DENVER – Novel fractional laser therapy achieved significant 12-month reductions in vaginal dryness, burning, pain, and itching associated with menopause, Eric Sokol, MD, reported at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.

Most patients – 92% – said they were satisfied or very satisfied with the treatment, said Dr. Sokol of Stanford (Calif.) University. “Treatments take 45 seconds and are painless,” he added. “We are part of a group that is planning a larger multicenter randomized trial of this laser, as well as some histologic studies.”

The two-center pilot study included 30 women with vulvovaginal atrophy treated with a novel fractional carbon dioxide laser system called SmartXide2 V2LR (MonaLisa Touch). The system has a maximum power of 60 W and emits laser energy at a 10,600-nm wavelength, Dr. Sokol noted. Patients underwent three treatments spaced by 6 weeks, and used 10-point visual analogue scales to score baseline and subsequent levels of vaginal pain, burning, itching, dryness, dyspareunia, and dysuria.

Amy Karon/Frontline Medical News

[email protected]

DENVER – Novel fractional laser therapy achieved significant 12-month reductions in vaginal dryness, burning, pain, and itching associated with menopause, Eric Sokol, MD, reported at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.

Most patients – 92% – said they were satisfied or very satisfied with the treatment, said Dr. Sokol of Stanford (Calif.) University. “Treatments take 45 seconds and are painless,” he added. “We are part of a group that is planning a larger multicenter randomized trial of this laser, as well as some histologic studies.”

The two-center pilot study included 30 women with vulvovaginal atrophy treated with a novel fractional carbon dioxide laser system called SmartXide2 V2LR (MonaLisa Touch). The system has a maximum power of 60 W and emits laser energy at a 10,600-nm wavelength, Dr. Sokol noted. Patients underwent three treatments spaced by 6 weeks, and used 10-point visual analogue scales to score baseline and subsequent levels of vaginal pain, burning, itching, dryness, dyspareunia, and dysuria.

Amy Karon/Frontline Medical News

[email protected]

DENVER – Novel fractional laser therapy achieved significant 12-month reductions in vaginal dryness, burning, pain, and itching associated with menopause, Eric Sokol, MD, reported at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.

Most patients – 92% – said they were satisfied or very satisfied with the treatment, said Dr. Sokol of Stanford (Calif.) University. “Treatments take 45 seconds and are painless,” he added. “We are part of a group that is planning a larger multicenter randomized trial of this laser, as well as some histologic studies.”

The two-center pilot study included 30 women with vulvovaginal atrophy treated with a novel fractional carbon dioxide laser system called SmartXide2 V2LR (MonaLisa Touch). The system has a maximum power of 60 W and emits laser energy at a 10,600-nm wavelength, Dr. Sokol noted. Patients underwent three treatments spaced by 6 weeks, and used 10-point visual analogue scales to score baseline and subsequent levels of vaginal pain, burning, itching, dryness, dyspareunia, and dysuria.

Amy Karon/Frontline Medical News

[email protected]

VIENNA – An investigational topical cholinergic receptor antagonist known as DRM04 achieved its efficacy and safety endpoints for the treatment of primary axillary hyperhidrosis in the pivotal phase III ATMOS-1 and ATMOS-2 trials.

“We haven’t had any good new treatment options for patients with hyperhidrosis for a long time,” Dr. David M. Pariser said, in presenting the pivotal trial outcomes data at the annual congress of the European Academy of Dermatology and Venereology.

ATMOS-1 and ATMOS-2 were identically designed 4-week, double-blind studies involving 697 patients with excessive underarm sweating who were randomized 2:1 to once daily use of DRM04 3.75% wipes or a vehicle control. The patients averaged 33 years of age, although as Dr. Pariser noted, primary axillary hyperhidrosis often begins in adolescence and patients as young as age 9 were enrolled. The majority of participants were female. Roughly two-thirds of subjects were grade 3 on the 4-point Hyperhidrosis Disease Severity Scale. The rest were grade 4.

The coprimary endpoints in ATMOS-1 and ATMOS-2 were a 4-point or greater improvement on the Axillary Sweating Daily Diary (ASDD) between baseline and week 4, and the absolute change from baseline in axillary sweat production measured gravimetrically.

The ASDD is a new patient-reported outcome measure developed specifically for the ATMOS trials. At baseline, participants scored a mean of 7.2 points on the 0-10 scale. A 4-point or greater improvement was seen at week 4 in 52.8% of ATMOS-1 participants on DRM04, compared with 28.3% of controls. In ATMOS-2, the spread was 66.1% vs. 26.9%.

Mean baseline sweat production was roughly 175 mg/5 min per armpit, a prodigious rate given that 50 mg/5 min is considered excessive. In ATMOS-1, the rate dropped by an adjusted average of 96.2 mg/5 min per armpit with active therapy, compared with 90.6 mg/5 min in the control group. In ATMOS-2, the DRM04 users had a mean drop in sweat production of 110.3 mg/5 min, compared with a reduction of 92.2 mg/5 min in the control group. Both of these differences were statistically significant and clinically meaningful, Dr. Pariser said.

The secondary endpoint in the studies was change in the Dermatology Life Quality Index from baseline to week 4. The improvement in DRM04 users averaged 8.1 points in ATMOS-1 and 8.6 points in ATMOS-2, both significantly greater than the 4.3- and 5.0-point improvements in the control arms.

In ATMOS-1, 9.2% of patients in the DRM04 arm dropped out of the study, in many cases because of anticholinergic side effects, the most common of which included dry mouth, dry eyes, urinary hesitation or less frequently retention, and constipation. These were mostly mild to moderate in nature and were generally responsive to temporary treatment discontinuation, which the study protocol allowed. The dropout rate in the DRM04 arm of ATMOS-2 was 6.8%.

Seven percent of subjects in the DRM04 study arms experienced mydriasis, most often unilaterally. Dr. Pariser said this might be due to patients touching an eye while they still had DRM04 on their hands, a problem that can be readily addressed in the medication use instructions.

The dropout rates in the control groups were 2.6% and 5%.

More than 80% of ATMOS-1 and ATMOS-2 participants enrolled in ARIDO, the 48-week, open label, phase III extension study of DRM04. Dermira, which is developing DRM04, has announced it plans to file for marketing approval by the Food and Drug Administration in the second half of 2017.

Dr. Pariser reported serving as an investigator for and consultant to Dermira, Brickell Biotech, and TheraVida.

[email protected]

VIENNA – An investigational topical cholinergic receptor antagonist known as DRM04 achieved its efficacy and safety endpoints for the treatment of primary axillary hyperhidrosis in the pivotal phase III ATMOS-1 and ATMOS-2 trials.

“We haven’t had any good new treatment options for patients with hyperhidrosis for a long time,” Dr. David M. Pariser said, in presenting the pivotal trial outcomes data at the annual congress of the European Academy of Dermatology and Venereology.

ATMOS-1 and ATMOS-2 were identically designed 4-week, double-blind studies involving 697 patients with excessive underarm sweating who were randomized 2:1 to once daily use of DRM04 3.75% wipes or a vehicle control. The patients averaged 33 years of age, although as Dr. Pariser noted, primary axillary hyperhidrosis often begins in adolescence and patients as young as age 9 were enrolled. The majority of participants were female. Roughly two-thirds of subjects were grade 3 on the 4-point Hyperhidrosis Disease Severity Scale. The rest were grade 4.

The coprimary endpoints in ATMOS-1 and ATMOS-2 were a 4-point or greater improvement on the Axillary Sweating Daily Diary (ASDD) between baseline and week 4, and the absolute change from baseline in axillary sweat production measured gravimetrically.

The ASDD is a new patient-reported outcome measure developed specifically for the ATMOS trials. At baseline, participants scored a mean of 7.2 points on the 0-10 scale. A 4-point or greater improvement was seen at week 4 in 52.8% of ATMOS-1 participants on DRM04, compared with 28.3% of controls. In ATMOS-2, the spread was 66.1% vs. 26.9%.

Mean baseline sweat production was roughly 175 mg/5 min per armpit, a prodigious rate given that 50 mg/5 min is considered excessive. In ATMOS-1, the rate dropped by an adjusted average of 96.2 mg/5 min per armpit with active therapy, compared with 90.6 mg/5 min in the control group. In ATMOS-2, the DRM04 users had a mean drop in sweat production of 110.3 mg/5 min, compared with a reduction of 92.2 mg/5 min in the control group. Both of these differences were statistically significant and clinically meaningful, Dr. Pariser said.

The secondary endpoint in the studies was change in the Dermatology Life Quality Index from baseline to week 4. The improvement in DRM04 users averaged 8.1 points in ATMOS-1 and 8.6 points in ATMOS-2, both significantly greater than the 4.3- and 5.0-point improvements in the control arms.

In ATMOS-1, 9.2% of patients in the DRM04 arm dropped out of the study, in many cases because of anticholinergic side effects, the most common of which included dry mouth, dry eyes, urinary hesitation or less frequently retention, and constipation. These were mostly mild to moderate in nature and were generally responsive to temporary treatment discontinuation, which the study protocol allowed. The dropout rate in the DRM04 arm of ATMOS-2 was 6.8%.

Seven percent of subjects in the DRM04 study arms experienced mydriasis, most often unilaterally. Dr. Pariser said this might be due to patients touching an eye while they still had DRM04 on their hands, a problem that can be readily addressed in the medication use instructions.

The dropout rates in the control groups were 2.6% and 5%.

More than 80% of ATMOS-1 and ATMOS-2 participants enrolled in ARIDO, the 48-week, open label, phase III extension study of DRM04. Dermira, which is developing DRM04, has announced it plans to file for marketing approval by the Food and Drug Administration in the second half of 2017.

Dr. Pariser reported serving as an investigator for and consultant to Dermira, Brickell Biotech, and TheraVida.

[email protected]

VIENNA – An investigational topical cholinergic receptor antagonist known as DRM04 achieved its efficacy and safety endpoints for the treatment of primary axillary hyperhidrosis in the pivotal phase III ATMOS-1 and ATMOS-2 trials.

“We haven’t had any good new treatment options for patients with hyperhidrosis for a long time,” Dr. David M. Pariser said, in presenting the pivotal trial outcomes data at the annual congress of the European Academy of Dermatology and Venereology.

ATMOS-1 and ATMOS-2 were identically designed 4-week, double-blind studies involving 697 patients with excessive underarm sweating who were randomized 2:1 to once daily use of DRM04 3.75% wipes or a vehicle control. The patients averaged 33 years of age, although as Dr. Pariser noted, primary axillary hyperhidrosis often begins in adolescence and patients as young as age 9 were enrolled. The majority of participants were female. Roughly two-thirds of subjects were grade 3 on the 4-point Hyperhidrosis Disease Severity Scale. The rest were grade 4.

The coprimary endpoints in ATMOS-1 and ATMOS-2 were a 4-point or greater improvement on the Axillary Sweating Daily Diary (ASDD) between baseline and week 4, and the absolute change from baseline in axillary sweat production measured gravimetrically.

The ASDD is a new patient-reported outcome measure developed specifically for the ATMOS trials. At baseline, participants scored a mean of 7.2 points on the 0-10 scale. A 4-point or greater improvement was seen at week 4 in 52.8% of ATMOS-1 participants on DRM04, compared with 28.3% of controls. In ATMOS-2, the spread was 66.1% vs. 26.9%.

Mean baseline sweat production was roughly 175 mg/5 min per armpit, a prodigious rate given that 50 mg/5 min is considered excessive. In ATMOS-1, the rate dropped by an adjusted average of 96.2 mg/5 min per armpit with active therapy, compared with 90.6 mg/5 min in the control group. In ATMOS-2, the DRM04 users had a mean drop in sweat production of 110.3 mg/5 min, compared with a reduction of 92.2 mg/5 min in the control group. Both of these differences were statistically significant and clinically meaningful, Dr. Pariser said.

The secondary endpoint in the studies was change in the Dermatology Life Quality Index from baseline to week 4. The improvement in DRM04 users averaged 8.1 points in ATMOS-1 and 8.6 points in ATMOS-2, both significantly greater than the 4.3- and 5.0-point improvements in the control arms.

In ATMOS-1, 9.2% of patients in the DRM04 arm dropped out of the study, in many cases because of anticholinergic side effects, the most common of which included dry mouth, dry eyes, urinary hesitation or less frequently retention, and constipation. These were mostly mild to moderate in nature and were generally responsive to temporary treatment discontinuation, which the study protocol allowed. The dropout rate in the DRM04 arm of ATMOS-2 was 6.8%.

Seven percent of subjects in the DRM04 study arms experienced mydriasis, most often unilaterally. Dr. Pariser said this might be due to patients touching an eye while they still had DRM04 on their hands, a problem that can be readily addressed in the medication use instructions.

The dropout rates in the control groups were 2.6% and 5%.

More than 80% of ATMOS-1 and ATMOS-2 participants enrolled in ARIDO, the 48-week, open label, phase III extension study of DRM04. Dermira, which is developing DRM04, has announced it plans to file for marketing approval by the Food and Drug Administration in the second half of 2017.

Dr. Pariser reported serving as an investigator for and consultant to Dermira, Brickell Biotech, and TheraVida.

[email protected]

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

Federal flexibility in compliance with the first year of MACRA reforms is a win for most physicians.

The American Gastroenterological Association “is pleased that CMS [the Centers for Medicare and Medicaid Services] is providing physicians woth more flexible options for reporting and that, most importantly, no physician will be penalized in 2019 for their reporting in 2017,” the association said in a statement. “Since the release of the MACRA [Medicare Access and CHIP Reauthorization Act of 2015] proposd rule, AGA has been advocating to Congress and CMS that the agency provide physicians with mor eflexibility to coply with the law and have opportunities to succeed in the new payment system.”

Option 1

Report “some data” in 2017. Doctors who report some data to the Quality Payments Program (QPP) – the official name for MACRA-required reforms – will not face a Medicare pay cut. CMS considers even this low level of reporting a test for whether physicians will be ready for more intense MACRA involvement in 2018 and 2019. Exactly how much “some data” is currently is not defined.

Option 2

Participate for part of 2017. Those who choose to report data to QPP for some of the year also will be testing their systems for future MACRA compliance and may end up with a small Medicare pay increase. Again, the duration of reporting was not defined by the CMS at press time.

Option 3

Participate for the full year. Doctors who begin to report data from all parts of QPP on Jan. 1 will be eligible for a “modest” Medicare pay increase in 2019. Data on quality measures, use of technology, and practice improvement must be reported.

For those who are eligible for participation in Advanced Alternative Payment Models (APMs), that track will begin Jan. 1, 2017.

The American Medical Association commended federal officials “for listening to physicians’ concerns about the timeline that was originally proposed for MACRA,” AMA President Andrew Gurman, MD, said in a statement. “The AMA believes the actions that the administration announced today will help give physicians a fair shot in the first year of MACRA implementation. This is the flexibility that physicians were seeking all along.”

Not all see the new flexibility as a good thing, particularly for larger group practices that are ready to fully participate in MACRA as of Jan. 1.

“This flexibility is especially important for small provider groups that may have legitimate logistical issues around MACRA’s reporting requirements,” Donald Fisher, PhD, president and CEO of AMGA, said in a statement. (AMGA was formerly known as the American Medical Group Association.)

“However, our membership is deeply concerned that the creation of these new reporting options will have the unintended result of penalizing the very provider groups that have made the largest investments to meet MACRA’s goals of better quality, improved clinical practice activities, better use of electronic medical records, and lower resource use. These groups have already begun the transition from volume to value, and it is disappointing the rewards for their effort will be compromised rather than rewarded, as was MACRA’s stated purpose by Congress and the administration.”

By offering options for compliance, the CMS could potentially limit the amount of bonus payments in order to meet MACRA’s budget-neutral requirements, according to Chet Speed, vice president of public policy at AMGA. There will be no potential penalties that would offset bonuses for organizations that are performing at a high rate, which could result in having to lower the maximum bonuses an organization would be eligible to receive.

“You’ve compressed rewards to a level where it just penalizes those who have made the investments” in upgrading their systems to prepare for the Jan. 1 start date, Mr. Speed said.

He emphasized that the CMS could still address this and make the full bonus payments available to those who are prepared to participate on Jan. 1, but that will not be known until the final rule is published. He applauded the agency’s efforts in continually reaching out to the physician community throughout the MACRA development process and said he is hopeful there will be resolution to these concerns in the final rule.

[email protected]

Federal flexibility in compliance with the first year of MACRA reforms is a win for most physicians.

The American Gastroenterological Association “is pleased that CMS [the Centers for Medicare and Medicaid Services] is providing physicians woth more flexible options for reporting and that, most importantly, no physician will be penalized in 2019 for their reporting in 2017,” the association said in a statement. “Since the release of the MACRA [Medicare Access and CHIP Reauthorization Act of 2015] proposd rule, AGA has been advocating to Congress and CMS that the agency provide physicians with mor eflexibility to coply with the law and have opportunities to succeed in the new payment system.”

Option 1

Report “some data” in 2017. Doctors who report some data to the Quality Payments Program (QPP) – the official name for MACRA-required reforms – will not face a Medicare pay cut. CMS considers even this low level of reporting a test for whether physicians will be ready for more intense MACRA involvement in 2018 and 2019. Exactly how much “some data” is currently is not defined.

Option 2

Participate for part of 2017. Those who choose to report data to QPP for some of the year also will be testing their systems for future MACRA compliance and may end up with a small Medicare pay increase. Again, the duration of reporting was not defined by the CMS at press time.

Option 3

Participate for the full year. Doctors who begin to report data from all parts of QPP on Jan. 1 will be eligible for a “modest” Medicare pay increase in 2019. Data on quality measures, use of technology, and practice improvement must be reported.

For those who are eligible for participation in Advanced Alternative Payment Models (APMs), that track will begin Jan. 1, 2017.

The American Medical Association commended federal officials “for listening to physicians’ concerns about the timeline that was originally proposed for MACRA,” AMA President Andrew Gurman, MD, said in a statement. “The AMA believes the actions that the administration announced today will help give physicians a fair shot in the first year of MACRA implementation. This is the flexibility that physicians were seeking all along.”

Not all see the new flexibility as a good thing, particularly for larger group practices that are ready to fully participate in MACRA as of Jan. 1.

“This flexibility is especially important for small provider groups that may have legitimate logistical issues around MACRA’s reporting requirements,” Donald Fisher, PhD, president and CEO of AMGA, said in a statement. (AMGA was formerly known as the American Medical Group Association.)

“However, our membership is deeply concerned that the creation of these new reporting options will have the unintended result of penalizing the very provider groups that have made the largest investments to meet MACRA’s goals of better quality, improved clinical practice activities, better use of electronic medical records, and lower resource use. These groups have already begun the transition from volume to value, and it is disappointing the rewards for their effort will be compromised rather than rewarded, as was MACRA’s stated purpose by Congress and the administration.”

By offering options for compliance, the CMS could potentially limit the amount of bonus payments in order to meet MACRA’s budget-neutral requirements, according to Chet Speed, vice president of public policy at AMGA. There will be no potential penalties that would offset bonuses for organizations that are performing at a high rate, which could result in having to lower the maximum bonuses an organization would be eligible to receive.

“You’ve compressed rewards to a level where it just penalizes those who have made the investments” in upgrading their systems to prepare for the Jan. 1 start date, Mr. Speed said.

He emphasized that the CMS could still address this and make the full bonus payments available to those who are prepared to participate on Jan. 1, but that will not be known until the final rule is published. He applauded the agency’s efforts in continually reaching out to the physician community throughout the MACRA development process and said he is hopeful there will be resolution to these concerns in the final rule.

[email protected]

Federal flexibility in compliance with the first year of MACRA reforms is a win for most physicians.

The American Gastroenterological Association “is pleased that CMS [the Centers for Medicare and Medicaid Services] is providing physicians woth more flexible options for reporting and that, most importantly, no physician will be penalized in 2019 for their reporting in 2017,” the association said in a statement. “Since the release of the MACRA [Medicare Access and CHIP Reauthorization Act of 2015] proposd rule, AGA has been advocating to Congress and CMS that the agency provide physicians with mor eflexibility to coply with the law and have opportunities to succeed in the new payment system.”

Option 1

Report “some data” in 2017. Doctors who report some data to the Quality Payments Program (QPP) – the official name for MACRA-required reforms – will not face a Medicare pay cut. CMS considers even this low level of reporting a test for whether physicians will be ready for more intense MACRA involvement in 2018 and 2019. Exactly how much “some data” is currently is not defined.

Option 2

Participate for part of 2017. Those who choose to report data to QPP for some of the year also will be testing their systems for future MACRA compliance and may end up with a small Medicare pay increase. Again, the duration of reporting was not defined by the CMS at press time.

Option 3

Participate for the full year. Doctors who begin to report data from all parts of QPP on Jan. 1 will be eligible for a “modest” Medicare pay increase in 2019. Data on quality measures, use of technology, and practice improvement must be reported.

For those who are eligible for participation in Advanced Alternative Payment Models (APMs), that track will begin Jan. 1, 2017.

The American Medical Association commended federal officials “for listening to physicians’ concerns about the timeline that was originally proposed for MACRA,” AMA President Andrew Gurman, MD, said in a statement. “The AMA believes the actions that the administration announced today will help give physicians a fair shot in the first year of MACRA implementation. This is the flexibility that physicians were seeking all along.”

Not all see the new flexibility as a good thing, particularly for larger group practices that are ready to fully participate in MACRA as of Jan. 1.

“This flexibility is especially important for small provider groups that may have legitimate logistical issues around MACRA’s reporting requirements,” Donald Fisher, PhD, president and CEO of AMGA, said in a statement. (AMGA was formerly known as the American Medical Group Association.)

“However, our membership is deeply concerned that the creation of these new reporting options will have the unintended result of penalizing the very provider groups that have made the largest investments to meet MACRA’s goals of better quality, improved clinical practice activities, better use of electronic medical records, and lower resource use. These groups have already begun the transition from volume to value, and it is disappointing the rewards for their effort will be compromised rather than rewarded, as was MACRA’s stated purpose by Congress and the administration.”

By offering options for compliance, the CMS could potentially limit the amount of bonus payments in order to meet MACRA’s budget-neutral requirements, according to Chet Speed, vice president of public policy at AMGA. There will be no potential penalties that would offset bonuses for organizations that are performing at a high rate, which could result in having to lower the maximum bonuses an organization would be eligible to receive.

“You’ve compressed rewards to a level where it just penalizes those who have made the investments” in upgrading their systems to prepare for the Jan. 1 start date, Mr. Speed said.

He emphasized that the CMS could still address this and make the full bonus payments available to those who are prepared to participate on Jan. 1, but that will not be known until the final rule is published. He applauded the agency’s efforts in continually reaching out to the physician community throughout the MACRA development process and said he is hopeful there will be resolution to these concerns in the final rule.

[email protected]

Extended use of systemic hormone therapy represents one area that clinicians commonly encounter. However, because randomized trial data are not available, helping women make decisions regarding long-term use of hormone therapy is controversial. When it is finalized, the 2016 hormone therapy position statement from the North American Menopause Society will address this topic.

Here I’m referring to the patient who likely started systemic hormone therapy when she was a younger, or more recently menopausal, woman (perhaps in her early 50s), but now she’s in her 60s. In my practice, a patient in this age range would likely be on a lower-than-standard dose of hormone therapy than what she began with originally.

And now the question is, Should she continue, or should she stop, hormone therapy? The median duration of bothersome symptoms is about 10 or 11 years, from the best available data – far longer than what many physicians assume.

References

1. Menopause. 2014 Jun;21(6):679-81.

Dr. Kaunitz is a professor and associate chair of the department of obstetrics and gynecology, University of Florida in Jacksonville. He is on the board of trustees of the North American Menopause Society. He reports being a consultant or on the advisory board or review panel of several pharmaceutical companies, and receiving grant support from several pharmaceutical companies. He receives royalties from UpToDate.

Extended use of systemic hormone therapy represents one area that clinicians commonly encounter. However, because randomized trial data are not available, helping women make decisions regarding long-term use of hormone therapy is controversial. When it is finalized, the 2016 hormone therapy position statement from the North American Menopause Society will address this topic.

Here I’m referring to the patient who likely started systemic hormone therapy when she was a younger, or more recently menopausal, woman (perhaps in her early 50s), but now she’s in her 60s. In my practice, a patient in this age range would likely be on a lower-than-standard dose of hormone therapy than what she began with originally.

And now the question is, Should she continue, or should she stop, hormone therapy? The median duration of bothersome symptoms is about 10 or 11 years, from the best available data – far longer than what many physicians assume.

References

1. Menopause. 2014 Jun;21(6):679-81.

Dr. Kaunitz is a professor and associate chair of the department of obstetrics and gynecology, University of Florida in Jacksonville. He is on the board of trustees of the North American Menopause Society. He reports being a consultant or on the advisory board or review panel of several pharmaceutical companies, and receiving grant support from several pharmaceutical companies. He receives royalties from UpToDate.

Extended use of systemic hormone therapy represents one area that clinicians commonly encounter. However, because randomized trial data are not available, helping women make decisions regarding long-term use of hormone therapy is controversial. When it is finalized, the 2016 hormone therapy position statement from the North American Menopause Society will address this topic.

Here I’m referring to the patient who likely started systemic hormone therapy when she was a younger, or more recently menopausal, woman (perhaps in her early 50s), but now she’s in her 60s. In my practice, a patient in this age range would likely be on a lower-than-standard dose of hormone therapy than what she began with originally.

And now the question is, Should she continue, or should she stop, hormone therapy? The median duration of bothersome symptoms is about 10 or 11 years, from the best available data – far longer than what many physicians assume.

References

1. Menopause. 2014 Jun;21(6):679-81.

Dr. Kaunitz is a professor and associate chair of the department of obstetrics and gynecology, University of Florida in Jacksonville. He is on the board of trustees of the North American Menopause Society. He reports being a consultant or on the advisory board or review panel of several pharmaceutical companies, and receiving grant support from several pharmaceutical companies. He receives royalties from UpToDate.

First, I want to correct a misstatement I made in a recent column regarding incident to billing by an extender (Dermatology News, July 2016, p. 1) When an extender sees a patient for an established problem, they can bill at 100% if there is a supervising physician in the house, AND it should be under that supervising physician’s number – NOT necessarily by the physician who saw the original problem. This change was promulgated by the Centers for Medicare & Medicaid Services in the proposed rule, and everyone thought it was a done deal, but the billing remained unchanged in the final rule. Apologies for any confusion.

Coding

As all of you know, in 2010, the Centers for Medicare & Medicaid Services stopped recognizing the Current Procedural Terminology (CPT) consultation codes for Medicare Part B payment CMS decided (after an Office of Inspector General study) that consultations were really just new patient visits and stopped paying for consultations. Visits are now coded with new or follow-up patient evaluation and management codes. This is unfortunate, because a consultation pays more, and importantly, does not establish the patient as a patient in your practice for the next three years. If originally billed as a consultation, the patient can be seen back for another problem in the next three years, and be billed for a consultation, or a new patient as appropriate. Therefore, it is a big advantage to be able to bill for a consultation, assuming another doctor has asked your opinion and you call with or send them a report of your findings.

Just because Medicare says you cannot bill for consultations does not mean that all insurers are the same. The consultation codes are still in the CPT code book and your contracts with private insurers probably stipulate that the insurers must comply with CPT convention. In this case, you can bill your private insurers (including Medicare Advantage Plans, which are private insurers) for consultations when your documentation supports it. Be aware, that some of the more popular electronic health records that perform billing automatically default to a new patient visit, when a new patient consultation might be more appropriate.

While discussing evaluation and management coding, you should be aware that 97% of visits billed by dermatologists are level 3 or lower. This means that, even if your EHR can propel you to heights unimagined before, that it could become a problem. You cannot bill a higher level beyond what is medically appropriate. For example, you don’t usually need to do a full-body skin exam during an acne follow-up.

I’ll never forget the poor soul who explained to me that she was being audited “because all my visits were level 4 or 5, and the software agreed with it.” The software company (or the consultant) will not be sharing the joys of an audit with you. You can do a quick and easy check of your evaluation and management patterns, compared with others by checking either of the online Medicare databases, the Wall Street Journal’s “Medicare Unmasked” site or the “Treatment Tracker” for Doctors and Services in Medicare Part B, on the ProPublica website.

While you are there, check your procedure numbers against others. Are you a freeze-y king? Are you the shave master? There are often valid and justifiable reasons for unusual billing patterns. If you are an outlier, make sure you have a good reason to be there. For example, I am in the top 10% paid per patient visit in the state of Ohio. The reason is that I treat only skin cancer, and it usually involves surgery. The world is looking at these data. So should you.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

First, I want to correct a misstatement I made in a recent column regarding incident to billing by an extender (Dermatology News, July 2016, p. 1) When an extender sees a patient for an established problem, they can bill at 100% if there is a supervising physician in the house, AND it should be under that supervising physician’s number – NOT necessarily by the physician who saw the original problem. This change was promulgated by the Centers for Medicare & Medicaid Services in the proposed rule, and everyone thought it was a done deal, but the billing remained unchanged in the final rule. Apologies for any confusion.

Coding

As all of you know, in 2010, the Centers for Medicare & Medicaid Services stopped recognizing the Current Procedural Terminology (CPT) consultation codes for Medicare Part B payment CMS decided (after an Office of Inspector General study) that consultations were really just new patient visits and stopped paying for consultations. Visits are now coded with new or follow-up patient evaluation and management codes. This is unfortunate, because a consultation pays more, and importantly, does not establish the patient as a patient in your practice for the next three years. If originally billed as a consultation, the patient can be seen back for another problem in the next three years, and be billed for a consultation, or a new patient as appropriate. Therefore, it is a big advantage to be able to bill for a consultation, assuming another doctor has asked your opinion and you call with or send them a report of your findings.

Just because Medicare says you cannot bill for consultations does not mean that all insurers are the same. The consultation codes are still in the CPT code book and your contracts with private insurers probably stipulate that the insurers must comply with CPT convention. In this case, you can bill your private insurers (including Medicare Advantage Plans, which are private insurers) for consultations when your documentation supports it. Be aware, that some of the more popular electronic health records that perform billing automatically default to a new patient visit, when a new patient consultation might be more appropriate.

While discussing evaluation and management coding, you should be aware that 97% of visits billed by dermatologists are level 3 or lower. This means that, even if your EHR can propel you to heights unimagined before, that it could become a problem. You cannot bill a higher level beyond what is medically appropriate. For example, you don’t usually need to do a full-body skin exam during an acne follow-up.

I’ll never forget the poor soul who explained to me that she was being audited “because all my visits were level 4 or 5, and the software agreed with it.” The software company (or the consultant) will not be sharing the joys of an audit with you. You can do a quick and easy check of your evaluation and management patterns, compared with others by checking either of the online Medicare databases, the Wall Street Journal’s “Medicare Unmasked” site or the “Treatment Tracker” for Doctors and Services in Medicare Part B, on the ProPublica website.

While you are there, check your procedure numbers against others. Are you a freeze-y king? Are you the shave master? There are often valid and justifiable reasons for unusual billing patterns. If you are an outlier, make sure you have a good reason to be there. For example, I am in the top 10% paid per patient visit in the state of Ohio. The reason is that I treat only skin cancer, and it usually involves surgery. The world is looking at these data. So should you.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

First, I want to correct a misstatement I made in a recent column regarding incident to billing by an extender (Dermatology News, July 2016, p. 1) When an extender sees a patient for an established problem, they can bill at 100% if there is a supervising physician in the house, AND it should be under that supervising physician’s number – NOT necessarily by the physician who saw the original problem. This change was promulgated by the Centers for Medicare & Medicaid Services in the proposed rule, and everyone thought it was a done deal, but the billing remained unchanged in the final rule. Apologies for any confusion.

Coding

As all of you know, in 2010, the Centers for Medicare & Medicaid Services stopped recognizing the Current Procedural Terminology (CPT) consultation codes for Medicare Part B payment CMS decided (after an Office of Inspector General study) that consultations were really just new patient visits and stopped paying for consultations. Visits are now coded with new or follow-up patient evaluation and management codes. This is unfortunate, because a consultation pays more, and importantly, does not establish the patient as a patient in your practice for the next three years. If originally billed as a consultation, the patient can be seen back for another problem in the next three years, and be billed for a consultation, or a new patient as appropriate. Therefore, it is a big advantage to be able to bill for a consultation, assuming another doctor has asked your opinion and you call with or send them a report of your findings.

Just because Medicare says you cannot bill for consultations does not mean that all insurers are the same. The consultation codes are still in the CPT code book and your contracts with private insurers probably stipulate that the insurers must comply with CPT convention. In this case, you can bill your private insurers (including Medicare Advantage Plans, which are private insurers) for consultations when your documentation supports it. Be aware, that some of the more popular electronic health records that perform billing automatically default to a new patient visit, when a new patient consultation might be more appropriate.

While discussing evaluation and management coding, you should be aware that 97% of visits billed by dermatologists are level 3 or lower. This means that, even if your EHR can propel you to heights unimagined before, that it could become a problem. You cannot bill a higher level beyond what is medically appropriate. For example, you don’t usually need to do a full-body skin exam during an acne follow-up.

I’ll never forget the poor soul who explained to me that she was being audited “because all my visits were level 4 or 5, and the software agreed with it.” The software company (or the consultant) will not be sharing the joys of an audit with you. You can do a quick and easy check of your evaluation and management patterns, compared with others by checking either of the online Medicare databases, the Wall Street Journal’s “Medicare Unmasked” site or the “Treatment Tracker” for Doctors and Services in Medicare Part B, on the ProPublica website.

While you are there, check your procedure numbers against others. Are you a freeze-y king? Are you the shave master? There are often valid and justifiable reasons for unusual billing patterns. If you are an outlier, make sure you have a good reason to be there. For example, I am in the top 10% paid per patient visit in the state of Ohio. The reason is that I treat only skin cancer, and it usually involves surgery. The world is looking at these data. So should you.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

Officials at the Centers for Medicare & Medicaid Services are launching a new initiative aimed at reducing administrative burdens for physicians who participate in certain value-based payment models.

Under an 18-month pilot, providers practicing within certain Advanced Alternative Payment Models (Advanced APMs) will be relieved of additional documentation scrutiny under Medicare medical review programs, according to an Oct. 13 CMS announcement. As part of the effort, the agency will direct Medicare Administrative Contractors and Recovery Audit Contractors to consider doctors participating in Advanced APMs as a low-priority for postpayment claim reviews.

Courtesy American College of Physicians

[email protected]

On Twitter @legal_med

Officials at the Centers for Medicare & Medicaid Services are launching a new initiative aimed at reducing administrative burdens for physicians who participate in certain value-based payment models.

Under an 18-month pilot, providers practicing within certain Advanced Alternative Payment Models (Advanced APMs) will be relieved of additional documentation scrutiny under Medicare medical review programs, according to an Oct. 13 CMS announcement. As part of the effort, the agency will direct Medicare Administrative Contractors and Recovery Audit Contractors to consider doctors participating in Advanced APMs as a low-priority for postpayment claim reviews.

Courtesy American College of Physicians

[email protected]

On Twitter @legal_med

Officials at the Centers for Medicare & Medicaid Services are launching a new initiative aimed at reducing administrative burdens for physicians who participate in certain value-based payment models.

Under an 18-month pilot, providers practicing within certain Advanced Alternative Payment Models (Advanced APMs) will be relieved of additional documentation scrutiny under Medicare medical review programs, according to an Oct. 13 CMS announcement. As part of the effort, the agency will direct Medicare Administrative Contractors and Recovery Audit Contractors to consider doctors participating in Advanced APMs as a low-priority for postpayment claim reviews.

Courtesy American College of Physicians

[email protected]

On Twitter @legal_med

Micrograph showing

sickle cell disease

Image by Graham Beards

Researchers have described a gene-editing technique that can correct the sickle cell mutation in hematopoietic stem and progenitor cells (HSPCs) isolated from patients with sickle cell disease (SCD).

The investigators said these edited HSPCs produced wild-type adult and fetal hemoglobin.

The HSPCs were also able to engraft in mice and maintained their SCD gene edits long-term without showing any signs of side effects.

“This is an important advance because, for the first time, we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

Dr Walters and his colleagues described this work in Science Translational Medicine.

The researchers said they used a ribonucleoprotein complex consisting of Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor, to enable efficient replacement of the SCD mutation in human HSPCs.

The team then differentiated pools of these HSPCs into enucleated erythrocytes and late-stage erythroblasts to measure hemoglobin production.

They said the edited HSPCs produced “substantial amounts” of adult wild-type hemoglobin. The cells also showed a decrease in sickle hemoglobin and an increase in fetal hemoglobin.

When implanted in mice, the edited HSPCs repopulated and maintained their SCD gene edits for 16 weeks, with no signs of side effects. (The mice were sacrificed at 16 weeks.)

“We’re very excited about the promise of this technology,” said study author Jacob Corn, PhD, of the University of California, Berkeley.

“There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”

In fact, Dr Corn and his lab have joined with Dr Walters to initiate an early phase clinical trial to test this gene-editing approach within the next 5 years.

The investigators also noted that the approach might be effective for treating other disorders, such as β-thalassemia, Wiskott-Aldrich syndrome, and Fanconi anemia.

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Dr Corn said. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”

Micrograph showing

sickle cell disease

Image by Graham Beards

Researchers have described a gene-editing technique that can correct the sickle cell mutation in hematopoietic stem and progenitor cells (HSPCs) isolated from patients with sickle cell disease (SCD).

The investigators said these edited HSPCs produced wild-type adult and fetal hemoglobin.

The HSPCs were also able to engraft in mice and maintained their SCD gene edits long-term without showing any signs of side effects.

“This is an important advance because, for the first time, we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

Dr Walters and his colleagues described this work in Science Translational Medicine.

The researchers said they used a ribonucleoprotein complex consisting of Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor, to enable efficient replacement of the SCD mutation in human HSPCs.

The team then differentiated pools of these HSPCs into enucleated erythrocytes and late-stage erythroblasts to measure hemoglobin production.

They said the edited HSPCs produced “substantial amounts” of adult wild-type hemoglobin. The cells also showed a decrease in sickle hemoglobin and an increase in fetal hemoglobin.

When implanted in mice, the edited HSPCs repopulated and maintained their SCD gene edits for 16 weeks, with no signs of side effects. (The mice were sacrificed at 16 weeks.)

“We’re very excited about the promise of this technology,” said study author Jacob Corn, PhD, of the University of California, Berkeley.

“There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”

In fact, Dr Corn and his lab have joined with Dr Walters to initiate an early phase clinical trial to test this gene-editing approach within the next 5 years.

The investigators also noted that the approach might be effective for treating other disorders, such as β-thalassemia, Wiskott-Aldrich syndrome, and Fanconi anemia.

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Dr Corn said. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”

Micrograph showing

sickle cell disease

Image by Graham Beards

Researchers have described a gene-editing technique that can correct the sickle cell mutation in hematopoietic stem and progenitor cells (HSPCs) isolated from patients with sickle cell disease (SCD).

The investigators said these edited HSPCs produced wild-type adult and fetal hemoglobin.

The HSPCs were also able to engraft in mice and maintained their SCD gene edits long-term without showing any signs of side effects.

“This is an important advance because, for the first time, we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

Dr Walters and his colleagues described this work in Science Translational Medicine.

The researchers said they used a ribonucleoprotein complex consisting of Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor, to enable efficient replacement of the SCD mutation in human HSPCs.

The team then differentiated pools of these HSPCs into enucleated erythrocytes and late-stage erythroblasts to measure hemoglobin production.

They said the edited HSPCs produced “substantial amounts” of adult wild-type hemoglobin. The cells also showed a decrease in sickle hemoglobin and an increase in fetal hemoglobin.

When implanted in mice, the edited HSPCs repopulated and maintained their SCD gene edits for 16 weeks, with no signs of side effects. (The mice were sacrificed at 16 weeks.)

“We’re very excited about the promise of this technology,” said study author Jacob Corn, PhD, of the University of California, Berkeley.

“There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”

In fact, Dr Corn and his lab have joined with Dr Walters to initiate an early phase clinical trial to test this gene-editing approach within the next 5 years.

The investigators also noted that the approach might be effective for treating other disorders, such as β-thalassemia, Wiskott-Aldrich syndrome, and Fanconi anemia.

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Dr Corn said. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”

Clinical Question: Can a collaborative quality improvement project improve the quality and efficiency of pediatric hospital discharges?

Background: Transitions of care, including at the time of hospital discharge, are a potential source of risk and can be associated with adverse events including medication errors and preventable readmissions. Some studies have shown that 10–20% of patients had an adverse event after discharge, and half of those were preventable; one adult study found nearly half of the discharged patients had at least one medication error.1,2 Although multiple projects to improve the discharge process have been published in adult literature, few have focused on the pediatric population. In this study, the Children’s Hospital Association (CHA) formed a pediatric quality improvement collaborative across multiple facilities to examine whether shared improvement strategies would affect failures of discharge-related care, parent-reported readiness for discharge, and readmission rates.

Study Design: Multicenter quality improvement collaborative.

Setting: 11 freestanding tertiary-care children’s hospitals in the United States.

Synopsis: Each of the 11 participating sites chose a specific target population, such as patients with sickle cell disease, asthma, or all discharged pediatric patients. Populations were selected at the discretion of the sites. A multidisciplinary expert advisory panel reviewed literature and developed a change package that included being proactive about discharge planning during hospitalization; improving throughput; arranging post-discharge treatment and support; and communicating post-discharge plan with patients, families, and providers. Each site selected elements of the change package to implement based on individual needs and preferences and incorporated via plan-do-study-act cycles during three action periods. Elements that were implemented by most or all sites included family education on diagnosis and discharge plans, use of discharge checklists, improvement of written discharge instructions, post-discharge follow-up phone calls to reinforce discharge instructions, and identifying and obtaining medications. Virtual learning conferences and monthly Web conferences were held for participants in the collaborative, and experienced improvement coaches guided teams through implementation.

The primary aim of the study was to reduce discharge-related care failures by 50% in 12 months. Failures were measured by phone calls to families two to seven days following discharge, and if any problem related to discharge occurred, the discharge was considered a failure (all-or-none measure). Components of this measure included understanding the diagnosis, receiving discharge instructions and education, complying with instructions, receiving necessary equipment, planning for follow-up pending tests, receiving help with appointments, and not requiring a related unplanned medical visit. Other measures evaluated in this study included patient/family readiness for discharge and unplanned readmission rates (72 hours and 30 days).

Overall, the rate of failures of discharge care was 34% at baseline, which decreased to 21% at the end of the collaborative, for a reduction of 40%. Some individual hospitals exceeded this mark as well. Among the hospitals reporting data on family readiness for discharge, there was a statistically significant improvement, with 85% of families at baseline rating readiness in the highest category and 91% in the last quarter of the study. There was no improvement in rates of unplanned readmission, with 72-hour readmission rates steady across the project (0.7% at onset, 1.1% at end of study; P = 0.29) and slight worsening of the 30-day rate (4.5% to 6.3%; P = 0.05).

Potential explanations for the findings related to readmission rates include seasonal variability in readmissions as well as high variability in patients included in the study. For example, one site focused on patients with sickle cell disease, another on patients with asthma, and others included all diagnoses. Overall, unplanned readmission rates were low (around 1% for 72-hour, 5% for 30-day), which is consistent with other pediatric studies.

Bottom Line: In this study, institutions using a collaborative approach improved the quality of inpatient discharges by using an intervention bundle in pediatric hospital settings. There was no improvement noted in readmission rates, although these rates were low.

Citation: Wu S, Tyler A, Logsdon T, et al. A quality improvement collaborative to improve the discharge process for hospitalized children. Pediatrics. 2016;138(2). pii:e20143604.

References:

1. Moore C, Wisnivesky J, Williams S, McGinn T. Medical errors related to discontinuity of care from an inpatient to an outpatient setting. J Gen Intern Med. 2003;18(8):646-651.
2. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital. CMAJ. 2004;170(3):345-349.

Clinical Question: Can a collaborative quality improvement project improve the quality and efficiency of pediatric hospital discharges?

Background: Transitions of care, including at the time of hospital discharge, are a potential source of risk and can be associated with adverse events including medication errors and preventable readmissions. Some studies have shown that 10–20% of patients had an adverse event after discharge, and half of those were preventable; one adult study found nearly half of the discharged patients had at least one medication error.1,2 Although multiple projects to improve the discharge process have been published in adult literature, few have focused on the pediatric population. In this study, the Children’s Hospital Association (CHA) formed a pediatric quality improvement collaborative across multiple facilities to examine whether shared improvement strategies would affect failures of discharge-related care, parent-reported readiness for discharge, and readmission rates.

Study Design: Multicenter quality improvement collaborative.

Setting: 11 freestanding tertiary-care children’s hospitals in the United States.

Synopsis: Each of the 11 participating sites chose a specific target population, such as patients with sickle cell disease, asthma, or all discharged pediatric patients. Populations were selected at the discretion of the sites. A multidisciplinary expert advisory panel reviewed literature and developed a change package that included being proactive about discharge planning during hospitalization; improving throughput; arranging post-discharge treatment and support; and communicating post-discharge plan with patients, families, and providers. Each site selected elements of the change package to implement based on individual needs and preferences and incorporated via plan-do-study-act cycles during three action periods. Elements that were implemented by most or all sites included family education on diagnosis and discharge plans, use of discharge checklists, improvement of written discharge instructions, post-discharge follow-up phone calls to reinforce discharge instructions, and identifying and obtaining medications. Virtual learning conferences and monthly Web conferences were held for participants in the collaborative, and experienced improvement coaches guided teams through implementation.

The primary aim of the study was to reduce discharge-related care failures by 50% in 12 months. Failures were measured by phone calls to families two to seven days following discharge, and if any problem related to discharge occurred, the discharge was considered a failure (all-or-none measure). Components of this measure included understanding the diagnosis, receiving discharge instructions and education, complying with instructions, receiving necessary equipment, planning for follow-up pending tests, receiving help with appointments, and not requiring a related unplanned medical visit. Other measures evaluated in this study included patient/family readiness for discharge and unplanned readmission rates (72 hours and 30 days).

Overall, the rate of failures of discharge care was 34% at baseline, which decreased to 21% at the end of the collaborative, for a reduction of 40%. Some individual hospitals exceeded this mark as well. Among the hospitals reporting data on family readiness for discharge, there was a statistically significant improvement, with 85% of families at baseline rating readiness in the highest category and 91% in the last quarter of the study. There was no improvement in rates of unplanned readmission, with 72-hour readmission rates steady across the project (0.7% at onset, 1.1% at end of study; P = 0.29) and slight worsening of the 30-day rate (4.5% to 6.3%; P = 0.05).

Potential explanations for the findings related to readmission rates include seasonal variability in readmissions as well as high variability in patients included in the study. For example, one site focused on patients with sickle cell disease, another on patients with asthma, and others included all diagnoses. Overall, unplanned readmission rates were low (around 1% for 72-hour, 5% for 30-day), which is consistent with other pediatric studies.

Bottom Line: In this study, institutions using a collaborative approach improved the quality of inpatient discharges by using an intervention bundle in pediatric hospital settings. There was no improvement noted in readmission rates, although these rates were low.

Citation: Wu S, Tyler A, Logsdon T, et al. A quality improvement collaborative to improve the discharge process for hospitalized children. Pediatrics. 2016;138(2). pii:e20143604.

References:

1. Moore C, Wisnivesky J, Williams S, McGinn T. Medical errors related to discontinuity of care from an inpatient to an outpatient setting. J Gen Intern Med. 2003;18(8):646-651.
2. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital. CMAJ. 2004;170(3):345-349.

Clinical Question: Can a collaborative quality improvement project improve the quality and efficiency of pediatric hospital discharges?

Background: Transitions of care, including at the time of hospital discharge, are a potential source of risk and can be associated with adverse events including medication errors and preventable readmissions. Some studies have shown that 10–20% of patients had an adverse event after discharge, and half of those were preventable; one adult study found nearly half of the discharged patients had at least one medication error.1,2 Although multiple projects to improve the discharge process have been published in adult literature, few have focused on the pediatric population. In this study, the Children’s Hospital Association (CHA) formed a pediatric quality improvement collaborative across multiple facilities to examine whether shared improvement strategies would affect failures of discharge-related care, parent-reported readiness for discharge, and readmission rates.

Study Design: Multicenter quality improvement collaborative.

Setting: 11 freestanding tertiary-care children’s hospitals in the United States.

Synopsis: Each of the 11 participating sites chose a specific target population, such as patients with sickle cell disease, asthma, or all discharged pediatric patients. Populations were selected at the discretion of the sites. A multidisciplinary expert advisory panel reviewed literature and developed a change package that included being proactive about discharge planning during hospitalization; improving throughput; arranging post-discharge treatment and support; and communicating post-discharge plan with patients, families, and providers. Each site selected elements of the change package to implement based on individual needs and preferences and incorporated via plan-do-study-act cycles during three action periods. Elements that were implemented by most or all sites included family education on diagnosis and discharge plans, use of discharge checklists, improvement of written discharge instructions, post-discharge follow-up phone calls to reinforce discharge instructions, and identifying and obtaining medications. Virtual learning conferences and monthly Web conferences were held for participants in the collaborative, and experienced improvement coaches guided teams through implementation.

The primary aim of the study was to reduce discharge-related care failures by 50% in 12 months. Failures were measured by phone calls to families two to seven days following discharge, and if any problem related to discharge occurred, the discharge was considered a failure (all-or-none measure). Components of this measure included understanding the diagnosis, receiving discharge instructions and education, complying with instructions, receiving necessary equipment, planning for follow-up pending tests, receiving help with appointments, and not requiring a related unplanned medical visit. Other measures evaluated in this study included patient/family readiness for discharge and unplanned readmission rates (72 hours and 30 days).

Overall, the rate of failures of discharge care was 34% at baseline, which decreased to 21% at the end of the collaborative, for a reduction of 40%. Some individual hospitals exceeded this mark as well. Among the hospitals reporting data on family readiness for discharge, there was a statistically significant improvement, with 85% of families at baseline rating readiness in the highest category and 91% in the last quarter of the study. There was no improvement in rates of unplanned readmission, with 72-hour readmission rates steady across the project (0.7% at onset, 1.1% at end of study; P = 0.29) and slight worsening of the 30-day rate (4.5% to 6.3%; P = 0.05).

Potential explanations for the findings related to readmission rates include seasonal variability in readmissions as well as high variability in patients included in the study. For example, one site focused on patients with sickle cell disease, another on patients with asthma, and others included all diagnoses. Overall, unplanned readmission rates were low (around 1% for 72-hour, 5% for 30-day), which is consistent with other pediatric studies.

Bottom Line: In this study, institutions using a collaborative approach improved the quality of inpatient discharges by using an intervention bundle in pediatric hospital settings. There was no improvement noted in readmission rates, although these rates were low.

Citation: Wu S, Tyler A, Logsdon T, et al. A quality improvement collaborative to improve the discharge process for hospitalized children. Pediatrics. 2016;138(2). pii:e20143604.

References:

1. Moore C, Wisnivesky J, Williams S, McGinn T. Medical errors related to discontinuity of care from an inpatient to an outpatient setting. J Gen Intern Med. 2003;18(8):646-651.
2. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital. CMAJ. 2004;170(3):345-349.

Clinical Question: What is the performance of the Step-by-Step approach to evaluate febrile infants, and how does it compare to other existing criteria?

Background: Multiple studies have been performed to find the best set of criteria to identify febrile infants at low risk for bacterial infection in order to manage them in a less invasive manner. Common criteria used in the United States include Rochester, Philadelphia, and Boston criteria, initially published in the early 1990s. Since that time, management has evolved with the introduction of newer biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), and epidemiology has changed with immunizations and improvement in intrapartum antibiotic prophylaxis.

A new algorithm, Step-by-Step, has been developed by a group of European pediatric emergency physicians and has been shown retrospectively to accurately identify groups of patients according to risk of noninvasive or invasive bacterial infection (IBI). This algorithm uses a sequential approach, evaluating the general appearance, age of the patient, urinalysis, and then other lab findings including CRP, PCT, and absolute neutrophil count (ANC). In this study, the authors sought to validate this algorithm prospectively in a larger multicenter population.

Study Design: Multicenter prospective study.

Setting: 11 European pediatric emergency departments in Spain, Italy, and Switzerland.

Synopsis: This study included infants ≤90 days of age presenting to the pediatric emergency department (PED) between September 2012 and August 2014 with fever without source (defined as temperature ≥38°C measured by thermometer at home or in the PED, with normal physical examination and no respiratory signs or symptoms or diarrheal process). Labs obtained for each patient included urinalysis, urine culture (obtained by bladder catheterization or suprapubic aspiration), white blood cell count, PCT, CRP, and blood culture. Further testing and management were determined by the treating physician and management protocols of each center.

Exclusion criteria included:

• Clear source of fever by history or physical examination.
• No fever in the PED and fever assessed only subjectively by parents prior to presentation without the use of a thermometer.
• Absence of one or more of the above lab tests.
• Refusal of parents to participate.

The study included 2,185 infants. Of these, 504 were diagnosed with bacterial infection, including 87 (3.9%) with IBI (defined as positive blood or cerebrospinal fluid culture) and 417 (19.1%) with non-IBI (409 of which were urinary tract infections). Following the first part of the Step-by-Step approach, which uses general appearance (well-appearing versus ill-appearing), age (older or younger than 21 days), and leukocyturia, identified 79.3% of patients with IBI and 98.5% of non-IBI. Adding the next steps in the approach, with PCT, CRP, and ANC, identified 991 low-risk patients (45.3% of the studied population). In this low-risk group, seven patients were subsequently identified as having IBI (0.7% of this group). Using the Step-by-Step approach led to a negative predictive value (NPV) of 99.3 for identifying IBI, with a negative likelihood ratio (LR) of 0.17.

In evaluation of the seven low-risk patients with IBI, three of these were noted to present to the PED within one hour of onset of fever, and three more patients had fever first detected on arrival in the PED. This short duration of fever, and the lack of time for a rise in biomarkers, is likely why these patients were missed in the initial assessment.

When the Rochester criteria were used for this group of 2,185 patients, 949 patients were identified as low risk, with 1.6% of the low-risk patients found to have IBI, leading to an NPV of 98.3 and negative LR of 0.41. The authors chose to compare their approach to the Rochester criteria because the other commonly used approaches (Boston, Philadelphia) recommend lumbar puncture in all febrile infants while Rochester does not, and more recent literature suggests an individualized approach rather than recommending the test systematically.

Limitations included:

• Prevalence of bacterial infection was similar to other European publications but higher than in many studies in the United States, primarily due to an increased rate of UTI. (In this study, the authors used a definition of leukocyturia and culture with ≥10,000 cfu/mL.)
• Band count, although part of the Rochester criteria, was not available in some of the centers and not included in analysis. Inclusion of this lab study could have changed the performance of the Rochester criteria.
• The Step-by-Step approach was not compared to other existing criteria.

Bottom Line: In this study, the Step-by-Step approach was very accurate in identifying febrile infants at low risk for invasive bacterial infection, performing better than the Rochester criteria, and may be helpful in evaluation of infants with fever in the emergency department. A cautious approach is warranted for patients with very short fever duration, as they may be missed by ancillary test results.

Citation: Gomez B, Mintegi S, Bressan S, et al. Validation of the “step-by-step” approach in the management of young febrile infants. Pediatrics. 2016;138(2). pic:e20154381.

Carl Galloway, MD, is a hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D.

Clinical Question: What is the performance of the Step-by-Step approach to evaluate febrile infants, and how does it compare to other existing criteria?

Background: Multiple studies have been performed to find the best set of criteria to identify febrile infants at low risk for bacterial infection in order to manage them in a less invasive manner. Common criteria used in the United States include Rochester, Philadelphia, and Boston criteria, initially published in the early 1990s. Since that time, management has evolved with the introduction of newer biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), and epidemiology has changed with immunizations and improvement in intrapartum antibiotic prophylaxis.

A new algorithm, Step-by-Step, has been developed by a group of European pediatric emergency physicians and has been shown retrospectively to accurately identify groups of patients according to risk of noninvasive or invasive bacterial infection (IBI). This algorithm uses a sequential approach, evaluating the general appearance, age of the patient, urinalysis, and then other lab findings including CRP, PCT, and absolute neutrophil count (ANC). In this study, the authors sought to validate this algorithm prospectively in a larger multicenter population.

Study Design: Multicenter prospective study.

Setting: 11 European pediatric emergency departments in Spain, Italy, and Switzerland.

Synopsis: This study included infants ≤90 days of age presenting to the pediatric emergency department (PED) between September 2012 and August 2014 with fever without source (defined as temperature ≥38°C measured by thermometer at home or in the PED, with normal physical examination and no respiratory signs or symptoms or diarrheal process). Labs obtained for each patient included urinalysis, urine culture (obtained by bladder catheterization or suprapubic aspiration), white blood cell count, PCT, CRP, and blood culture. Further testing and management were determined by the treating physician and management protocols of each center.

Exclusion criteria included:

• Clear source of fever by history or physical examination.
• No fever in the PED and fever assessed only subjectively by parents prior to presentation without the use of a thermometer.
• Absence of one or more of the above lab tests.
• Refusal of parents to participate.

The study included 2,185 infants. Of these, 504 were diagnosed with bacterial infection, including 87 (3.9%) with IBI (defined as positive blood or cerebrospinal fluid culture) and 417 (19.1%) with non-IBI (409 of which were urinary tract infections). Following the first part of the Step-by-Step approach, which uses general appearance (well-appearing versus ill-appearing), age (older or younger than 21 days), and leukocyturia, identified 79.3% of patients with IBI and 98.5% of non-IBI. Adding the next steps in the approach, with PCT, CRP, and ANC, identified 991 low-risk patients (45.3% of the studied population). In this low-risk group, seven patients were subsequently identified as having IBI (0.7% of this group). Using the Step-by-Step approach led to a negative predictive value (NPV) of 99.3 for identifying IBI, with a negative likelihood ratio (LR) of 0.17.

In evaluation of the seven low-risk patients with IBI, three of these were noted to present to the PED within one hour of onset of fever, and three more patients had fever first detected on arrival in the PED. This short duration of fever, and the lack of time for a rise in biomarkers, is likely why these patients were missed in the initial assessment.

When the Rochester criteria were used for this group of 2,185 patients, 949 patients were identified as low risk, with 1.6% of the low-risk patients found to have IBI, leading to an NPV of 98.3 and negative LR of 0.41. The authors chose to compare their approach to the Rochester criteria because the other commonly used approaches (Boston, Philadelphia) recommend lumbar puncture in all febrile infants while Rochester does not, and more recent literature suggests an individualized approach rather than recommending the test systematically.

Limitations included:

• Prevalence of bacterial infection was similar to other European publications but higher than in many studies in the United States, primarily due to an increased rate of UTI. (In this study, the authors used a definition of leukocyturia and culture with ≥10,000 cfu/mL.)
• Band count, although part of the Rochester criteria, was not available in some of the centers and not included in analysis. Inclusion of this lab study could have changed the performance of the Rochester criteria.
• The Step-by-Step approach was not compared to other existing criteria.

Bottom Line: In this study, the Step-by-Step approach was very accurate in identifying febrile infants at low risk for invasive bacterial infection, performing better than the Rochester criteria, and may be helpful in evaluation of infants with fever in the emergency department. A cautious approach is warranted for patients with very short fever duration, as they may be missed by ancillary test results.

Citation: Gomez B, Mintegi S, Bressan S, et al. Validation of the “step-by-step” approach in the management of young febrile infants. Pediatrics. 2016;138(2). pic:e20154381.

Carl Galloway, MD, is a hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D.

Clinical Question: What is the performance of the Step-by-Step approach to evaluate febrile infants, and how does it compare to other existing criteria?

Background: Multiple studies have been performed to find the best set of criteria to identify febrile infants at low risk for bacterial infection in order to manage them in a less invasive manner. Common criteria used in the United States include Rochester, Philadelphia, and Boston criteria, initially published in the early 1990s. Since that time, management has evolved with the introduction of newer biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), and epidemiology has changed with immunizations and improvement in intrapartum antibiotic prophylaxis.

A new algorithm, Step-by-Step, has been developed by a group of European pediatric emergency physicians and has been shown retrospectively to accurately identify groups of patients according to risk of noninvasive or invasive bacterial infection (IBI). This algorithm uses a sequential approach, evaluating the general appearance, age of the patient, urinalysis, and then other lab findings including CRP, PCT, and absolute neutrophil count (ANC). In this study, the authors sought to validate this algorithm prospectively in a larger multicenter population.

Study Design: Multicenter prospective study.

Setting: 11 European pediatric emergency departments in Spain, Italy, and Switzerland.

Synopsis: This study included infants ≤90 days of age presenting to the pediatric emergency department (PED) between September 2012 and August 2014 with fever without source (defined as temperature ≥38°C measured by thermometer at home or in the PED, with normal physical examination and no respiratory signs or symptoms or diarrheal process). Labs obtained for each patient included urinalysis, urine culture (obtained by bladder catheterization or suprapubic aspiration), white blood cell count, PCT, CRP, and blood culture. Further testing and management were determined by the treating physician and management protocols of each center.

Exclusion criteria included:

• Clear source of fever by history or physical examination.
• No fever in the PED and fever assessed only subjectively by parents prior to presentation without the use of a thermometer.
• Absence of one or more of the above lab tests.
• Refusal of parents to participate.

The study included 2,185 infants. Of these, 504 were diagnosed with bacterial infection, including 87 (3.9%) with IBI (defined as positive blood or cerebrospinal fluid culture) and 417 (19.1%) with non-IBI (409 of which were urinary tract infections). Following the first part of the Step-by-Step approach, which uses general appearance (well-appearing versus ill-appearing), age (older or younger than 21 days), and leukocyturia, identified 79.3% of patients with IBI and 98.5% of non-IBI. Adding the next steps in the approach, with PCT, CRP, and ANC, identified 991 low-risk patients (45.3% of the studied population). In this low-risk group, seven patients were subsequently identified as having IBI (0.7% of this group). Using the Step-by-Step approach led to a negative predictive value (NPV) of 99.3 for identifying IBI, with a negative likelihood ratio (LR) of 0.17.

In evaluation of the seven low-risk patients with IBI, three of these were noted to present to the PED within one hour of onset of fever, and three more patients had fever first detected on arrival in the PED. This short duration of fever, and the lack of time for a rise in biomarkers, is likely why these patients were missed in the initial assessment.

When the Rochester criteria were used for this group of 2,185 patients, 949 patients were identified as low risk, with 1.6% of the low-risk patients found to have IBI, leading to an NPV of 98.3 and negative LR of 0.41. The authors chose to compare their approach to the Rochester criteria because the other commonly used approaches (Boston, Philadelphia) recommend lumbar puncture in all febrile infants while Rochester does not, and more recent literature suggests an individualized approach rather than recommending the test systematically.

Limitations included:

• Prevalence of bacterial infection was similar to other European publications but higher than in many studies in the United States, primarily due to an increased rate of UTI. (In this study, the authors used a definition of leukocyturia and culture with ≥10,000 cfu/mL.)
• Band count, although part of the Rochester criteria, was not available in some of the centers and not included in analysis. Inclusion of this lab study could have changed the performance of the Rochester criteria.
• The Step-by-Step approach was not compared to other existing criteria.

Bottom Line: In this study, the Step-by-Step approach was very accurate in identifying febrile infants at low risk for invasive bacterial infection, performing better than the Rochester criteria, and may be helpful in evaluation of infants with fever in the emergency department. A cautious approach is warranted for patients with very short fever duration, as they may be missed by ancillary test results.

Citation: Gomez B, Mintegi S, Bressan S, et al. Validation of the “step-by-step” approach in the management of young febrile infants. Pediatrics. 2016;138(2). pic:e20154381.

Carl Galloway, MD, is a hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D.