CMV infection

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to maribavir (SHP620) as a treatment for cytomegalovirus (CMV) infection and disease in transplant recipients who are resistant or refractory to prior therapy.

Maribavir, an antiviral therapy that belongs to a class of drugs called benzimidazole ribosides, is being evaluated in patients who have CMV infection after undergoing hematopoietic stem cell transplant or solid organ transplant.

The drug inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.

The FDA granted maribavir breakthrough designation based on data from two phase 2 studies. For one of these studies (NCT00223925), data are not yet available.

The other study (NCT01611974) was presented at IDWeek 2016. This study included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant.

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment. Sixty-seven percent (80/120) of patients met this endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

The incidence of treatment-emergent adverse events (AEs) was 78% (n=93) overall, 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

CMV infection

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to maribavir (SHP620) as a treatment for cytomegalovirus (CMV) infection and disease in transplant recipients who are resistant or refractory to prior therapy.

Maribavir, an antiviral therapy that belongs to a class of drugs called benzimidazole ribosides, is being evaluated in patients who have CMV infection after undergoing hematopoietic stem cell transplant or solid organ transplant.

The drug inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.

The FDA granted maribavir breakthrough designation based on data from two phase 2 studies. For one of these studies (NCT00223925), data are not yet available.

The other study (NCT01611974) was presented at IDWeek 2016. This study included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant.

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment. Sixty-seven percent (80/120) of patients met this endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

The incidence of treatment-emergent adverse events (AEs) was 78% (n=93) overall, 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

CMV infection

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to maribavir (SHP620) as a treatment for cytomegalovirus (CMV) infection and disease in transplant recipients who are resistant or refractory to prior therapy.

Maribavir, an antiviral therapy that belongs to a class of drugs called benzimidazole ribosides, is being evaluated in patients who have CMV infection after undergoing hematopoietic stem cell transplant or solid organ transplant.

The drug inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.

The FDA granted maribavir breakthrough designation based on data from two phase 2 studies. For one of these studies (NCT00223925), data are not yet available.

The other study (NCT01611974) was presented at IDWeek 2016. This study included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant.

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment. Sixty-seven percent (80/120) of patients met this endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

The incidence of treatment-emergent adverse events (AEs) was 78% (n=93) overall, 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

showing MM

The US Food and Drug Administration (FDA) has approved denosumab (XGEVA®) for use in patients with multiple myeloma (MM).

The drug was previously approved to prevent skeletal-related events in patients with bone metastases from solid tumors.

Now, denosumab is FDA-approved to prevent skeletal-related events in MM patients as well.

Denosumab is a fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function, and survival of osteoclasts—thereby inhibiting osteoclast-mediated bone destruction.

The FDA’s approval of denosumab in MM is based on data from the phase 3 '482 study, which were presented at the 2017 ASCO Annual Meeting last June.

In this trial, researchers compared denosumab to zoledronic acid for the prevention of skeletal-related events in 1718 adults with newly diagnosed MM and bone disease.

Patients were randomized to receive either subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function) and subcutaneous placebo every 4 weeks (n=859).

Denosumab proved non-inferior to zoledronic acid in delaying the time to first on-study skeletal-related event (pathologic fracture, radiation to bone, surgery to bone, or spinal cord compression). The hazard ratio (HR) was 0.98 (95% CI: 0.85, 1.14; P=0.01).

Denosumab was not superior to zoledronic acid in delaying the time to a first skeletal-related event or delaying the time to first-and-subsequent skeletal-related events.

Overall survival was comparable between the treatment arms. The HR was 0.90 (95% CI: 0.70, 1.16; P=0.41).

The median difference in progression-free survival favored denosumab by 10.7 months (HR=0.82, 95% CI: 0.68-0.99; descriptive P=0.036). The median progression-free survival was 46.1 months for denosumab and 35.4 months for zoledronic acid.

The most common adverse events in patients who received denosumab were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%) and headache (11%).

The most common adverse event resulting in discontinuation of denosumab was osteonecrosis of the jaw.

In the primary treatment phase of the study, osteonecrosis of the jaw was confirmed in 4.1% of patients in the denosumab arm (median exposure of 16 months; range, 1-50) and 2.8% of those in the zoledronic acid arm (median 15 months; range, 1-45 months).

showing MM

The US Food and Drug Administration (FDA) has approved denosumab (XGEVA®) for use in patients with multiple myeloma (MM).

The drug was previously approved to prevent skeletal-related events in patients with bone metastases from solid tumors.

Now, denosumab is FDA-approved to prevent skeletal-related events in MM patients as well.

Denosumab is a fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function, and survival of osteoclasts—thereby inhibiting osteoclast-mediated bone destruction.

The FDA’s approval of denosumab in MM is based on data from the phase 3 '482 study, which were presented at the 2017 ASCO Annual Meeting last June.

In this trial, researchers compared denosumab to zoledronic acid for the prevention of skeletal-related events in 1718 adults with newly diagnosed MM and bone disease.

Patients were randomized to receive either subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function) and subcutaneous placebo every 4 weeks (n=859).

Denosumab proved non-inferior to zoledronic acid in delaying the time to first on-study skeletal-related event (pathologic fracture, radiation to bone, surgery to bone, or spinal cord compression). The hazard ratio (HR) was 0.98 (95% CI: 0.85, 1.14; P=0.01).

Denosumab was not superior to zoledronic acid in delaying the time to a first skeletal-related event or delaying the time to first-and-subsequent skeletal-related events.

Overall survival was comparable between the treatment arms. The HR was 0.90 (95% CI: 0.70, 1.16; P=0.41).

The median difference in progression-free survival favored denosumab by 10.7 months (HR=0.82, 95% CI: 0.68-0.99; descriptive P=0.036). The median progression-free survival was 46.1 months for denosumab and 35.4 months for zoledronic acid.

The most common adverse events in patients who received denosumab were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%) and headache (11%).

The most common adverse event resulting in discontinuation of denosumab was osteonecrosis of the jaw.

In the primary treatment phase of the study, osteonecrosis of the jaw was confirmed in 4.1% of patients in the denosumab arm (median exposure of 16 months; range, 1-50) and 2.8% of those in the zoledronic acid arm (median 15 months; range, 1-45 months).

showing MM

The US Food and Drug Administration (FDA) has approved denosumab (XGEVA®) for use in patients with multiple myeloma (MM).

The drug was previously approved to prevent skeletal-related events in patients with bone metastases from solid tumors.

Now, denosumab is FDA-approved to prevent skeletal-related events in MM patients as well.

Denosumab is a fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function, and survival of osteoclasts—thereby inhibiting osteoclast-mediated bone destruction.

The FDA’s approval of denosumab in MM is based on data from the phase 3 '482 study, which were presented at the 2017 ASCO Annual Meeting last June.

In this trial, researchers compared denosumab to zoledronic acid for the prevention of skeletal-related events in 1718 adults with newly diagnosed MM and bone disease.

Patients were randomized to receive either subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function) and subcutaneous placebo every 4 weeks (n=859).

Denosumab proved non-inferior to zoledronic acid in delaying the time to first on-study skeletal-related event (pathologic fracture, radiation to bone, surgery to bone, or spinal cord compression). The hazard ratio (HR) was 0.98 (95% CI: 0.85, 1.14; P=0.01).

Denosumab was not superior to zoledronic acid in delaying the time to a first skeletal-related event or delaying the time to first-and-subsequent skeletal-related events.

Overall survival was comparable between the treatment arms. The HR was 0.90 (95% CI: 0.70, 1.16; P=0.41).

The median difference in progression-free survival favored denosumab by 10.7 months (HR=0.82, 95% CI: 0.68-0.99; descriptive P=0.036). The median progression-free survival was 46.1 months for denosumab and 35.4 months for zoledronic acid.

The most common adverse events in patients who received denosumab were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%) and headache (11%).

The most common adverse event resulting in discontinuation of denosumab was osteonecrosis of the jaw.

In the primary treatment phase of the study, osteonecrosis of the jaw was confirmed in 4.1% of patients in the denosumab arm (median exposure of 16 months; range, 1-50) and 2.8% of those in the zoledronic acid arm (median 15 months; range, 1-45 months).

Rituxamab succeeded as a single, long-term maintenance therapy for patients with severe, difficult-to-treat pemphigus, based on data from a case series of 11 patients.

“We found that treatment with rituximab alone, even at a low dose, not only prevented relapse but also maintained complete remission with a better benefit-to-risk ratio than treatment with corticosteroids,” Julia Sanchez, MD, of Reims (France) University Hospital and her colleagues reported in a research letter in JAMA Dermatology.

The study population consisted of patients diagnosed with pemphigus at a single center from Jan. 1, 2014, to Dec. 31, 2014, and treated with at least one cycle of rituximab for corticosteroid dependence, corticosteroid resistance, or adverse events. All the patients were in remission at the time of the first maintenance dose of rituximab.

All patients received a 1-g rituximab infusion every 6 months for 24-67 months; some patients changed to a once-yearly dose after 18 months. Although 5 patients experienced grade 3 or 4 adverse events (1 patient had sepsis; 2, diabetes; 1, hypertension; and 2, endocrine disorders) between the initial therapy cycle and the first rituximab maintenance infusion, no adverse events were reported by any of the 11 patients during the maintenance therapy period.

All 11 patients remained in remission after their last follow-up visit (an average of 78 months after the first cycle), at which point 10 patients had discontinued the therapy.

“A progressive decrease in serum anti-desmoglein autoantibody levels to less than 14 U/mL occurred in all cases along with clinical complete remission even after maintenance therapy cessation,” Dr. Sanchez and her associates noted.

Future research should address questions including the optimal dose and dosing frequency of rituximab, as well as the cost-effectiveness of the treatment and criteria for treatment withdrawal, they said.

The researchers had no relevant financial conflicts disclosures.

SOURCE: JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.5176.

[email protected]

Rituxamab succeeded as a single, long-term maintenance therapy for patients with severe, difficult-to-treat pemphigus, based on data from a case series of 11 patients.

“We found that treatment with rituximab alone, even at a low dose, not only prevented relapse but also maintained complete remission with a better benefit-to-risk ratio than treatment with corticosteroids,” Julia Sanchez, MD, of Reims (France) University Hospital and her colleagues reported in a research letter in JAMA Dermatology.

The study population consisted of patients diagnosed with pemphigus at a single center from Jan. 1, 2014, to Dec. 31, 2014, and treated with at least one cycle of rituximab for corticosteroid dependence, corticosteroid resistance, or adverse events. All the patients were in remission at the time of the first maintenance dose of rituximab.

All patients received a 1-g rituximab infusion every 6 months for 24-67 months; some patients changed to a once-yearly dose after 18 months. Although 5 patients experienced grade 3 or 4 adverse events (1 patient had sepsis; 2, diabetes; 1, hypertension; and 2, endocrine disorders) between the initial therapy cycle and the first rituximab maintenance infusion, no adverse events were reported by any of the 11 patients during the maintenance therapy period.

All 11 patients remained in remission after their last follow-up visit (an average of 78 months after the first cycle), at which point 10 patients had discontinued the therapy.

“A progressive decrease in serum anti-desmoglein autoantibody levels to less than 14 U/mL occurred in all cases along with clinical complete remission even after maintenance therapy cessation,” Dr. Sanchez and her associates noted.

Future research should address questions including the optimal dose and dosing frequency of rituximab, as well as the cost-effectiveness of the treatment and criteria for treatment withdrawal, they said.

The researchers had no relevant financial conflicts disclosures.

SOURCE: JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.5176.

[email protected]

Rituxamab succeeded as a single, long-term maintenance therapy for patients with severe, difficult-to-treat pemphigus, based on data from a case series of 11 patients.

“We found that treatment with rituximab alone, even at a low dose, not only prevented relapse but also maintained complete remission with a better benefit-to-risk ratio than treatment with corticosteroids,” Julia Sanchez, MD, of Reims (France) University Hospital and her colleagues reported in a research letter in JAMA Dermatology.

The study population consisted of patients diagnosed with pemphigus at a single center from Jan. 1, 2014, to Dec. 31, 2014, and treated with at least one cycle of rituximab for corticosteroid dependence, corticosteroid resistance, or adverse events. All the patients were in remission at the time of the first maintenance dose of rituximab.

All patients received a 1-g rituximab infusion every 6 months for 24-67 months; some patients changed to a once-yearly dose after 18 months. Although 5 patients experienced grade 3 or 4 adverse events (1 patient had sepsis; 2, diabetes; 1, hypertension; and 2, endocrine disorders) between the initial therapy cycle and the first rituximab maintenance infusion, no adverse events were reported by any of the 11 patients during the maintenance therapy period.

All 11 patients remained in remission after their last follow-up visit (an average of 78 months after the first cycle), at which point 10 patients had discontinued the therapy.

“A progressive decrease in serum anti-desmoglein autoantibody levels to less than 14 U/mL occurred in all cases along with clinical complete remission even after maintenance therapy cessation,” Dr. Sanchez and her associates noted.

Future research should address questions including the optimal dose and dosing frequency of rituximab, as well as the cost-effectiveness of the treatment and criteria for treatment withdrawal, they said.

The researchers had no relevant financial conflicts disclosures.

SOURCE: JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.5176.

[email protected]

An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

SOURCE: FDA warning letter

An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

SOURCE: FDA warning letter

An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

SOURCE: FDA warning letter

Very preterm birth is associated with a significantly lower risk of eczema, compared with full-term birth, according to data from a meta-analysis of 18 studies.

Previous research suggests that low birth weight is protective against the development of atopic dermatitis, said Tingting Zhu, PhD, of West China Second University Hospital, Chengdu, and colleagues.

LucaLorenzelli/Thinkstock

SOURCE: Zhu T et al. J Amer Dermatol. 2018. doi: 10.1016/j.jaad.2017.12.015.

[email protected]

Very preterm birth is associated with a significantly lower risk of eczema, compared with full-term birth, according to data from a meta-analysis of 18 studies.

Previous research suggests that low birth weight is protective against the development of atopic dermatitis, said Tingting Zhu, PhD, of West China Second University Hospital, Chengdu, and colleagues.

LucaLorenzelli/Thinkstock

SOURCE: Zhu T et al. J Amer Dermatol. 2018. doi: 10.1016/j.jaad.2017.12.015.

[email protected]

Very preterm birth is associated with a significantly lower risk of eczema, compared with full-term birth, according to data from a meta-analysis of 18 studies.

Previous research suggests that low birth weight is protective against the development of atopic dermatitis, said Tingting Zhu, PhD, of West China Second University Hospital, Chengdu, and colleagues.

LucaLorenzelli/Thinkstock

SOURCE: Zhu T et al. J Amer Dermatol. 2018. doi: 10.1016/j.jaad.2017.12.015.

[email protected]

It’s very likely that you have at least one or two female patients who play lacrosse. The sport has been reported to be the fastest-growing high school sport in the United States. (“Lacrosse is Actually America’s Fastest-Growing Sport,” by John Templon, BuzzFeed News, June 30, 2014). When I played in college, most of my teammates were products of prep schools in the Northeast or one of the few local hotbeds in Baltimore, Long Island, or the Finger Lakes Region of New York. But pickings were slim, and there was room for walk-ons like me looking to learn a new sport and stay in shape for football. Now hundreds of high schools in all parts of the country offer the sport for both boys and girls.

kjuniper/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It’s very likely that you have at least one or two female patients who play lacrosse. The sport has been reported to be the fastest-growing high school sport in the United States. (“Lacrosse is Actually America’s Fastest-Growing Sport,” by John Templon, BuzzFeed News, June 30, 2014). When I played in college, most of my teammates were products of prep schools in the Northeast or one of the few local hotbeds in Baltimore, Long Island, or the Finger Lakes Region of New York. But pickings were slim, and there was room for walk-ons like me looking to learn a new sport and stay in shape for football. Now hundreds of high schools in all parts of the country offer the sport for both boys and girls.

kjuniper/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It’s very likely that you have at least one or two female patients who play lacrosse. The sport has been reported to be the fastest-growing high school sport in the United States. (“Lacrosse is Actually America’s Fastest-Growing Sport,” by John Templon, BuzzFeed News, June 30, 2014). When I played in college, most of my teammates were products of prep schools in the Northeast or one of the few local hotbeds in Baltimore, Long Island, or the Finger Lakes Region of New York. But pickings were slim, and there was room for walk-ons like me looking to learn a new sport and stay in shape for football. Now hundreds of high schools in all parts of the country offer the sport for both boys and girls.

kjuniper/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Study Overview

Objective. To determine the association between wait times for hip fracture surgery and outcomes after surgery and to identify the optimal time window for conducting hip fracture surgery.

Design. Observational cohort study.

Setting and participants. The study was conducted using population-based health administrative databases in Ontario, Canada. The databases collected information on health care services, physician and hospital information, and demographic characteristics in Ontario. The investigators used the databases to identify adults undergoing hip fracture surgery between April 2009 and March 2014. Excluded were adults who are non-Ontario residents, those with elective hospital admissions, those with prior hip fractures, and patients without hospital arrival time data. Other exclusion criteria include age younger than 45 years, those with delay in surgery longer than 10 days, surgery performed by a nonorthopedic surgeon, and those at hospitals with fewer than 5 hip fracture surgeries during the study period.

The primary independent variable was wait time for surgery, calculated from time from emergency department arrival until surgery and rounded in hours. Other covariates included in the analysis were patient characteristics including age, sex and comorbid conditions using the Deyo-Charlson comorbidity index, the Johns Hopkins Collapsed Aggregated Diagnosis Groups, and other validated algorithms. In addition, other conditions associated with hip fracture were included—osteomyelitis, bone cancer, other fractures, history of total hip arthroplasty, and multiple trauma. Additional covariates included median neighborhood household income quintile as a proxy for socioeconomic status, patient’s discharge disposition, and rural status. Characteristics of the procedure including procedure type, duration and timing (working vs. after hours) were assessed. Surgeon- and hospital-related factors included years since orthopedic certification as a proxy for surgeon experience and number of hip fracture procedures performed in the year preceding the event for surgeon and hospital. Other hospital characteristics included academic or community-based hospital, hospital size, and hospital’s capacity for performing nonelective surgery.

Main outcome measures. The main outcome measure was mortality within 30 days of being admitted for hip fracture surgery. Other secondary outcomes included mortality at 90 and 365 days after admission, medical complications within 30, 90, and 365 days, and a composite of mortality and any complications at these timeframes. Complications included myocardial infarction, deep vein thrombosis, pulmonary embolism and pneumonia. Statistical analysis include modeling for the probability of complications according to the time elapsed from emergency department arrival to surgery using risk adjusted spline analyses. The association between surgical wait time and mortality was graphically represented to visualize an inflection point when complications begin to rise. The area under the receiver operating characteristic curve was calculated at time thresholds around the area of inflection and the time producing the maximum area under the curve was selected as the threshold to classify patients
as receiving early or delayed surgery. Early and delayed patients were matched using propensity score with 1:1 matching without replacement. Outcomes were compared between early and delayed groups after matching and absolute risk differences were calculated using generalized estimating equations.

Main results. A total of 42,230 adults were included, with a mean age of 80.1 (SD 10.7) years; 70.5% were women. The average time from arrival to emergency room to surgery was 38.8 (SD 28.8) hours. The spline models identified an area of inflection at 24 hours when the risk of complications begins to rise. The investigators used 24 hours as a time point to classify patients into early or delayed surgery group. 33.6% of patients received early surgery and 66.4% had delayed surgery. Propensity score matching yielded a sample of 13,731 in each group. Patients with delayed surgery compared with early surgery had higher 30-day mortality (6.5% vs. 5.8%, absolute risk difference 0.79%), rate of pulmonary embolism (1.2% vs. 0.7%, absolute risk difference 0.51%), rate of myocardial infarction (1.2% vs. 0.8%, absolute risk difference 0.39%), and rate of pneumonia (4.6% vs. 3.7%, absolute risk difference 0.95%). For the composite outcome, 12.1% vs. 10.1% had mortality or complications in the delayed group and the early group respectively with an absolute difference of 2.16%. Outcomes at 90 days and 365 days were similar and remained significant. In subgroups of patients without comorbidity and those receiving surgery within 36 hours the results remained similar.

Conclusion. Early hip fracture surgery, defined as within 24 hours after arrival to emergency room, is associated with lower mortality and complications when compared to delayed surgery.

Commentary

Hip fracture affects predominantly older adults and leads to potential devastating consequences. Older adults who experience hip fracture have increased risk of functional decline, institutionalization, and death [1]. As hip fracture care often include surgical repair, many studies have examined the impact of timing of surgery on hip fracture outcomes, as the timing of surgery is a potentially modifiable factor that could impact patient outcomes [2]. Prior smaller cohort studies have demonstrated that delayed surgery may impact outcomes but the reasons for the delay, such as medical complexity, may also play a role in increasing the risk of adverse outcomes [3]. The current study adds to the previous literature by examining a large population-based cohort, thereby allowing for analysis that takes into account medical comorbidities using matching methods and sensitivity analyses that examined a sample without comorbidities. The study also employs a different approach to defining early vs. delayed surgery by using analytical methods to determine when risk of complications begins to rise. The results indicate that early surgery is associated with better outcomes at 30 days and beyond and that delaying surgery beyond 24 hours is associated with poorer patient outcomes.

Patients with hip fracture require care from multiple disciplines and care across multiple settings. These care components may also have an impact on patient outcomes, particularly outcomes at 90 and 365 days; some examples include anesthesia care during hip fracture surgery [4], pain control, early mobilization, and delirium prevention [1,5]. A limitation of utilizing administrative databases is that some of these potentially important factors that may affect outcome may not be included and thus cannot be controlled for. It is conceivable that early surgery may be associated with care characteristics that may also be favorable to outcomes. Another limitation is that it is still difficult to tease out the effect of medical complexity at the
time of hip fracture presentation, which may impact both timing of surgery and patient outcomes, despite sensitivity analyses that limit the sample to those who had surgery within 36 hours and also those without medical comorbidities according to the administrative data, and adjusting for antiplatelet or anticoagulant medications. It is also important to note that a randomized controlled trial may further elucidate the causal relationship between timing of surgery and patient outcomes. Despite the limitations of the study, the results make a strong case for limiting surgical wait time to within 24 hours from the time when the patient arrives in the emergency room.

Applications for Clinical Practice

Similar to how hospitals organize their care for patients with acute myocardial infarction for early reperfusion, and for patients with acute ischemic stroke with early thombolytic therapy, hip fracture care may need to be organized and coordinated in order to reduce surgical wait time to within 24 hours. Timely assessments by an orthopedic surgeon, anesthesiologist, and medical consultants to prepare patients for surgery and making available operating room and staff for hip fracture patients are necessary steps to reach the goal of reducing surgical wait time.

—William W. Hung, MD, MPH

Study Overview

Objective. To determine the association between wait times for hip fracture surgery and outcomes after surgery and to identify the optimal time window for conducting hip fracture surgery.

Design. Observational cohort study.

Setting and participants. The study was conducted using population-based health administrative databases in Ontario, Canada. The databases collected information on health care services, physician and hospital information, and demographic characteristics in Ontario. The investigators used the databases to identify adults undergoing hip fracture surgery between April 2009 and March 2014. Excluded were adults who are non-Ontario residents, those with elective hospital admissions, those with prior hip fractures, and patients without hospital arrival time data. Other exclusion criteria include age younger than 45 years, those with delay in surgery longer than 10 days, surgery performed by a nonorthopedic surgeon, and those at hospitals with fewer than 5 hip fracture surgeries during the study period.

The primary independent variable was wait time for surgery, calculated from time from emergency department arrival until surgery and rounded in hours. Other covariates included in the analysis were patient characteristics including age, sex and comorbid conditions using the Deyo-Charlson comorbidity index, the Johns Hopkins Collapsed Aggregated Diagnosis Groups, and other validated algorithms. In addition, other conditions associated with hip fracture were included—osteomyelitis, bone cancer, other fractures, history of total hip arthroplasty, and multiple trauma. Additional covariates included median neighborhood household income quintile as a proxy for socioeconomic status, patient’s discharge disposition, and rural status. Characteristics of the procedure including procedure type, duration and timing (working vs. after hours) were assessed. Surgeon- and hospital-related factors included years since orthopedic certification as a proxy for surgeon experience and number of hip fracture procedures performed in the year preceding the event for surgeon and hospital. Other hospital characteristics included academic or community-based hospital, hospital size, and hospital’s capacity for performing nonelective surgery.

Main outcome measures. The main outcome measure was mortality within 30 days of being admitted for hip fracture surgery. Other secondary outcomes included mortality at 90 and 365 days after admission, medical complications within 30, 90, and 365 days, and a composite of mortality and any complications at these timeframes. Complications included myocardial infarction, deep vein thrombosis, pulmonary embolism and pneumonia. Statistical analysis include modeling for the probability of complications according to the time elapsed from emergency department arrival to surgery using risk adjusted spline analyses. The association between surgical wait time and mortality was graphically represented to visualize an inflection point when complications begin to rise. The area under the receiver operating characteristic curve was calculated at time thresholds around the area of inflection and the time producing the maximum area under the curve was selected as the threshold to classify patients
as receiving early or delayed surgery. Early and delayed patients were matched using propensity score with 1:1 matching without replacement. Outcomes were compared between early and delayed groups after matching and absolute risk differences were calculated using generalized estimating equations.

Main results. A total of 42,230 adults were included, with a mean age of 80.1 (SD 10.7) years; 70.5% were women. The average time from arrival to emergency room to surgery was 38.8 (SD 28.8) hours. The spline models identified an area of inflection at 24 hours when the risk of complications begins to rise. The investigators used 24 hours as a time point to classify patients into early or delayed surgery group. 33.6% of patients received early surgery and 66.4% had delayed surgery. Propensity score matching yielded a sample of 13,731 in each group. Patients with delayed surgery compared with early surgery had higher 30-day mortality (6.5% vs. 5.8%, absolute risk difference 0.79%), rate of pulmonary embolism (1.2% vs. 0.7%, absolute risk difference 0.51%), rate of myocardial infarction (1.2% vs. 0.8%, absolute risk difference 0.39%), and rate of pneumonia (4.6% vs. 3.7%, absolute risk difference 0.95%). For the composite outcome, 12.1% vs. 10.1% had mortality or complications in the delayed group and the early group respectively with an absolute difference of 2.16%. Outcomes at 90 days and 365 days were similar and remained significant. In subgroups of patients without comorbidity and those receiving surgery within 36 hours the results remained similar.

Conclusion. Early hip fracture surgery, defined as within 24 hours after arrival to emergency room, is associated with lower mortality and complications when compared to delayed surgery.

Commentary

Hip fracture affects predominantly older adults and leads to potential devastating consequences. Older adults who experience hip fracture have increased risk of functional decline, institutionalization, and death [1]. As hip fracture care often include surgical repair, many studies have examined the impact of timing of surgery on hip fracture outcomes, as the timing of surgery is a potentially modifiable factor that could impact patient outcomes [2]. Prior smaller cohort studies have demonstrated that delayed surgery may impact outcomes but the reasons for the delay, such as medical complexity, may also play a role in increasing the risk of adverse outcomes [3]. The current study adds to the previous literature by examining a large population-based cohort, thereby allowing for analysis that takes into account medical comorbidities using matching methods and sensitivity analyses that examined a sample without comorbidities. The study also employs a different approach to defining early vs. delayed surgery by using analytical methods to determine when risk of complications begins to rise. The results indicate that early surgery is associated with better outcomes at 30 days and beyond and that delaying surgery beyond 24 hours is associated with poorer patient outcomes.

Patients with hip fracture require care from multiple disciplines and care across multiple settings. These care components may also have an impact on patient outcomes, particularly outcomes at 90 and 365 days; some examples include anesthesia care during hip fracture surgery [4], pain control, early mobilization, and delirium prevention [1,5]. A limitation of utilizing administrative databases is that some of these potentially important factors that may affect outcome may not be included and thus cannot be controlled for. It is conceivable that early surgery may be associated with care characteristics that may also be favorable to outcomes. Another limitation is that it is still difficult to tease out the effect of medical complexity at the
time of hip fracture presentation, which may impact both timing of surgery and patient outcomes, despite sensitivity analyses that limit the sample to those who had surgery within 36 hours and also those without medical comorbidities according to the administrative data, and adjusting for antiplatelet or anticoagulant medications. It is also important to note that a randomized controlled trial may further elucidate the causal relationship between timing of surgery and patient outcomes. Despite the limitations of the study, the results make a strong case for limiting surgical wait time to within 24 hours from the time when the patient arrives in the emergency room.

Applications for Clinical Practice

Similar to how hospitals organize their care for patients with acute myocardial infarction for early reperfusion, and for patients with acute ischemic stroke with early thombolytic therapy, hip fracture care may need to be organized and coordinated in order to reduce surgical wait time to within 24 hours. Timely assessments by an orthopedic surgeon, anesthesiologist, and medical consultants to prepare patients for surgery and making available operating room and staff for hip fracture patients are necessary steps to reach the goal of reducing surgical wait time.

—William W. Hung, MD, MPH

Study Overview

Objective. To determine the association between wait times for hip fracture surgery and outcomes after surgery and to identify the optimal time window for conducting hip fracture surgery.

Design. Observational cohort study.

Setting and participants. The study was conducted using population-based health administrative databases in Ontario, Canada. The databases collected information on health care services, physician and hospital information, and demographic characteristics in Ontario. The investigators used the databases to identify adults undergoing hip fracture surgery between April 2009 and March 2014. Excluded were adults who are non-Ontario residents, those with elective hospital admissions, those with prior hip fractures, and patients without hospital arrival time data. Other exclusion criteria include age younger than 45 years, those with delay in surgery longer than 10 days, surgery performed by a nonorthopedic surgeon, and those at hospitals with fewer than 5 hip fracture surgeries during the study period.

The primary independent variable was wait time for surgery, calculated from time from emergency department arrival until surgery and rounded in hours. Other covariates included in the analysis were patient characteristics including age, sex and comorbid conditions using the Deyo-Charlson comorbidity index, the Johns Hopkins Collapsed Aggregated Diagnosis Groups, and other validated algorithms. In addition, other conditions associated with hip fracture were included—osteomyelitis, bone cancer, other fractures, history of total hip arthroplasty, and multiple trauma. Additional covariates included median neighborhood household income quintile as a proxy for socioeconomic status, patient’s discharge disposition, and rural status. Characteristics of the procedure including procedure type, duration and timing (working vs. after hours) were assessed. Surgeon- and hospital-related factors included years since orthopedic certification as a proxy for surgeon experience and number of hip fracture procedures performed in the year preceding the event for surgeon and hospital. Other hospital characteristics included academic or community-based hospital, hospital size, and hospital’s capacity for performing nonelective surgery.

Main outcome measures. The main outcome measure was mortality within 30 days of being admitted for hip fracture surgery. Other secondary outcomes included mortality at 90 and 365 days after admission, medical complications within 30, 90, and 365 days, and a composite of mortality and any complications at these timeframes. Complications included myocardial infarction, deep vein thrombosis, pulmonary embolism and pneumonia. Statistical analysis include modeling for the probability of complications according to the time elapsed from emergency department arrival to surgery using risk adjusted spline analyses. The association between surgical wait time and mortality was graphically represented to visualize an inflection point when complications begin to rise. The area under the receiver operating characteristic curve was calculated at time thresholds around the area of inflection and the time producing the maximum area under the curve was selected as the threshold to classify patients
as receiving early or delayed surgery. Early and delayed patients were matched using propensity score with 1:1 matching without replacement. Outcomes were compared between early and delayed groups after matching and absolute risk differences were calculated using generalized estimating equations.

Main results. A total of 42,230 adults were included, with a mean age of 80.1 (SD 10.7) years; 70.5% were women. The average time from arrival to emergency room to surgery was 38.8 (SD 28.8) hours. The spline models identified an area of inflection at 24 hours when the risk of complications begins to rise. The investigators used 24 hours as a time point to classify patients into early or delayed surgery group. 33.6% of patients received early surgery and 66.4% had delayed surgery. Propensity score matching yielded a sample of 13,731 in each group. Patients with delayed surgery compared with early surgery had higher 30-day mortality (6.5% vs. 5.8%, absolute risk difference 0.79%), rate of pulmonary embolism (1.2% vs. 0.7%, absolute risk difference 0.51%), rate of myocardial infarction (1.2% vs. 0.8%, absolute risk difference 0.39%), and rate of pneumonia (4.6% vs. 3.7%, absolute risk difference 0.95%). For the composite outcome, 12.1% vs. 10.1% had mortality or complications in the delayed group and the early group respectively with an absolute difference of 2.16%. Outcomes at 90 days and 365 days were similar and remained significant. In subgroups of patients without comorbidity and those receiving surgery within 36 hours the results remained similar.

Conclusion. Early hip fracture surgery, defined as within 24 hours after arrival to emergency room, is associated with lower mortality and complications when compared to delayed surgery.

Commentary

Hip fracture affects predominantly older adults and leads to potential devastating consequences. Older adults who experience hip fracture have increased risk of functional decline, institutionalization, and death [1]. As hip fracture care often include surgical repair, many studies have examined the impact of timing of surgery on hip fracture outcomes, as the timing of surgery is a potentially modifiable factor that could impact patient outcomes [2]. Prior smaller cohort studies have demonstrated that delayed surgery may impact outcomes but the reasons for the delay, such as medical complexity, may also play a role in increasing the risk of adverse outcomes [3]. The current study adds to the previous literature by examining a large population-based cohort, thereby allowing for analysis that takes into account medical comorbidities using matching methods and sensitivity analyses that examined a sample without comorbidities. The study also employs a different approach to defining early vs. delayed surgery by using analytical methods to determine when risk of complications begins to rise. The results indicate that early surgery is associated with better outcomes at 30 days and beyond and that delaying surgery beyond 24 hours is associated with poorer patient outcomes.

Patients with hip fracture require care from multiple disciplines and care across multiple settings. These care components may also have an impact on patient outcomes, particularly outcomes at 90 and 365 days; some examples include anesthesia care during hip fracture surgery [4], pain control, early mobilization, and delirium prevention [1,5]. A limitation of utilizing administrative databases is that some of these potentially important factors that may affect outcome may not be included and thus cannot be controlled for. It is conceivable that early surgery may be associated with care characteristics that may also be favorable to outcomes. Another limitation is that it is still difficult to tease out the effect of medical complexity at the
time of hip fracture presentation, which may impact both timing of surgery and patient outcomes, despite sensitivity analyses that limit the sample to those who had surgery within 36 hours and also those without medical comorbidities according to the administrative data, and adjusting for antiplatelet or anticoagulant medications. It is also important to note that a randomized controlled trial may further elucidate the causal relationship between timing of surgery and patient outcomes. Despite the limitations of the study, the results make a strong case for limiting surgical wait time to within 24 hours from the time when the patient arrives in the emergency room.

Applications for Clinical Practice

Similar to how hospitals organize their care for patients with acute myocardial infarction for early reperfusion, and for patients with acute ischemic stroke with early thombolytic therapy, hip fracture care may need to be organized and coordinated in order to reduce surgical wait time to within 24 hours. Timely assessments by an orthopedic surgeon, anesthesiologist, and medical consultants to prepare patients for surgery and making available operating room and staff for hip fracture patients are necessary steps to reach the goal of reducing surgical wait time.

—William W. Hung, MD, MPH

Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.

Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.

MonthiraYodtiwong/Thinkstock

SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888

Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.

Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.

MonthiraYodtiwong/Thinkstock

SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888

Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.

Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.

MonthiraYodtiwong/Thinkstock

SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888

From the Geriatric Education and Research in Aging Sciences Centre, McMaster University Hamilton, ON (Dr. McArthur) and the University of Waterloo and Research Institute for Aging, Waterloo, ON (Dr. Giangregorio), Canada

Abstract

• Objective: To synthesize the available literature on exercise and falls reduction interventions in long-term care (LTC) and provide practical information for clinicians and other decision makers.
• Methods: Review of positive trials included in systematic reviews.
• Results: Falls are a major concern for residents, families, clinicians, and decision-makers in LTC. Exercise is recommended as part of a multifactorial falls prevention program for residents in LTC. Strength and balance exercises should be incorporated into the multifactorial falls prevention program. They should be challenging and progressed as the residents’ abilities improve. Evidence suggests that exercises should be completed 2 to 3 times per week for a period longer than 6 months. Exercise programs in LTC should be resident-centered and should consider residents’ potential physical and cognitive impairments. Exercises in standing should be prioritized where appropriate.
• Conclusion: Appropriately challenging and progressive strength and balance exercises should be included in a multifactorial falls prevention program for residents in LTC.

Key words: long-term care; nursing homes; falls reduction; exercise.

Falls are common in long-term care (LTC) homes: the estimated falls rate is 1.5 falls per bed per year, which is 3 times greater than that for older adults living in the community [1]. Falls can have significant consequences for residents in LTC, including functional disability, fractures, pain, reduced quality of life, and death [1–6]. Indeed, 25% of residents who are hospitalized after a fall die within 1 year [3]. Consequently, falls prevention programs are important to help in reducing falls and averting the associated negative consequences.

Exercise may address the circumstances and physical deconditioning that often contribute to falls in LTC residents. Weight shifting [7], walking, and transferring [8–10], are common activities that precede falls, suggesting that balance, gait, and functional mobility training may be possible targets for prevention. Additionally, it is estimated that LTC residents spend three quarters of their waking time in sedentary activities [11,12] and have a high prevalence of sarcopenia [13–16]. Challenging balance training and resistance exercise are well-known intervention for reducing falls [17] and improving muscle strength for community-dwelling older adults [18]. However, evidence around balance and strength training for preventing falls in LTC is mixed [17,19,20], and careful planning and modification of exercises is necessary to meet the needs of LTC residents.

Residents in LTC are often medically complex, with multiple comorbidities [21] that can affect their ability to meaningfully participate in exercise. In Canada, 56.3% of residents have a diagnosis of Alzheimer’s or other dementias, 25.0% have diabetes, 14.4% have chronic obstructive pulmonary disease, and 21.2% have experienced a stroke [21]. Residents also often have significant functional impairments. For example, 97% of residents require assistance with basic activities of daily living [21]. Therefore, the lack of effect of exercise as a single falls prevention strategy observed in previous studies may be because the often complex, multimorbid LTC population likely requires a multifactorial approach to fall prevention [17]. Additionally, organizational aspects of LTC homes (eg, specific funds dedicated to employing exercise professionals and to support exercise programming) can affect residents’ engagement in exercise [22,23]. Subsequently, prescribing exercises in the LTC context must consider both resident characteristics and organizational features of the LTC home (eg, professionals available to support exercise programming).

A comprehensive exercise prescription describes the elements of an appropriate exercise program to facilitate implementation of that program. The exercise prescription should include a description of the type (eg, balance, strength) and intensity of exercises (eg, subjective or objective measurement of how hard the resident is working) included in the program [24]. The prescription should also include a description of the dose of exercise: frequency of exercise participation (eg, 2 days per week), duration of individual exercise sessions (eg, 30-minute sessions), and duration of exercise program (eg, 12-week program) [24]. Lastly, the prescription should describe the setting of the exercise program (eg, group or individual basis) and the professional delivering the program (eg, physiotherapist, fitness instructor) [24].

Therefore, the objectives of this article are to (1) synthesize studies demonstrating a positive effect of exercise on reducing falls for residents in LTC; (2) provide an overview of the principles of balance and strength training to guide clinicians in designing appropriate exercise prescription; and (3) make suggestions for clinical practice regarding an appropriate strength and balance exercise protocol by considering the influence of the LTC context.

Methods

To provide clinicians and other policy-makers with a description of which balance and strength exercises may be effective for preventing falls, we synthesized trials that demonstrated a positive effect on reducing falls or falls risk for residents in LTC. Studies were identified through a database search for systematic reviews in PubMed, Ovid, and Google Scholar using the keywords falls, long-term care, nursing homes, exercise, strength, balance, and systematic reviews. Our purpose was to provide practical information on what works to prevent falls through balance and strength training for residents in LTC rather than to evaluate the available evidence. Therefore, only positive trials from systematic reviews were discussed, as we wanted to present exercises that seem to have a positive effect on decreasing falls. Positive trials were defined as those included in identified systematic reviews with a risk or rate ratio and confidence intervals below 1.0.

We first provide an overview of the conclusions of the systematic reviews found in our search. Next, for each positive trial we describe the following elements of the exercise component of the intervention: frequency, time of sessions, length of program, intensity, type of exercise including a description of the specific exercises performed, whether the intervention was delivered in a group or on an individual basis, the professional delivering the intervention, and any other features of the intervention aside from the exercise component. We used the ProFaNE taxonomy definitions [25] to identify and describe each element of the exercise interventions. Frequency is the number of times per week that residents engage in sessions, time of sessions is the amount allocated to each exercise session, duration of program is how long the resident participates in the exercise program, and intensity is the subjective or objective report of how hard the resident is working [25]. The types of exercises described were those targeting balance defined as “...the efficient transfer of bodyweight from one part of the body to another or challenges specific aspects of the balance systems (eg, vestibular system)” [25], and strength defined as “...contracting the muscles against a resistance to ‘overload’ and bring about a training effect in the muscular system” [25]. Strength could be either an external resistance (eg, dumbbell) or using body weight against gravity (eg, squat) [25].

Results

We found 3 systematic reviews that include exercise programs to reduce falls in LTC homes [17,19,20]. Overall, evidence suggests that exercise should be included as part of a multifactorial falls prevention program for residents in LTC. There is limited evidence that exercise as a single intervention prevents falls, and some trials, albeit underpowered, even demonstrate an increased risk of falling in the exercise group compared to control [19]. With regards to specific exercise programs, the Cochrane review found that gait, balance, and functional training decrease the rate of falls but not the risk of falling [26–28], and the 2013 review by Silva et al [20] concluded that combined exercise programs (ie, multiple types of exercise) that include balance tasks, are completed frequently (2–3 times per week), and over a long term (greater than 6 months) were most effective at preventing falls [20].

A more recent systematic review and meta-analysis [17] also concluded that there was no evidence that exercise as a single intervention can prevent falls for residents in LTC. Table 1 provides a description of the exercise component of the seven positive trials [29–35] that were included in the 3 systematic reviews we identified in our search.

Type of Exercise

Balance Exercises

There were 4 positive trials that included balance exercises in their intervention [31,33–35]. Trials that had a positive effect on reducing falls and included balance training employed mostly dynamic balance exercises in standing (Table 1). However, only 2 of the 7 trials provided a detailed description of their balance exercises (Table 1) [26,34]. Jensen et al [30] and Dyer et al [31] did not include a description of the balance training performed but stated that balance was part of the multicomponent exercise program. Becker et al [36] stated that participants performed standing balance exercises, while Schnelle et al [39] and Huang et al [32] did not include balance training in their trial.

Strength Exercises

Of the 7 positive trials included in this review, 6 included strength exercises [29–32,34,35]. The strength activities used in trials where exercise had a positive effect on decreasing falls included functional activities [29,31] and progressive resistance training [31,36] (Table 1). Functional activities are those that replicate what a resident might be required to do in their everyday life, such as performing sit-to-stands out of a chair (Figure) 

Frequency, Time of Sessions, Duration of Program

In our description of positive trials, exercise was performed on 2 to 3 days per week for 20 to 75 minutes per session, for periods ranging from 4 to 52 weeks (Table 1).

Intensity

For the trials including balance exercises, one trial described the intensity as resident-specific [37] and another as individualized [33]. Two studies did not describe the intensity of their balance exercises [31,34]. The intensity of strength exercises included in the positive trials was individualized for one of the trial [29]. Two trials had participants complete 2 to 3 sets of 10 repetitions [32,35], with one indicating an intensity of 12–13 or “somewhat difficult” on the Borg Rating of Perceived Exertion Scale [32] and the other using a 10-rep max [35]. Two studies described their strength exercises as progressive [31,37], and one at a moderate to high intensity [30]. Lord et al prescribed 30 repetitions of each strength exercise [34].

Delivery of Intervention

Exercise was delivered in a group setting for 4 of the trials [31,32,34,36], individually for 2 of the trials [26,29], and the setting was not described for one of the trials (Table 1) [30]. Finally, only 3 of the 7 articles reported the professional delivering the intervention: one was research staff [29], one was geriatric nurses [32], and one was exercise assistants supported by a physiotherapist [31].

Discussion

There is limited evidence to support the use of strength and balance exercise as a single intervention to prevent falls in LTC. However, exercise should be included as part of a multifactorial falls prevention program. Trials that had a positive effect on decreasing falls training used dynamic balance exercises in standing, functional training, and progressive resistance training on 2 to 3 days per week, for 20 to 75 minutes per session, over 4 to 52 weeks. The intensity of balance exercises was individualized, and strength exercises were described as somewhat difficult or performed at a moderate to high intensity. Exercise was performed in a group or individually, and was delivered by research staff, geriatric nurses, exercise assistants supervised by physiotherapists, or more frequently, it was not reported who delivered the intervention.

Balance Training

Our work suggests that standing, dynamic balance exercises may be best to decrease falls. Example balance exercises include reducing the base of support (eg, standing with feet together instead of apart, or tandem with one foot in front), moving the center of gravity and control body position while standing (eg, reaching, weight shifting, stepping up or down), and standing without using arms for support or reducing reliance on the upper limbs for support (eg, use one hand on a handrail instead of two, or two fingers instead of the whole hand) [17]. It is well established that balance training programs, especially those including challenging exercises, can prevent falls in community-dwelling older adults [17]. However, the relationship is not as clear in LTC.

Strength Training

Reduced muscle strength has been identified as an important risk factor for falls [38]. There are also many psychological and metabolic benefits to strength training [39]. To induce change in muscular strength, resistance exercises need to be challenging and progressive. Our work suggests that strength training that is effective at decreasing falls is functional and progressive, and is completed at a moderate to high intensity. A resident should be able to do a strength exercise for one to two sets of 6 to 8 repetitions before being fatigued [40]. Once the resident can complete two sets of 13 to 15 repetitions easily the exercise should be progressed. Residents who are particularly deconditioned may need to begin with lower intensity strength exercises (eg, only do one set, with a lower resistance and progress to a higher resistance) [40]. Residents should perform resistance exercises for all major muscle groups [40]. Progression could include increasing the number of sets (eg, increase from one to two sets), the resistance (eg, holding dumbbells while squatting), or the intensity of the exercise (eg, squat lower or faster) [41].

Implementing Exercise Programs in LTC

Implementation of exercise programs into LTC homes should consider the dose of exercise (eg, time and frequency of sessions, duration of program), if they are delivered in a group or individual setting, and who is delivering them. First, trials included in this paper suggest that strength and balance exercises to prevent falls were delivered 2 to 3 times per week, for 20 to 75 minutes per session, over 4 to 52 weeks. Second, previous work has established that exercise programs delivered on 2 to 3 days per week over a period of more than 6 months are most effective at reducing falls in LTC [20]. Finally, a recent task force report from an international group of clinician researchers in LTC recommends twice weekly exercise sessions lasting 35 to 45 minutes each [40]. Therefore, strength and balance exercises to prevent falls in LTC should be delivered at least twice per week, for at least 20 minutes, for greater than 6 weeks’ duration.

Whether exercise should be performed in a group or individual setting remains unclear. Two of the 6 positive trials in this paper were completed individually, while 3 were in a group. The aforementioned task force also recommended that every resident who does not have contraindications to exercise must have an individualized exercise program as part of their health care plan [40]. However, whether the exercise program is provided on an individual basis or in a group setting was not delineated. Indeed, there are currently no recommendations concerning prioritizing group or individual exercise programs. Therefore, exercise programs being implemented into LTC homes should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings.

Finally, which professionals should deliver the exercise program is also uncertain. Only 3 of the positive trials in this paper described the professional delivering the intervention, with one being research staff, one geriatric nurses, and one exercise assistants supported by a physiotherapist. We suggest that professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC.

Modifications for Physical Impairments

Residents in LTC often have complex health needs, with multiple comorbidities (eg, stroke, Parkinson’s disease, multiple sclerosis) [21]. Modifications of strength and balance exercises may be required to accommodate for physical impairments (eg, hemiplegia, drop foot, freezing gait). For example, if a resident has hemiplegia and cannot fully activate the muscles of one arm, one can do resistance exercises with a dumbbell on the functioning side and active assisted range of motion (ie, the exercise provider assists the resident to achieve full range of motion against gravity) on the hemiparetic side. A resident with Parkinson’s disease who has freezing gait may need visual or rhythmical verbal cues to be able to accomplish standing balance tasks such as altered walking patterns (eg, wide or narrow stepping) [42].

Modifications for Cognitive Impairments

More than 80% of residents in LTC have some degree of cognitive impairment [21]. Cognitive impairment may be the result of stroke, depression, traumatic injuries, medications, and degenerative diseases such as Parkinson’s and Alzheimer’s disease [43]. A common misconception is that residents with cognitive impairment cannot benefit from exercise because they cannot learn new skills and have difficulty following directions. On the contrary, evidence suggests that exercise can improve functional mobility for residents with cognitive impairment [44,45].

Residents with cognitive impairment may require a different approach to facilitate participation in the desired exercises because of difficulty following multi-step directions, responsive behaviors, or increased distractibility [46]. Clear communication is key in improving the quality of interaction for residents with cognitive impairment. The Alzheimer Society of Ontario suggests 10 strategies for communicating with people with dementia [47], and we have provided suggestions of how to apply these communication strategies to the exercise context in LTC (Table 2). Other suggestions for engaging residents with cognitive impairment in strength and balance training include making the exercises functional (eg, ask them to pick something up of the floor to perform a squat, or reach a point on the wall to do calf raises) and playful (eg, toss a ball back and forth or sing a song about rowing to promote weight shifting) [48].

Standing versus Seated Exercises

Residents may not be able to participate in standing exercises for several reasons: perhaps the resident cannot stand or has severe balance impairments and a high falls risk; the resident may have poor insight into which exercises are safe to perform in standing versus sitting; or there may be limited supervision of a large group exercise class where the risk of falls is a concern. If balance impairments are a concern, where the risk of injury or falling while completing exercises in standing outweighs the benefit of doing the exercises, then seated exercises are appropriate. However, when residents are able, we recommend encouraging some or all exercises in standing, to facilitate carry over of strength gains into functional tasks such as being able to rise from a chair and walking. A recent study, comparing standing versus seated exercises for community dwelling older adults, saw greater functional gains for those who completed the standing exercises [49]. Therefore, strength and balance exercises should be performed in standing, where appropriate.

Resident-Centered Exercise for Falls Prevention

Putting the resident at the center of falls prevention is important. Previous work has found that older adults have expressed a strong preference for care that transcends traditional biomedical care and that values efficiency, consistency, and hierarchical decision making [50]. On the contrary, resident-centered care emphasizes well-being and quality of life as defined by the resident, values giving residents greater control over the nature of services they receive, and respects their rights to be involved in every day decision making [51,52]. Indeed, residents may choose to engage in risky behaviors that increase their risk of falls but also increases their quality of life. Previous work has found disconnects between residents’ perceived frailty and the potential ability of protective devices to prevent adverse events, such as falls and fractures [53]. Additionally, one study identified that older residents feared being labelled, so instead hid impairments and chose to refuse assistance and assistive devices [54]. For example, a resident with impaired balance and gait may choose to walk independently when they have been deemed as requiring a gait aid (eg, rollator walker). However, they may value walking without a gait aid and accept the increased risk of falling. Therefore, it is essential to find the delicate balance between respecting a resident’s right to make their own decisions and preventing adverse events, such as falls [52]. An example of this would be respecting a resident’s right to refuse to attend exercise programming even though the team may think they can benefit from strength and balance training.

There is limited evidence around falls prevention and resident-centered care. A recent systematic review [55] revealed that resident-centered care may increase falls rates [56,57]. However, the authors of the review attributed the increase in falls to differences in frailty between the control and intervention group [56], and to environmental factors (eg, slippery flooring material, lack of handrails) [57]. Additionally, these trials did not include an exercise program as part of the resident-centered care program. On the other hand, resident-centered care has been associated with reduction of boredom, helplessness, and depression [58,59]. Most studies included in the review were quasi-experimental, which significantly limits the evidence quality [55]. At this point in time, the evidence suggests that resident-centered care is important for mood and quality of life but may have a negative or no effect on reducing falls.

Multifactorial Falls Prevention Programs

While there are mixed results about the effect of exercise as a single intervention for reducing falls for residents in LTC, the literature clearly supports exercise as part of a multifactorial falls prevention program [17,20,60–62]. A 2015 umbrella review [62] of meta-analyses of randomized controlled trials of falls prevention interventions in LTC concluded that multifactorial interventions were the most effective at preventing falls in LTC. Additionally, recently developed recommendations for fracture prevention in LTC [61] suggest that balance, strength, and functional training should be included for residents who are not at high risk of fracture, while for those at high risk, exercise should be provided as part of a multifactorial falls prevention intervention. Clinicians must therefore incorporate elements aside from exercise into their falls prevention strategies. Interventions that have shown positive effects on reducing falls when delivered as part of multifactorial interventions include: staff and resident education [31,35,37], environmental modifications [31,35], supply/repair/provision of assistive devices [30], falls problem-solving conferences [30], urinary incontinence management [29], medication review [30], optician review [31], and cognitive behavioral therapy [32].

Conclusion and Suggestions for Clinical Practice

We suggest incorporating strength and balance exercises as part of a multifactorial falls prevention program for residents in LTC. Balance exercises should be challenging and dynamic (eg, weight shifting). Strength exercises should be of a moderate to high intensity (eg, can complete one to sets of 6 to 8 repetitions) and need to be progressed as the residents’ abilities improve. Residents should participate in strength and balance training on 2 to 3 days per week, for 30- to 45-minute sessions, for at least 6 months. Exercises in standing should be prioritized where appropriate. Exercise could be delivered in a group or individual format, but should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings. Professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC. Exercise programs in LTC should be resident-centered and consider residents’ potential physical and cognitive impairments.

Funding/support: Dr. Giangregorio was supported by grants from the Canadian Frailty Network and Canadian Institutes of Health Research.

From the Geriatric Education and Research in Aging Sciences Centre, McMaster University Hamilton, ON (Dr. McArthur) and the University of Waterloo and Research Institute for Aging, Waterloo, ON (Dr. Giangregorio), Canada

Abstract

• Objective: To synthesize the available literature on exercise and falls reduction interventions in long-term care (LTC) and provide practical information for clinicians and other decision makers.
• Methods: Review of positive trials included in systematic reviews.
• Results: Falls are a major concern for residents, families, clinicians, and decision-makers in LTC. Exercise is recommended as part of a multifactorial falls prevention program for residents in LTC. Strength and balance exercises should be incorporated into the multifactorial falls prevention program. They should be challenging and progressed as the residents’ abilities improve. Evidence suggests that exercises should be completed 2 to 3 times per week for a period longer than 6 months. Exercise programs in LTC should be resident-centered and should consider residents’ potential physical and cognitive impairments. Exercises in standing should be prioritized where appropriate.
• Conclusion: Appropriately challenging and progressive strength and balance exercises should be included in a multifactorial falls prevention program for residents in LTC.

Key words: long-term care; nursing homes; falls reduction; exercise.

Falls are common in long-term care (LTC) homes: the estimated falls rate is 1.5 falls per bed per year, which is 3 times greater than that for older adults living in the community [1]. Falls can have significant consequences for residents in LTC, including functional disability, fractures, pain, reduced quality of life, and death [1–6]. Indeed, 25% of residents who are hospitalized after a fall die within 1 year [3]. Consequently, falls prevention programs are important to help in reducing falls and averting the associated negative consequences.

Exercise may address the circumstances and physical deconditioning that often contribute to falls in LTC residents. Weight shifting [7], walking, and transferring [8–10], are common activities that precede falls, suggesting that balance, gait, and functional mobility training may be possible targets for prevention. Additionally, it is estimated that LTC residents spend three quarters of their waking time in sedentary activities [11,12] and have a high prevalence of sarcopenia [13–16]. Challenging balance training and resistance exercise are well-known intervention for reducing falls [17] and improving muscle strength for community-dwelling older adults [18]. However, evidence around balance and strength training for preventing falls in LTC is mixed [17,19,20], and careful planning and modification of exercises is necessary to meet the needs of LTC residents.

Residents in LTC are often medically complex, with multiple comorbidities [21] that can affect their ability to meaningfully participate in exercise. In Canada, 56.3% of residents have a diagnosis of Alzheimer’s or other dementias, 25.0% have diabetes, 14.4% have chronic obstructive pulmonary disease, and 21.2% have experienced a stroke [21]. Residents also often have significant functional impairments. For example, 97% of residents require assistance with basic activities of daily living [21]. Therefore, the lack of effect of exercise as a single falls prevention strategy observed in previous studies may be because the often complex, multimorbid LTC population likely requires a multifactorial approach to fall prevention [17]. Additionally, organizational aspects of LTC homes (eg, specific funds dedicated to employing exercise professionals and to support exercise programming) can affect residents’ engagement in exercise [22,23]. Subsequently, prescribing exercises in the LTC context must consider both resident characteristics and organizational features of the LTC home (eg, professionals available to support exercise programming).

A comprehensive exercise prescription describes the elements of an appropriate exercise program to facilitate implementation of that program. The exercise prescription should include a description of the type (eg, balance, strength) and intensity of exercises (eg, subjective or objective measurement of how hard the resident is working) included in the program [24]. The prescription should also include a description of the dose of exercise: frequency of exercise participation (eg, 2 days per week), duration of individual exercise sessions (eg, 30-minute sessions), and duration of exercise program (eg, 12-week program) [24]. Lastly, the prescription should describe the setting of the exercise program (eg, group or individual basis) and the professional delivering the program (eg, physiotherapist, fitness instructor) [24].

Therefore, the objectives of this article are to (1) synthesize studies demonstrating a positive effect of exercise on reducing falls for residents in LTC; (2) provide an overview of the principles of balance and strength training to guide clinicians in designing appropriate exercise prescription; and (3) make suggestions for clinical practice regarding an appropriate strength and balance exercise protocol by considering the influence of the LTC context.

Methods

To provide clinicians and other policy-makers with a description of which balance and strength exercises may be effective for preventing falls, we synthesized trials that demonstrated a positive effect on reducing falls or falls risk for residents in LTC. Studies were identified through a database search for systematic reviews in PubMed, Ovid, and Google Scholar using the keywords falls, long-term care, nursing homes, exercise, strength, balance, and systematic reviews. Our purpose was to provide practical information on what works to prevent falls through balance and strength training for residents in LTC rather than to evaluate the available evidence. Therefore, only positive trials from systematic reviews were discussed, as we wanted to present exercises that seem to have a positive effect on decreasing falls. Positive trials were defined as those included in identified systematic reviews with a risk or rate ratio and confidence intervals below 1.0.

We first provide an overview of the conclusions of the systematic reviews found in our search. Next, for each positive trial we describe the following elements of the exercise component of the intervention: frequency, time of sessions, length of program, intensity, type of exercise including a description of the specific exercises performed, whether the intervention was delivered in a group or on an individual basis, the professional delivering the intervention, and any other features of the intervention aside from the exercise component. We used the ProFaNE taxonomy definitions [25] to identify and describe each element of the exercise interventions. Frequency is the number of times per week that residents engage in sessions, time of sessions is the amount allocated to each exercise session, duration of program is how long the resident participates in the exercise program, and intensity is the subjective or objective report of how hard the resident is working [25]. The types of exercises described were those targeting balance defined as “...the efficient transfer of bodyweight from one part of the body to another or challenges specific aspects of the balance systems (eg, vestibular system)” [25], and strength defined as “...contracting the muscles against a resistance to ‘overload’ and bring about a training effect in the muscular system” [25]. Strength could be either an external resistance (eg, dumbbell) or using body weight against gravity (eg, squat) [25].

Results

We found 3 systematic reviews that include exercise programs to reduce falls in LTC homes [17,19,20]. Overall, evidence suggests that exercise should be included as part of a multifactorial falls prevention program for residents in LTC. There is limited evidence that exercise as a single intervention prevents falls, and some trials, albeit underpowered, even demonstrate an increased risk of falling in the exercise group compared to control [19]. With regards to specific exercise programs, the Cochrane review found that gait, balance, and functional training decrease the rate of falls but not the risk of falling [26–28], and the 2013 review by Silva et al [20] concluded that combined exercise programs (ie, multiple types of exercise) that include balance tasks, are completed frequently (2–3 times per week), and over a long term (greater than 6 months) were most effective at preventing falls [20].

A more recent systematic review and meta-analysis [17] also concluded that there was no evidence that exercise as a single intervention can prevent falls for residents in LTC. Table 1 provides a description of the exercise component of the seven positive trials [29–35] that were included in the 3 systematic reviews we identified in our search.

Type of Exercise

Balance Exercises

There were 4 positive trials that included balance exercises in their intervention [31,33–35]. Trials that had a positive effect on reducing falls and included balance training employed mostly dynamic balance exercises in standing (Table 1). However, only 2 of the 7 trials provided a detailed description of their balance exercises (Table 1) [26,34]. Jensen et al [30] and Dyer et al [31] did not include a description of the balance training performed but stated that balance was part of the multicomponent exercise program. Becker et al [36] stated that participants performed standing balance exercises, while Schnelle et al [39] and Huang et al [32] did not include balance training in their trial.

Strength Exercises

Of the 7 positive trials included in this review, 6 included strength exercises [29–32,34,35]. The strength activities used in trials where exercise had a positive effect on decreasing falls included functional activities [29,31] and progressive resistance training [31,36] (Table 1). Functional activities are those that replicate what a resident might be required to do in their everyday life, such as performing sit-to-stands out of a chair (Figure) 

Frequency, Time of Sessions, Duration of Program

In our description of positive trials, exercise was performed on 2 to 3 days per week for 20 to 75 minutes per session, for periods ranging from 4 to 52 weeks (Table 1).

Intensity

For the trials including balance exercises, one trial described the intensity as resident-specific [37] and another as individualized [33]. Two studies did not describe the intensity of their balance exercises [31,34]. The intensity of strength exercises included in the positive trials was individualized for one of the trial [29]. Two trials had participants complete 2 to 3 sets of 10 repetitions [32,35], with one indicating an intensity of 12–13 or “somewhat difficult” on the Borg Rating of Perceived Exertion Scale [32] and the other using a 10-rep max [35]. Two studies described their strength exercises as progressive [31,37], and one at a moderate to high intensity [30]. Lord et al prescribed 30 repetitions of each strength exercise [34].

Delivery of Intervention

Exercise was delivered in a group setting for 4 of the trials [31,32,34,36], individually for 2 of the trials [26,29], and the setting was not described for one of the trials (Table 1) [30]. Finally, only 3 of the 7 articles reported the professional delivering the intervention: one was research staff [29], one was geriatric nurses [32], and one was exercise assistants supported by a physiotherapist [31].

Discussion

There is limited evidence to support the use of strength and balance exercise as a single intervention to prevent falls in LTC. However, exercise should be included as part of a multifactorial falls prevention program. Trials that had a positive effect on decreasing falls training used dynamic balance exercises in standing, functional training, and progressive resistance training on 2 to 3 days per week, for 20 to 75 minutes per session, over 4 to 52 weeks. The intensity of balance exercises was individualized, and strength exercises were described as somewhat difficult or performed at a moderate to high intensity. Exercise was performed in a group or individually, and was delivered by research staff, geriatric nurses, exercise assistants supervised by physiotherapists, or more frequently, it was not reported who delivered the intervention.

Balance Training

Our work suggests that standing, dynamic balance exercises may be best to decrease falls. Example balance exercises include reducing the base of support (eg, standing with feet together instead of apart, or tandem with one foot in front), moving the center of gravity and control body position while standing (eg, reaching, weight shifting, stepping up or down), and standing without using arms for support or reducing reliance on the upper limbs for support (eg, use one hand on a handrail instead of two, or two fingers instead of the whole hand) [17]. It is well established that balance training programs, especially those including challenging exercises, can prevent falls in community-dwelling older adults [17]. However, the relationship is not as clear in LTC.

Strength Training

Reduced muscle strength has been identified as an important risk factor for falls [38]. There are also many psychological and metabolic benefits to strength training [39]. To induce change in muscular strength, resistance exercises need to be challenging and progressive. Our work suggests that strength training that is effective at decreasing falls is functional and progressive, and is completed at a moderate to high intensity. A resident should be able to do a strength exercise for one to two sets of 6 to 8 repetitions before being fatigued [40]. Once the resident can complete two sets of 13 to 15 repetitions easily the exercise should be progressed. Residents who are particularly deconditioned may need to begin with lower intensity strength exercises (eg, only do one set, with a lower resistance and progress to a higher resistance) [40]. Residents should perform resistance exercises for all major muscle groups [40]. Progression could include increasing the number of sets (eg, increase from one to two sets), the resistance (eg, holding dumbbells while squatting), or the intensity of the exercise (eg, squat lower or faster) [41].

Implementing Exercise Programs in LTC

Implementation of exercise programs into LTC homes should consider the dose of exercise (eg, time and frequency of sessions, duration of program), if they are delivered in a group or individual setting, and who is delivering them. First, trials included in this paper suggest that strength and balance exercises to prevent falls were delivered 2 to 3 times per week, for 20 to 75 minutes per session, over 4 to 52 weeks. Second, previous work has established that exercise programs delivered on 2 to 3 days per week over a period of more than 6 months are most effective at reducing falls in LTC [20]. Finally, a recent task force report from an international group of clinician researchers in LTC recommends twice weekly exercise sessions lasting 35 to 45 minutes each [40]. Therefore, strength and balance exercises to prevent falls in LTC should be delivered at least twice per week, for at least 20 minutes, for greater than 6 weeks’ duration.

Whether exercise should be performed in a group or individual setting remains unclear. Two of the 6 positive trials in this paper were completed individually, while 3 were in a group. The aforementioned task force also recommended that every resident who does not have contraindications to exercise must have an individualized exercise program as part of their health care plan [40]. However, whether the exercise program is provided on an individual basis or in a group setting was not delineated. Indeed, there are currently no recommendations concerning prioritizing group or individual exercise programs. Therefore, exercise programs being implemented into LTC homes should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings.

Finally, which professionals should deliver the exercise program is also uncertain. Only 3 of the positive trials in this paper described the professional delivering the intervention, with one being research staff, one geriatric nurses, and one exercise assistants supported by a physiotherapist. We suggest that professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC.

Modifications for Physical Impairments

Residents in LTC often have complex health needs, with multiple comorbidities (eg, stroke, Parkinson’s disease, multiple sclerosis) [21]. Modifications of strength and balance exercises may be required to accommodate for physical impairments (eg, hemiplegia, drop foot, freezing gait). For example, if a resident has hemiplegia and cannot fully activate the muscles of one arm, one can do resistance exercises with a dumbbell on the functioning side and active assisted range of motion (ie, the exercise provider assists the resident to achieve full range of motion against gravity) on the hemiparetic side. A resident with Parkinson’s disease who has freezing gait may need visual or rhythmical verbal cues to be able to accomplish standing balance tasks such as altered walking patterns (eg, wide or narrow stepping) [42].

Modifications for Cognitive Impairments

More than 80% of residents in LTC have some degree of cognitive impairment [21]. Cognitive impairment may be the result of stroke, depression, traumatic injuries, medications, and degenerative diseases such as Parkinson’s and Alzheimer’s disease [43]. A common misconception is that residents with cognitive impairment cannot benefit from exercise because they cannot learn new skills and have difficulty following directions. On the contrary, evidence suggests that exercise can improve functional mobility for residents with cognitive impairment [44,45].

Residents with cognitive impairment may require a different approach to facilitate participation in the desired exercises because of difficulty following multi-step directions, responsive behaviors, or increased distractibility [46]. Clear communication is key in improving the quality of interaction for residents with cognitive impairment. The Alzheimer Society of Ontario suggests 10 strategies for communicating with people with dementia [47], and we have provided suggestions of how to apply these communication strategies to the exercise context in LTC (Table 2). Other suggestions for engaging residents with cognitive impairment in strength and balance training include making the exercises functional (eg, ask them to pick something up of the floor to perform a squat, or reach a point on the wall to do calf raises) and playful (eg, toss a ball back and forth or sing a song about rowing to promote weight shifting) [48].

Standing versus Seated Exercises

Residents may not be able to participate in standing exercises for several reasons: perhaps the resident cannot stand or has severe balance impairments and a high falls risk; the resident may have poor insight into which exercises are safe to perform in standing versus sitting; or there may be limited supervision of a large group exercise class where the risk of falls is a concern. If balance impairments are a concern, where the risk of injury or falling while completing exercises in standing outweighs the benefit of doing the exercises, then seated exercises are appropriate. However, when residents are able, we recommend encouraging some or all exercises in standing, to facilitate carry over of strength gains into functional tasks such as being able to rise from a chair and walking. A recent study, comparing standing versus seated exercises for community dwelling older adults, saw greater functional gains for those who completed the standing exercises [49]. Therefore, strength and balance exercises should be performed in standing, where appropriate.

Resident-Centered Exercise for Falls Prevention

Putting the resident at the center of falls prevention is important. Previous work has found that older adults have expressed a strong preference for care that transcends traditional biomedical care and that values efficiency, consistency, and hierarchical decision making [50]. On the contrary, resident-centered care emphasizes well-being and quality of life as defined by the resident, values giving residents greater control over the nature of services they receive, and respects their rights to be involved in every day decision making [51,52]. Indeed, residents may choose to engage in risky behaviors that increase their risk of falls but also increases their quality of life. Previous work has found disconnects between residents’ perceived frailty and the potential ability of protective devices to prevent adverse events, such as falls and fractures [53]. Additionally, one study identified that older residents feared being labelled, so instead hid impairments and chose to refuse assistance and assistive devices [54]. For example, a resident with impaired balance and gait may choose to walk independently when they have been deemed as requiring a gait aid (eg, rollator walker). However, they may value walking without a gait aid and accept the increased risk of falling. Therefore, it is essential to find the delicate balance between respecting a resident’s right to make their own decisions and preventing adverse events, such as falls [52]. An example of this would be respecting a resident’s right to refuse to attend exercise programming even though the team may think they can benefit from strength and balance training.

There is limited evidence around falls prevention and resident-centered care. A recent systematic review [55] revealed that resident-centered care may increase falls rates [56,57]. However, the authors of the review attributed the increase in falls to differences in frailty between the control and intervention group [56], and to environmental factors (eg, slippery flooring material, lack of handrails) [57]. Additionally, these trials did not include an exercise program as part of the resident-centered care program. On the other hand, resident-centered care has been associated with reduction of boredom, helplessness, and depression [58,59]. Most studies included in the review were quasi-experimental, which significantly limits the evidence quality [55]. At this point in time, the evidence suggests that resident-centered care is important for mood and quality of life but may have a negative or no effect on reducing falls.

Multifactorial Falls Prevention Programs

While there are mixed results about the effect of exercise as a single intervention for reducing falls for residents in LTC, the literature clearly supports exercise as part of a multifactorial falls prevention program [17,20,60–62]. A 2015 umbrella review [62] of meta-analyses of randomized controlled trials of falls prevention interventions in LTC concluded that multifactorial interventions were the most effective at preventing falls in LTC. Additionally, recently developed recommendations for fracture prevention in LTC [61] suggest that balance, strength, and functional training should be included for residents who are not at high risk of fracture, while for those at high risk, exercise should be provided as part of a multifactorial falls prevention intervention. Clinicians must therefore incorporate elements aside from exercise into their falls prevention strategies. Interventions that have shown positive effects on reducing falls when delivered as part of multifactorial interventions include: staff and resident education [31,35,37], environmental modifications [31,35], supply/repair/provision of assistive devices [30], falls problem-solving conferences [30], urinary incontinence management [29], medication review [30], optician review [31], and cognitive behavioral therapy [32].

Conclusion and Suggestions for Clinical Practice

We suggest incorporating strength and balance exercises as part of a multifactorial falls prevention program for residents in LTC. Balance exercises should be challenging and dynamic (eg, weight shifting). Strength exercises should be of a moderate to high intensity (eg, can complete one to sets of 6 to 8 repetitions) and need to be progressed as the residents’ abilities improve. Residents should participate in strength and balance training on 2 to 3 days per week, for 30- to 45-minute sessions, for at least 6 months. Exercises in standing should be prioritized where appropriate. Exercise could be delivered in a group or individual format, but should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings. Professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC. Exercise programs in LTC should be resident-centered and consider residents’ potential physical and cognitive impairments.

Funding/support: Dr. Giangregorio was supported by grants from the Canadian Frailty Network and Canadian Institutes of Health Research.

From the Geriatric Education and Research in Aging Sciences Centre, McMaster University Hamilton, ON (Dr. McArthur) and the University of Waterloo and Research Institute for Aging, Waterloo, ON (Dr. Giangregorio), Canada

Abstract

• Objective: To synthesize the available literature on exercise and falls reduction interventions in long-term care (LTC) and provide practical information for clinicians and other decision makers.
• Methods: Review of positive trials included in systematic reviews.
• Results: Falls are a major concern for residents, families, clinicians, and decision-makers in LTC. Exercise is recommended as part of a multifactorial falls prevention program for residents in LTC. Strength and balance exercises should be incorporated into the multifactorial falls prevention program. They should be challenging and progressed as the residents’ abilities improve. Evidence suggests that exercises should be completed 2 to 3 times per week for a period longer than 6 months. Exercise programs in LTC should be resident-centered and should consider residents’ potential physical and cognitive impairments. Exercises in standing should be prioritized where appropriate.
• Conclusion: Appropriately challenging and progressive strength and balance exercises should be included in a multifactorial falls prevention program for residents in LTC.

Key words: long-term care; nursing homes; falls reduction; exercise.

Falls are common in long-term care (LTC) homes: the estimated falls rate is 1.5 falls per bed per year, which is 3 times greater than that for older adults living in the community [1]. Falls can have significant consequences for residents in LTC, including functional disability, fractures, pain, reduced quality of life, and death [1–6]. Indeed, 25% of residents who are hospitalized after a fall die within 1 year [3]. Consequently, falls prevention programs are important to help in reducing falls and averting the associated negative consequences.

Exercise may address the circumstances and physical deconditioning that often contribute to falls in LTC residents. Weight shifting [7], walking, and transferring [8–10], are common activities that precede falls, suggesting that balance, gait, and functional mobility training may be possible targets for prevention. Additionally, it is estimated that LTC residents spend three quarters of their waking time in sedentary activities [11,12] and have a high prevalence of sarcopenia [13–16]. Challenging balance training and resistance exercise are well-known intervention for reducing falls [17] and improving muscle strength for community-dwelling older adults [18]. However, evidence around balance and strength training for preventing falls in LTC is mixed [17,19,20], and careful planning and modification of exercises is necessary to meet the needs of LTC residents.

Residents in LTC are often medically complex, with multiple comorbidities [21] that can affect their ability to meaningfully participate in exercise. In Canada, 56.3% of residents have a diagnosis of Alzheimer’s or other dementias, 25.0% have diabetes, 14.4% have chronic obstructive pulmonary disease, and 21.2% have experienced a stroke [21]. Residents also often have significant functional impairments. For example, 97% of residents require assistance with basic activities of daily living [21]. Therefore, the lack of effect of exercise as a single falls prevention strategy observed in previous studies may be because the often complex, multimorbid LTC population likely requires a multifactorial approach to fall prevention [17]. Additionally, organizational aspects of LTC homes (eg, specific funds dedicated to employing exercise professionals and to support exercise programming) can affect residents’ engagement in exercise [22,23]. Subsequently, prescribing exercises in the LTC context must consider both resident characteristics and organizational features of the LTC home (eg, professionals available to support exercise programming).

A comprehensive exercise prescription describes the elements of an appropriate exercise program to facilitate implementation of that program. The exercise prescription should include a description of the type (eg, balance, strength) and intensity of exercises (eg, subjective or objective measurement of how hard the resident is working) included in the program [24]. The prescription should also include a description of the dose of exercise: frequency of exercise participation (eg, 2 days per week), duration of individual exercise sessions (eg, 30-minute sessions), and duration of exercise program (eg, 12-week program) [24]. Lastly, the prescription should describe the setting of the exercise program (eg, group or individual basis) and the professional delivering the program (eg, physiotherapist, fitness instructor) [24].

Therefore, the objectives of this article are to (1) synthesize studies demonstrating a positive effect of exercise on reducing falls for residents in LTC; (2) provide an overview of the principles of balance and strength training to guide clinicians in designing appropriate exercise prescription; and (3) make suggestions for clinical practice regarding an appropriate strength and balance exercise protocol by considering the influence of the LTC context.

Methods

To provide clinicians and other policy-makers with a description of which balance and strength exercises may be effective for preventing falls, we synthesized trials that demonstrated a positive effect on reducing falls or falls risk for residents in LTC. Studies were identified through a database search for systematic reviews in PubMed, Ovid, and Google Scholar using the keywords falls, long-term care, nursing homes, exercise, strength, balance, and systematic reviews. Our purpose was to provide practical information on what works to prevent falls through balance and strength training for residents in LTC rather than to evaluate the available evidence. Therefore, only positive trials from systematic reviews were discussed, as we wanted to present exercises that seem to have a positive effect on decreasing falls. Positive trials were defined as those included in identified systematic reviews with a risk or rate ratio and confidence intervals below 1.0.

We first provide an overview of the conclusions of the systematic reviews found in our search. Next, for each positive trial we describe the following elements of the exercise component of the intervention: frequency, time of sessions, length of program, intensity, type of exercise including a description of the specific exercises performed, whether the intervention was delivered in a group or on an individual basis, the professional delivering the intervention, and any other features of the intervention aside from the exercise component. We used the ProFaNE taxonomy definitions [25] to identify and describe each element of the exercise interventions. Frequency is the number of times per week that residents engage in sessions, time of sessions is the amount allocated to each exercise session, duration of program is how long the resident participates in the exercise program, and intensity is the subjective or objective report of how hard the resident is working [25]. The types of exercises described were those targeting balance defined as “...the efficient transfer of bodyweight from one part of the body to another or challenges specific aspects of the balance systems (eg, vestibular system)” [25], and strength defined as “...contracting the muscles against a resistance to ‘overload’ and bring about a training effect in the muscular system” [25]. Strength could be either an external resistance (eg, dumbbell) or using body weight against gravity (eg, squat) [25].

Results

We found 3 systematic reviews that include exercise programs to reduce falls in LTC homes [17,19,20]. Overall, evidence suggests that exercise should be included as part of a multifactorial falls prevention program for residents in LTC. There is limited evidence that exercise as a single intervention prevents falls, and some trials, albeit underpowered, even demonstrate an increased risk of falling in the exercise group compared to control [19]. With regards to specific exercise programs, the Cochrane review found that gait, balance, and functional training decrease the rate of falls but not the risk of falling [26–28], and the 2013 review by Silva et al [20] concluded that combined exercise programs (ie, multiple types of exercise) that include balance tasks, are completed frequently (2–3 times per week), and over a long term (greater than 6 months) were most effective at preventing falls [20].

A more recent systematic review and meta-analysis [17] also concluded that there was no evidence that exercise as a single intervention can prevent falls for residents in LTC. Table 1 provides a description of the exercise component of the seven positive trials [29–35] that were included in the 3 systematic reviews we identified in our search.

Type of Exercise

Balance Exercises

There were 4 positive trials that included balance exercises in their intervention [31,33–35]. Trials that had a positive effect on reducing falls and included balance training employed mostly dynamic balance exercises in standing (Table 1). However, only 2 of the 7 trials provided a detailed description of their balance exercises (Table 1) [26,34]. Jensen et al [30] and Dyer et al [31] did not include a description of the balance training performed but stated that balance was part of the multicomponent exercise program. Becker et al [36] stated that participants performed standing balance exercises, while Schnelle et al [39] and Huang et al [32] did not include balance training in their trial.

Strength Exercises

Of the 7 positive trials included in this review, 6 included strength exercises [29–32,34,35]. The strength activities used in trials where exercise had a positive effect on decreasing falls included functional activities [29,31] and progressive resistance training [31,36] (Table 1). Functional activities are those that replicate what a resident might be required to do in their everyday life, such as performing sit-to-stands out of a chair (Figure) 

Frequency, Time of Sessions, Duration of Program

In our description of positive trials, exercise was performed on 2 to 3 days per week for 20 to 75 minutes per session, for periods ranging from 4 to 52 weeks (Table 1).

Intensity

For the trials including balance exercises, one trial described the intensity as resident-specific [37] and another as individualized [33]. Two studies did not describe the intensity of their balance exercises [31,34]. The intensity of strength exercises included in the positive trials was individualized for one of the trial [29]. Two trials had participants complete 2 to 3 sets of 10 repetitions [32,35], with one indicating an intensity of 12–13 or “somewhat difficult” on the Borg Rating of Perceived Exertion Scale [32] and the other using a 10-rep max [35]. Two studies described their strength exercises as progressive [31,37], and one at a moderate to high intensity [30]. Lord et al prescribed 30 repetitions of each strength exercise [34].

Delivery of Intervention

Exercise was delivered in a group setting for 4 of the trials [31,32,34,36], individually for 2 of the trials [26,29], and the setting was not described for one of the trials (Table 1) [30]. Finally, only 3 of the 7 articles reported the professional delivering the intervention: one was research staff [29], one was geriatric nurses [32], and one was exercise assistants supported by a physiotherapist [31].

Discussion

There is limited evidence to support the use of strength and balance exercise as a single intervention to prevent falls in LTC. However, exercise should be included as part of a multifactorial falls prevention program. Trials that had a positive effect on decreasing falls training used dynamic balance exercises in standing, functional training, and progressive resistance training on 2 to 3 days per week, for 20 to 75 minutes per session, over 4 to 52 weeks. The intensity of balance exercises was individualized, and strength exercises were described as somewhat difficult or performed at a moderate to high intensity. Exercise was performed in a group or individually, and was delivered by research staff, geriatric nurses, exercise assistants supervised by physiotherapists, or more frequently, it was not reported who delivered the intervention.

Balance Training

Our work suggests that standing, dynamic balance exercises may be best to decrease falls. Example balance exercises include reducing the base of support (eg, standing with feet together instead of apart, or tandem with one foot in front), moving the center of gravity and control body position while standing (eg, reaching, weight shifting, stepping up or down), and standing without using arms for support or reducing reliance on the upper limbs for support (eg, use one hand on a handrail instead of two, or two fingers instead of the whole hand) [17]. It is well established that balance training programs, especially those including challenging exercises, can prevent falls in community-dwelling older adults [17]. However, the relationship is not as clear in LTC.

Strength Training

Reduced muscle strength has been identified as an important risk factor for falls [38]. There are also many psychological and metabolic benefits to strength training [39]. To induce change in muscular strength, resistance exercises need to be challenging and progressive. Our work suggests that strength training that is effective at decreasing falls is functional and progressive, and is completed at a moderate to high intensity. A resident should be able to do a strength exercise for one to two sets of 6 to 8 repetitions before being fatigued [40]. Once the resident can complete two sets of 13 to 15 repetitions easily the exercise should be progressed. Residents who are particularly deconditioned may need to begin with lower intensity strength exercises (eg, only do one set, with a lower resistance and progress to a higher resistance) [40]. Residents should perform resistance exercises for all major muscle groups [40]. Progression could include increasing the number of sets (eg, increase from one to two sets), the resistance (eg, holding dumbbells while squatting), or the intensity of the exercise (eg, squat lower or faster) [41].

Implementing Exercise Programs in LTC

Implementation of exercise programs into LTC homes should consider the dose of exercise (eg, time and frequency of sessions, duration of program), if they are delivered in a group or individual setting, and who is delivering them. First, trials included in this paper suggest that strength and balance exercises to prevent falls were delivered 2 to 3 times per week, for 20 to 75 minutes per session, over 4 to 52 weeks. Second, previous work has established that exercise programs delivered on 2 to 3 days per week over a period of more than 6 months are most effective at reducing falls in LTC [20]. Finally, a recent task force report from an international group of clinician researchers in LTC recommends twice weekly exercise sessions lasting 35 to 45 minutes each [40]. Therefore, strength and balance exercises to prevent falls in LTC should be delivered at least twice per week, for at least 20 minutes, for greater than 6 weeks’ duration.

Whether exercise should be performed in a group or individual setting remains unclear. Two of the 6 positive trials in this paper were completed individually, while 3 were in a group. The aforementioned task force also recommended that every resident who does not have contraindications to exercise must have an individualized exercise program as part of their health care plan [40]. However, whether the exercise program is provided on an individual basis or in a group setting was not delineated. Indeed, there are currently no recommendations concerning prioritizing group or individual exercise programs. Therefore, exercise programs being implemented into LTC homes should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings.

Finally, which professionals should deliver the exercise program is also uncertain. Only 3 of the positive trials in this paper described the professional delivering the intervention, with one being research staff, one geriatric nurses, and one exercise assistants supported by a physiotherapist. We suggest that professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC.

Modifications for Physical Impairments

Residents in LTC often have complex health needs, with multiple comorbidities (eg, stroke, Parkinson’s disease, multiple sclerosis) [21]. Modifications of strength and balance exercises may be required to accommodate for physical impairments (eg, hemiplegia, drop foot, freezing gait). For example, if a resident has hemiplegia and cannot fully activate the muscles of one arm, one can do resistance exercises with a dumbbell on the functioning side and active assisted range of motion (ie, the exercise provider assists the resident to achieve full range of motion against gravity) on the hemiparetic side. A resident with Parkinson’s disease who has freezing gait may need visual or rhythmical verbal cues to be able to accomplish standing balance tasks such as altered walking patterns (eg, wide or narrow stepping) [42].

Modifications for Cognitive Impairments

More than 80% of residents in LTC have some degree of cognitive impairment [21]. Cognitive impairment may be the result of stroke, depression, traumatic injuries, medications, and degenerative diseases such as Parkinson’s and Alzheimer’s disease [43]. A common misconception is that residents with cognitive impairment cannot benefit from exercise because they cannot learn new skills and have difficulty following directions. On the contrary, evidence suggests that exercise can improve functional mobility for residents with cognitive impairment [44,45].

Residents with cognitive impairment may require a different approach to facilitate participation in the desired exercises because of difficulty following multi-step directions, responsive behaviors, or increased distractibility [46]. Clear communication is key in improving the quality of interaction for residents with cognitive impairment. The Alzheimer Society of Ontario suggests 10 strategies for communicating with people with dementia [47], and we have provided suggestions of how to apply these communication strategies to the exercise context in LTC (Table 2). Other suggestions for engaging residents with cognitive impairment in strength and balance training include making the exercises functional (eg, ask them to pick something up of the floor to perform a squat, or reach a point on the wall to do calf raises) and playful (eg, toss a ball back and forth or sing a song about rowing to promote weight shifting) [48].

Standing versus Seated Exercises

Residents may not be able to participate in standing exercises for several reasons: perhaps the resident cannot stand or has severe balance impairments and a high falls risk; the resident may have poor insight into which exercises are safe to perform in standing versus sitting; or there may be limited supervision of a large group exercise class where the risk of falls is a concern. If balance impairments are a concern, where the risk of injury or falling while completing exercises in standing outweighs the benefit of doing the exercises, then seated exercises are appropriate. However, when residents are able, we recommend encouraging some or all exercises in standing, to facilitate carry over of strength gains into functional tasks such as being able to rise from a chair and walking. A recent study, comparing standing versus seated exercises for community dwelling older adults, saw greater functional gains for those who completed the standing exercises [49]. Therefore, strength and balance exercises should be performed in standing, where appropriate.

Resident-Centered Exercise for Falls Prevention

Putting the resident at the center of falls prevention is important. Previous work has found that older adults have expressed a strong preference for care that transcends traditional biomedical care and that values efficiency, consistency, and hierarchical decision making [50]. On the contrary, resident-centered care emphasizes well-being and quality of life as defined by the resident, values giving residents greater control over the nature of services they receive, and respects their rights to be involved in every day decision making [51,52]. Indeed, residents may choose to engage in risky behaviors that increase their risk of falls but also increases their quality of life. Previous work has found disconnects between residents’ perceived frailty and the potential ability of protective devices to prevent adverse events, such as falls and fractures [53]. Additionally, one study identified that older residents feared being labelled, so instead hid impairments and chose to refuse assistance and assistive devices [54]. For example, a resident with impaired balance and gait may choose to walk independently when they have been deemed as requiring a gait aid (eg, rollator walker). However, they may value walking without a gait aid and accept the increased risk of falling. Therefore, it is essential to find the delicate balance between respecting a resident’s right to make their own decisions and preventing adverse events, such as falls [52]. An example of this would be respecting a resident’s right to refuse to attend exercise programming even though the team may think they can benefit from strength and balance training.

There is limited evidence around falls prevention and resident-centered care. A recent systematic review [55] revealed that resident-centered care may increase falls rates [56,57]. However, the authors of the review attributed the increase in falls to differences in frailty between the control and intervention group [56], and to environmental factors (eg, slippery flooring material, lack of handrails) [57]. Additionally, these trials did not include an exercise program as part of the resident-centered care program. On the other hand, resident-centered care has been associated with reduction of boredom, helplessness, and depression [58,59]. Most studies included in the review were quasi-experimental, which significantly limits the evidence quality [55]. At this point in time, the evidence suggests that resident-centered care is important for mood and quality of life but may have a negative or no effect on reducing falls.

Multifactorial Falls Prevention Programs

While there are mixed results about the effect of exercise as a single intervention for reducing falls for residents in LTC, the literature clearly supports exercise as part of a multifactorial falls prevention program [17,20,60–62]. A 2015 umbrella review [62] of meta-analyses of randomized controlled trials of falls prevention interventions in LTC concluded that multifactorial interventions were the most effective at preventing falls in LTC. Additionally, recently developed recommendations for fracture prevention in LTC [61] suggest that balance, strength, and functional training should be included for residents who are not at high risk of fracture, while for those at high risk, exercise should be provided as part of a multifactorial falls prevention intervention. Clinicians must therefore incorporate elements aside from exercise into their falls prevention strategies. Interventions that have shown positive effects on reducing falls when delivered as part of multifactorial interventions include: staff and resident education [31,35,37], environmental modifications [31,35], supply/repair/provision of assistive devices [30], falls problem-solving conferences [30], urinary incontinence management [29], medication review [30], optician review [31], and cognitive behavioral therapy [32].

Conclusion and Suggestions for Clinical Practice

We suggest incorporating strength and balance exercises as part of a multifactorial falls prevention program for residents in LTC. Balance exercises should be challenging and dynamic (eg, weight shifting). Strength exercises should be of a moderate to high intensity (eg, can complete one to sets of 6 to 8 repetitions) and need to be progressed as the residents’ abilities improve. Residents should participate in strength and balance training on 2 to 3 days per week, for 30- to 45-minute sessions, for at least 6 months. Exercises in standing should be prioritized where appropriate. Exercise could be delivered in a group or individual format, but should consider the residents’ preferences, the social benefits of group exercise, and the feasibility of individualizing exercises for the complex needs of residents in LTC in large group settings. Professionals delivering an exercise program should be trained in exercise planning, delivery, and progression, be familiar with the principles of balance and strength training, and have training in working with older adults in LTC. Exercise programs in LTC should be resident-centered and consider residents’ potential physical and cognitive impairments.

Funding/support: Dr. Giangregorio was supported by grants from the Canadian Frailty Network and Canadian Institutes of Health Research.

From the University of California San Francisco, Department of Psychiatry, Weill Institute for Neurosciences, San Francisco, CA.

Abstract

• Objective: To review screening for metabolic syndrome in people with severe mental illness (SMI).
• Methods: Review of the literature.
• Results: Despite evidence-based metabolic screening guidelines, rates of metabolic screening remain low among people with SMI. Barriers to screening exist at the individual, organizational, and systems levels. Interventions to address these barriers range from point-of-care tools to systems-level reorganization towards population-based care.
• Conclusion: Greater systems-level interventions, particularly those that improve collaboration between mental health and primary care, are needed to improve metabolic monitoring and identify cardiovascular disease risk among people with SMI.

Key words: metabolic monitoring; severe mental illness; metabolic syndrome; integrated care.

People with severe mental illness (SMI) have a life expectancy 10 to 20 years shorter than the general population, and cardiometabolic risk factors contribute significantly to the increased morbidity and mortality seen in this population. To address this health disparity, metabolic monitoring guidelines have been proposed as a mechanism to identify metabolic risk factors. This paper aims to discuss metabolic syndrome and its risk factors, describe metabolic monitoring including current rates and barriers to screening, and identify interventions that may improve rates of screening for metabolic syndrome among people with SMI.

Metabolic syndrome has been conceptualized as a state of chronic low-grade inflammation and hypercoagulation associated with hypertension, dyslipidemia, glucose intolerance, insulin resistance, and visceral adiposity [1]. Per the modified National Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) guidelines, metabolic syndrome is defined as the presence of 3 of the following 5 parameters: (1) blood glucose > 100 mg/dL (or a person is taking a hypoglycemic medication), (2) high density lipoprotein (HDL) < 40 mg/dL in men or < 50 mg/dL in women, (3) triglycerides > 150 mg/dL (or taking a lipid lowering agent), (4) waist circumference > 40 inches in men or > 35 inches in women, and/or (5) blood pressure > 130/85 mm Hg (or taking an antihypertensive medication) [2,3] (Table 1).

Epidemiology and Risk Factors

An estimated 34% of people in the United States meet criteria for metabolic syndrome, with worldwide estimates ranging widely from less than 10% to 84%. People with SMI (eg, bipolar disorder, schizoaffective disorder, schizophrenia) are at even greater risk of developing metabolic syndrome than the general population [4,5]. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study demonstrated metabolic syndrome rates of 40.9% and 51.6% in men and women with a diagnosis of schizophrenia, respectively [6]. In a systematic review of bipolar disorder and metabolic syndrome, people with bipolar disorder showed higher rates of hypertriglyceridemia and hyperglycemia than controls [5].

People with SMI have been found to have significantly increased morbidity and mortality as compared to people without an SMI diagnosis, much of which has been attributed to increased cardiometabolic risk related to multiple factors [7]. Among adults with schizophrenia receiving Medicaid, Olfson et al found diabetes mellitus, ischemic heart disease, nonischemic heart disease, and cerebrovascular accident to be among the top 10 causes of death [7]. The mortality rate for people with SMI is estimated to be 2 to 3 times higher than the general population, and the life expectancy for people with SMI is estimated to be 10 to 20 years shorter than the general population [8–10]. Contributors to this disparity include modifiable health-related behaviors, social determinants of health, and iatrogenic sequelae of prescribed medications. Behavioral factors include poor nutrition, food insecurity, sedentary lifestyle, and smoking; side effects of commonly prescribed psychotropic medications, most notably atypical antipsychotics and mood stabilizers, also contribute to this disparity [7,11].

Both first- and second-generation antipsychotics have been shown to be associated with metabolic sequelae, including weight gain, elevated blood glucose, and insulin resistance [12–14]. Among psychotropic medications, the atypical or second-generation antipsychotics (SGAs) are a class of medications known to have significant metabolic side effects [15,16]. Studies comparing the metabolic consequences of individual SGAs have found significant variation within the class. Clozapine, olanzapine, quetiapine, and risperidone show significant likelihood of weight gain, hyperlipidemia, and hyperglycemia as well as other metabolic consequences [17]. Aripiprazole, lurasidone, and ziprasidone have shown little to no risk of metabolic sequelae [17].

Metabolic side effects of SGAs have been demonstrated in children, adolescents, and adults. There is evidence that adolescents may be particularly sensitive to these sequelae. Galling and colleagues found that adolescents treated with antipsychotics were at greater risk of developing type 2 diabetes mellitus as compared to both healthy controls and controls with psychiatric illness [18]. Kryzhanovskaya et al, looking at metabolic parameters associated with olanzapine use in adolescents and adults, found that both adolescents and adults showed metabolic sequelae and that adolescents had larger changes in weight gain and lipids compared with adults [19].

The mechanism of SGA impact on metabolic parameters remains incompletely understood, though is thought to be multifactorial, mediated primarily through weight gain with increased adiposity. SGA histamine (H1) receptor binding affinity is implicated in weight gain [20] and 5HT2C antagonism may also lead to an increase in appetite [21]. Other proposed mechanisms include changes in appetite through leptin resistance or decreased sensitivity to leptin, the hormone that mediates satiety. Zhang and colleagues found an increase in leptin levels in patients with schizophrenia prescribed antipsychotics, suggesting leptin dysregulation [21]. Additional studies suggest metabolic disturbances independent of weight gain including direct effects of SGAs on glucose and lipid metabolism [22].

If a person experiences a weight gain of 5% after starting an SGA, it is recommended that the dose be decreased or that they be switched to another psychotropic medication with lower likelihood of metabolic consequences [23]. The effectiveness of switching antipsychotic medications to one with lower metabolic risk to improve weight and lipids has been previously demonstrated [24]. If a patient develops diabetes in the context of an antipsychotic prescription, it is also recommended that the medication be switched to an antipsychotic with less risk of hyperglycemia, and if not possible, to target additional risk factors including weight, poor nutrition, and sedentary lifestyle [25]. The decision to switch medications or decrease dosage is often weighed against the psychiatric stability of the person and their overall response to the medication in the context of their treatment course [14].

Metabolic Monitoring

Given the increased risk of metabolic syndrome among people with SMI, and the association of metabolic syndrome with increased morbidity and all-cause mortality, there has been a growing awareness of the importance of screening for metabolic syndrome among people with SMI. Metabolic monitoring involves routine screening for metabolic parameters and assessment of metabolic risk factors among people with SMI who are prescribed antipsychotic medications. Various practice guidelines have been developed in the United States and internationally to assess for metabolic risk factors in people prescribed antipsychotic medications [26]. Current metabolic monitoring guidelines in the United States stem from 2004 consensus recommendations of the American Diabetes Association and American Psychiatric Association along with the American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity for metabolic monitoring among people prescribed SGAs [23]. These recommendations include a time line for routine monitoring of weight/body mass index, waist circumference, blood pressure, fasting blood glucose or hemoglobin A1c, and fasting lipids (Table 2). Guidelines recommend screening at baseline, more frequently within the first 3 months, and then annually [23].

Though guidelines recommend measurement of waist circumference as a marker for metabolic health, body mass index is often used alone as a measure of obesity [27,28]. This may be due to the relative ease of obtaining weight over waist circumference. For example, weight is more likely to be part of clinic workflows and many providers may not be accustomed to measuring waist circumference. However, waist circumference does provide additional information regarding metabolic health [29], as central adiposity is a marker of cardiometabolic risk and related to insulin resistance [21]. Further modifications of the guidelines have included ethnicity-specific waist measurements [30].

There is evidence that non-fasting lipids may be substituted for fasting lipid panels, particularly for patients who may have difficulty adhering to fasting due to cognitive difficulties. Vanderlip and colleagues argue that fasting serum cholesterol panels are not necessary for screening for dyslipidemia given that non-HDL cholesterol is calculated based on total cholesterol and HDL, which do not substantially differ between fasting and non-fasting values [31]. Hemoglobin A1c is recommended as a screening test for blood glucose abnormalities given that it does not require a fasting state and can therefore be more easily obtained for many patients. The choice to obtain a fasting blood glucose versus hemoglobin A1c may depend on multiple factors, including that a person can adhere to fasting and the cost of the laboratory test.

Routine monitoring of metabolic parameters is an integral step in targeting interventions to treat metabolic syndrome. These interventions include lifestyle modifications and evidence-based treatment guidelines for management of associated dyslipidemia, hypertension, and type 2 diabetes mellitus.

Current Metabolic Screening Practices

Despite the presence of defined guidelines, estimates show persistently low rates of metabolic monitoring among adults prescribed SGAs [32]. One study of 3 state Medicaid programs showed little to no improvement in screening rates for glucose and lipids post dissemination of the 2004 APA/ADA guidelines [33]. They noted a nonsignificant change in rates of glucose testing from 27% to 30% and small change in lipid testing from 10% to 11% among patients prescribed SGAs between 2002–2005 [33]. Examining screening rates among Medicaid recipients in Missouri between 2010–2012, Morrato and colleagues found glucose testing rates of 80% with lipid testing remaining at 41% [34]. A retrospective study of adult Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 showed rates of screening for lipids and glucose to increase over time; glucose monitoring increased from 56.6% to 72.6% and lipids from 38.3% to 41.2% [35]. A review by Mangurian and colleagues suggested rates of glucose (fasting blood glucose or hemoglobin A1c) and lipid screening as low as 30% among people prescribed antipsychotic medications [14]. Furthermore, they underscore the impact of low screening rates, stating that if 20% of adults with SMI have diabetes and 70% remain unscreened, then approximately 2 million adults with SMI and diabetes in the United States would not be identified within our current system [14].

Higher rates of screening have been shown for Medicaid populations than commercially insured populations [36]. Haupt et al compared lipid and glucose testing pre- and post- ADA/APA guideline implementation among commercially insured patients. They found an increase from 8.4% to 10.5% post guideline implementation for baseline lipid testing and from 6.8% to 9.0% for lipid testing at 12 weeks post-antipsychotic initiation [36]. Baseline glucose testing increased from 17.3% to 21.8% and from 14.1% to 17.9 % at 12-week post antipsychotic initiation. In alignment with findings from other studies, testing rates were particularly low for children [36].

Low screening rates have been found among children and adolescents prescribed SGAs [37] despite evidence that youth may be at risk of developing more significant metabolic sequelae from SGAs [19]. Edelsohn and colleagues found an increase from 30% to 50% for glucose screening and from 19% to 28% for lipid screening among youth Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 [35]. Connolly and colleagues reported on metabolic screening rates for children and adolescents prescribed SGAs over the 8 years following announcement of the 2004 ADA/APA guidelines. Using insurance claims data, they found screening rates for fasting blood glucose and hemoglobin A1c temporarily increased following guideline dissemination, then dropped during the period 2004–2008, and again increased slightly [38].

Barriers to Screening

Barriers to screening exist at the level of the individual patient and provider as well as at the clinic and larger systems levels. Lack of provider awareness of evidence-based guidelines for metabolic monitoring despite the presence of the 2004 ADA/APA guidelines has been cited by researchers as an impediment to screening. In a survey of primary care clinicians in San Francisco, Mangurian et al found that 40% of primary care providers did not know about the ADA/APA consensus guidelines for metabolic monitoring. The same survey of primary care providers identified additional impediments to screening, including obstacles to collaboration with psychiatric providers and to scheduling patients for psychiatric follow-up [39]. Another clinician survey conducted by Parameswaran et al found that psychiatrists viewed psychiatric illness severity, lack of staff time, and lack of clinician time as significant barriers to metabolic screening. In addition, clinicians identified factors related to the complexity of coordinating care across systems as obstacles; these included barriers to coordinating follow-up with medical providers, long wait times for patients to see medical providers, and difficulty collaborating with medical providers [40].

Other systems-level barriers include lack of a population-based approach to screening (eg, registries) and lack of electronic record integration, which impedes the ability of primary care and psychiatry providers to share information related to the ordering of metabolic screening tests and prescribing of medications [41]. Mangurian calls for integration of electronic medical record systems between primary care and psychiatry, a population-based approach to metabolic monitoring utilizing registries and other elements of collaborative care models, and primary care consultation to aid in the treatment of metabolic abnormalities [41]. Amiel et al point to systems-level factors “including but not limited to … poor access to general medical services, inadequate medical record-keeping infrastructure, lack of in-system compliance incentives and lack of centralized oversight” [26].

Based on their experience implementing a computer-based intervention for metabolic monitoring, Lai et al propose that the following factors may influence providers’ engagement in metabolic monitoring: lack of apparent symptoms to suggest metabolic syndrome, patients’ lack of engagement in care, and poor access to care. They identify additional factors at the clinician level to include under-recognition of the need for metabolic monitoring, lack of familiarity with screening guidelines, lack of agreement with guidelines, and the potential for individual clinicians to forget to order tests [42]. At the systems-level, they identify the absence of ongoing training as a potential reason why sustained testing was not observed in their intervention [42].

In a 2011 survey of providers prescribing antipsychotic medication to Medicaid beneficiaries in Missouri, Morrato and colleagues found that factors limiting frequency of health care utilization were closely linked to lack of metabolic testing. They also noted disparities in screening guidelines may lead to lack of routine metabolic monitoring; providers may screen based on prescribed medication, diagnosis, or other risk factor based stratification depending on the guidelines followed [34].

Current Unmet Needs

Vulnerable Populations

Though rates of metabolic screening remain low for all groups prescribed antipsychotic medications, studies have consistently shown low rates of screening among children and adolescents [35,36]. Edelsohn and colleagues hypothesize that the cause of these low rates is multifactorial, including that guardians may be reluctant to have young people undergo blood draws [35]. Morrato and colleagues suggest that policymakers should focus initiatives on younger, healthier adults, who they found to have lower rates of screening [37].

Racial and ethnic minorities with SMI constitute another particularly vulnerable population, with some studies showing an increased risk of metabolic sequelae and lower likelihood of treatment for diabetes and other metabolic derangements among African American and Latino populations with SMI [14,43,44].

Integration of Care

Lack of widespread integration of care between mental health and primary care remains another unmet need [41]. Hasnain and colleagues recommend improved communication between mental health and primary care clinicians to coordinate care to improve rates of monitoring, facilitate early follow-up of metabolic abnormalities, and avoid duplication of monitoring efforts [45]. Morrato and colleagues recommend that efforts to increase rates of metabolic monitoring be targeted not only to providers practicing in community mental health centers, but also to other practice settings including primary care. They found that for 75% of people prescribed antipsychotic medications, the prescriptions were started by prescribing providers who practiced outside of a community mental health center [34] and recommend that educational initiatives and performance improvement interventions broaden to include primary care and other care settings [34].

Potential Interventions for Improvement

Early interventions to improve metabolic screening rates have included educational initiatives to teach providers about consensus guidelines. However, initiatives to educate clinicians on metabolic monitoring have shown to be inadequate to significantly improve rates of screening [33]. Therefore, subsequent initiatives have sought to influence screening rates by targeting behavior of individual clinicians with point-of-care tools, electronic reminders, or through systems-level reorganization towards population-based care [27,42,46].

A variety of clinical interventions focus on technologies that remind clinicians to order metabolic monitoring tests according to screening guidelines. One public mental health service in Queensland, Australia, created a standardized metabolic monitoring form to be uploaded to the electronic medical record. In their implementation study examining the efficacy of the metabolic monitoring form, they found that only 36% of the forms contained data. When data were recorded, there were significantly higher rates of documentation of measurements (weight, body mass index, blood pressure) rather than laboratory tests (including lipids and fasting blood glucose) [27].

Computerized reminder systems for metabolic monitoring have been studied in both outpatient and inpatient settings. Lai and colleagues studied the impact of a computerized reminder system on lab monitoring for metabolic parameters among outpatients with schizophrenia prescribed SGAs [42]. This intervention also included an educational component with discussion of metabolic monitoring for people prescribed SGAs at meetings with attending psychiatrists. Computer reminders were displayed when a provider failed to order fasting plasma glucose or lipids (cholesterol, triglyceride) for patients prescribed clozapine, olanzapine, quetiapine, or risperidone. The study found a statistically significant improvement in laboratory metabolic screening for patients prescribed SGAs after implementation, with the greatest impact 6-months post-intervention, though with subsequent decline in screening rates [42].

Psychiatric inpatient hospitalizations provide an opportunity to obtain testing at the time of treatment initiation and also for ongoing monitoring in a location where fasting laboratory tests may be more easily obtained given onsite phlebotomy. One intervention targeting psychiatric inpatients utilized a computerized physician order entry system with the goal to improve metabolic screening among patients prescribed SGAs. Set in a large academic medical setting, the study found inpatient metabolic monitoring rates did not change significantly after implementation of these pop-up computer alerts, comparing rates immediately and 4 years after implementation [46].

There has been increasing focus on integrating mental health and medical care in an effort to improve the health of people with mental illness [47]. Mangurian and colleagues found that the likelihood of diabetes mellitus screening doubled for people with severe mental illness who were seen for at least one primary care visit in addition to mental health treatment [48]. Haupt similarly found higher rates of metabolic screening among patients who had greater than one primary care visit [36]. Models of integration include both integration of medical services into mental health treatment as well as incorporation of mental health services into primary care. For people with SMI, integration efforts have largely focused on integrating primary care services into community mental health settings [49]. The Substance Abuse and Mental Health Service Administration’s (SAMHSA) Primary and Behavioral Health Care Integration (PBHCI) grants program and the Affordable Care Act’s Health Home Initiative are examples of federal incentive programs for improved integration between behavioral health and primary care [49]. In their evaluation of the PBHCI grant program, Scharf and colleagues presented findings that patients at 3 matched clinics with PCBHI grants showed improvement in some lipids, diastolic blood pressure, and fasting blood glucose, though not smoking or body mass index [50].

Conclusion

Several risk factors contribute to an increase in cardiometabolic risk for people with severe mental illness, including poor nutrition, sedentary lifestyle, social determinants of health, and prescribed antipsychotic medications. Metabolic monitoring aims to address these health disparities by screening for metabolic parameters and identifying abnormalities in order to target appropriate health interventions. Screening rates for metabolic parameters remain low for children, adolescents, and adults prescribed second-generation antipsychotics despite published guidelines and clinical interventions to improve screening. More system-wide interventions to improve collaboration between mental health and primary care are needed to enhance screening and prevent cardiovascular disease risk in this vulnerable population.

Corresponding author: Carrie Cunningham, MD, MPH, Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Suite 7M, San Francisco, CA 94110, [email protected].

Funding/support: Dr. Cunningham was supported by the UCSF-Zuckerberg San Francisco General Public Psychiatry Fellowship. Mr. Riano was supported by the NIH Center Grant from the National Institute of Diabetes and Digestive and Kidney Diseases for The Health Delivery Systems-Center for Diabetes Translational Research (CDTR) (P30DK092924) and by the UCSF-San Francisco General Hospital Public Psychiatry Fellowship. Dr. Mangurian received support from a grant from the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R03 DK101857), as well as NIH Career Development Award (K23MH093689).

From the University of California San Francisco, Department of Psychiatry, Weill Institute for Neurosciences, San Francisco, CA.

Abstract

• Objective: To review screening for metabolic syndrome in people with severe mental illness (SMI).
• Methods: Review of the literature.
• Results: Despite evidence-based metabolic screening guidelines, rates of metabolic screening remain low among people with SMI. Barriers to screening exist at the individual, organizational, and systems levels. Interventions to address these barriers range from point-of-care tools to systems-level reorganization towards population-based care.
• Conclusion: Greater systems-level interventions, particularly those that improve collaboration between mental health and primary care, are needed to improve metabolic monitoring and identify cardiovascular disease risk among people with SMI.

Key words: metabolic monitoring; severe mental illness; metabolic syndrome; integrated care.

People with severe mental illness (SMI) have a life expectancy 10 to 20 years shorter than the general population, and cardiometabolic risk factors contribute significantly to the increased morbidity and mortality seen in this population. To address this health disparity, metabolic monitoring guidelines have been proposed as a mechanism to identify metabolic risk factors. This paper aims to discuss metabolic syndrome and its risk factors, describe metabolic monitoring including current rates and barriers to screening, and identify interventions that may improve rates of screening for metabolic syndrome among people with SMI.

Metabolic syndrome has been conceptualized as a state of chronic low-grade inflammation and hypercoagulation associated with hypertension, dyslipidemia, glucose intolerance, insulin resistance, and visceral adiposity [1]. Per the modified National Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) guidelines, metabolic syndrome is defined as the presence of 3 of the following 5 parameters: (1) blood glucose > 100 mg/dL (or a person is taking a hypoglycemic medication), (2) high density lipoprotein (HDL) < 40 mg/dL in men or < 50 mg/dL in women, (3) triglycerides > 150 mg/dL (or taking a lipid lowering agent), (4) waist circumference > 40 inches in men or > 35 inches in women, and/or (5) blood pressure > 130/85 mm Hg (or taking an antihypertensive medication) [2,3] (Table 1).

Epidemiology and Risk Factors

An estimated 34% of people in the United States meet criteria for metabolic syndrome, with worldwide estimates ranging widely from less than 10% to 84%. People with SMI (eg, bipolar disorder, schizoaffective disorder, schizophrenia) are at even greater risk of developing metabolic syndrome than the general population [4,5]. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study demonstrated metabolic syndrome rates of 40.9% and 51.6% in men and women with a diagnosis of schizophrenia, respectively [6]. In a systematic review of bipolar disorder and metabolic syndrome, people with bipolar disorder showed higher rates of hypertriglyceridemia and hyperglycemia than controls [5].

People with SMI have been found to have significantly increased morbidity and mortality as compared to people without an SMI diagnosis, much of which has been attributed to increased cardiometabolic risk related to multiple factors [7]. Among adults with schizophrenia receiving Medicaid, Olfson et al found diabetes mellitus, ischemic heart disease, nonischemic heart disease, and cerebrovascular accident to be among the top 10 causes of death [7]. The mortality rate for people with SMI is estimated to be 2 to 3 times higher than the general population, and the life expectancy for people with SMI is estimated to be 10 to 20 years shorter than the general population [8–10]. Contributors to this disparity include modifiable health-related behaviors, social determinants of health, and iatrogenic sequelae of prescribed medications. Behavioral factors include poor nutrition, food insecurity, sedentary lifestyle, and smoking; side effects of commonly prescribed psychotropic medications, most notably atypical antipsychotics and mood stabilizers, also contribute to this disparity [7,11].

Both first- and second-generation antipsychotics have been shown to be associated with metabolic sequelae, including weight gain, elevated blood glucose, and insulin resistance [12–14]. Among psychotropic medications, the atypical or second-generation antipsychotics (SGAs) are a class of medications known to have significant metabolic side effects [15,16]. Studies comparing the metabolic consequences of individual SGAs have found significant variation within the class. Clozapine, olanzapine, quetiapine, and risperidone show significant likelihood of weight gain, hyperlipidemia, and hyperglycemia as well as other metabolic consequences [17]. Aripiprazole, lurasidone, and ziprasidone have shown little to no risk of metabolic sequelae [17].

Metabolic side effects of SGAs have been demonstrated in children, adolescents, and adults. There is evidence that adolescents may be particularly sensitive to these sequelae. Galling and colleagues found that adolescents treated with antipsychotics were at greater risk of developing type 2 diabetes mellitus as compared to both healthy controls and controls with psychiatric illness [18]. Kryzhanovskaya et al, looking at metabolic parameters associated with olanzapine use in adolescents and adults, found that both adolescents and adults showed metabolic sequelae and that adolescents had larger changes in weight gain and lipids compared with adults [19].

The mechanism of SGA impact on metabolic parameters remains incompletely understood, though is thought to be multifactorial, mediated primarily through weight gain with increased adiposity. SGA histamine (H1) receptor binding affinity is implicated in weight gain [20] and 5HT2C antagonism may also lead to an increase in appetite [21]. Other proposed mechanisms include changes in appetite through leptin resistance or decreased sensitivity to leptin, the hormone that mediates satiety. Zhang and colleagues found an increase in leptin levels in patients with schizophrenia prescribed antipsychotics, suggesting leptin dysregulation [21]. Additional studies suggest metabolic disturbances independent of weight gain including direct effects of SGAs on glucose and lipid metabolism [22].

If a person experiences a weight gain of 5% after starting an SGA, it is recommended that the dose be decreased or that they be switched to another psychotropic medication with lower likelihood of metabolic consequences [23]. The effectiveness of switching antipsychotic medications to one with lower metabolic risk to improve weight and lipids has been previously demonstrated [24]. If a patient develops diabetes in the context of an antipsychotic prescription, it is also recommended that the medication be switched to an antipsychotic with less risk of hyperglycemia, and if not possible, to target additional risk factors including weight, poor nutrition, and sedentary lifestyle [25]. The decision to switch medications or decrease dosage is often weighed against the psychiatric stability of the person and their overall response to the medication in the context of their treatment course [14].

Metabolic Monitoring

Given the increased risk of metabolic syndrome among people with SMI, and the association of metabolic syndrome with increased morbidity and all-cause mortality, there has been a growing awareness of the importance of screening for metabolic syndrome among people with SMI. Metabolic monitoring involves routine screening for metabolic parameters and assessment of metabolic risk factors among people with SMI who are prescribed antipsychotic medications. Various practice guidelines have been developed in the United States and internationally to assess for metabolic risk factors in people prescribed antipsychotic medications [26]. Current metabolic monitoring guidelines in the United States stem from 2004 consensus recommendations of the American Diabetes Association and American Psychiatric Association along with the American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity for metabolic monitoring among people prescribed SGAs [23]. These recommendations include a time line for routine monitoring of weight/body mass index, waist circumference, blood pressure, fasting blood glucose or hemoglobin A1c, and fasting lipids (Table 2). Guidelines recommend screening at baseline, more frequently within the first 3 months, and then annually [23].

Though guidelines recommend measurement of waist circumference as a marker for metabolic health, body mass index is often used alone as a measure of obesity [27,28]. This may be due to the relative ease of obtaining weight over waist circumference. For example, weight is more likely to be part of clinic workflows and many providers may not be accustomed to measuring waist circumference. However, waist circumference does provide additional information regarding metabolic health [29], as central adiposity is a marker of cardiometabolic risk and related to insulin resistance [21]. Further modifications of the guidelines have included ethnicity-specific waist measurements [30].

There is evidence that non-fasting lipids may be substituted for fasting lipid panels, particularly for patients who may have difficulty adhering to fasting due to cognitive difficulties. Vanderlip and colleagues argue that fasting serum cholesterol panels are not necessary for screening for dyslipidemia given that non-HDL cholesterol is calculated based on total cholesterol and HDL, which do not substantially differ between fasting and non-fasting values [31]. Hemoglobin A1c is recommended as a screening test for blood glucose abnormalities given that it does not require a fasting state and can therefore be more easily obtained for many patients. The choice to obtain a fasting blood glucose versus hemoglobin A1c may depend on multiple factors, including that a person can adhere to fasting and the cost of the laboratory test.

Routine monitoring of metabolic parameters is an integral step in targeting interventions to treat metabolic syndrome. These interventions include lifestyle modifications and evidence-based treatment guidelines for management of associated dyslipidemia, hypertension, and type 2 diabetes mellitus.

Current Metabolic Screening Practices

Despite the presence of defined guidelines, estimates show persistently low rates of metabolic monitoring among adults prescribed SGAs [32]. One study of 3 state Medicaid programs showed little to no improvement in screening rates for glucose and lipids post dissemination of the 2004 APA/ADA guidelines [33]. They noted a nonsignificant change in rates of glucose testing from 27% to 30% and small change in lipid testing from 10% to 11% among patients prescribed SGAs between 2002–2005 [33]. Examining screening rates among Medicaid recipients in Missouri between 2010–2012, Morrato and colleagues found glucose testing rates of 80% with lipid testing remaining at 41% [34]. A retrospective study of adult Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 showed rates of screening for lipids and glucose to increase over time; glucose monitoring increased from 56.6% to 72.6% and lipids from 38.3% to 41.2% [35]. A review by Mangurian and colleagues suggested rates of glucose (fasting blood glucose or hemoglobin A1c) and lipid screening as low as 30% among people prescribed antipsychotic medications [14]. Furthermore, they underscore the impact of low screening rates, stating that if 20% of adults with SMI have diabetes and 70% remain unscreened, then approximately 2 million adults with SMI and diabetes in the United States would not be identified within our current system [14].

Higher rates of screening have been shown for Medicaid populations than commercially insured populations [36]. Haupt et al compared lipid and glucose testing pre- and post- ADA/APA guideline implementation among commercially insured patients. They found an increase from 8.4% to 10.5% post guideline implementation for baseline lipid testing and from 6.8% to 9.0% for lipid testing at 12 weeks post-antipsychotic initiation [36]. Baseline glucose testing increased from 17.3% to 21.8% and from 14.1% to 17.9 % at 12-week post antipsychotic initiation. In alignment with findings from other studies, testing rates were particularly low for children [36].

Low screening rates have been found among children and adolescents prescribed SGAs [37] despite evidence that youth may be at risk of developing more significant metabolic sequelae from SGAs [19]. Edelsohn and colleagues found an increase from 30% to 50% for glucose screening and from 19% to 28% for lipid screening among youth Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 [35]. Connolly and colleagues reported on metabolic screening rates for children and adolescents prescribed SGAs over the 8 years following announcement of the 2004 ADA/APA guidelines. Using insurance claims data, they found screening rates for fasting blood glucose and hemoglobin A1c temporarily increased following guideline dissemination, then dropped during the period 2004–2008, and again increased slightly [38].

Barriers to Screening

Barriers to screening exist at the level of the individual patient and provider as well as at the clinic and larger systems levels. Lack of provider awareness of evidence-based guidelines for metabolic monitoring despite the presence of the 2004 ADA/APA guidelines has been cited by researchers as an impediment to screening. In a survey of primary care clinicians in San Francisco, Mangurian et al found that 40% of primary care providers did not know about the ADA/APA consensus guidelines for metabolic monitoring. The same survey of primary care providers identified additional impediments to screening, including obstacles to collaboration with psychiatric providers and to scheduling patients for psychiatric follow-up [39]. Another clinician survey conducted by Parameswaran et al found that psychiatrists viewed psychiatric illness severity, lack of staff time, and lack of clinician time as significant barriers to metabolic screening. In addition, clinicians identified factors related to the complexity of coordinating care across systems as obstacles; these included barriers to coordinating follow-up with medical providers, long wait times for patients to see medical providers, and difficulty collaborating with medical providers [40].

Other systems-level barriers include lack of a population-based approach to screening (eg, registries) and lack of electronic record integration, which impedes the ability of primary care and psychiatry providers to share information related to the ordering of metabolic screening tests and prescribing of medications [41]. Mangurian calls for integration of electronic medical record systems between primary care and psychiatry, a population-based approach to metabolic monitoring utilizing registries and other elements of collaborative care models, and primary care consultation to aid in the treatment of metabolic abnormalities [41]. Amiel et al point to systems-level factors “including but not limited to … poor access to general medical services, inadequate medical record-keeping infrastructure, lack of in-system compliance incentives and lack of centralized oversight” [26].

Based on their experience implementing a computer-based intervention for metabolic monitoring, Lai et al propose that the following factors may influence providers’ engagement in metabolic monitoring: lack of apparent symptoms to suggest metabolic syndrome, patients’ lack of engagement in care, and poor access to care. They identify additional factors at the clinician level to include under-recognition of the need for metabolic monitoring, lack of familiarity with screening guidelines, lack of agreement with guidelines, and the potential for individual clinicians to forget to order tests [42]. At the systems-level, they identify the absence of ongoing training as a potential reason why sustained testing was not observed in their intervention [42].

In a 2011 survey of providers prescribing antipsychotic medication to Medicaid beneficiaries in Missouri, Morrato and colleagues found that factors limiting frequency of health care utilization were closely linked to lack of metabolic testing. They also noted disparities in screening guidelines may lead to lack of routine metabolic monitoring; providers may screen based on prescribed medication, diagnosis, or other risk factor based stratification depending on the guidelines followed [34].

Current Unmet Needs

Vulnerable Populations

Though rates of metabolic screening remain low for all groups prescribed antipsychotic medications, studies have consistently shown low rates of screening among children and adolescents [35,36]. Edelsohn and colleagues hypothesize that the cause of these low rates is multifactorial, including that guardians may be reluctant to have young people undergo blood draws [35]. Morrato and colleagues suggest that policymakers should focus initiatives on younger, healthier adults, who they found to have lower rates of screening [37].

Racial and ethnic minorities with SMI constitute another particularly vulnerable population, with some studies showing an increased risk of metabolic sequelae and lower likelihood of treatment for diabetes and other metabolic derangements among African American and Latino populations with SMI [14,43,44].

Integration of Care

Lack of widespread integration of care between mental health and primary care remains another unmet need [41]. Hasnain and colleagues recommend improved communication between mental health and primary care clinicians to coordinate care to improve rates of monitoring, facilitate early follow-up of metabolic abnormalities, and avoid duplication of monitoring efforts [45]. Morrato and colleagues recommend that efforts to increase rates of metabolic monitoring be targeted not only to providers practicing in community mental health centers, but also to other practice settings including primary care. They found that for 75% of people prescribed antipsychotic medications, the prescriptions were started by prescribing providers who practiced outside of a community mental health center [34] and recommend that educational initiatives and performance improvement interventions broaden to include primary care and other care settings [34].

Potential Interventions for Improvement

Early interventions to improve metabolic screening rates have included educational initiatives to teach providers about consensus guidelines. However, initiatives to educate clinicians on metabolic monitoring have shown to be inadequate to significantly improve rates of screening [33]. Therefore, subsequent initiatives have sought to influence screening rates by targeting behavior of individual clinicians with point-of-care tools, electronic reminders, or through systems-level reorganization towards population-based care [27,42,46].

A variety of clinical interventions focus on technologies that remind clinicians to order metabolic monitoring tests according to screening guidelines. One public mental health service in Queensland, Australia, created a standardized metabolic monitoring form to be uploaded to the electronic medical record. In their implementation study examining the efficacy of the metabolic monitoring form, they found that only 36% of the forms contained data. When data were recorded, there were significantly higher rates of documentation of measurements (weight, body mass index, blood pressure) rather than laboratory tests (including lipids and fasting blood glucose) [27].

Computerized reminder systems for metabolic monitoring have been studied in both outpatient and inpatient settings. Lai and colleagues studied the impact of a computerized reminder system on lab monitoring for metabolic parameters among outpatients with schizophrenia prescribed SGAs [42]. This intervention also included an educational component with discussion of metabolic monitoring for people prescribed SGAs at meetings with attending psychiatrists. Computer reminders were displayed when a provider failed to order fasting plasma glucose or lipids (cholesterol, triglyceride) for patients prescribed clozapine, olanzapine, quetiapine, or risperidone. The study found a statistically significant improvement in laboratory metabolic screening for patients prescribed SGAs after implementation, with the greatest impact 6-months post-intervention, though with subsequent decline in screening rates [42].

Psychiatric inpatient hospitalizations provide an opportunity to obtain testing at the time of treatment initiation and also for ongoing monitoring in a location where fasting laboratory tests may be more easily obtained given onsite phlebotomy. One intervention targeting psychiatric inpatients utilized a computerized physician order entry system with the goal to improve metabolic screening among patients prescribed SGAs. Set in a large academic medical setting, the study found inpatient metabolic monitoring rates did not change significantly after implementation of these pop-up computer alerts, comparing rates immediately and 4 years after implementation [46].

There has been increasing focus on integrating mental health and medical care in an effort to improve the health of people with mental illness [47]. Mangurian and colleagues found that the likelihood of diabetes mellitus screening doubled for people with severe mental illness who were seen for at least one primary care visit in addition to mental health treatment [48]. Haupt similarly found higher rates of metabolic screening among patients who had greater than one primary care visit [36]. Models of integration include both integration of medical services into mental health treatment as well as incorporation of mental health services into primary care. For people with SMI, integration efforts have largely focused on integrating primary care services into community mental health settings [49]. The Substance Abuse and Mental Health Service Administration’s (SAMHSA) Primary and Behavioral Health Care Integration (PBHCI) grants program and the Affordable Care Act’s Health Home Initiative are examples of federal incentive programs for improved integration between behavioral health and primary care [49]. In their evaluation of the PBHCI grant program, Scharf and colleagues presented findings that patients at 3 matched clinics with PCBHI grants showed improvement in some lipids, diastolic blood pressure, and fasting blood glucose, though not smoking or body mass index [50].

Conclusion

Several risk factors contribute to an increase in cardiometabolic risk for people with severe mental illness, including poor nutrition, sedentary lifestyle, social determinants of health, and prescribed antipsychotic medications. Metabolic monitoring aims to address these health disparities by screening for metabolic parameters and identifying abnormalities in order to target appropriate health interventions. Screening rates for metabolic parameters remain low for children, adolescents, and adults prescribed second-generation antipsychotics despite published guidelines and clinical interventions to improve screening. More system-wide interventions to improve collaboration between mental health and primary care are needed to enhance screening and prevent cardiovascular disease risk in this vulnerable population.

Corresponding author: Carrie Cunningham, MD, MPH, Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Suite 7M, San Francisco, CA 94110, [email protected].

Funding/support: Dr. Cunningham was supported by the UCSF-Zuckerberg San Francisco General Public Psychiatry Fellowship. Mr. Riano was supported by the NIH Center Grant from the National Institute of Diabetes and Digestive and Kidney Diseases for The Health Delivery Systems-Center for Diabetes Translational Research (CDTR) (P30DK092924) and by the UCSF-San Francisco General Hospital Public Psychiatry Fellowship. Dr. Mangurian received support from a grant from the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R03 DK101857), as well as NIH Career Development Award (K23MH093689).

From the University of California San Francisco, Department of Psychiatry, Weill Institute for Neurosciences, San Francisco, CA.

Abstract

• Objective: To review screening for metabolic syndrome in people with severe mental illness (SMI).
• Methods: Review of the literature.
• Results: Despite evidence-based metabolic screening guidelines, rates of metabolic screening remain low among people with SMI. Barriers to screening exist at the individual, organizational, and systems levels. Interventions to address these barriers range from point-of-care tools to systems-level reorganization towards population-based care.
• Conclusion: Greater systems-level interventions, particularly those that improve collaboration between mental health and primary care, are needed to improve metabolic monitoring and identify cardiovascular disease risk among people with SMI.

Key words: metabolic monitoring; severe mental illness; metabolic syndrome; integrated care.

People with severe mental illness (SMI) have a life expectancy 10 to 20 years shorter than the general population, and cardiometabolic risk factors contribute significantly to the increased morbidity and mortality seen in this population. To address this health disparity, metabolic monitoring guidelines have been proposed as a mechanism to identify metabolic risk factors. This paper aims to discuss metabolic syndrome and its risk factors, describe metabolic monitoring including current rates and barriers to screening, and identify interventions that may improve rates of screening for metabolic syndrome among people with SMI.

Metabolic syndrome has been conceptualized as a state of chronic low-grade inflammation and hypercoagulation associated with hypertension, dyslipidemia, glucose intolerance, insulin resistance, and visceral adiposity [1]. Per the modified National Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) guidelines, metabolic syndrome is defined as the presence of 3 of the following 5 parameters: (1) blood glucose > 100 mg/dL (or a person is taking a hypoglycemic medication), (2) high density lipoprotein (HDL) < 40 mg/dL in men or < 50 mg/dL in women, (3) triglycerides > 150 mg/dL (or taking a lipid lowering agent), (4) waist circumference > 40 inches in men or > 35 inches in women, and/or (5) blood pressure > 130/85 mm Hg (or taking an antihypertensive medication) [2,3] (Table 1).

Epidemiology and Risk Factors

An estimated 34% of people in the United States meet criteria for metabolic syndrome, with worldwide estimates ranging widely from less than 10% to 84%. People with SMI (eg, bipolar disorder, schizoaffective disorder, schizophrenia) are at even greater risk of developing metabolic syndrome than the general population [4,5]. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study demonstrated metabolic syndrome rates of 40.9% and 51.6% in men and women with a diagnosis of schizophrenia, respectively [6]. In a systematic review of bipolar disorder and metabolic syndrome, people with bipolar disorder showed higher rates of hypertriglyceridemia and hyperglycemia than controls [5].

People with SMI have been found to have significantly increased morbidity and mortality as compared to people without an SMI diagnosis, much of which has been attributed to increased cardiometabolic risk related to multiple factors [7]. Among adults with schizophrenia receiving Medicaid, Olfson et al found diabetes mellitus, ischemic heart disease, nonischemic heart disease, and cerebrovascular accident to be among the top 10 causes of death [7]. The mortality rate for people with SMI is estimated to be 2 to 3 times higher than the general population, and the life expectancy for people with SMI is estimated to be 10 to 20 years shorter than the general population [8–10]. Contributors to this disparity include modifiable health-related behaviors, social determinants of health, and iatrogenic sequelae of prescribed medications. Behavioral factors include poor nutrition, food insecurity, sedentary lifestyle, and smoking; side effects of commonly prescribed psychotropic medications, most notably atypical antipsychotics and mood stabilizers, also contribute to this disparity [7,11].

Both first- and second-generation antipsychotics have been shown to be associated with metabolic sequelae, including weight gain, elevated blood glucose, and insulin resistance [12–14]. Among psychotropic medications, the atypical or second-generation antipsychotics (SGAs) are a class of medications known to have significant metabolic side effects [15,16]. Studies comparing the metabolic consequences of individual SGAs have found significant variation within the class. Clozapine, olanzapine, quetiapine, and risperidone show significant likelihood of weight gain, hyperlipidemia, and hyperglycemia as well as other metabolic consequences [17]. Aripiprazole, lurasidone, and ziprasidone have shown little to no risk of metabolic sequelae [17].

Metabolic side effects of SGAs have been demonstrated in children, adolescents, and adults. There is evidence that adolescents may be particularly sensitive to these sequelae. Galling and colleagues found that adolescents treated with antipsychotics were at greater risk of developing type 2 diabetes mellitus as compared to both healthy controls and controls with psychiatric illness [18]. Kryzhanovskaya et al, looking at metabolic parameters associated with olanzapine use in adolescents and adults, found that both adolescents and adults showed metabolic sequelae and that adolescents had larger changes in weight gain and lipids compared with adults [19].

The mechanism of SGA impact on metabolic parameters remains incompletely understood, though is thought to be multifactorial, mediated primarily through weight gain with increased adiposity. SGA histamine (H1) receptor binding affinity is implicated in weight gain [20] and 5HT2C antagonism may also lead to an increase in appetite [21]. Other proposed mechanisms include changes in appetite through leptin resistance or decreased sensitivity to leptin, the hormone that mediates satiety. Zhang and colleagues found an increase in leptin levels in patients with schizophrenia prescribed antipsychotics, suggesting leptin dysregulation [21]. Additional studies suggest metabolic disturbances independent of weight gain including direct effects of SGAs on glucose and lipid metabolism [22].

If a person experiences a weight gain of 5% after starting an SGA, it is recommended that the dose be decreased or that they be switched to another psychotropic medication with lower likelihood of metabolic consequences [23]. The effectiveness of switching antipsychotic medications to one with lower metabolic risk to improve weight and lipids has been previously demonstrated [24]. If a patient develops diabetes in the context of an antipsychotic prescription, it is also recommended that the medication be switched to an antipsychotic with less risk of hyperglycemia, and if not possible, to target additional risk factors including weight, poor nutrition, and sedentary lifestyle [25]. The decision to switch medications or decrease dosage is often weighed against the psychiatric stability of the person and their overall response to the medication in the context of their treatment course [14].

Metabolic Monitoring

Given the increased risk of metabolic syndrome among people with SMI, and the association of metabolic syndrome with increased morbidity and all-cause mortality, there has been a growing awareness of the importance of screening for metabolic syndrome among people with SMI. Metabolic monitoring involves routine screening for metabolic parameters and assessment of metabolic risk factors among people with SMI who are prescribed antipsychotic medications. Various practice guidelines have been developed in the United States and internationally to assess for metabolic risk factors in people prescribed antipsychotic medications [26]. Current metabolic monitoring guidelines in the United States stem from 2004 consensus recommendations of the American Diabetes Association and American Psychiatric Association along with the American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity for metabolic monitoring among people prescribed SGAs [23]. These recommendations include a time line for routine monitoring of weight/body mass index, waist circumference, blood pressure, fasting blood glucose or hemoglobin A1c, and fasting lipids (Table 2). Guidelines recommend screening at baseline, more frequently within the first 3 months, and then annually [23].

Though guidelines recommend measurement of waist circumference as a marker for metabolic health, body mass index is often used alone as a measure of obesity [27,28]. This may be due to the relative ease of obtaining weight over waist circumference. For example, weight is more likely to be part of clinic workflows and many providers may not be accustomed to measuring waist circumference. However, waist circumference does provide additional information regarding metabolic health [29], as central adiposity is a marker of cardiometabolic risk and related to insulin resistance [21]. Further modifications of the guidelines have included ethnicity-specific waist measurements [30].

There is evidence that non-fasting lipids may be substituted for fasting lipid panels, particularly for patients who may have difficulty adhering to fasting due to cognitive difficulties. Vanderlip and colleagues argue that fasting serum cholesterol panels are not necessary for screening for dyslipidemia given that non-HDL cholesterol is calculated based on total cholesterol and HDL, which do not substantially differ between fasting and non-fasting values [31]. Hemoglobin A1c is recommended as a screening test for blood glucose abnormalities given that it does not require a fasting state and can therefore be more easily obtained for many patients. The choice to obtain a fasting blood glucose versus hemoglobin A1c may depend on multiple factors, including that a person can adhere to fasting and the cost of the laboratory test.

Routine monitoring of metabolic parameters is an integral step in targeting interventions to treat metabolic syndrome. These interventions include lifestyle modifications and evidence-based treatment guidelines for management of associated dyslipidemia, hypertension, and type 2 diabetes mellitus.

Current Metabolic Screening Practices

Despite the presence of defined guidelines, estimates show persistently low rates of metabolic monitoring among adults prescribed SGAs [32]. One study of 3 state Medicaid programs showed little to no improvement in screening rates for glucose and lipids post dissemination of the 2004 APA/ADA guidelines [33]. They noted a nonsignificant change in rates of glucose testing from 27% to 30% and small change in lipid testing from 10% to 11% among patients prescribed SGAs between 2002–2005 [33]. Examining screening rates among Medicaid recipients in Missouri between 2010–2012, Morrato and colleagues found glucose testing rates of 80% with lipid testing remaining at 41% [34]. A retrospective study of adult Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 showed rates of screening for lipids and glucose to increase over time; glucose monitoring increased from 56.6% to 72.6% and lipids from 38.3% to 41.2% [35]. A review by Mangurian and colleagues suggested rates of glucose (fasting blood glucose or hemoglobin A1c) and lipid screening as low as 30% among people prescribed antipsychotic medications [14]. Furthermore, they underscore the impact of low screening rates, stating that if 20% of adults with SMI have diabetes and 70% remain unscreened, then approximately 2 million adults with SMI and diabetes in the United States would not be identified within our current system [14].

Higher rates of screening have been shown for Medicaid populations than commercially insured populations [36]. Haupt et al compared lipid and glucose testing pre- and post- ADA/APA guideline implementation among commercially insured patients. They found an increase from 8.4% to 10.5% post guideline implementation for baseline lipid testing and from 6.8% to 9.0% for lipid testing at 12 weeks post-antipsychotic initiation [36]. Baseline glucose testing increased from 17.3% to 21.8% and from 14.1% to 17.9 % at 12-week post antipsychotic initiation. In alignment with findings from other studies, testing rates were particularly low for children [36].

Low screening rates have been found among children and adolescents prescribed SGAs [37] despite evidence that youth may be at risk of developing more significant metabolic sequelae from SGAs [19]. Edelsohn and colleagues found an increase from 30% to 50% for glucose screening and from 19% to 28% for lipid screening among youth Medicaid recipients prescribed first- and second-generation antipsychotics between 2008 and 2012 [35]. Connolly and colleagues reported on metabolic screening rates for children and adolescents prescribed SGAs over the 8 years following announcement of the 2004 ADA/APA guidelines. Using insurance claims data, they found screening rates for fasting blood glucose and hemoglobin A1c temporarily increased following guideline dissemination, then dropped during the period 2004–2008, and again increased slightly [38].

Barriers to Screening

Barriers to screening exist at the level of the individual patient and provider as well as at the clinic and larger systems levels. Lack of provider awareness of evidence-based guidelines for metabolic monitoring despite the presence of the 2004 ADA/APA guidelines has been cited by researchers as an impediment to screening. In a survey of primary care clinicians in San Francisco, Mangurian et al found that 40% of primary care providers did not know about the ADA/APA consensus guidelines for metabolic monitoring. The same survey of primary care providers identified additional impediments to screening, including obstacles to collaboration with psychiatric providers and to scheduling patients for psychiatric follow-up [39]. Another clinician survey conducted by Parameswaran et al found that psychiatrists viewed psychiatric illness severity, lack of staff time, and lack of clinician time as significant barriers to metabolic screening. In addition, clinicians identified factors related to the complexity of coordinating care across systems as obstacles; these included barriers to coordinating follow-up with medical providers, long wait times for patients to see medical providers, and difficulty collaborating with medical providers [40].

Other systems-level barriers include lack of a population-based approach to screening (eg, registries) and lack of electronic record integration, which impedes the ability of primary care and psychiatry providers to share information related to the ordering of metabolic screening tests and prescribing of medications [41]. Mangurian calls for integration of electronic medical record systems between primary care and psychiatry, a population-based approach to metabolic monitoring utilizing registries and other elements of collaborative care models, and primary care consultation to aid in the treatment of metabolic abnormalities [41]. Amiel et al point to systems-level factors “including but not limited to … poor access to general medical services, inadequate medical record-keeping infrastructure, lack of in-system compliance incentives and lack of centralized oversight” [26].

Based on their experience implementing a computer-based intervention for metabolic monitoring, Lai et al propose that the following factors may influence providers’ engagement in metabolic monitoring: lack of apparent symptoms to suggest metabolic syndrome, patients’ lack of engagement in care, and poor access to care. They identify additional factors at the clinician level to include under-recognition of the need for metabolic monitoring, lack of familiarity with screening guidelines, lack of agreement with guidelines, and the potential for individual clinicians to forget to order tests [42]. At the systems-level, they identify the absence of ongoing training as a potential reason why sustained testing was not observed in their intervention [42].

In a 2011 survey of providers prescribing antipsychotic medication to Medicaid beneficiaries in Missouri, Morrato and colleagues found that factors limiting frequency of health care utilization were closely linked to lack of metabolic testing. They also noted disparities in screening guidelines may lead to lack of routine metabolic monitoring; providers may screen based on prescribed medication, diagnosis, or other risk factor based stratification depending on the guidelines followed [34].

Current Unmet Needs

Vulnerable Populations

Though rates of metabolic screening remain low for all groups prescribed antipsychotic medications, studies have consistently shown low rates of screening among children and adolescents [35,36]. Edelsohn and colleagues hypothesize that the cause of these low rates is multifactorial, including that guardians may be reluctant to have young people undergo blood draws [35]. Morrato and colleagues suggest that policymakers should focus initiatives on younger, healthier adults, who they found to have lower rates of screening [37].

Racial and ethnic minorities with SMI constitute another particularly vulnerable population, with some studies showing an increased risk of metabolic sequelae and lower likelihood of treatment for diabetes and other metabolic derangements among African American and Latino populations with SMI [14,43,44].

Integration of Care

Lack of widespread integration of care between mental health and primary care remains another unmet need [41]. Hasnain and colleagues recommend improved communication between mental health and primary care clinicians to coordinate care to improve rates of monitoring, facilitate early follow-up of metabolic abnormalities, and avoid duplication of monitoring efforts [45]. Morrato and colleagues recommend that efforts to increase rates of metabolic monitoring be targeted not only to providers practicing in community mental health centers, but also to other practice settings including primary care. They found that for 75% of people prescribed antipsychotic medications, the prescriptions were started by prescribing providers who practiced outside of a community mental health center [34] and recommend that educational initiatives and performance improvement interventions broaden to include primary care and other care settings [34].

Potential Interventions for Improvement

Early interventions to improve metabolic screening rates have included educational initiatives to teach providers about consensus guidelines. However, initiatives to educate clinicians on metabolic monitoring have shown to be inadequate to significantly improve rates of screening [33]. Therefore, subsequent initiatives have sought to influence screening rates by targeting behavior of individual clinicians with point-of-care tools, electronic reminders, or through systems-level reorganization towards population-based care [27,42,46].

A variety of clinical interventions focus on technologies that remind clinicians to order metabolic monitoring tests according to screening guidelines. One public mental health service in Queensland, Australia, created a standardized metabolic monitoring form to be uploaded to the electronic medical record. In their implementation study examining the efficacy of the metabolic monitoring form, they found that only 36% of the forms contained data. When data were recorded, there were significantly higher rates of documentation of measurements (weight, body mass index, blood pressure) rather than laboratory tests (including lipids and fasting blood glucose) [27].

Computerized reminder systems for metabolic monitoring have been studied in both outpatient and inpatient settings. Lai and colleagues studied the impact of a computerized reminder system on lab monitoring for metabolic parameters among outpatients with schizophrenia prescribed SGAs [42]. This intervention also included an educational component with discussion of metabolic monitoring for people prescribed SGAs at meetings with attending psychiatrists. Computer reminders were displayed when a provider failed to order fasting plasma glucose or lipids (cholesterol, triglyceride) for patients prescribed clozapine, olanzapine, quetiapine, or risperidone. The study found a statistically significant improvement in laboratory metabolic screening for patients prescribed SGAs after implementation, with the greatest impact 6-months post-intervention, though with subsequent decline in screening rates [42].

Psychiatric inpatient hospitalizations provide an opportunity to obtain testing at the time of treatment initiation and also for ongoing monitoring in a location where fasting laboratory tests may be more easily obtained given onsite phlebotomy. One intervention targeting psychiatric inpatients utilized a computerized physician order entry system with the goal to improve metabolic screening among patients prescribed SGAs. Set in a large academic medical setting, the study found inpatient metabolic monitoring rates did not change significantly after implementation of these pop-up computer alerts, comparing rates immediately and 4 years after implementation [46].

There has been increasing focus on integrating mental health and medical care in an effort to improve the health of people with mental illness [47]. Mangurian and colleagues found that the likelihood of diabetes mellitus screening doubled for people with severe mental illness who were seen for at least one primary care visit in addition to mental health treatment [48]. Haupt similarly found higher rates of metabolic screening among patients who had greater than one primary care visit [36]. Models of integration include both integration of medical services into mental health treatment as well as incorporation of mental health services into primary care. For people with SMI, integration efforts have largely focused on integrating primary care services into community mental health settings [49]. The Substance Abuse and Mental Health Service Administration’s (SAMHSA) Primary and Behavioral Health Care Integration (PBHCI) grants program and the Affordable Care Act’s Health Home Initiative are examples of federal incentive programs for improved integration between behavioral health and primary care [49]. In their evaluation of the PBHCI grant program, Scharf and colleagues presented findings that patients at 3 matched clinics with PCBHI grants showed improvement in some lipids, diastolic blood pressure, and fasting blood glucose, though not smoking or body mass index [50].

Conclusion

Several risk factors contribute to an increase in cardiometabolic risk for people with severe mental illness, including poor nutrition, sedentary lifestyle, social determinants of health, and prescribed antipsychotic medications. Metabolic monitoring aims to address these health disparities by screening for metabolic parameters and identifying abnormalities in order to target appropriate health interventions. Screening rates for metabolic parameters remain low for children, adolescents, and adults prescribed second-generation antipsychotics despite published guidelines and clinical interventions to improve screening. More system-wide interventions to improve collaboration between mental health and primary care are needed to enhance screening and prevent cardiovascular disease risk in this vulnerable population.

Corresponding author: Carrie Cunningham, MD, MPH, Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Suite 7M, San Francisco, CA 94110, [email protected].

Funding/support: Dr. Cunningham was supported by the UCSF-Zuckerberg San Francisco General Public Psychiatry Fellowship. Mr. Riano was supported by the NIH Center Grant from the National Institute of Diabetes and Digestive and Kidney Diseases for The Health Delivery Systems-Center for Diabetes Translational Research (CDTR) (P30DK092924) and by the UCSF-San Francisco General Hospital Public Psychiatry Fellowship. Dr. Mangurian received support from a grant from the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R03 DK101857), as well as NIH Career Development Award (K23MH093689).