ANSWER
The correct interpretation of this ECG includes sinus tachycardia and left ventricular hypertrophy.

Sinus tachycardia is evidenced by an atrial rate greater than 100 beats/min with a P wave for every QRS complex and a QRS complex for every P wave.

Left ventricular hypertrophy is present when either the sum of the R wave voltage in lead I and the S wave in lead III is 25 mm or higher or the sum of the S wave in lead V₁ and the R wave in either V₅ or V₆ is 35 mm or higher.

In follow-up to these findings, an echocardiogram was recommended and performed. It revealed a normal heart consistent with that of a young athlete.

The patient and his parents were reassured as to the young man’s condition but decided to seek a second opinion.  

ANSWER
The correct interpretation of this ECG includes sinus tachycardia and left ventricular hypertrophy.

Sinus tachycardia is evidenced by an atrial rate greater than 100 beats/min with a P wave for every QRS complex and a QRS complex for every P wave.

Left ventricular hypertrophy is present when either the sum of the R wave voltage in lead I and the S wave in lead III is 25 mm or higher or the sum of the S wave in lead V₁ and the R wave in either V₅ or V₆ is 35 mm or higher.

In follow-up to these findings, an echocardiogram was recommended and performed. It revealed a normal heart consistent with that of a young athlete.

The patient and his parents were reassured as to the young man’s condition but decided to seek a second opinion.  

ANSWER
The correct interpretation of this ECG includes sinus tachycardia and left ventricular hypertrophy.

Sinus tachycardia is evidenced by an atrial rate greater than 100 beats/min with a P wave for every QRS complex and a QRS complex for every P wave.

Left ventricular hypertrophy is present when either the sum of the R wave voltage in lead I and the S wave in lead III is 25 mm or higher or the sum of the S wave in lead V₁ and the R wave in either V₅ or V₆ is 35 mm or higher.

In follow-up to these findings, an echocardiogram was recommended and performed. It revealed a normal heart consistent with that of a young athlete.

The patient and his parents were reassured as to the young man’s condition but decided to seek a second opinion.  

Researchers in the lab

Credit: Rhoda Baer

Investigators have identified drug combinations that may overcome resistance to ibrutinib in patients with mantle cell lymphoma (MCL).

The group discovered a mutation in Bruton’s tyrosine kinase (BTK) that confers resistance to the drug.

They also found that high levels of PI3K-AKT and CDK4 signaling could explain innate resistance to ibrutinib, so combining a CDK4 inhibitor and a PI3K inhibitor might be effective in patients who don’t respond to ibrutinib.

Selina Chen-Kiang, PhD, of Weill Cornell Medical College in New York, and her colleagues detailed these findings in Cancer Discovery. Some of Dr Chen-Kiang’s colleagues reported relationships with Janssen and Pharmacyclics, the companies developing ibrutinib.

“[Ibrutinib] doesn’t work for about 32% of patients, and their lymphomas are said to have primary resistance to ibrutinib,” Dr Chen-Kiang noted. “We are also learning that most patients whose lymphomas respond to ibrutinib eventually relapse because their tumors acquire resistance to the drug.”

“The knowledge that we gained from longitudinal RNA and genomic sequencing of mantle cell lymphomas with primary and acquired resistance to ibrutinib allowed us to identify rational drug combinations that may overcome resistance in these 2 settings.”

Dr Chen-Kiang and her colleagues conducted whole-exome and whole-transcriptome analyses of 5 serial biopsies from a patient with MCL who initially responded to ibrutinib before progressing.

After comparing these data with results from an analysis of healthy tissues from the same patient, the investigators found that a mutation in BTK, the C481S mutation, appeared at relapse.

The researchers found the same mutation at relapse in a second MCL patient with acquired resistance to ibrutinib but not in any patients with primary resistance to the drug.

Further analyses revealed the consequences of the relapse-specific BTK C481S mutation, including activation of the PI3K and CDK4 signaling pathways, which promote cell survival and proliferation.

Inhibiting CDK4 with the investigational anticancer drug palbociclib made ibrutinib-resistant lymphoma cells carrying the BTK C481S mutation sensitive to investigational drugs that inhibit PI3K.

And palbociclib made ibrutinib-resistant lymphoma cells harboring normal BTK sensitive to both ibrutinib and investigational drugs that inhibit PI3K. The researchers recently opened a clinical trial to test ibrutinib and palbociclib in combination (NCT02159755).

“We are very excited to have generated data . . . that may be meaningful for patients,” Dr Chen-Kiang said. “It is also exciting because CDK4 is a new kind of drug target. It controls the cell cycle, which is a central cancer pathway. As such, it is not just important for mantle cell lymphoma but for many forms of cancer.”

Researchers in the lab

Credit: Rhoda Baer

Investigators have identified drug combinations that may overcome resistance to ibrutinib in patients with mantle cell lymphoma (MCL).

The group discovered a mutation in Bruton’s tyrosine kinase (BTK) that confers resistance to the drug.

They also found that high levels of PI3K-AKT and CDK4 signaling could explain innate resistance to ibrutinib, so combining a CDK4 inhibitor and a PI3K inhibitor might be effective in patients who don’t respond to ibrutinib.

Selina Chen-Kiang, PhD, of Weill Cornell Medical College in New York, and her colleagues detailed these findings in Cancer Discovery. Some of Dr Chen-Kiang’s colleagues reported relationships with Janssen and Pharmacyclics, the companies developing ibrutinib.

“[Ibrutinib] doesn’t work for about 32% of patients, and their lymphomas are said to have primary resistance to ibrutinib,” Dr Chen-Kiang noted. “We are also learning that most patients whose lymphomas respond to ibrutinib eventually relapse because their tumors acquire resistance to the drug.”

“The knowledge that we gained from longitudinal RNA and genomic sequencing of mantle cell lymphomas with primary and acquired resistance to ibrutinib allowed us to identify rational drug combinations that may overcome resistance in these 2 settings.”

Dr Chen-Kiang and her colleagues conducted whole-exome and whole-transcriptome analyses of 5 serial biopsies from a patient with MCL who initially responded to ibrutinib before progressing.

After comparing these data with results from an analysis of healthy tissues from the same patient, the investigators found that a mutation in BTK, the C481S mutation, appeared at relapse.

The researchers found the same mutation at relapse in a second MCL patient with acquired resistance to ibrutinib but not in any patients with primary resistance to the drug.

Further analyses revealed the consequences of the relapse-specific BTK C481S mutation, including activation of the PI3K and CDK4 signaling pathways, which promote cell survival and proliferation.

Inhibiting CDK4 with the investigational anticancer drug palbociclib made ibrutinib-resistant lymphoma cells carrying the BTK C481S mutation sensitive to investigational drugs that inhibit PI3K.

And palbociclib made ibrutinib-resistant lymphoma cells harboring normal BTK sensitive to both ibrutinib and investigational drugs that inhibit PI3K. The researchers recently opened a clinical trial to test ibrutinib and palbociclib in combination (NCT02159755).

“We are very excited to have generated data . . . that may be meaningful for patients,” Dr Chen-Kiang said. “It is also exciting because CDK4 is a new kind of drug target. It controls the cell cycle, which is a central cancer pathway. As such, it is not just important for mantle cell lymphoma but for many forms of cancer.”

Researchers in the lab

Credit: Rhoda Baer

Investigators have identified drug combinations that may overcome resistance to ibrutinib in patients with mantle cell lymphoma (MCL).

The group discovered a mutation in Bruton’s tyrosine kinase (BTK) that confers resistance to the drug.

They also found that high levels of PI3K-AKT and CDK4 signaling could explain innate resistance to ibrutinib, so combining a CDK4 inhibitor and a PI3K inhibitor might be effective in patients who don’t respond to ibrutinib.

Selina Chen-Kiang, PhD, of Weill Cornell Medical College in New York, and her colleagues detailed these findings in Cancer Discovery. Some of Dr Chen-Kiang’s colleagues reported relationships with Janssen and Pharmacyclics, the companies developing ibrutinib.

“[Ibrutinib] doesn’t work for about 32% of patients, and their lymphomas are said to have primary resistance to ibrutinib,” Dr Chen-Kiang noted. “We are also learning that most patients whose lymphomas respond to ibrutinib eventually relapse because their tumors acquire resistance to the drug.”

“The knowledge that we gained from longitudinal RNA and genomic sequencing of mantle cell lymphomas with primary and acquired resistance to ibrutinib allowed us to identify rational drug combinations that may overcome resistance in these 2 settings.”

Dr Chen-Kiang and her colleagues conducted whole-exome and whole-transcriptome analyses of 5 serial biopsies from a patient with MCL who initially responded to ibrutinib before progressing.

After comparing these data with results from an analysis of healthy tissues from the same patient, the investigators found that a mutation in BTK, the C481S mutation, appeared at relapse.

The researchers found the same mutation at relapse in a second MCL patient with acquired resistance to ibrutinib but not in any patients with primary resistance to the drug.

Further analyses revealed the consequences of the relapse-specific BTK C481S mutation, including activation of the PI3K and CDK4 signaling pathways, which promote cell survival and proliferation.

Inhibiting CDK4 with the investigational anticancer drug palbociclib made ibrutinib-resistant lymphoma cells carrying the BTK C481S mutation sensitive to investigational drugs that inhibit PI3K.

And palbociclib made ibrutinib-resistant lymphoma cells harboring normal BTK sensitive to both ibrutinib and investigational drugs that inhibit PI3K. The researchers recently opened a clinical trial to test ibrutinib and palbociclib in combination (NCT02159755).

“We are very excited to have generated data . . . that may be meaningful for patients,” Dr Chen-Kiang said. “It is also exciting because CDK4 is a new kind of drug target. It controls the cell cycle, which is a central cancer pathway. As such, it is not just important for mantle cell lymphoma but for many forms of cancer.”

Sickle cells in blood

Credit: Graham Beards

Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.

The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.

The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).

“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.

He and his colleagues conducted this research and reported the results in Annals of Human Genetics.

The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.

And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.

While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.

Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.

Both HMIP-2A and HMIP2-B occur in Sub-Saharan Africa, but only at low frequencies. In much of the rest of the world, the alleles have combined, forming HMIP-2A-B, and this combination is relatively common in Europe, South Asia, and China. HMIP-2B alone is common in Far-East Asian peoples and in Amerindians.

The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.

The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia have arisen twice in modern humans, in Africa, and then spread to the rest of the world.

However, this likely occurred long before inherited blood disorders became prevalent, so the environmental factors that favored such variants in these early humans are not clear.

For the next stage of this research, Dr Menzel and his colleagues plan to explore which selection pressures or benefits might have contributed to the present population distribution of the variants.

Selection pressures could include nutritional factors, such as the availability of iron in the diet, or specific demands on red blood cell production, such as adaptation to high altitudes.

Sickle cells in blood

Credit: Graham Beards

Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.

The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.

The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).

“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.

He and his colleagues conducted this research and reported the results in Annals of Human Genetics.

The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.

And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.

While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.

Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.

Both HMIP-2A and HMIP2-B occur in Sub-Saharan Africa, but only at low frequencies. In much of the rest of the world, the alleles have combined, forming HMIP-2A-B, and this combination is relatively common in Europe, South Asia, and China. HMIP-2B alone is common in Far-East Asian peoples and in Amerindians.

The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.

The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia have arisen twice in modern humans, in Africa, and then spread to the rest of the world.

However, this likely occurred long before inherited blood disorders became prevalent, so the environmental factors that favored such variants in these early humans are not clear.

For the next stage of this research, Dr Menzel and his colleagues plan to explore which selection pressures or benefits might have contributed to the present population distribution of the variants.

Selection pressures could include nutritional factors, such as the availability of iron in the diet, or specific demands on red blood cell production, such as adaptation to high altitudes.

Sickle cells in blood

Credit: Graham Beards

Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.

The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.

The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).

“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.

He and his colleagues conducted this research and reported the results in Annals of Human Genetics.

The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.

And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.

While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.

Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.

Both HMIP-2A and HMIP2-B occur in Sub-Saharan Africa, but only at low frequencies. In much of the rest of the world, the alleles have combined, forming HMIP-2A-B, and this combination is relatively common in Europe, South Asia, and China. HMIP-2B alone is common in Far-East Asian peoples and in Amerindians.

The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.

The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia have arisen twice in modern humans, in Africa, and then spread to the rest of the world.

However, this likely occurred long before inherited blood disorders became prevalent, so the environmental factors that favored such variants in these early humans are not clear.

For the next stage of this research, Dr Menzel and his colleagues plan to explore which selection pressures or benefits might have contributed to the present population distribution of the variants.

Selection pressures could include nutritional factors, such as the availability of iron in the diet, or specific demands on red blood cell production, such as adaptation to high altitudes.

Child receiving RTS,S/AS01

Credit: Caitlin Kleiboer

A candidate malaria vaccine is more effective in children aged 5 months to 17 months than in infants 3 months of age or younger, results of a phase 3 study suggest.

Previous research indicated the vaccine— RTS,S/AS01—may prevent malaria in young children, but its efficacy wanes over time.

Now, researchers have reported that RTS,S/AS01 can sometimes prevent clinical malaria, severe malaria, and malaria hospitalization in children aged 5 to 17 months.

In the younger age group, the vaccine offered some protection against clinical malaria but did not significantly impact the rates of severe malaria or hospitalization.

The RTS,S Clinical Trials Partnership committee reported these findings in PLOS Medicine.

The study was sponsored by GSK Biologicals SA, the developer and manufacturer of RTS,S/AS01, and funded by both GSK Biologicals SA and the PATH Malaria Vaccine Initiative.

The researchers studied 6537 infants aged 6 to 12 weeks and 8923 children aged 5 to 17 months treated at 11 sites in Africa.

Subjects were randomized to receive 3 doses of RTS,S/AS01 or a comparator vaccine—a rabies vaccine (VeroRab) for the children and a meningococcal C conjugate vaccine (Menjugate) for the infants.

The primary outcome, vaccine efficacy (VE), was the reduction in malaria incidence among subjects who received RTS,S/AS01 compared to the incidence among subjects who received a comparator vaccine.

In the 18 months following vaccination, VE was 46% in children aged 5 to 17 months and 27% in infants aged 6 to 12 weeks. In both age groups, VE was highest in the first 6 months after vaccination.

RTS,S/AS01 averted an average of 829 cases of clinical malaria per 1000 children vaccinated (range, 37 to 2365) and 449 cases per 1000 infants (range, -10 to 1402) within 18 months of vaccination.

In children aged 5 to 17 months, VE was 34% for severe malaria, 41% for malaria hospitalization, and 19% for all-cause hospitalization. In the infants, there was no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization.

Serious adverse events occurred less often in children who received RTS,S/AS01 than in those who received a comparator vaccine—18.6% and 22.7%, respectively. In infants, the rate of serious adverse events was similar between the 2 vaccination groups.

Meningitis was more common in subjects who received RTS,S/AS01 than in those who received a comparator. However, the researchers have not established a causal relationship.

There were 16 cases of meningitis among the 5949 children in the RTS,S/AS01 group, 1 case among the 2974 children in the control group, 9 cases among the 4358 infants in the RTS,S/AS01 group, and 3 cases among the 2179 infants in the control group.

Despite the adverse events associated with RTS,S/AS01 and its decreased efficacy over time, the researchers believe the vaccine shows promise. They noted that, “even at modest levels of VE, the number of malaria cases averted was substantial.”

Now, the group is evaluating whether a booster immunization given 18 months after the primary vaccination can improve the efficacy of RTS,S/AS01.

Results of this study were previously reported at the Multilateral Initiative on Malaria Pan African Conference in October 2013 and published in The New England Journal of Medicine in October 2011 and November 2012. Long-term results of a phase 2 trial of RTS,S/AS01 were published in The New England Journal of Medicine in March 2013.

Child receiving RTS,S/AS01

Credit: Caitlin Kleiboer

A candidate malaria vaccine is more effective in children aged 5 months to 17 months than in infants 3 months of age or younger, results of a phase 3 study suggest.

Previous research indicated the vaccine— RTS,S/AS01—may prevent malaria in young children, but its efficacy wanes over time.

Now, researchers have reported that RTS,S/AS01 can sometimes prevent clinical malaria, severe malaria, and malaria hospitalization in children aged 5 to 17 months.

In the younger age group, the vaccine offered some protection against clinical malaria but did not significantly impact the rates of severe malaria or hospitalization.

The RTS,S Clinical Trials Partnership committee reported these findings in PLOS Medicine.

The study was sponsored by GSK Biologicals SA, the developer and manufacturer of RTS,S/AS01, and funded by both GSK Biologicals SA and the PATH Malaria Vaccine Initiative.

The researchers studied 6537 infants aged 6 to 12 weeks and 8923 children aged 5 to 17 months treated at 11 sites in Africa.

Subjects were randomized to receive 3 doses of RTS,S/AS01 or a comparator vaccine—a rabies vaccine (VeroRab) for the children and a meningococcal C conjugate vaccine (Menjugate) for the infants.

The primary outcome, vaccine efficacy (VE), was the reduction in malaria incidence among subjects who received RTS,S/AS01 compared to the incidence among subjects who received a comparator vaccine.

In the 18 months following vaccination, VE was 46% in children aged 5 to 17 months and 27% in infants aged 6 to 12 weeks. In both age groups, VE was highest in the first 6 months after vaccination.

RTS,S/AS01 averted an average of 829 cases of clinical malaria per 1000 children vaccinated (range, 37 to 2365) and 449 cases per 1000 infants (range, -10 to 1402) within 18 months of vaccination.

In children aged 5 to 17 months, VE was 34% for severe malaria, 41% for malaria hospitalization, and 19% for all-cause hospitalization. In the infants, there was no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization.

Serious adverse events occurred less often in children who received RTS,S/AS01 than in those who received a comparator vaccine—18.6% and 22.7%, respectively. In infants, the rate of serious adverse events was similar between the 2 vaccination groups.

Meningitis was more common in subjects who received RTS,S/AS01 than in those who received a comparator. However, the researchers have not established a causal relationship.

There were 16 cases of meningitis among the 5949 children in the RTS,S/AS01 group, 1 case among the 2974 children in the control group, 9 cases among the 4358 infants in the RTS,S/AS01 group, and 3 cases among the 2179 infants in the control group.

Despite the adverse events associated with RTS,S/AS01 and its decreased efficacy over time, the researchers believe the vaccine shows promise. They noted that, “even at modest levels of VE, the number of malaria cases averted was substantial.”

Now, the group is evaluating whether a booster immunization given 18 months after the primary vaccination can improve the efficacy of RTS,S/AS01.

Results of this study were previously reported at the Multilateral Initiative on Malaria Pan African Conference in October 2013 and published in The New England Journal of Medicine in October 2011 and November 2012. Long-term results of a phase 2 trial of RTS,S/AS01 were published in The New England Journal of Medicine in March 2013.

Child receiving RTS,S/AS01

Credit: Caitlin Kleiboer

A candidate malaria vaccine is more effective in children aged 5 months to 17 months than in infants 3 months of age or younger, results of a phase 3 study suggest.

Previous research indicated the vaccine— RTS,S/AS01—may prevent malaria in young children, but its efficacy wanes over time.

Now, researchers have reported that RTS,S/AS01 can sometimes prevent clinical malaria, severe malaria, and malaria hospitalization in children aged 5 to 17 months.

In the younger age group, the vaccine offered some protection against clinical malaria but did not significantly impact the rates of severe malaria or hospitalization.

The RTS,S Clinical Trials Partnership committee reported these findings in PLOS Medicine.

The study was sponsored by GSK Biologicals SA, the developer and manufacturer of RTS,S/AS01, and funded by both GSK Biologicals SA and the PATH Malaria Vaccine Initiative.

The researchers studied 6537 infants aged 6 to 12 weeks and 8923 children aged 5 to 17 months treated at 11 sites in Africa.

Subjects were randomized to receive 3 doses of RTS,S/AS01 or a comparator vaccine—a rabies vaccine (VeroRab) for the children and a meningococcal C conjugate vaccine (Menjugate) for the infants.

The primary outcome, vaccine efficacy (VE), was the reduction in malaria incidence among subjects who received RTS,S/AS01 compared to the incidence among subjects who received a comparator vaccine.

In the 18 months following vaccination, VE was 46% in children aged 5 to 17 months and 27% in infants aged 6 to 12 weeks. In both age groups, VE was highest in the first 6 months after vaccination.

RTS,S/AS01 averted an average of 829 cases of clinical malaria per 1000 children vaccinated (range, 37 to 2365) and 449 cases per 1000 infants (range, -10 to 1402) within 18 months of vaccination.

In children aged 5 to 17 months, VE was 34% for severe malaria, 41% for malaria hospitalization, and 19% for all-cause hospitalization. In the infants, there was no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization.

Serious adverse events occurred less often in children who received RTS,S/AS01 than in those who received a comparator vaccine—18.6% and 22.7%, respectively. In infants, the rate of serious adverse events was similar between the 2 vaccination groups.

Meningitis was more common in subjects who received RTS,S/AS01 than in those who received a comparator. However, the researchers have not established a causal relationship.

There were 16 cases of meningitis among the 5949 children in the RTS,S/AS01 group, 1 case among the 2974 children in the control group, 9 cases among the 4358 infants in the RTS,S/AS01 group, and 3 cases among the 2179 infants in the control group.

Despite the adverse events associated with RTS,S/AS01 and its decreased efficacy over time, the researchers believe the vaccine shows promise. They noted that, “even at modest levels of VE, the number of malaria cases averted was substantial.”

Now, the group is evaluating whether a booster immunization given 18 months after the primary vaccination can improve the efficacy of RTS,S/AS01.

Results of this study were previously reported at the Multilateral Initiative on Malaria Pan African Conference in October 2013 and published in The New England Journal of Medicine in October 2011 and November 2012. Long-term results of a phase 2 trial of RTS,S/AS01 were published in The New England Journal of Medicine in March 2013.

Malaria-carrying mosquito

Credit: James Gathany

Drug-resistant malaria parasites have spread to critical border regions of Southeast Asia, according to a study published in The New England Journal of Medicine.

The study confirms that resistance to the world’s most effective antimalarial drug, artemisinin, is now widespread in Southeast Asia.

This is not the first time malaria parasites have developed resistance to front-line drugs, and, each time, resistance has emerged from the same corner of Asia on the Cambodia-Thailand border.

To assess the extent of artemisinin resistance, researchers analyzed blood samples from 1241 malaria patients in 10 countries across Asia and Africa.

This revealed that artemisinin resistance in Plasmodium falciparum is now firmly established in western Cambodia, Thailand, Vietnam, eastern Myanmar, and northern Cambodia. There are also signs of emerging resistance in central Myanmar, southern Laos, and northeastern Cambodia.

There are no signs of resistance in the 3 African sites included in the study, located in Kenya, Nigeria, and the Democratic Republic of the Congo.

The study also suggested that extending the course of antimalarial treatment in areas with established resistance—for 6 days rather than the standard 3 days—could offer a temporary solution to this worsening problem.

“It may still be possible to prevent the spread of artemisinin-resistant malaria parasites across Asia and then to Africa by eliminating them, but that window of opportunity is closing fast,” said study author Nicholas White, FRS, of the University of Oxford in the UK.

“Conventional malaria control approaches won’t be enough. We will need to take more radical action and make this a global public health priority, without delay.”

He and his colleagues conducted this study by analyzing malaria-infected adults and children at 15 trial sites in 10 malaria-endemic countries between May 2011 and April 2013.

Patients received a 6-day antimalarial treatment—3 days of an artemisinin derivative and a 3-day course of artemisinin combination treatment (ACT). Then, the researchers analyzed patients’ blood to determine the rate at which the parasites were cleared.

The median parasite clearance half-life ranged from 1.8 hours in the Democratic Republic of the Congo to 7 hours at the Thailand-Cambodia border, where artemisinin resistance has been known to exist since 2005.

The proportion of patients with parasites in their blood 72 hours after treatment, a widely used test for artemisinin resistance, ranged from 0% in Kenya to 68% in Eastern Thailand.

Malaria infections that were slow to clear were strongly associated with a single point mutation in a P falciparum gene called kelch 13, an important validation of the recently discovered genetic marker (k13) in the DNA of the malaria parasite.

The researchers also found that patients who had slow-clearing infections were more likely to have parasite stages that can infect mosquitoes. This suggests artemisinin-resistant P falciparum parasites have a transmission advantage over parasites that are not resistant, which drives their spread.

“Frontline ACTs are still very effective at curing the majority of patients, but we need to be vigilant, as cure rates have fallen in areas where artemisinin resistance is established,” said study author Elizabeth Ashley, MBBS, PhD, also of the University of Oxford.

“Action is needed to prevent the spread of resistance from Myanmar into neighboring Bangladesh and India. The artemisinin drugs are arguably the best antimalarials we have ever had. We need to conserve them in areas where they are still working well.”

Malaria-carrying mosquito

Credit: James Gathany

Drug-resistant malaria parasites have spread to critical border regions of Southeast Asia, according to a study published in The New England Journal of Medicine.

The study confirms that resistance to the world’s most effective antimalarial drug, artemisinin, is now widespread in Southeast Asia.

This is not the first time malaria parasites have developed resistance to front-line drugs, and, each time, resistance has emerged from the same corner of Asia on the Cambodia-Thailand border.

To assess the extent of artemisinin resistance, researchers analyzed blood samples from 1241 malaria patients in 10 countries across Asia and Africa.

This revealed that artemisinin resistance in Plasmodium falciparum is now firmly established in western Cambodia, Thailand, Vietnam, eastern Myanmar, and northern Cambodia. There are also signs of emerging resistance in central Myanmar, southern Laos, and northeastern Cambodia.

There are no signs of resistance in the 3 African sites included in the study, located in Kenya, Nigeria, and the Democratic Republic of the Congo.

The study also suggested that extending the course of antimalarial treatment in areas with established resistance—for 6 days rather than the standard 3 days—could offer a temporary solution to this worsening problem.

“It may still be possible to prevent the spread of artemisinin-resistant malaria parasites across Asia and then to Africa by eliminating them, but that window of opportunity is closing fast,” said study author Nicholas White, FRS, of the University of Oxford in the UK.

“Conventional malaria control approaches won’t be enough. We will need to take more radical action and make this a global public health priority, without delay.”

He and his colleagues conducted this study by analyzing malaria-infected adults and children at 15 trial sites in 10 malaria-endemic countries between May 2011 and April 2013.

Patients received a 6-day antimalarial treatment—3 days of an artemisinin derivative and a 3-day course of artemisinin combination treatment (ACT). Then, the researchers analyzed patients’ blood to determine the rate at which the parasites were cleared.

The median parasite clearance half-life ranged from 1.8 hours in the Democratic Republic of the Congo to 7 hours at the Thailand-Cambodia border, where artemisinin resistance has been known to exist since 2005.

The proportion of patients with parasites in their blood 72 hours after treatment, a widely used test for artemisinin resistance, ranged from 0% in Kenya to 68% in Eastern Thailand.

Malaria infections that were slow to clear were strongly associated with a single point mutation in a P falciparum gene called kelch 13, an important validation of the recently discovered genetic marker (k13) in the DNA of the malaria parasite.

The researchers also found that patients who had slow-clearing infections were more likely to have parasite stages that can infect mosquitoes. This suggests artemisinin-resistant P falciparum parasites have a transmission advantage over parasites that are not resistant, which drives their spread.

“Frontline ACTs are still very effective at curing the majority of patients, but we need to be vigilant, as cure rates have fallen in areas where artemisinin resistance is established,” said study author Elizabeth Ashley, MBBS, PhD, also of the University of Oxford.

“Action is needed to prevent the spread of resistance from Myanmar into neighboring Bangladesh and India. The artemisinin drugs are arguably the best antimalarials we have ever had. We need to conserve them in areas where they are still working well.”

Malaria-carrying mosquito

Credit: James Gathany

Drug-resistant malaria parasites have spread to critical border regions of Southeast Asia, according to a study published in The New England Journal of Medicine.

The study confirms that resistance to the world’s most effective antimalarial drug, artemisinin, is now widespread in Southeast Asia.

This is not the first time malaria parasites have developed resistance to front-line drugs, and, each time, resistance has emerged from the same corner of Asia on the Cambodia-Thailand border.

To assess the extent of artemisinin resistance, researchers analyzed blood samples from 1241 malaria patients in 10 countries across Asia and Africa.

This revealed that artemisinin resistance in Plasmodium falciparum is now firmly established in western Cambodia, Thailand, Vietnam, eastern Myanmar, and northern Cambodia. There are also signs of emerging resistance in central Myanmar, southern Laos, and northeastern Cambodia.

There are no signs of resistance in the 3 African sites included in the study, located in Kenya, Nigeria, and the Democratic Republic of the Congo.

The study also suggested that extending the course of antimalarial treatment in areas with established resistance—for 6 days rather than the standard 3 days—could offer a temporary solution to this worsening problem.

“It may still be possible to prevent the spread of artemisinin-resistant malaria parasites across Asia and then to Africa by eliminating them, but that window of opportunity is closing fast,” said study author Nicholas White, FRS, of the University of Oxford in the UK.

“Conventional malaria control approaches won’t be enough. We will need to take more radical action and make this a global public health priority, without delay.”

He and his colleagues conducted this study by analyzing malaria-infected adults and children at 15 trial sites in 10 malaria-endemic countries between May 2011 and April 2013.

Patients received a 6-day antimalarial treatment—3 days of an artemisinin derivative and a 3-day course of artemisinin combination treatment (ACT). Then, the researchers analyzed patients’ blood to determine the rate at which the parasites were cleared.

The median parasite clearance half-life ranged from 1.8 hours in the Democratic Republic of the Congo to 7 hours at the Thailand-Cambodia border, where artemisinin resistance has been known to exist since 2005.

The proportion of patients with parasites in their blood 72 hours after treatment, a widely used test for artemisinin resistance, ranged from 0% in Kenya to 68% in Eastern Thailand.

Malaria infections that were slow to clear were strongly associated with a single point mutation in a P falciparum gene called kelch 13, an important validation of the recently discovered genetic marker (k13) in the DNA of the malaria parasite.

The researchers also found that patients who had slow-clearing infections were more likely to have parasite stages that can infect mosquitoes. This suggests artemisinin-resistant P falciparum parasites have a transmission advantage over parasites that are not resistant, which drives their spread.

“Frontline ACTs are still very effective at curing the majority of patients, but we need to be vigilant, as cure rates have fallen in areas where artemisinin resistance is established,” said study author Elizabeth Ashley, MBBS, PhD, also of the University of Oxford.

“Action is needed to prevent the spread of resistance from Myanmar into neighboring Bangladesh and India. The artemisinin drugs are arguably the best antimalarials we have ever had. We need to conserve them in areas where they are still working well.”

Recent meta-analysis that suggests aspirin might be as effective as some commonly used anticoagulants in preventing VTE following hip and knee replacement surgeries makes a case for further study, says a veteran hospitalist.

"Whereas we currently have a number of alternatives [at variable cost and efficacy] for preoperative prophylaxis against DVT and ensuing complications, we may be able to ultimately standardize a prophylactic regimen," Jairy C. Hunter, MD, MBA, SFHM, associate executive medical director for case management and care transitions at the Medical University of South Carolina in Charleston told The Hospitalist in an email. "If aspirin is found to be effective and safe as part of that regimen, then we can improve outcomes, as well as cost, while reducing the risk of complications from the prophylactic regimen itself."

Recently published in the Journal of Hospital Medicine, the paper reviewed eight randomized clinical trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity surgery (hip or knee replacement). Researchers' analysis included 1,408 participants and compared data on VTE, bleeding, and mortality risk with the type of medication involved.

The authors found aspirin to be as effective as anticoagulants for preventing VTE after lower extremity arthroplasty and linked it with lower bleeding risk after these surgeries. Aspirin also carried a lower risk of bleeding in patients following hip fracture repair, but researchers noted it might be linked with a higher risk of DVT in these patients, making anticoagulants a better choice for VTE prophylaxis post-hip fracture repair.

Frank Drescher, MD, assistant professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H., and lead author of the research, says he was surprised to see anticoagulants—often considered the stronger medication—made no difference compared with aspirin in lowering DVT risk with hip and knee replacement surgeries. He contends that patients' behavior post-surgery may make a difference.

Check out SHM's VTE prevention toolkit

"Early mobilization and pneumatic compression devices can help to prevent [VTE]," Dr. Dresher told The Hospitalist in an email. "It's possible that increasing use of non-pharmacological measures helps to mitigate differences between different pharmacological agents."

Hospitalists routinely see hip fracture repair patients and become involved in the orthopedic management of DVT prophylaxis, according to Anand Kartha, MD, MS, an academic hospitalist in the Veterans Affairs Boston Healthcare System and a member of Team Hospitalist. He says the research strengthens the idea "that physicians should not use aspirin on hip fracture patients for DVT prophylaxis or prevention" after surgery.

Dr. Drescher acknowledges some limitations of his meta-analysis, including the fact that researchers found few randomized trials with direct comparisons between aspirin and anticoagulants, and some trials were more than 10 years old. In the future, Dr. Drescher says he hopes to see more research on this topic.

Dr. Kartha agrees but says the first step is ensuring consistent use of the existing research. "Rather than debating the validity of one therapy versus the other…what is needed is consistent application of what is already known," he explains. "That is, there needs to be a standardized, institutional approach to this issue."TH

Visit our website for more information on VTE prophylaxis.

Recent meta-analysis that suggests aspirin might be as effective as some commonly used anticoagulants in preventing VTE following hip and knee replacement surgeries makes a case for further study, says a veteran hospitalist.

"Whereas we currently have a number of alternatives [at variable cost and efficacy] for preoperative prophylaxis against DVT and ensuing complications, we may be able to ultimately standardize a prophylactic regimen," Jairy C. Hunter, MD, MBA, SFHM, associate executive medical director for case management and care transitions at the Medical University of South Carolina in Charleston told The Hospitalist in an email. "If aspirin is found to be effective and safe as part of that regimen, then we can improve outcomes, as well as cost, while reducing the risk of complications from the prophylactic regimen itself."

Recently published in the Journal of Hospital Medicine, the paper reviewed eight randomized clinical trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity surgery (hip or knee replacement). Researchers' analysis included 1,408 participants and compared data on VTE, bleeding, and mortality risk with the type of medication involved.

The authors found aspirin to be as effective as anticoagulants for preventing VTE after lower extremity arthroplasty and linked it with lower bleeding risk after these surgeries. Aspirin also carried a lower risk of bleeding in patients following hip fracture repair, but researchers noted it might be linked with a higher risk of DVT in these patients, making anticoagulants a better choice for VTE prophylaxis post-hip fracture repair.

Frank Drescher, MD, assistant professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H., and lead author of the research, says he was surprised to see anticoagulants—often considered the stronger medication—made no difference compared with aspirin in lowering DVT risk with hip and knee replacement surgeries. He contends that patients' behavior post-surgery may make a difference.

Check out SHM's VTE prevention toolkit

"Early mobilization and pneumatic compression devices can help to prevent [VTE]," Dr. Dresher told The Hospitalist in an email. "It's possible that increasing use of non-pharmacological measures helps to mitigate differences between different pharmacological agents."

Hospitalists routinely see hip fracture repair patients and become involved in the orthopedic management of DVT prophylaxis, according to Anand Kartha, MD, MS, an academic hospitalist in the Veterans Affairs Boston Healthcare System and a member of Team Hospitalist. He says the research strengthens the idea "that physicians should not use aspirin on hip fracture patients for DVT prophylaxis or prevention" after surgery.

Dr. Drescher acknowledges some limitations of his meta-analysis, including the fact that researchers found few randomized trials with direct comparisons between aspirin and anticoagulants, and some trials were more than 10 years old. In the future, Dr. Drescher says he hopes to see more research on this topic.

Dr. Kartha agrees but says the first step is ensuring consistent use of the existing research. "Rather than debating the validity of one therapy versus the other…what is needed is consistent application of what is already known," he explains. "That is, there needs to be a standardized, institutional approach to this issue."TH

Visit our website for more information on VTE prophylaxis.

Recent meta-analysis that suggests aspirin might be as effective as some commonly used anticoagulants in preventing VTE following hip and knee replacement surgeries makes a case for further study, says a veteran hospitalist.

"Whereas we currently have a number of alternatives [at variable cost and efficacy] for preoperative prophylaxis against DVT and ensuing complications, we may be able to ultimately standardize a prophylactic regimen," Jairy C. Hunter, MD, MBA, SFHM, associate executive medical director for case management and care transitions at the Medical University of South Carolina in Charleston told The Hospitalist in an email. "If aspirin is found to be effective and safe as part of that regimen, then we can improve outcomes, as well as cost, while reducing the risk of complications from the prophylactic regimen itself."

Recently published in the Journal of Hospital Medicine, the paper reviewed eight randomized clinical trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity surgery (hip or knee replacement). Researchers' analysis included 1,408 participants and compared data on VTE, bleeding, and mortality risk with the type of medication involved.

The authors found aspirin to be as effective as anticoagulants for preventing VTE after lower extremity arthroplasty and linked it with lower bleeding risk after these surgeries. Aspirin also carried a lower risk of bleeding in patients following hip fracture repair, but researchers noted it might be linked with a higher risk of DVT in these patients, making anticoagulants a better choice for VTE prophylaxis post-hip fracture repair.

Frank Drescher, MD, assistant professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H., and lead author of the research, says he was surprised to see anticoagulants—often considered the stronger medication—made no difference compared with aspirin in lowering DVT risk with hip and knee replacement surgeries. He contends that patients' behavior post-surgery may make a difference.

Check out SHM's VTE prevention toolkit

"Early mobilization and pneumatic compression devices can help to prevent [VTE]," Dr. Dresher told The Hospitalist in an email. "It's possible that increasing use of non-pharmacological measures helps to mitigate differences between different pharmacological agents."

Hospitalists routinely see hip fracture repair patients and become involved in the orthopedic management of DVT prophylaxis, according to Anand Kartha, MD, MS, an academic hospitalist in the Veterans Affairs Boston Healthcare System and a member of Team Hospitalist. He says the research strengthens the idea "that physicians should not use aspirin on hip fracture patients for DVT prophylaxis or prevention" after surgery.

Dr. Drescher acknowledges some limitations of his meta-analysis, including the fact that researchers found few randomized trials with direct comparisons between aspirin and anticoagulants, and some trials were more than 10 years old. In the future, Dr. Drescher says he hopes to see more research on this topic.

Dr. Kartha agrees but says the first step is ensuring consistent use of the existing research. "Rather than debating the validity of one therapy versus the other…what is needed is consistent application of what is already known," he explains. "That is, there needs to be a standardized, institutional approach to this issue."TH

Visit our website for more information on VTE prophylaxis.

In March 2012, physicians and staff of the hospital medicine division at the University of California San Francisco (UCSF) kicked off a high-value care (HVC) program to more efficiently tie quality care delivery to healthcare costs. Early results suggest the plan is working, and the lead author of a recent paper believes other HM groups could use the program as a guide to implement similar plans in their own practices.

"There are a lot of idiosyncrasies between different programs and different medical centers, particularly when it comes to cost," says Christopher Moriates, MD, co-chair of the UCSF division's high-value care committee. "Many of the things we're identifying are indeed transplantable…but not all of them."

Published online this month in the Journal of Hospital Medicine, authors identify six ongoing HVC projects that have shown encouraging data in promoting improved healthcare value and clinician engagement. The projects are designed to:

• Reduce unnecessary nebulizer use;
• Curb overuse and inappropriate use of gastric stress ulcer prophylaxis;
• Encourage better blood utilization stewardship;
• Improve the use of telemetry;
• Scale back on inappropriate, repeat inpatient echocardiograms; and
• Reduce the number of ionized calcium labs.

To date, the nebulizer program has dropped usage rates by more than 50% on a high-acuity medical floor. Along with merely identifying waste-reduction and cost-savings plans, the program spells out goals for each initiative, strategies for reaching those goals, and next steps.

"We're not just creating these pilot programs and asking people to do more," Dr. Moriates says. "We're really thinking through these interventions as complete packages. We're really baking it into our culture. As we address what people actually do and change the systems around and change the way we think about things, it becomes standard practice and thus more likely to be sustainable." TH

Visit our website for more information on cost-effective, value-based patient care.

In March 2012, physicians and staff of the hospital medicine division at the University of California San Francisco (UCSF) kicked off a high-value care (HVC) program to more efficiently tie quality care delivery to healthcare costs. Early results suggest the plan is working, and the lead author of a recent paper believes other HM groups could use the program as a guide to implement similar plans in their own practices.

"There are a lot of idiosyncrasies between different programs and different medical centers, particularly when it comes to cost," says Christopher Moriates, MD, co-chair of the UCSF division's high-value care committee. "Many of the things we're identifying are indeed transplantable…but not all of them."

Published online this month in the Journal of Hospital Medicine, authors identify six ongoing HVC projects that have shown encouraging data in promoting improved healthcare value and clinician engagement. The projects are designed to:

• Reduce unnecessary nebulizer use;
• Curb overuse and inappropriate use of gastric stress ulcer prophylaxis;
• Encourage better blood utilization stewardship;
• Improve the use of telemetry;
• Scale back on inappropriate, repeat inpatient echocardiograms; and
• Reduce the number of ionized calcium labs.

To date, the nebulizer program has dropped usage rates by more than 50% on a high-acuity medical floor. Along with merely identifying waste-reduction and cost-savings plans, the program spells out goals for each initiative, strategies for reaching those goals, and next steps.

"We're not just creating these pilot programs and asking people to do more," Dr. Moriates says. "We're really thinking through these interventions as complete packages. We're really baking it into our culture. As we address what people actually do and change the systems around and change the way we think about things, it becomes standard practice and thus more likely to be sustainable." TH

Visit our website for more information on cost-effective, value-based patient care.

In March 2012, physicians and staff of the hospital medicine division at the University of California San Francisco (UCSF) kicked off a high-value care (HVC) program to more efficiently tie quality care delivery to healthcare costs. Early results suggest the plan is working, and the lead author of a recent paper believes other HM groups could use the program as a guide to implement similar plans in their own practices.

"There are a lot of idiosyncrasies between different programs and different medical centers, particularly when it comes to cost," says Christopher Moriates, MD, co-chair of the UCSF division's high-value care committee. "Many of the things we're identifying are indeed transplantable…but not all of them."

Published online this month in the Journal of Hospital Medicine, authors identify six ongoing HVC projects that have shown encouraging data in promoting improved healthcare value and clinician engagement. The projects are designed to:

• Reduce unnecessary nebulizer use;
• Curb overuse and inappropriate use of gastric stress ulcer prophylaxis;
• Encourage better blood utilization stewardship;
• Improve the use of telemetry;
• Scale back on inappropriate, repeat inpatient echocardiograms; and
• Reduce the number of ionized calcium labs.

To date, the nebulizer program has dropped usage rates by more than 50% on a high-acuity medical floor. Along with merely identifying waste-reduction and cost-savings plans, the program spells out goals for each initiative, strategies for reaching those goals, and next steps.

"We're not just creating these pilot programs and asking people to do more," Dr. Moriates says. "We're really thinking through these interventions as complete packages. We're really baking it into our culture. As we address what people actually do and change the systems around and change the way we think about things, it becomes standard practice and thus more likely to be sustainable." TH

Visit our website for more information on cost-effective, value-based patient care.

Presenter

Vincent Chiang, MD, Harvard Medical School and Boston Children's Hospital

Summary

Physicians suffer from “arrested development,” said Dr. Chiang, a hospitalist and chief of inpatient services at Boston Children’s Hospital, during a PHM2014 workshop on the basics of negotiation. Dr. Chiang was referring to the fact that in several professional realms, including negotiation, most physicians have not had the traditional experience of interviewing for and negotiating for jobs after high school or college.

An understanding of several negotiation concepts can help the negotiator achieve an agreeable solution. Awareness of values and limits prior to the actual discussion or negotiation will increase the chance of a successful negotiation. Examples of some of these concepts are:

1. Best alternative to a negotiation agreement (BATNA). This is the course of action if negotiations fail. The negotiator should not accept a worse resolution than the BATNA.
2. Reservation value (RV). This is the lowest value a negotiator will accept in a deal.
3. Zone of possible agreement (ZOPA). This is the intellectual zone between two parties in a negotiation where an agreement can be reached.

The twin tasks of negotiation are a) the need to learn about the true ZOPA in advance; and b) how to influence the other person’s perception of this zone.

There are several negotiation methods and strategies of influence that can be used to support your position or goals. For example, status quo bias is very common. By addressing the specific reason a person is not willing to change from the status quo, progress can be made.

While it is important to advocate for one’s position, fairness is an important variable in reaching an agreement. Fairness often is not universally defined. Communication is essential in understanding each group’s position.

Key Takeaways

1. Before entering a negotiation, understand your best alternative to a negotiation agreement and reservation value.
2. Understand your zone of possible agreement and then be aware of the zone of possible agreement of the person you are working with.
3. Learn strategies of influence to assist negotiations.
4. Fairness will assist in reaching agreement. TH

Dr. Hale is a member of Team Hospitalist and is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston.

Presenter

Vincent Chiang, MD, Harvard Medical School and Boston Children's Hospital

Summary

Physicians suffer from “arrested development,” said Dr. Chiang, a hospitalist and chief of inpatient services at Boston Children’s Hospital, during a PHM2014 workshop on the basics of negotiation. Dr. Chiang was referring to the fact that in several professional realms, including negotiation, most physicians have not had the traditional experience of interviewing for and negotiating for jobs after high school or college.

An understanding of several negotiation concepts can help the negotiator achieve an agreeable solution. Awareness of values and limits prior to the actual discussion or negotiation will increase the chance of a successful negotiation. Examples of some of these concepts are:

1. Best alternative to a negotiation agreement (BATNA). This is the course of action if negotiations fail. The negotiator should not accept a worse resolution than the BATNA.
2. Reservation value (RV). This is the lowest value a negotiator will accept in a deal.
3. Zone of possible agreement (ZOPA). This is the intellectual zone between two parties in a negotiation where an agreement can be reached.

The twin tasks of negotiation are a) the need to learn about the true ZOPA in advance; and b) how to influence the other person’s perception of this zone.

There are several negotiation methods and strategies of influence that can be used to support your position or goals. For example, status quo bias is very common. By addressing the specific reason a person is not willing to change from the status quo, progress can be made.

While it is important to advocate for one’s position, fairness is an important variable in reaching an agreement. Fairness often is not universally defined. Communication is essential in understanding each group’s position.

Key Takeaways

1. Before entering a negotiation, understand your best alternative to a negotiation agreement and reservation value.
2. Understand your zone of possible agreement and then be aware of the zone of possible agreement of the person you are working with.
3. Learn strategies of influence to assist negotiations.
4. Fairness will assist in reaching agreement. TH

Dr. Hale is a member of Team Hospitalist and is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston.

Presenter

Vincent Chiang, MD, Harvard Medical School and Boston Children's Hospital

Summary

Physicians suffer from “arrested development,” said Dr. Chiang, a hospitalist and chief of inpatient services at Boston Children’s Hospital, during a PHM2014 workshop on the basics of negotiation. Dr. Chiang was referring to the fact that in several professional realms, including negotiation, most physicians have not had the traditional experience of interviewing for and negotiating for jobs after high school or college.

An understanding of several negotiation concepts can help the negotiator achieve an agreeable solution. Awareness of values and limits prior to the actual discussion or negotiation will increase the chance of a successful negotiation. Examples of some of these concepts are:

1. Best alternative to a negotiation agreement (BATNA). This is the course of action if negotiations fail. The negotiator should not accept a worse resolution than the BATNA.
2. Reservation value (RV). This is the lowest value a negotiator will accept in a deal.
3. Zone of possible agreement (ZOPA). This is the intellectual zone between two parties in a negotiation where an agreement can be reached.

The twin tasks of negotiation are a) the need to learn about the true ZOPA in advance; and b) how to influence the other person’s perception of this zone.

There are several negotiation methods and strategies of influence that can be used to support your position or goals. For example, status quo bias is very common. By addressing the specific reason a person is not willing to change from the status quo, progress can be made.

While it is important to advocate for one’s position, fairness is an important variable in reaching an agreement. Fairness often is not universally defined. Communication is essential in understanding each group’s position.

Key Takeaways

1. Before entering a negotiation, understand your best alternative to a negotiation agreement and reservation value.
2. Understand your zone of possible agreement and then be aware of the zone of possible agreement of the person you are working with.
3. Learn strategies of influence to assist negotiations.
4. Fairness will assist in reaching agreement. TH

Dr. Hale is a member of Team Hospitalist and is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston.

Presenters

--- Welcome Remarks: Doug Carlson, MD, FAAP, chief of pediatric hospital medicine programs, St. Louis Children’s Hospital

--- The Next Phase of Delivery System Reform: Patrick Conway, MD, MSc, FAAP, MHM, deputy administrator for innovation and quality, CMO for the Centers for Medicare & Medicaid Services (CMS)

--- Hospitals and Health Systems: What’s on the Mind of Your CEO?: David J. Bailey, MD, MBA, president and CEO, the Nemours Foundation; Steve Narang, MD, MHCM, CEO, Banner Good Samaritan Medical Center, Phoenix, Ariz.; Jeff Sperring, MD, FAAP, president and CEO, Riley Hospital for Children at Indiana University Health, Indianapolis.

Summary

PHM 2014 began to heat up in steamy Orlando, as Dr. Carlson, chair of the PHM 2014 Organizing Committee, welcomed more than 800 pediatric hospitalists at the four-day annual meeting dedicated to pediatric hospital medicine.

Dr. Conway, a pediatric hospitalist prior to joining CMS, updated the crowd of ongoing reforms in the U.S. healthcare delivery system, with a focus on pediatrics. Healthcare delivery, Dr. Conway asserted, needs to move from an unsustainable, volume-driven, fee-for-service system to a people-centered, sustainable system where payment can be shaped by value-based purchasing, ACO-shared savings, and episode-based payments.

“Pediatrics,” Dr. Conway said, “is a leader in patient and family engagement, and population health.”

As such, the six goals of the CMS Quality Strategy align well with ongoing PHM efforts:

• Make care safer by reducing harm caused in care delivery;
•  Strengthen patient and family engagement as partners in their care;
•  Promote effective communication and coordination of care;
•  Promote effective prevention and treatment of chronic disease;
•  Work with communities to promote healthy living; and
•  Make care affordable.

Citing Maryland as an example, where a plan is being considered to shift 80% of hospital revenues to global models by 2018, Dr. Conway painted a picture of a rapidly-shifting reimbursement landscape that will soon be dominated by value-based purchasing, penalties for readmissions and healthcare-acquired conditions, and increasing emphasis on bundled payments, ACOs, and primary care medical homes.

“Hospitals are getting paid to keep people out of the hospital,” he said, and concurrently per capita spending on healthcare is now at historic lows. While pediatric quality measures are not as mature as those for adult patients, many opportunities for increasing value in pediatric care have been developed, such as the Choosing Wisely campaign and the Value in Inpatient Pediatrics (VIP) network.

Although not restricted to pediatrics, the CMS Partnership for Patients also aims to have a major impact on child health. Goals of a 40% reduction in HACs and 20% reduction in preventable 30-day readmissions have been set by the Partnership, with specific focus on 10 core patient-safety areas. Preliminary data have been promising, with a 9% reduction in HACs between 2010 and 2012 across all measures.

“This is a historical reduction,” said Dr. Conway, representing more than 500,000 patient harm events avoided, over 15,000 lives saved, and more than $4 billion in cost savings.

Within pediatrics, a number of research efforts have added to this reduction, including the Pediatric Research in Inpatient Settings (PRIS) Network, PHIS+, I-PASS, as well as several collaborative improvement networks.

Looking to the future, Medicaid and Children’s Health Insurance Program will continue to focus on quality initiatives and system transformation. These will include developing more pediatric-focused quality measures, improving health information technology, and continuing to award innovation in pediatrics. Pediatrics will continue to be a leader in these efforts, Dr. Conway said, because “we should care about longer time horizons.”

Four healthcare system CEOs also took the stage to answer questions from the audience, with Mark Shen, MD, president of Dell Children’s Medical Center, posing questions like a seasoned talk-show host. Panel members fielded a wide range of questions, including:

— How did you become a CEO?

“All I had to do was keep on saying ‘yes,’” Dr. Bailey said.

— What are you doing as a CEO to move from a fee-for-service system to a population-based system?

“We are still living in two different worlds…It depends on ACO penetration whether quality or volume will be the driver over the next 3-5 years,” Dr. Narang said.

“We have to create an accountable health community,” Dr. Shen said.

“The question is, how can you build a model that will allow you to flip the switch when this change occurs?” Dr. Sperring said.

— What is the role of hospitalists as care progresses from the most intensive but sometimes least appropriate site?

“I think the environment will drastically change, but there will be an ever enlarging role for hospitalists. … Hospitalists will likely be moving to LTACs, SNFs, even outpatient work.” Dr. Bailey said.

— If PHM fellowship becomes a requirement, will your hospital fund them?

“It’s hard to define what we do, but we know there are core competencies. … I don’t think we’re going to be at a point where certification will limit being a hospitalist any time soon,” Dr. Shen said.

— How can we make health care pricing more transparent?

“Why is it that in other industries, things are getting cheaper and higher quality, but in healthcare we seem to be going in the opposite direction?” Dr. Bailey said. “There has to be transparency for the patient. How about transparency for the provider? Every EMR should have a price for everything your order.”

— What do you think we can do to get more women into executive roles?

“Based on the percentages of women in medical school, residencies, and fellowships, I think it is inevitable that women will be the future leaders for our system,” Dr. Sperring said.

— What are the three most important things from a CEO perspective that a hospitalist should know?

“You have to have self-awareness…as a leader, are you a listener, are you a delegator?” Dr. Bailey said.

“Know where your organization wants to go,” Dr. Sperring said.

Dr. Chang is associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital. He is pediatric editor of The Hospitalist.

Presenters

--- Welcome Remarks: Doug Carlson, MD, FAAP, chief of pediatric hospital medicine programs, St. Louis Children’s Hospital

--- The Next Phase of Delivery System Reform: Patrick Conway, MD, MSc, FAAP, MHM, deputy administrator for innovation and quality, CMO for the Centers for Medicare & Medicaid Services (CMS)

--- Hospitals and Health Systems: What’s on the Mind of Your CEO?: David J. Bailey, MD, MBA, president and CEO, the Nemours Foundation; Steve Narang, MD, MHCM, CEO, Banner Good Samaritan Medical Center, Phoenix, Ariz.; Jeff Sperring, MD, FAAP, president and CEO, Riley Hospital for Children at Indiana University Health, Indianapolis.

Summary

PHM 2014 began to heat up in steamy Orlando, as Dr. Carlson, chair of the PHM 2014 Organizing Committee, welcomed more than 800 pediatric hospitalists at the four-day annual meeting dedicated to pediatric hospital medicine.

Dr. Conway, a pediatric hospitalist prior to joining CMS, updated the crowd of ongoing reforms in the U.S. healthcare delivery system, with a focus on pediatrics. Healthcare delivery, Dr. Conway asserted, needs to move from an unsustainable, volume-driven, fee-for-service system to a people-centered, sustainable system where payment can be shaped by value-based purchasing, ACO-shared savings, and episode-based payments.

“Pediatrics,” Dr. Conway said, “is a leader in patient and family engagement, and population health.”

As such, the six goals of the CMS Quality Strategy align well with ongoing PHM efforts:

• Make care safer by reducing harm caused in care delivery;
•  Strengthen patient and family engagement as partners in their care;
•  Promote effective communication and coordination of care;
•  Promote effective prevention and treatment of chronic disease;
•  Work with communities to promote healthy living; and
•  Make care affordable.

Citing Maryland as an example, where a plan is being considered to shift 80% of hospital revenues to global models by 2018, Dr. Conway painted a picture of a rapidly-shifting reimbursement landscape that will soon be dominated by value-based purchasing, penalties for readmissions and healthcare-acquired conditions, and increasing emphasis on bundled payments, ACOs, and primary care medical homes.

“Hospitals are getting paid to keep people out of the hospital,” he said, and concurrently per capita spending on healthcare is now at historic lows. While pediatric quality measures are not as mature as those for adult patients, many opportunities for increasing value in pediatric care have been developed, such as the Choosing Wisely campaign and the Value in Inpatient Pediatrics (VIP) network.

Although not restricted to pediatrics, the CMS Partnership for Patients also aims to have a major impact on child health. Goals of a 40% reduction in HACs and 20% reduction in preventable 30-day readmissions have been set by the Partnership, with specific focus on 10 core patient-safety areas. Preliminary data have been promising, with a 9% reduction in HACs between 2010 and 2012 across all measures.

“This is a historical reduction,” said Dr. Conway, representing more than 500,000 patient harm events avoided, over 15,000 lives saved, and more than $4 billion in cost savings.

Within pediatrics, a number of research efforts have added to this reduction, including the Pediatric Research in Inpatient Settings (PRIS) Network, PHIS+, I-PASS, as well as several collaborative improvement networks.

Looking to the future, Medicaid and Children’s Health Insurance Program will continue to focus on quality initiatives and system transformation. These will include developing more pediatric-focused quality measures, improving health information technology, and continuing to award innovation in pediatrics. Pediatrics will continue to be a leader in these efforts, Dr. Conway said, because “we should care about longer time horizons.”

Four healthcare system CEOs also took the stage to answer questions from the audience, with Mark Shen, MD, president of Dell Children’s Medical Center, posing questions like a seasoned talk-show host. Panel members fielded a wide range of questions, including:

— How did you become a CEO?

“All I had to do was keep on saying ‘yes,’” Dr. Bailey said.

— What are you doing as a CEO to move from a fee-for-service system to a population-based system?

“We are still living in two different worlds…It depends on ACO penetration whether quality or volume will be the driver over the next 3-5 years,” Dr. Narang said.

“We have to create an accountable health community,” Dr. Shen said.

“The question is, how can you build a model that will allow you to flip the switch when this change occurs?” Dr. Sperring said.

— What is the role of hospitalists as care progresses from the most intensive but sometimes least appropriate site?

“I think the environment will drastically change, but there will be an ever enlarging role for hospitalists. … Hospitalists will likely be moving to LTACs, SNFs, even outpatient work.” Dr. Bailey said.

— If PHM fellowship becomes a requirement, will your hospital fund them?

“It’s hard to define what we do, but we know there are core competencies. … I don’t think we’re going to be at a point where certification will limit being a hospitalist any time soon,” Dr. Shen said.

— How can we make health care pricing more transparent?

“Why is it that in other industries, things are getting cheaper and higher quality, but in healthcare we seem to be going in the opposite direction?” Dr. Bailey said. “There has to be transparency for the patient. How about transparency for the provider? Every EMR should have a price for everything your order.”

— What do you think we can do to get more women into executive roles?

“Based on the percentages of women in medical school, residencies, and fellowships, I think it is inevitable that women will be the future leaders for our system,” Dr. Sperring said.

— What are the three most important things from a CEO perspective that a hospitalist should know?

“You have to have self-awareness…as a leader, are you a listener, are you a delegator?” Dr. Bailey said.

“Know where your organization wants to go,” Dr. Sperring said.

Dr. Chang is associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital. He is pediatric editor of The Hospitalist.

Presenters

--- Welcome Remarks: Doug Carlson, MD, FAAP, chief of pediatric hospital medicine programs, St. Louis Children’s Hospital

--- The Next Phase of Delivery System Reform: Patrick Conway, MD, MSc, FAAP, MHM, deputy administrator for innovation and quality, CMO for the Centers for Medicare & Medicaid Services (CMS)

--- Hospitals and Health Systems: What’s on the Mind of Your CEO?: David J. Bailey, MD, MBA, president and CEO, the Nemours Foundation; Steve Narang, MD, MHCM, CEO, Banner Good Samaritan Medical Center, Phoenix, Ariz.; Jeff Sperring, MD, FAAP, president and CEO, Riley Hospital for Children at Indiana University Health, Indianapolis.

Summary

PHM 2014 began to heat up in steamy Orlando, as Dr. Carlson, chair of the PHM 2014 Organizing Committee, welcomed more than 800 pediatric hospitalists at the four-day annual meeting dedicated to pediatric hospital medicine.

Dr. Conway, a pediatric hospitalist prior to joining CMS, updated the crowd of ongoing reforms in the U.S. healthcare delivery system, with a focus on pediatrics. Healthcare delivery, Dr. Conway asserted, needs to move from an unsustainable, volume-driven, fee-for-service system to a people-centered, sustainable system where payment can be shaped by value-based purchasing, ACO-shared savings, and episode-based payments.

“Pediatrics,” Dr. Conway said, “is a leader in patient and family engagement, and population health.”

As such, the six goals of the CMS Quality Strategy align well with ongoing PHM efforts:

• Make care safer by reducing harm caused in care delivery;
•  Strengthen patient and family engagement as partners in their care;
•  Promote effective communication and coordination of care;
•  Promote effective prevention and treatment of chronic disease;
•  Work with communities to promote healthy living; and
•  Make care affordable.

Citing Maryland as an example, where a plan is being considered to shift 80% of hospital revenues to global models by 2018, Dr. Conway painted a picture of a rapidly-shifting reimbursement landscape that will soon be dominated by value-based purchasing, penalties for readmissions and healthcare-acquired conditions, and increasing emphasis on bundled payments, ACOs, and primary care medical homes.

“Hospitals are getting paid to keep people out of the hospital,” he said, and concurrently per capita spending on healthcare is now at historic lows. While pediatric quality measures are not as mature as those for adult patients, many opportunities for increasing value in pediatric care have been developed, such as the Choosing Wisely campaign and the Value in Inpatient Pediatrics (VIP) network.

Although not restricted to pediatrics, the CMS Partnership for Patients also aims to have a major impact on child health. Goals of a 40% reduction in HACs and 20% reduction in preventable 30-day readmissions have been set by the Partnership, with specific focus on 10 core patient-safety areas. Preliminary data have been promising, with a 9% reduction in HACs between 2010 and 2012 across all measures.

“This is a historical reduction,” said Dr. Conway, representing more than 500,000 patient harm events avoided, over 15,000 lives saved, and more than $4 billion in cost savings.

Within pediatrics, a number of research efforts have added to this reduction, including the Pediatric Research in Inpatient Settings (PRIS) Network, PHIS+, I-PASS, as well as several collaborative improvement networks.

Looking to the future, Medicaid and Children’s Health Insurance Program will continue to focus on quality initiatives and system transformation. These will include developing more pediatric-focused quality measures, improving health information technology, and continuing to award innovation in pediatrics. Pediatrics will continue to be a leader in these efforts, Dr. Conway said, because “we should care about longer time horizons.”

Four healthcare system CEOs also took the stage to answer questions from the audience, with Mark Shen, MD, president of Dell Children’s Medical Center, posing questions like a seasoned talk-show host. Panel members fielded a wide range of questions, including:

— How did you become a CEO?

“All I had to do was keep on saying ‘yes,’” Dr. Bailey said.

— What are you doing as a CEO to move from a fee-for-service system to a population-based system?

“We are still living in two different worlds…It depends on ACO penetration whether quality or volume will be the driver over the next 3-5 years,” Dr. Narang said.

“We have to create an accountable health community,” Dr. Shen said.

“The question is, how can you build a model that will allow you to flip the switch when this change occurs?” Dr. Sperring said.

— What is the role of hospitalists as care progresses from the most intensive but sometimes least appropriate site?

“I think the environment will drastically change, but there will be an ever enlarging role for hospitalists. … Hospitalists will likely be moving to LTACs, SNFs, even outpatient work.” Dr. Bailey said.

— If PHM fellowship becomes a requirement, will your hospital fund them?

“It’s hard to define what we do, but we know there are core competencies. … I don’t think we’re going to be at a point where certification will limit being a hospitalist any time soon,” Dr. Shen said.

— How can we make health care pricing more transparent?

“Why is it that in other industries, things are getting cheaper and higher quality, but in healthcare we seem to be going in the opposite direction?” Dr. Bailey said. “There has to be transparency for the patient. How about transparency for the provider? Every EMR should have a price for everything your order.”

— What do you think we can do to get more women into executive roles?

“Based on the percentages of women in medical school, residencies, and fellowships, I think it is inevitable that women will be the future leaders for our system,” Dr. Sperring said.

— What are the three most important things from a CEO perspective that a hospitalist should know?

“You have to have self-awareness…as a leader, are you a listener, are you a delegator?” Dr. Bailey said.

“Know where your organization wants to go,” Dr. Sperring said.

Dr. Chang is associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital. He is pediatric editor of The Hospitalist.