HR, 0.47), they said.

“Median PFS was 56 months for MRD-negative patients and 34 months for MRD-positive patients, and median OS was 112 and 82 months, respectively. The OS rate was higher for MRD-negative patients, compared with MRD-positive patients at 3 years (94% vs. 80%), 5 years (80% vs. 61%), and 7 years (67% vs. 47%),” they wrote.

Although none of the studies included in the analysis compared the effect of two different treatment approaches on MRD status, five did evaluate MRD status before and after autologous stem cell transplantation, and all indicated that the treatment increased the proportion of MRD-negative patients.

Maintenance therapy also appeared, based on some of the studies, to have a beneficial effect on MRD status. In one study, MRD-negative status was maintained in 96% of patients receiving thalidomide maintenance therapy vs. 69% of MRD-negative patients receiving no maintenance therapy.

Minimal residual disease status is already considered an important prognostic factor in patients with multiple myeloma, and testing could be used to monitor response to therapy and guide subsequent treatment decisions, the investigators wrote, noting that “recent development of multiparameter flow cytometry– and next-generation sequencing–based methods has allowed for MRD assessment in larger studies.”

The findings provide quantitative evidence to support the conceptual basis for integrating MRD assessment after initial treatment in clinical trials as a surrogate end point for PFS and/or OS and in clinical practice to aid in prognostication and to guide treatment. However, “integration of MRD testing into standard practice requires optimization and standardization of MRD assessment and standardization of its timing,” they said.

This study was supported by the National Institutes of Health, the Medical Research Council, and Celgene. Dr. Munshi reported consultancy positions and advisory committee memberships with Celgene, Takeda, Janssen, and Merck.

[email protected]

Minimal residual disease negativity following treatment for newly diagnosed multiple myeloma is associated with long-term survival, according to findings from a meta-analysis of relevant data.

The findings suggest that assessment for minimal residual disease (MRD) should be included as an end point in clinical trials of multiple myeloma, Nikhil C. Munshi, MD, of Harvard Medical School, Boston, and his colleagues reported online Sept. 15 in JAMA Oncology.

Dana-Farber Cancer Institute

“This large cohort meta-analysis confirms that MRD status has prognostic value and is a valid surrogate marker for both PFS [progression-free survival] and OS [overall survival] in patients with multiple myeloma, including those who had achieved a CR [complete response],” the researchers wrote, noting that all of the studies confirmed the impact of MRD status on outcome, indicating that the predictive value of MRD status was independent of the type of treatment used.

Of 1,273 patients from 14 studies that looked at the impact of MRD status on PFS, 660 were MRD-negative and 613 were MRD-positive. Of 1,100 patients from 12 studies that looked at the impact of MRD on OS, 599 were MRD-negative, and 501 were MRD-positive. MRD-negative vs. -positive status was associated with better PFS and OS (hazard ratio, 0.41 and 0.57, respectively).

“Median PFS was 54 months for MRD-negative patients and 26 months for MRD-positive patients; median OS was 98 and 82 months, respectively,” the researchers wrote (JAMA Oncol. 2016 Sep 15. doi: 10.1001/jamaoncol.2016.3160).

Further, to evaluate the impact of MRD status on PFS and OS in patients who achieved conventional CR, they analyzed data from five studies looking at PFS in 396 MRD-negative and 178 MRD-positive patients, and 6 studies looking at OS in 430 MRD-negative and 186 MRD-positive patients. In patients achieving CR, the presence of MRD predicted shorter PFS (HR, 0.44) and shorter OS (HR, 0.47), they said.

“Median PFS was 56 months for MRD-negative patients and 34 months for MRD-positive patients, and median OS was 112 and 82 months, respectively. The OS rate was higher for MRD-negative patients, compared with MRD-positive patients at 3 years (94% vs. 80%), 5 years (80% vs. 61%), and 7 years (67% vs. 47%),” they wrote.

Although none of the studies included in the analysis compared the effect of two different treatment approaches on MRD status, five did evaluate MRD status before and after autologous stem cell transplantation, and all indicated that the treatment increased the proportion of MRD-negative patients.

Maintenance therapy also appeared, based on some of the studies, to have a beneficial effect on MRD status. In one study, MRD-negative status was maintained in 96% of patients receiving thalidomide maintenance therapy vs. 69% of MRD-negative patients receiving no maintenance therapy.

Minimal residual disease status is already considered an important prognostic factor in patients with multiple myeloma, and testing could be used to monitor response to therapy and guide subsequent treatment decisions, the investigators wrote, noting that “recent development of multiparameter flow cytometry– and next-generation sequencing–based methods has allowed for MRD assessment in larger studies.”

The findings provide quantitative evidence to support the conceptual basis for integrating MRD assessment after initial treatment in clinical trials as a surrogate end point for PFS and/or OS and in clinical practice to aid in prognostication and to guide treatment. However, “integration of MRD testing into standard practice requires optimization and standardization of MRD assessment and standardization of its timing,” they said.

This study was supported by the National Institutes of Health, the Medical Research Council, and Celgene. Dr. Munshi reported consultancy positions and advisory committee memberships with Celgene, Takeda, Janssen, and Merck.

[email protected]

Minimal residual disease negativity following treatment for newly diagnosed multiple myeloma is associated with long-term survival, according to findings from a meta-analysis of relevant data.

The findings suggest that assessment for minimal residual disease (MRD) should be included as an end point in clinical trials of multiple myeloma, Nikhil C. Munshi, MD, of Harvard Medical School, Boston, and his colleagues reported online Sept. 15 in JAMA Oncology.

Dana-Farber Cancer Institute

“This large cohort meta-analysis confirms that MRD status has prognostic value and is a valid surrogate marker for both PFS [progression-free survival] and OS [overall survival] in patients with multiple myeloma, including those who had achieved a CR [complete response],” the researchers wrote, noting that all of the studies confirmed the impact of MRD status on outcome, indicating that the predictive value of MRD status was independent of the type of treatment used.

Of 1,273 patients from 14 studies that looked at the impact of MRD status on PFS, 660 were MRD-negative and 613 were MRD-positive. Of 1,100 patients from 12 studies that looked at the impact of MRD on OS, 599 were MRD-negative, and 501 were MRD-positive. MRD-negative vs. -positive status was associated with better PFS and OS (hazard ratio, 0.41 and 0.57, respectively).

“Median PFS was 54 months for MRD-negative patients and 26 months for MRD-positive patients; median OS was 98 and 82 months, respectively,” the researchers wrote (JAMA Oncol. 2016 Sep 15. doi: 10.1001/jamaoncol.2016.3160).

Further, to evaluate the impact of MRD status on PFS and OS in patients who achieved conventional CR, they analyzed data from five studies looking at PFS in 396 MRD-negative and 178 MRD-positive patients, and 6 studies looking at OS in 430 MRD-negative and 186 MRD-positive patients. In patients achieving CR, the presence of MRD predicted shorter PFS (HR, 0.44) and shorter OS (HR, 0.47), they said.

“Median PFS was 56 months for MRD-negative patients and 34 months for MRD-positive patients, and median OS was 112 and 82 months, respectively. The OS rate was higher for MRD-negative patients, compared with MRD-positive patients at 3 years (94% vs. 80%), 5 years (80% vs. 61%), and 7 years (67% vs. 47%),” they wrote.

Although none of the studies included in the analysis compared the effect of two different treatment approaches on MRD status, five did evaluate MRD status before and after autologous stem cell transplantation, and all indicated that the treatment increased the proportion of MRD-negative patients.

Maintenance therapy also appeared, based on some of the studies, to have a beneficial effect on MRD status. In one study, MRD-negative status was maintained in 96% of patients receiving thalidomide maintenance therapy vs. 69% of MRD-negative patients receiving no maintenance therapy.

Minimal residual disease status is already considered an important prognostic factor in patients with multiple myeloma, and testing could be used to monitor response to therapy and guide subsequent treatment decisions, the investigators wrote, noting that “recent development of multiparameter flow cytometry– and next-generation sequencing–based methods has allowed for MRD assessment in larger studies.”

The findings provide quantitative evidence to support the conceptual basis for integrating MRD assessment after initial treatment in clinical trials as a surrogate end point for PFS and/or OS and in clinical practice to aid in prognostication and to guide treatment. However, “integration of MRD testing into standard practice requires optimization and standardization of MRD assessment and standardization of its timing,” they said.

This study was supported by the National Institutes of Health, the Medical Research Council, and Celgene. Dr. Munshi reported consultancy positions and advisory committee memberships with Celgene, Takeda, Janssen, and Merck.

[email protected]

There were 60 more pregnant women in the 50 states and the District of Columbia with laboratory evidence of Zika infection for the week ending Sept. 8, according to the Centers for Disease Control and Prevention.

That is the largest weekly increase yet among that population, and it brings the total number of Zika-infected pregnant women to 731 in the 50 states and D.C. so far in 2016. The U.S. territories reported 76 new cases for the week ending Sept. 8, for a territorial total of 1,156 and a combined U.S. total of 1,887 pregnant women with Zika virus, the CDC reported Sept. 15.

For the second week in a row, a liveborn infant with Zika-related birth defects was born in the 50 states/D.C. The total is now 19 for the year: 18 in the states/D.C. and 1 in the territories. There were no new pregnancy losses with Zika-related birth defects, so the number holds at six for the year: five in the states/D.C. and one in the territories, the CDC said.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

[email protected]

There were 60 more pregnant women in the 50 states and the District of Columbia with laboratory evidence of Zika infection for the week ending Sept. 8, according to the Centers for Disease Control and Prevention.

That is the largest weekly increase yet among that population, and it brings the total number of Zika-infected pregnant women to 731 in the 50 states and D.C. so far in 2016. The U.S. territories reported 76 new cases for the week ending Sept. 8, for a territorial total of 1,156 and a combined U.S. total of 1,887 pregnant women with Zika virus, the CDC reported Sept. 15.

For the second week in a row, a liveborn infant with Zika-related birth defects was born in the 50 states/D.C. The total is now 19 for the year: 18 in the states/D.C. and 1 in the territories. There were no new pregnancy losses with Zika-related birth defects, so the number holds at six for the year: five in the states/D.C. and one in the territories, the CDC said.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

[email protected]

There were 60 more pregnant women in the 50 states and the District of Columbia with laboratory evidence of Zika infection for the week ending Sept. 8, according to the Centers for Disease Control and Prevention.

That is the largest weekly increase yet among that population, and it brings the total number of Zika-infected pregnant women to 731 in the 50 states and D.C. so far in 2016. The U.S. territories reported 76 new cases for the week ending Sept. 8, for a territorial total of 1,156 and a combined U.S. total of 1,887 pregnant women with Zika virus, the CDC reported Sept. 15.

For the second week in a row, a liveborn infant with Zika-related birth defects was born in the 50 states/D.C. The total is now 19 for the year: 18 in the states/D.C. and 1 in the territories. There were no new pregnancy losses with Zika-related birth defects, so the number holds at six for the year: five in the states/D.C. and one in the territories, the CDC said.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

[email protected]

People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.

In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.

The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).

Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.

The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).

When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.

“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.

The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”

While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”

Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”

The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.

[email protected]

People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.

In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.

The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).

Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.

The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).

When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.

“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.

The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”

While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”

Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”

The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.

[email protected]

People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.

In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.

The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).

Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.

The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).

When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.

“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.

The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”

While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”

Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”

The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.

[email protected]