TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

sworcester@mdedge.com

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

sworcester@mdedge.com

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

sworcester@mdedge.com

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

Fecal blood test outreach and patient navigation have robust evidence to show they improve colorectal cancer screening rates, results of a meta-analysis show.

Both strategies increased screening rates by about 20 percentage points, according to results of the systematic review and meta-analysis reported in JAMA Internal Medicine.

“This finding suggests that broad implementation of either of these interventions could bring the current national screening rate of 63% close to the national goal of 80%,” wrote Michael K. Dougherty, MD, of the University of North Carolina at Chapel Hill, and his coauthors in the report.

Active distribution of fecal blood tests (FBTs) was tested in 17 of the studies in the main meta-analysis, which was limited to 73 trials that the researchers said were at low to medium risk of bias.

Most of those studies looked at mailing FBTs, though a few studies tied distribution to a patient encounter. Compared with usual care, FBT outreach was associated with increased screening, with a risk ratio of 2.26, Dr. Dougherty and his coauthors reported.

Patient navigation interventions, tested in 16 studies of low to medium bias risk, were usually done by health care professionals, though in a few cases, they involved lay or peer navigators.

Navigation was also associated with increased screening when compared with usual care, the investigators found. The risk ratio was 2.01, which increased to 2.33 for interventions that included some additional component more than a standardized reminder or mailing, such as a video decision aid or intensive automated reminders.

Patient reminders and patient education strategies were also associated with increased screening in the meta-analysis, both with risk ratios of 1.20.

Incorporating clinician reminders or academic detailing appeared to improve the net benefit of interventions, according to the investigators.

“Clinicians, health administrators, and policy makers should consider how to incorporate patient navigation, FBT outreach, and/or clinician prompts into their health care settings and sociocultural contexts,” Dr. Dougherty and his colleagues wrote in their report.

Multicomponent interventions appeared to have an edge over single-component interventions, they added.

In general, the aim of FBT outreach is to improve test distribution and thus overcome structural barriers to screening, the study authors wrote. Similarly, patient navigation is designed to help guide patients through the complex health care system and avoid barriers to care, which may be sociocultural, logistical, or educational.

Major funding for the study came from the University Cancer Research Fund of the University of North Carolina Lineberger Comprehensive Cancer Center. One coinvestigator reported institutional grant funding from Pfizer unrelated to the current study.

SOURCE: Dougherty MK et al. JAMA Intern Med. 2018 Oct 15. doi: 10.1001/jamainternmed.2018.4637.

Fecal blood test outreach and patient navigation have robust evidence to show they improve colorectal cancer screening rates, results of a meta-analysis show.

Both strategies increased screening rates by about 20 percentage points, according to results of the systematic review and meta-analysis reported in JAMA Internal Medicine.

“This finding suggests that broad implementation of either of these interventions could bring the current national screening rate of 63% close to the national goal of 80%,” wrote Michael K. Dougherty, MD, of the University of North Carolina at Chapel Hill, and his coauthors in the report.

Active distribution of fecal blood tests (FBTs) was tested in 17 of the studies in the main meta-analysis, which was limited to 73 trials that the researchers said were at low to medium risk of bias.

Most of those studies looked at mailing FBTs, though a few studies tied distribution to a patient encounter. Compared with usual care, FBT outreach was associated with increased screening, with a risk ratio of 2.26, Dr. Dougherty and his coauthors reported.

Patient navigation interventions, tested in 16 studies of low to medium bias risk, were usually done by health care professionals, though in a few cases, they involved lay or peer navigators.

Navigation was also associated with increased screening when compared with usual care, the investigators found. The risk ratio was 2.01, which increased to 2.33 for interventions that included some additional component more than a standardized reminder or mailing, such as a video decision aid or intensive automated reminders.

Patient reminders and patient education strategies were also associated with increased screening in the meta-analysis, both with risk ratios of 1.20.

Incorporating clinician reminders or academic detailing appeared to improve the net benefit of interventions, according to the investigators.

“Clinicians, health administrators, and policy makers should consider how to incorporate patient navigation, FBT outreach, and/or clinician prompts into their health care settings and sociocultural contexts,” Dr. Dougherty and his colleagues wrote in their report.

Multicomponent interventions appeared to have an edge over single-component interventions, they added.

In general, the aim of FBT outreach is to improve test distribution and thus overcome structural barriers to screening, the study authors wrote. Similarly, patient navigation is designed to help guide patients through the complex health care system and avoid barriers to care, which may be sociocultural, logistical, or educational.

Major funding for the study came from the University Cancer Research Fund of the University of North Carolina Lineberger Comprehensive Cancer Center. One coinvestigator reported institutional grant funding from Pfizer unrelated to the current study.

SOURCE: Dougherty MK et al. JAMA Intern Med. 2018 Oct 15. doi: 10.1001/jamainternmed.2018.4637.

Fecal blood test outreach and patient navigation have robust evidence to show they improve colorectal cancer screening rates, results of a meta-analysis show.

Both strategies increased screening rates by about 20 percentage points, according to results of the systematic review and meta-analysis reported in JAMA Internal Medicine.

“This finding suggests that broad implementation of either of these interventions could bring the current national screening rate of 63% close to the national goal of 80%,” wrote Michael K. Dougherty, MD, of the University of North Carolina at Chapel Hill, and his coauthors in the report.

Active distribution of fecal blood tests (FBTs) was tested in 17 of the studies in the main meta-analysis, which was limited to 73 trials that the researchers said were at low to medium risk of bias.

Most of those studies looked at mailing FBTs, though a few studies tied distribution to a patient encounter. Compared with usual care, FBT outreach was associated with increased screening, with a risk ratio of 2.26, Dr. Dougherty and his coauthors reported.

Patient navigation interventions, tested in 16 studies of low to medium bias risk, were usually done by health care professionals, though in a few cases, they involved lay or peer navigators.

Navigation was also associated with increased screening when compared with usual care, the investigators found. The risk ratio was 2.01, which increased to 2.33 for interventions that included some additional component more than a standardized reminder or mailing, such as a video decision aid or intensive automated reminders.

Patient reminders and patient education strategies were also associated with increased screening in the meta-analysis, both with risk ratios of 1.20.

Incorporating clinician reminders or academic detailing appeared to improve the net benefit of interventions, according to the investigators.

“Clinicians, health administrators, and policy makers should consider how to incorporate patient navigation, FBT outreach, and/or clinician prompts into their health care settings and sociocultural contexts,” Dr. Dougherty and his colleagues wrote in their report.

Multicomponent interventions appeared to have an edge over single-component interventions, they added.

In general, the aim of FBT outreach is to improve test distribution and thus overcome structural barriers to screening, the study authors wrote. Similarly, patient navigation is designed to help guide patients through the complex health care system and avoid barriers to care, which may be sociocultural, logistical, or educational.

Major funding for the study came from the University Cancer Research Fund of the University of North Carolina Lineberger Comprehensive Cancer Center. One coinvestigator reported institutional grant funding from Pfizer unrelated to the current study.

SOURCE: Dougherty MK et al. JAMA Intern Med. 2018 Oct 15. doi: 10.1001/jamainternmed.2018.4637.

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

Patients with chronic obstructive pulmonary disease who are taking benzodiazepines have more than double the risk of suicide compared with patients who are not on those medications. Also today, the feds say that the ACA’s silver plan premiums will drop in 2019, bias in the clinical setting can impact patient care, and managing asthma in children mean that pets do not always have to go.

The Postcall Podcast is available here: https://www.mdedge.com/podcasts


 

Patients with chronic obstructive pulmonary disease who are taking benzodiazepines have more than double the risk of suicide compared with patients who are not on those medications. Also today, the feds say that the ACA’s silver plan premiums will drop in 2019, bias in the clinical setting can impact patient care, and managing asthma in children mean that pets do not always have to go.

The Postcall Podcast is available here: https://www.mdedge.com/podcasts


 

Patients with chronic obstructive pulmonary disease who are taking benzodiazepines have more than double the risk of suicide compared with patients who are not on those medications. Also today, the feds say that the ACA’s silver plan premiums will drop in 2019, bias in the clinical setting can impact patient care, and managing asthma in children mean that pets do not always have to go.

The Postcall Podcast is available here: https://www.mdedge.com/podcasts


 

Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.

They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.

The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.

Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.

They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.

The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.

Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.

They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.

The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.

Photo by Cristina Granados

BOSTON—Drone-delivered blood products may be coming soon to a hospital near you, experts said at AABB 2018.

Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.

“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries,” Kenney said. “That’s almost 20,000 units of blood.”

One-third of all deliveries are needed for urgent, life-saving interventions, he added.

The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, according to Kenney.

How it works

Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section.

The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.

They placed an order for more blood products, which can be done by text message or via WhatsApp, a free messaging and voiceover IP calling service.

After the order was placed, Zipline was able to deliver blood products using multiple drone launches over the course of 90 minutes. The deliveries consisted of 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.

Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15 to 25 minutes by air, Kenney said.

The drones—more formally known as “unmanned aerial vehicles”—fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters, and drop the package, which has a parachute attached.

Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Kenney said.

“The whole process is 100% autonomous,” he noted. “The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package.”

As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.

Airborne deliveries are significantly cheaper than ground-based services for local delivery, according to Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.

Dr. Eastvold cited statistics suggesting the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more. However, drone delivery could be as cheap as 5 cents per mile.

Barriers to drone delivery

Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, according to Dr. Eastvold.

He described the hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters in the United States.

Dr. Eastvold said the barriers to adoption of drone-based delivery systems include differences in state laws about when, where, and how drones can be used and who can operate them as well as Federal Aviation Administration (FAA) airspace restrictions and regulations.

For example, the FAA currently requires “line-of-sight” operation for most drone operators, meaning the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.

In addition, federal regulations require commercial drone pilots to be 16 or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.

Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery.

In 2015, Johns Hopkins researchers reported that transporting blood samples on hobby-sized drones did not affect the results of common and routine blood tests.

In 2016, the researchers showed that large bags of blood products can maintain temperature and cellular integrity when transported by drones.

In 2017, the researchers demonstrated that a drone could deliver blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.

Kenney said his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.

Photo by Cristina Granados

BOSTON—Drone-delivered blood products may be coming soon to a hospital near you, experts said at AABB 2018.

Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.

“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries,” Kenney said. “That’s almost 20,000 units of blood.”

One-third of all deliveries are needed for urgent, life-saving interventions, he added.

The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, according to Kenney.

How it works

Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section.

The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.

They placed an order for more blood products, which can be done by text message or via WhatsApp, a free messaging and voiceover IP calling service.

After the order was placed, Zipline was able to deliver blood products using multiple drone launches over the course of 90 minutes. The deliveries consisted of 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.

Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15 to 25 minutes by air, Kenney said.

The drones—more formally known as “unmanned aerial vehicles”—fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters, and drop the package, which has a parachute attached.

Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Kenney said.

“The whole process is 100% autonomous,” he noted. “The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package.”

As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.

Airborne deliveries are significantly cheaper than ground-based services for local delivery, according to Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.

Dr. Eastvold cited statistics suggesting the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more. However, drone delivery could be as cheap as 5 cents per mile.

Barriers to drone delivery

Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, according to Dr. Eastvold.

He described the hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters in the United States.

Dr. Eastvold said the barriers to adoption of drone-based delivery systems include differences in state laws about when, where, and how drones can be used and who can operate them as well as Federal Aviation Administration (FAA) airspace restrictions and regulations.

For example, the FAA currently requires “line-of-sight” operation for most drone operators, meaning the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.

In addition, federal regulations require commercial drone pilots to be 16 or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.

Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery.

In 2015, Johns Hopkins researchers reported that transporting blood samples on hobby-sized drones did not affect the results of common and routine blood tests.

In 2016, the researchers showed that large bags of blood products can maintain temperature and cellular integrity when transported by drones.

In 2017, the researchers demonstrated that a drone could deliver blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.

Kenney said his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.

Photo by Cristina Granados

BOSTON—Drone-delivered blood products may be coming soon to a hospital near you, experts said at AABB 2018.

Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.

“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries,” Kenney said. “That’s almost 20,000 units of blood.”

One-third of all deliveries are needed for urgent, life-saving interventions, he added.

The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, according to Kenney.

How it works

Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section.

The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.

They placed an order for more blood products, which can be done by text message or via WhatsApp, a free messaging and voiceover IP calling service.

After the order was placed, Zipline was able to deliver blood products using multiple drone launches over the course of 90 minutes. The deliveries consisted of 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.

Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15 to 25 minutes by air, Kenney said.

The drones—more formally known as “unmanned aerial vehicles”—fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters, and drop the package, which has a parachute attached.

Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Kenney said.

“The whole process is 100% autonomous,” he noted. “The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package.”

As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.

Airborne deliveries are significantly cheaper than ground-based services for local delivery, according to Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.

Dr. Eastvold cited statistics suggesting the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more. However, drone delivery could be as cheap as 5 cents per mile.

Barriers to drone delivery

Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, according to Dr. Eastvold.

He described the hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters in the United States.

Dr. Eastvold said the barriers to adoption of drone-based delivery systems include differences in state laws about when, where, and how drones can be used and who can operate them as well as Federal Aviation Administration (FAA) airspace restrictions and regulations.

For example, the FAA currently requires “line-of-sight” operation for most drone operators, meaning the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.

In addition, federal regulations require commercial drone pilots to be 16 or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.

Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery.

In 2015, Johns Hopkins researchers reported that transporting blood samples on hobby-sized drones did not affect the results of common and routine blood tests.

In 2016, the researchers showed that large bags of blood products can maintain temperature and cellular integrity when transported by drones.

In 2017, the researchers demonstrated that a drone could deliver blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.

Kenney said his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.

Woman on a scale

SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.

The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.

“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”

Dr. Khan discussed this result in a presentation at CHEST 2018.

Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.

His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.

Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.

Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.

Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).

The obese PE patients were more often female, black, and younger than 65 years of age.

Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.

The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.

“I think it’s a rich area for more and further research, especially in basic science,” he added.

Dr. Khan and his coauthors said they had no relationships relevant to the study.

Woman on a scale

SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.

The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.

“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”

Dr. Khan discussed this result in a presentation at CHEST 2018.

Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.

His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.

Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.

Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.

Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).

The obese PE patients were more often female, black, and younger than 65 years of age.

Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.

The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.

“I think it’s a rich area for more and further research, especially in basic science,” he added.

Dr. Khan and his coauthors said they had no relationships relevant to the study.

Woman on a scale

SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.

The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.

“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”

Dr. Khan discussed this result in a presentation at CHEST 2018.

Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.

His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.

Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.

Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.

Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).

The obese PE patients were more often female, black, and younger than 65 years of age.

Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.

The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.

“I think it’s a rich area for more and further research, especially in basic science,” he added.

Dr. Khan and his coauthors said they had no relationships relevant to the study.

A 65-year-old man with moderately severe osteoarthritis (OA) of the knee presents to your office for his annual exam. During the medication review, the patient mentions he is using glucosamine and chondroitin for his knee pain, which was recommended by a family member. Should you tell the patient to continue taking the medication?

Knee OA is a common condition in the United States, affecting an estimated 12% of adults ages 60 and older and 16% of those ages 70 and older.² The primary goals of OA therapy are to minimize pain and improve function. The American Academy of Orthopedic Surgeons (AAOS) and the American College of Rheumatology (ACR) agree that firstline treatment recommendations include aerobic exercise, resistance training, and weight loss.

Initial pharmacologic therapies include full-strength acetaminophen or oral/topical NSAIDs; the latter are also used if pain is unresponsive to acetaminophen.^3,4 If initial therapy is inadequate to control pain, tramadol, other opioids, duloxetine, or intra-articular injections with corticosteroids or hyaluronate are alternatives.^3,4 Total knee replacement may be indicated in moderate or severe knee OA with radiographic evidence.⁵ Vitamin D, lateral wedge insoles, and antioxidants are not currently recommended.⁶

Prior studies evaluating glucosamine and/or chondroitin have provided conflicting results regarding evidence on pain reduction, function, and quality of life. Therefore, guidelines on OA management do not recommend their use (AAOS, strong; ACR, conditional).^3,4 However, consumption remains high, with 6.5 million US adults reporting use of glucosamine and/or chondroitin in the prior 30 days.⁷

A 2015 systematic review of 43 randomized trials evaluating oral chondroitin sulfate for OA of varying severity suggested there may be a significant decrease in short-term and long-term pain with doses ≥ 800 mg/d compared with placebo (level of evidence, low; risk for bias, high).⁸ However, no significant difference was noted in short- or long-term function, and the trials were highly heterogeneous.

Studies included in the 2015 systematic review found that glucosamine plus chondroitin did not have a significant effect on short- or long-term pain or physical function compared with placebo. Although glucosamine plus chondroitin led to significantly decreased pain compared with other medication, sensitivity analyses conducted for larger studies (N > 200) with adequate methods of blinding and allocation concealment found no difference in pain.⁸ There was no statistically significant difference in adverse events for glucosamine plus chondroitin vs placebo, based on data from three studies included in the review.⁸

This RCT from Roman-Blas et al evaluated chondroitin and glucosamine vs placebo in patients with more severe OA. The study was supported by Tedec-Meiji Farma (Madrid), maker of the combination of chondroitin plus glucosamine used in the study.¹

Continue to: STUDY SUMMARY

Chondroitin + glucosamine not better than placebo

This multicenter, randomized, double-blind, placebo-controlled trial was conducted in nine rheumatology referral centers and one orthopedic center in Spain. The trial evaluated the efficacy of chondroitin sulfate (1,200 mg) plus glucosamine sulfate (1,500 mg) (CS/GS) compared with placebo in 164 patients with Grade 2 or 3 knee OA and moderate-to-severe knee pain. OA grade was ascertained using the Kellgren-Lawrence scale, corresponding to osteophytes and either possible (Grade 2) or definite (Grade 3) joint space narrowing. Knee pain severity was defined by a self-reported global pain score of 40 to 80 mm on a 100-mm visual analog scale (VAS).

No significant difference was noted in group characteristics; average age in the CS/GS group was 67 and in the placebo group, 65. Exclusion criteria included BMI ≥ 35, concurrent arthritic conditions, and any coexisting chronic disease that would prevent successful completion of the trial.¹

The primary endpoint was mean reduction in global pain score on a 0- to 100-mm VAS at six months. Secondary outcomes included mean reduction in total and subscale scores in pain and function on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (0–100-mm VAS for each) and the use of rescue medication.

Baseline global pain scores were 62 mm in both groups. Acetaminophen, up to 3 g/d, was the only allowed rescue medication. Clinic visits occurred at 4, 12, and 24 weeks. A statistically significant difference between groups was defined as P < .03.¹

Results. In the intention-to-treat analysis at six months, patients in the placebo group had a greater reduction in pain than the CS/GC group (–20 mm vs –12 mm; P = .029). No other difference was noted between the placebo and CS/GS groups in the total or subscales of the WOMAC index, and no difference was noted in use of acetaminophen. More patients in the placebo group had at least a 50% improvement in pain or function compared with the CS/GS group (47.4% vs 27.5%; P = .01).

Continue to: In the CS/GS group...

In the CS/GS group, 31% did not complete the six-month treatment period, compared with 18% in the placebo group. More patients dropped out because of adverse effects (diarrhea, upper abdominal pain, and constipation) in the CS/GS group than the placebo group (33 vs 19; P = .018).¹

WHAT’S NEW

Pharma-sponsored study finds treatment ineffective

The effectiveness of CS/GS for the treatment of knee OA has been in question for years, but this RCT is the first trial sponsored by a pharmaceutical company to evaluate CS/GS efficacy. This trial found evidence of a lack of efficacy. In patients with more severe OA of the knee, placebo was more effective than CS/GS, and CS/GS had significantly more adverse events. Therefore, it may be time to advise patients to stop taking their CS/GS supplement.

CAVEATS

Cannot generalize findings

The study compared only one medication dosing regimen using a combination of CS and GS. Whether either agent alone, or different dosing, would lead to the same outcome is unknown.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[9]:566-568).

A 65-year-old man with moderately severe osteoarthritis (OA) of the knee presents to your office for his annual exam. During the medication review, the patient mentions he is using glucosamine and chondroitin for his knee pain, which was recommended by a family member. Should you tell the patient to continue taking the medication?

Knee OA is a common condition in the United States, affecting an estimated 12% of adults ages 60 and older and 16% of those ages 70 and older.² The primary goals of OA therapy are to minimize pain and improve function. The American Academy of Orthopedic Surgeons (AAOS) and the American College of Rheumatology (ACR) agree that firstline treatment recommendations include aerobic exercise, resistance training, and weight loss.

Initial pharmacologic therapies include full-strength acetaminophen or oral/topical NSAIDs; the latter are also used if pain is unresponsive to acetaminophen.^3,4 If initial therapy is inadequate to control pain, tramadol, other opioids, duloxetine, or intra-articular injections with corticosteroids or hyaluronate are alternatives.^3,4 Total knee replacement may be indicated in moderate or severe knee OA with radiographic evidence.⁵ Vitamin D, lateral wedge insoles, and antioxidants are not currently recommended.⁶

Prior studies evaluating glucosamine and/or chondroitin have provided conflicting results regarding evidence on pain reduction, function, and quality of life. Therefore, guidelines on OA management do not recommend their use (AAOS, strong; ACR, conditional).^3,4 However, consumption remains high, with 6.5 million US adults reporting use of glucosamine and/or chondroitin in the prior 30 days.⁷

A 2015 systematic review of 43 randomized trials evaluating oral chondroitin sulfate for OA of varying severity suggested there may be a significant decrease in short-term and long-term pain with doses ≥ 800 mg/d compared with placebo (level of evidence, low; risk for bias, high).⁸ However, no significant difference was noted in short- or long-term function, and the trials were highly heterogeneous.

Studies included in the 2015 systematic review found that glucosamine plus chondroitin did not have a significant effect on short- or long-term pain or physical function compared with placebo. Although glucosamine plus chondroitin led to significantly decreased pain compared with other medication, sensitivity analyses conducted for larger studies (N > 200) with adequate methods of blinding and allocation concealment found no difference in pain.⁸ There was no statistically significant difference in adverse events for glucosamine plus chondroitin vs placebo, based on data from three studies included in the review.⁸

This RCT from Roman-Blas et al evaluated chondroitin and glucosamine vs placebo in patients with more severe OA. The study was supported by Tedec-Meiji Farma (Madrid), maker of the combination of chondroitin plus glucosamine used in the study.¹

Continue to: STUDY SUMMARY

Chondroitin + glucosamine not better than placebo

This multicenter, randomized, double-blind, placebo-controlled trial was conducted in nine rheumatology referral centers and one orthopedic center in Spain. The trial evaluated the efficacy of chondroitin sulfate (1,200 mg) plus glucosamine sulfate (1,500 mg) (CS/GS) compared with placebo in 164 patients with Grade 2 or 3 knee OA and moderate-to-severe knee pain. OA grade was ascertained using the Kellgren-Lawrence scale, corresponding to osteophytes and either possible (Grade 2) or definite (Grade 3) joint space narrowing. Knee pain severity was defined by a self-reported global pain score of 40 to 80 mm on a 100-mm visual analog scale (VAS).

No significant difference was noted in group characteristics; average age in the CS/GS group was 67 and in the placebo group, 65. Exclusion criteria included BMI ≥ 35, concurrent arthritic conditions, and any coexisting chronic disease that would prevent successful completion of the trial.¹

The primary endpoint was mean reduction in global pain score on a 0- to 100-mm VAS at six months. Secondary outcomes included mean reduction in total and subscale scores in pain and function on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (0–100-mm VAS for each) and the use of rescue medication.

Baseline global pain scores were 62 mm in both groups. Acetaminophen, up to 3 g/d, was the only allowed rescue medication. Clinic visits occurred at 4, 12, and 24 weeks. A statistically significant difference between groups was defined as P < .03.¹

Results. In the intention-to-treat analysis at six months, patients in the placebo group had a greater reduction in pain than the CS/GC group (–20 mm vs –12 mm; P = .029). No other difference was noted between the placebo and CS/GS groups in the total or subscales of the WOMAC index, and no difference was noted in use of acetaminophen. More patients in the placebo group had at least a 50% improvement in pain or function compared with the CS/GS group (47.4% vs 27.5%; P = .01).

Continue to: In the CS/GS group...

In the CS/GS group, 31% did not complete the six-month treatment period, compared with 18% in the placebo group. More patients dropped out because of adverse effects (diarrhea, upper abdominal pain, and constipation) in the CS/GS group than the placebo group (33 vs 19; P = .018).¹

WHAT’S NEW

Pharma-sponsored study finds treatment ineffective

The effectiveness of CS/GS for the treatment of knee OA has been in question for years, but this RCT is the first trial sponsored by a pharmaceutical company to evaluate CS/GS efficacy. This trial found evidence of a lack of efficacy. In patients with more severe OA of the knee, placebo was more effective than CS/GS, and CS/GS had significantly more adverse events. Therefore, it may be time to advise patients to stop taking their CS/GS supplement.

CAVEATS

Cannot generalize findings

The study compared only one medication dosing regimen using a combination of CS and GS. Whether either agent alone, or different dosing, would lead to the same outcome is unknown.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[9]:566-568).

A 65-year-old man with moderately severe osteoarthritis (OA) of the knee presents to your office for his annual exam. During the medication review, the patient mentions he is using glucosamine and chondroitin for his knee pain, which was recommended by a family member. Should you tell the patient to continue taking the medication?

Knee OA is a common condition in the United States, affecting an estimated 12% of adults ages 60 and older and 16% of those ages 70 and older.² The primary goals of OA therapy are to minimize pain and improve function. The American Academy of Orthopedic Surgeons (AAOS) and the American College of Rheumatology (ACR) agree that firstline treatment recommendations include aerobic exercise, resistance training, and weight loss.

Initial pharmacologic therapies include full-strength acetaminophen or oral/topical NSAIDs; the latter are also used if pain is unresponsive to acetaminophen.^3,4 If initial therapy is inadequate to control pain, tramadol, other opioids, duloxetine, or intra-articular injections with corticosteroids or hyaluronate are alternatives.^3,4 Total knee replacement may be indicated in moderate or severe knee OA with radiographic evidence.⁵ Vitamin D, lateral wedge insoles, and antioxidants are not currently recommended.⁶

Prior studies evaluating glucosamine and/or chondroitin have provided conflicting results regarding evidence on pain reduction, function, and quality of life. Therefore, guidelines on OA management do not recommend their use (AAOS, strong; ACR, conditional).^3,4 However, consumption remains high, with 6.5 million US adults reporting use of glucosamine and/or chondroitin in the prior 30 days.⁷

A 2015 systematic review of 43 randomized trials evaluating oral chondroitin sulfate for OA of varying severity suggested there may be a significant decrease in short-term and long-term pain with doses ≥ 800 mg/d compared with placebo (level of evidence, low; risk for bias, high).⁸ However, no significant difference was noted in short- or long-term function, and the trials were highly heterogeneous.

Studies included in the 2015 systematic review found that glucosamine plus chondroitin did not have a significant effect on short- or long-term pain or physical function compared with placebo. Although glucosamine plus chondroitin led to significantly decreased pain compared with other medication, sensitivity analyses conducted for larger studies (N > 200) with adequate methods of blinding and allocation concealment found no difference in pain.⁸ There was no statistically significant difference in adverse events for glucosamine plus chondroitin vs placebo, based on data from three studies included in the review.⁸

This RCT from Roman-Blas et al evaluated chondroitin and glucosamine vs placebo in patients with more severe OA. The study was supported by Tedec-Meiji Farma (Madrid), maker of the combination of chondroitin plus glucosamine used in the study.¹

Continue to: STUDY SUMMARY

Chondroitin + glucosamine not better than placebo

This multicenter, randomized, double-blind, placebo-controlled trial was conducted in nine rheumatology referral centers and one orthopedic center in Spain. The trial evaluated the efficacy of chondroitin sulfate (1,200 mg) plus glucosamine sulfate (1,500 mg) (CS/GS) compared with placebo in 164 patients with Grade 2 or 3 knee OA and moderate-to-severe knee pain. OA grade was ascertained using the Kellgren-Lawrence scale, corresponding to osteophytes and either possible (Grade 2) or definite (Grade 3) joint space narrowing. Knee pain severity was defined by a self-reported global pain score of 40 to 80 mm on a 100-mm visual analog scale (VAS).

No significant difference was noted in group characteristics; average age in the CS/GS group was 67 and in the placebo group, 65. Exclusion criteria included BMI ≥ 35, concurrent arthritic conditions, and any coexisting chronic disease that would prevent successful completion of the trial.¹

The primary endpoint was mean reduction in global pain score on a 0- to 100-mm VAS at six months. Secondary outcomes included mean reduction in total and subscale scores in pain and function on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (0–100-mm VAS for each) and the use of rescue medication.

Baseline global pain scores were 62 mm in both groups. Acetaminophen, up to 3 g/d, was the only allowed rescue medication. Clinic visits occurred at 4, 12, and 24 weeks. A statistically significant difference between groups was defined as P < .03.¹

Results. In the intention-to-treat analysis at six months, patients in the placebo group had a greater reduction in pain than the CS/GC group (–20 mm vs –12 mm; P = .029). No other difference was noted between the placebo and CS/GS groups in the total or subscales of the WOMAC index, and no difference was noted in use of acetaminophen. More patients in the placebo group had at least a 50% improvement in pain or function compared with the CS/GS group (47.4% vs 27.5%; P = .01).

Continue to: In the CS/GS group...

In the CS/GS group, 31% did not complete the six-month treatment period, compared with 18% in the placebo group. More patients dropped out because of adverse effects (diarrhea, upper abdominal pain, and constipation) in the CS/GS group than the placebo group (33 vs 19; P = .018).¹

WHAT’S NEW

Pharma-sponsored study finds treatment ineffective

The effectiveness of CS/GS for the treatment of knee OA has been in question for years, but this RCT is the first trial sponsored by a pharmaceutical company to evaluate CS/GS efficacy. This trial found evidence of a lack of efficacy. In patients with more severe OA of the knee, placebo was more effective than CS/GS, and CS/GS had significantly more adverse events. Therefore, it may be time to advise patients to stop taking their CS/GS supplement.

CAVEATS

Cannot generalize findings

The study compared only one medication dosing regimen using a combination of CS and GS. Whether either agent alone, or different dosing, would lead to the same outcome is unknown.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[9]:566-568).