Clinical Inquiries

Evidence summary

NSAIDs are commonly prescribed to control pain in patients with fractures. Laboratory studies have found that their antiprostaglandin properties delay callus formation and subsequent healing.¹ However, human studies evaluating the effects of NSAIDs on fracture healing have found variable results (TABLE).

TABLE
Fracture healing with NSAIDs: What the studies show

An RCT finds no delay in healing
An RCT of 42 postmenopausal women with displaced Colles’ fractures who were given piroxicam or placebo found no difference in the rate of healing between the intervention and control groups.² After 8 weeks, the bone mineral content of the radius and ulna, measured by bone density, was similar in both groups. Patients in the piroxicam group had significantly less pain at 10 days and 4 weeks, and used significantly less rescue medication.

Other studies beg to differ
Three observational studies of patients with different types of fractures found an increase in nonunion associated with NSAIDs.^3-5 Two retrospective studies of patients with long-bone fractures reported a higher rate of nonunion among patients taking indomethacin, diclofenac, or ibuprofen.^3,4 The third study, a retrospective analysis of postoperative spinal fusion patients who took ketorolac, also found an association between increased risk of nonunion and NSAIDs⁵ (TABLE).

A retrospective study of 94 patients with tibial fractures reported delayed healing in patients who had taken any NSAID. This association persisted after elimination for age, sex, fracture severity, and high-energy injuries.⁶

A relationship, but is it causal?
A larger retrospective cohort study of 9995 patients with humeral shaft fractures found an increased risk of nonunion in patients exposed to NSAIDs during the 90 days after the fracture. On further analysis, however, only NSAID exposure 60 to 90 days after the fracture was significantly associated with nonunion. Because patients with painful nonunion fractures are likely to use more NSAIDs, the relationship may not be causal.⁷

Benefits of NSAIDs outweigh concerns
Three reviews of the effect of NSAIDs on fracture healing all come to the same conclusion: Although animal studies raise theoretical concerns that NSAIDs affect fracture healing, no conclusive evidence supports denying patients the analgesic benefits of these drugs for managing fractures.^8-10

Recommendations

The American Academy of Family Physicians recommends using NSAIDs temporarily along with other measures—such as stretching, ice, and a steady return to the aggravating exercise—to relieve the pain of stress fractures until the patient is pain-free.¹¹

The American College of Sports Medicine, The American Academy of Orthopedic Surgeons, and the American Academy of Physical Medicine and Rehabilitation haven’t issued definitive guidelines concerning whether to use NSAIDs in managing fractures.

Evidence summary

NSAIDs are commonly prescribed to control pain in patients with fractures. Laboratory studies have found that their antiprostaglandin properties delay callus formation and subsequent healing.¹ However, human studies evaluating the effects of NSAIDs on fracture healing have found variable results (TABLE).

TABLE
Fracture healing with NSAIDs: What the studies show

An RCT finds no delay in healing
An RCT of 42 postmenopausal women with displaced Colles’ fractures who were given piroxicam or placebo found no difference in the rate of healing between the intervention and control groups.² After 8 weeks, the bone mineral content of the radius and ulna, measured by bone density, was similar in both groups. Patients in the piroxicam group had significantly less pain at 10 days and 4 weeks, and used significantly less rescue medication.

Other studies beg to differ
Three observational studies of patients with different types of fractures found an increase in nonunion associated with NSAIDs.^3-5 Two retrospective studies of patients with long-bone fractures reported a higher rate of nonunion among patients taking indomethacin, diclofenac, or ibuprofen.^3,4 The third study, a retrospective analysis of postoperative spinal fusion patients who took ketorolac, also found an association between increased risk of nonunion and NSAIDs⁵ (TABLE).

A retrospective study of 94 patients with tibial fractures reported delayed healing in patients who had taken any NSAID. This association persisted after elimination for age, sex, fracture severity, and high-energy injuries.⁶

A relationship, but is it causal?
A larger retrospective cohort study of 9995 patients with humeral shaft fractures found an increased risk of nonunion in patients exposed to NSAIDs during the 90 days after the fracture. On further analysis, however, only NSAID exposure 60 to 90 days after the fracture was significantly associated with nonunion. Because patients with painful nonunion fractures are likely to use more NSAIDs, the relationship may not be causal.⁷

Benefits of NSAIDs outweigh concerns
Three reviews of the effect of NSAIDs on fracture healing all come to the same conclusion: Although animal studies raise theoretical concerns that NSAIDs affect fracture healing, no conclusive evidence supports denying patients the analgesic benefits of these drugs for managing fractures.^8-10

Recommendations

The American Academy of Family Physicians recommends using NSAIDs temporarily along with other measures—such as stretching, ice, and a steady return to the aggravating exercise—to relieve the pain of stress fractures until the patient is pain-free.¹¹

The American College of Sports Medicine, The American Academy of Orthopedic Surgeons, and the American Academy of Physical Medicine and Rehabilitation haven’t issued definitive guidelines concerning whether to use NSAIDs in managing fractures.

Evidence summary

NSAIDs are commonly prescribed to control pain in patients with fractures. Laboratory studies have found that their antiprostaglandin properties delay callus formation and subsequent healing.¹ However, human studies evaluating the effects of NSAIDs on fracture healing have found variable results (TABLE).

TABLE
Fracture healing with NSAIDs: What the studies show

An RCT finds no delay in healing
An RCT of 42 postmenopausal women with displaced Colles’ fractures who were given piroxicam or placebo found no difference in the rate of healing between the intervention and control groups.² After 8 weeks, the bone mineral content of the radius and ulna, measured by bone density, was similar in both groups. Patients in the piroxicam group had significantly less pain at 10 days and 4 weeks, and used significantly less rescue medication.

Other studies beg to differ
Three observational studies of patients with different types of fractures found an increase in nonunion associated with NSAIDs.^3-5 Two retrospective studies of patients with long-bone fractures reported a higher rate of nonunion among patients taking indomethacin, diclofenac, or ibuprofen.^3,4 The third study, a retrospective analysis of postoperative spinal fusion patients who took ketorolac, also found an association between increased risk of nonunion and NSAIDs⁵ (TABLE).

A retrospective study of 94 patients with tibial fractures reported delayed healing in patients who had taken any NSAID. This association persisted after elimination for age, sex, fracture severity, and high-energy injuries.⁶

A relationship, but is it causal?
A larger retrospective cohort study of 9995 patients with humeral shaft fractures found an increased risk of nonunion in patients exposed to NSAIDs during the 90 days after the fracture. On further analysis, however, only NSAID exposure 60 to 90 days after the fracture was significantly associated with nonunion. Because patients with painful nonunion fractures are likely to use more NSAIDs, the relationship may not be causal.⁷

Benefits of NSAIDs outweigh concerns
Three reviews of the effect of NSAIDs on fracture healing all come to the same conclusion: Although animal studies raise theoretical concerns that NSAIDs affect fracture healing, no conclusive evidence supports denying patients the analgesic benefits of these drugs for managing fractures.^8-10

Recommendations

The American Academy of Family Physicians recommends using NSAIDs temporarily along with other measures—such as stretching, ice, and a steady return to the aggravating exercise—to relieve the pain of stress fractures until the patient is pain-free.¹¹

The American College of Sports Medicine, The American Academy of Orthopedic Surgeons, and the American Academy of Physical Medicine and Rehabilitation haven’t issued definitive guidelines concerning whether to use NSAIDs in managing fractures.

Evidence summary

A small, prospective, controlled trial found no significant difference in breastfeeding success between infants with and without tongue-tie. The authors selected 36 infants with untreated tongue-tie and 36 matched controls from among 1041 newborns. At 2 months, 30 infants with tongue-tie (83%) were breastfeeding, compared with 33 (92%) in the control group (P=.29). The authors graded infants with tongue-tie by subjective impression as either “mild” or “moderate,” but found no significant difference in breastfeeding between grades.¹

A case-control study compared 49 infants with untreated tongue-tie (documented using a standardized assessment tool for lingual frenulum function) with 98 normal controls and evaluated the prevalence of breast vs bottle feeding. Mothers reported that breastfeeding was “going well” in 29 of 30 infants with tongue-tie (97%) and 63 of 67 controls (94%). At 1 month, both groups continued to breastfeed at equal rates.²

When breastfeeding is difficult, frenotomy helps
Five studies that evaluated frenotomy (surgical division of the frenulum) in infants with tongue-tie who had breastfeeding difficulties found improved maternal breastfeeding scores after the procedure.^3-7 In all trials, frenotomy caused minimal bleeding (a few drops) and minor crying (?15 seconds), but no other complications.

In one trial, 40 infants (3-70 days of age) with tongue-tie and breastfeeding difficulties were randomized to receive frenotomy or intensive lactation support. Investigators graded the severity of tongue-tie and found no correlation with breastfeeding difficulty.

Nineteen mothers (95%) in the frenotomy group reported improved latching and decreased nipple pain, compared with 1 mother (5%) who received lactation support (P<.01; number needed to treat [NNT]=1.1). At 48 hours, all the mothers in the lactation support group elected frenotomy, after which 96% reported less nipple pain and improved latching. No long-term follow-up was done.³

A second trial randomized 25 infants (1-21 days of age) with tongue-tie (defined by an inability to protrude the tip of the tongue beyond the lower gum line) and breastfeeding difficulties (maternal nipple pain, poor latching) to receive either frenotomy or sham frenotomy. Investigators recorded nipple pain scores (with a maximum score of 10 for most intense pain) at the first breastfeeding after the intervention. The infants then received the other procedure, followed by breastfeeding.

Immediately after true frenotomy, mothers reported a significant reduction in nipple pain scores (5.3 after the procedure compared with 7.1 before; P=.001). The investigators didn’t report pain score changes after sham frenotomy.⁴

Severity of tongue-tie doesn’t affect breastfeeding success after frenotomy
A prospective, uncontrolled cohort study followed 35 infants (3-98 days of age) with tongue-tie and breastfeeding difficulties after they had a frenotomy. At 3 months, 29 of 35 mothers reported improved breastfeeding.⁵

Another prospective, uncontrolled cohort study followed 215 infants (mean age 19 days) with tongue-tie and breastfeeding difficulties despite lactation support. Investigators gauged the extent of tongue-tie by visual inspection before frenotomy.

At 24 hours after frenotomy, 57% of mothers reported improved breastfeeding and 64% breastfed through 3 months (compared with the British national average of 30%). The likelihood of breastfeeding at 3 months after frenotomy didn’t correlate with the original extent of tongue-tie.⁶

A prospective, uncontrolled case series measured the overall incidence of tongue-tie—88 infants out of 2763 consecutive births (3.2%)—and the incidence of tongue-tie among infants with breastfeeding problems—35 infants among 273 presenting to a lactation center (12.8%). Mothers reported significant improvements in latching and nipple pain 3 days after frenotomy.⁷

Recommendations

The Community Paediatrics Committee of the Canadian Paediatric Society says that most of the time, tongue-tie is an anatomical finding without significant consequences for breastfeeding. Surgical intervention isn’t usually warranted, but may be necessary if significant tongue-tie is associated with major breastfeeding problems.⁸

The Academy of Breastfeeding Medicine also says that breastfeeding assistance, patient education, and reassurance may be sufficient; if frenotomy is necessary, a physician should do it.⁹

Evidence summary

A small, prospective, controlled trial found no significant difference in breastfeeding success between infants with and without tongue-tie. The authors selected 36 infants with untreated tongue-tie and 36 matched controls from among 1041 newborns. At 2 months, 30 infants with tongue-tie (83%) were breastfeeding, compared with 33 (92%) in the control group (P=.29). The authors graded infants with tongue-tie by subjective impression as either “mild” or “moderate,” but found no significant difference in breastfeeding between grades.¹

A case-control study compared 49 infants with untreated tongue-tie (documented using a standardized assessment tool for lingual frenulum function) with 98 normal controls and evaluated the prevalence of breast vs bottle feeding. Mothers reported that breastfeeding was “going well” in 29 of 30 infants with tongue-tie (97%) and 63 of 67 controls (94%). At 1 month, both groups continued to breastfeed at equal rates.²

When breastfeeding is difficult, frenotomy helps
Five studies that evaluated frenotomy (surgical division of the frenulum) in infants with tongue-tie who had breastfeeding difficulties found improved maternal breastfeeding scores after the procedure.^3-7 In all trials, frenotomy caused minimal bleeding (a few drops) and minor crying (?15 seconds), but no other complications.

In one trial, 40 infants (3-70 days of age) with tongue-tie and breastfeeding difficulties were randomized to receive frenotomy or intensive lactation support. Investigators graded the severity of tongue-tie and found no correlation with breastfeeding difficulty.

Nineteen mothers (95%) in the frenotomy group reported improved latching and decreased nipple pain, compared with 1 mother (5%) who received lactation support (P<.01; number needed to treat [NNT]=1.1). At 48 hours, all the mothers in the lactation support group elected frenotomy, after which 96% reported less nipple pain and improved latching. No long-term follow-up was done.³

A second trial randomized 25 infants (1-21 days of age) with tongue-tie (defined by an inability to protrude the tip of the tongue beyond the lower gum line) and breastfeeding difficulties (maternal nipple pain, poor latching) to receive either frenotomy or sham frenotomy. Investigators recorded nipple pain scores (with a maximum score of 10 for most intense pain) at the first breastfeeding after the intervention. The infants then received the other procedure, followed by breastfeeding.

Immediately after true frenotomy, mothers reported a significant reduction in nipple pain scores (5.3 after the procedure compared with 7.1 before; P=.001). The investigators didn’t report pain score changes after sham frenotomy.⁴

Severity of tongue-tie doesn’t affect breastfeeding success after frenotomy
A prospective, uncontrolled cohort study followed 35 infants (3-98 days of age) with tongue-tie and breastfeeding difficulties after they had a frenotomy. At 3 months, 29 of 35 mothers reported improved breastfeeding.⁵

Another prospective, uncontrolled cohort study followed 215 infants (mean age 19 days) with tongue-tie and breastfeeding difficulties despite lactation support. Investigators gauged the extent of tongue-tie by visual inspection before frenotomy.

At 24 hours after frenotomy, 57% of mothers reported improved breastfeeding and 64% breastfed through 3 months (compared with the British national average of 30%). The likelihood of breastfeeding at 3 months after frenotomy didn’t correlate with the original extent of tongue-tie.⁶

A prospective, uncontrolled case series measured the overall incidence of tongue-tie—88 infants out of 2763 consecutive births (3.2%)—and the incidence of tongue-tie among infants with breastfeeding problems—35 infants among 273 presenting to a lactation center (12.8%). Mothers reported significant improvements in latching and nipple pain 3 days after frenotomy.⁷

Recommendations

The Community Paediatrics Committee of the Canadian Paediatric Society says that most of the time, tongue-tie is an anatomical finding without significant consequences for breastfeeding. Surgical intervention isn’t usually warranted, but may be necessary if significant tongue-tie is associated with major breastfeeding problems.⁸

The Academy of Breastfeeding Medicine also says that breastfeeding assistance, patient education, and reassurance may be sufficient; if frenotomy is necessary, a physician should do it.⁹

Evidence summary

A small, prospective, controlled trial found no significant difference in breastfeeding success between infants with and without tongue-tie. The authors selected 36 infants with untreated tongue-tie and 36 matched controls from among 1041 newborns. At 2 months, 30 infants with tongue-tie (83%) were breastfeeding, compared with 33 (92%) in the control group (P=.29). The authors graded infants with tongue-tie by subjective impression as either “mild” or “moderate,” but found no significant difference in breastfeeding between grades.¹

A case-control study compared 49 infants with untreated tongue-tie (documented using a standardized assessment tool for lingual frenulum function) with 98 normal controls and evaluated the prevalence of breast vs bottle feeding. Mothers reported that breastfeeding was “going well” in 29 of 30 infants with tongue-tie (97%) and 63 of 67 controls (94%). At 1 month, both groups continued to breastfeed at equal rates.²

When breastfeeding is difficult, frenotomy helps
Five studies that evaluated frenotomy (surgical division of the frenulum) in infants with tongue-tie who had breastfeeding difficulties found improved maternal breastfeeding scores after the procedure.^3-7 In all trials, frenotomy caused minimal bleeding (a few drops) and minor crying (?15 seconds), but no other complications.

In one trial, 40 infants (3-70 days of age) with tongue-tie and breastfeeding difficulties were randomized to receive frenotomy or intensive lactation support. Investigators graded the severity of tongue-tie and found no correlation with breastfeeding difficulty.

Nineteen mothers (95%) in the frenotomy group reported improved latching and decreased nipple pain, compared with 1 mother (5%) who received lactation support (P<.01; number needed to treat [NNT]=1.1). At 48 hours, all the mothers in the lactation support group elected frenotomy, after which 96% reported less nipple pain and improved latching. No long-term follow-up was done.³

A second trial randomized 25 infants (1-21 days of age) with tongue-tie (defined by an inability to protrude the tip of the tongue beyond the lower gum line) and breastfeeding difficulties (maternal nipple pain, poor latching) to receive either frenotomy or sham frenotomy. Investigators recorded nipple pain scores (with a maximum score of 10 for most intense pain) at the first breastfeeding after the intervention. The infants then received the other procedure, followed by breastfeeding.

Immediately after true frenotomy, mothers reported a significant reduction in nipple pain scores (5.3 after the procedure compared with 7.1 before; P=.001). The investigators didn’t report pain score changes after sham frenotomy.⁴

Severity of tongue-tie doesn’t affect breastfeeding success after frenotomy
A prospective, uncontrolled cohort study followed 35 infants (3-98 days of age) with tongue-tie and breastfeeding difficulties after they had a frenotomy. At 3 months, 29 of 35 mothers reported improved breastfeeding.⁵

Another prospective, uncontrolled cohort study followed 215 infants (mean age 19 days) with tongue-tie and breastfeeding difficulties despite lactation support. Investigators gauged the extent of tongue-tie by visual inspection before frenotomy.

At 24 hours after frenotomy, 57% of mothers reported improved breastfeeding and 64% breastfed through 3 months (compared with the British national average of 30%). The likelihood of breastfeeding at 3 months after frenotomy didn’t correlate with the original extent of tongue-tie.⁶

A prospective, uncontrolled case series measured the overall incidence of tongue-tie—88 infants out of 2763 consecutive births (3.2%)—and the incidence of tongue-tie among infants with breastfeeding problems—35 infants among 273 presenting to a lactation center (12.8%). Mothers reported significant improvements in latching and nipple pain 3 days after frenotomy.⁷

Recommendations

The Community Paediatrics Committee of the Canadian Paediatric Society says that most of the time, tongue-tie is an anatomical finding without significant consequences for breastfeeding. Surgical intervention isn’t usually warranted, but may be necessary if significant tongue-tie is associated with major breastfeeding problems.⁸

The Academy of Breastfeeding Medicine also says that breastfeeding assistance, patient education, and reassurance may be sufficient; if frenotomy is necessary, a physician should do it.⁹

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

The National Cholesterol Expert Panel (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults defines high-risk patients as having known CHD, diabetes, noncoronary atherosclerotic disease, or multiple risk factors for CHD.¹ (Moderate-or low-risk patients are defined as having a 10-year risk of CHD <20%.) The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) also includes in the high-risk group patients with stage 5 kidney disease (glomerular filtration rate <15 mL/min or on dialysis).²

The NCEP goes on to define very-high-risk patients as those with known CHD and multiple risk factors. These risks include acute coronary syndrome, diabetes, metabolic syndrome, or poorly controlled or severe risk factors, especially cigarette smoking.¹

An LDL target of <100 mg/dL for high-risk patients and an optional target of <70 mg/dL for very-high-risk patients were determined by expert interpretation of evidence from large trials and meta-analyses of a log-linear relationship between LDL levels and CHD risk (TABLE).^3,4

TABLE
Target LDL measurements for high-risk and very-high-risk patients^1,2,7,8

Lowering LDL reduces first coronary events in high-risk patients
A large 2005 meta-analysis pooled 90,056 high-risk patients in 14 trials of statin use compared with placebo (11 studies), no treatment (1 study), very-low-dose statin use (1 study), or usual care (1 study). Primary outcomes were a change in LDL cholesterol, all-cause mortality, CHD mortality, and non-CHD mortality.⁵

The meta-analysis showed that high-risk patients had a 21% reduction in the 5-year incidence of first major coronary events for every 39 mg/dL decrease in LDL cholesterol (relative risk [RR]=0.79; 95% confidence interval [CI], 0.77-0.81; number needed to treat [NNT]=27). A subanalysis of 447 high-risk patients with LDL levels <100 mg/dL at baseline found that the risk of major coronary events decreased with statin therapy, but the 99% CI included 1 (RR=0.75; 99% CI, 0.56-1.01).⁵

Simvastatin decreases MI and stroke regardless of baseline LDL
One RCT included in the meta-analysis warrants special attention. This study evaluated the use of simvastatin 40 mg daily compared with placebo for 5 years in 20,536 high-risk patients who were grouped according to initial LDL level (<115 mg/dL, 115-135 mg/dL, and >135 mg/dL). Simvastatin lowered the average patient’s LDL by 39 mg/dL (no CIs provided).⁶

Regardless of the baseline LDL, simvastatin decreased the rate of first myocardial infarction (MI), stroke, or need for revascularization compared with placebo (RR=0.76; 95% CI, 0.72-0.81; NNT=18). Subgroup analysis of 3421 high-risk patients with LDL levels <100 mg/dL at baseline showed fewer major coronary events with simvastatin than with placebo (RR=0.78; 95% CI, 0.68-0.90).⁶

High-dose statins decrease MI more than standard doses
A 2008 meta-analysis of 29,395 high-risk patients in 7 trials examined high-dose compared with standard statin use for secondary prevention. Six trials used atorvastatin 80 mg daily as the high-dose regimen; 1 trial used simvastatin 80 mg daily. The standard regimens were 5 to 40 mg of pravastatin, simvastatin, atorvastatin, or lovastatin.

The weighted mean difference of LDL lowering between the 2 groups was 28 mg/dL (95% CI, 23-32 mg/dL), and fewer than 50% of patients achieved the treatment target (LDL <80 mg/dL). Nevertheless, intensive statin use decreased MIs compared with standard dosing (RR=0.83; 95% CI, 0.77-0.91).⁷

This meta-analysis included a key RCT, which enrolled 4162 high-risk patients and compared pravastatin 40 mg (standard therapy) with atorvastatin 80 mg (intensive therapy) over an average of 24 months. The pravastatin group achieved a median LDL of 95 mg/dL and the atorvastatin group achieved a median LDL of 62 mg/dL. The atorvastatin group had fewer deaths from any cause or a major cardiovascular event (RR=0.85; 95% CI, 0.76-0.95; NNT=25).⁸

Does benefit result from lower LDL, or some other statin effect?
Since most lipid studies have been done using a statin as the sole treatment agent, it is unclear whether patients benefit more from a lower LDL or from some effect of the statin medication class.⁹ Statins reduce the risk of cardiovascular events in patients with an elevated C-reactive protein,¹⁰ perhaps indicating an anti-inflammatory effect. However, fibrates and niacin have also been shown to decrease coronary events in high-risk patients in a few studies.^11,12

Recommendations

The NCEP Adult Treatment Panel III guidelines recommend treating high-risk patients to a target LDL of <100 mg/dL.¹ A target LDL of <70 mg/dL is optional for very-high-risk patients (TABLE).^1,3

The K/DOQI recommends that patients with stage 5 kidney disease be treated according to the NCEP guidelines for high-risk patients.² The expected release date for the NCEP Adult Treatment Panel IV guidelines is fall 2011.¹³

Acknowledgement
The authors gratefully acknowledge the work of Dr. Marguerite Elliott, who co-authored this Clinical Inquiry, and who passed away on February 15, 2010.

Evidence summary

The National Cholesterol Expert Panel (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults defines high-risk patients as having known CHD, diabetes, noncoronary atherosclerotic disease, or multiple risk factors for CHD.¹ (Moderate-or low-risk patients are defined as having a 10-year risk of CHD <20%.) The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) also includes in the high-risk group patients with stage 5 kidney disease (glomerular filtration rate <15 mL/min or on dialysis).²

The NCEP goes on to define very-high-risk patients as those with known CHD and multiple risk factors. These risks include acute coronary syndrome, diabetes, metabolic syndrome, or poorly controlled or severe risk factors, especially cigarette smoking.¹

An LDL target of <100 mg/dL for high-risk patients and an optional target of <70 mg/dL for very-high-risk patients were determined by expert interpretation of evidence from large trials and meta-analyses of a log-linear relationship between LDL levels and CHD risk (TABLE).^3,4

TABLE
Target LDL measurements for high-risk and very-high-risk patients^1,2,7,8

Lowering LDL reduces first coronary events in high-risk patients
A large 2005 meta-analysis pooled 90,056 high-risk patients in 14 trials of statin use compared with placebo (11 studies), no treatment (1 study), very-low-dose statin use (1 study), or usual care (1 study). Primary outcomes were a change in LDL cholesterol, all-cause mortality, CHD mortality, and non-CHD mortality.⁵

The meta-analysis showed that high-risk patients had a 21% reduction in the 5-year incidence of first major coronary events for every 39 mg/dL decrease in LDL cholesterol (relative risk [RR]=0.79; 95% confidence interval [CI], 0.77-0.81; number needed to treat [NNT]=27). A subanalysis of 447 high-risk patients with LDL levels <100 mg/dL at baseline found that the risk of major coronary events decreased with statin therapy, but the 99% CI included 1 (RR=0.75; 99% CI, 0.56-1.01).⁵

Simvastatin decreases MI and stroke regardless of baseline LDL
One RCT included in the meta-analysis warrants special attention. This study evaluated the use of simvastatin 40 mg daily compared with placebo for 5 years in 20,536 high-risk patients who were grouped according to initial LDL level (<115 mg/dL, 115-135 mg/dL, and >135 mg/dL). Simvastatin lowered the average patient’s LDL by 39 mg/dL (no CIs provided).⁶

Regardless of the baseline LDL, simvastatin decreased the rate of first myocardial infarction (MI), stroke, or need for revascularization compared with placebo (RR=0.76; 95% CI, 0.72-0.81; NNT=18). Subgroup analysis of 3421 high-risk patients with LDL levels <100 mg/dL at baseline showed fewer major coronary events with simvastatin than with placebo (RR=0.78; 95% CI, 0.68-0.90).⁶

High-dose statins decrease MI more than standard doses
A 2008 meta-analysis of 29,395 high-risk patients in 7 trials examined high-dose compared with standard statin use for secondary prevention. Six trials used atorvastatin 80 mg daily as the high-dose regimen; 1 trial used simvastatin 80 mg daily. The standard regimens were 5 to 40 mg of pravastatin, simvastatin, atorvastatin, or lovastatin.

The weighted mean difference of LDL lowering between the 2 groups was 28 mg/dL (95% CI, 23-32 mg/dL), and fewer than 50% of patients achieved the treatment target (LDL <80 mg/dL). Nevertheless, intensive statin use decreased MIs compared with standard dosing (RR=0.83; 95% CI, 0.77-0.91).⁷

This meta-analysis included a key RCT, which enrolled 4162 high-risk patients and compared pravastatin 40 mg (standard therapy) with atorvastatin 80 mg (intensive therapy) over an average of 24 months. The pravastatin group achieved a median LDL of 95 mg/dL and the atorvastatin group achieved a median LDL of 62 mg/dL. The atorvastatin group had fewer deaths from any cause or a major cardiovascular event (RR=0.85; 95% CI, 0.76-0.95; NNT=25).⁸

Does benefit result from lower LDL, or some other statin effect?
Since most lipid studies have been done using a statin as the sole treatment agent, it is unclear whether patients benefit more from a lower LDL or from some effect of the statin medication class.⁹ Statins reduce the risk of cardiovascular events in patients with an elevated C-reactive protein,¹⁰ perhaps indicating an anti-inflammatory effect. However, fibrates and niacin have also been shown to decrease coronary events in high-risk patients in a few studies.^11,12

Recommendations

The NCEP Adult Treatment Panel III guidelines recommend treating high-risk patients to a target LDL of <100 mg/dL.¹ A target LDL of <70 mg/dL is optional for very-high-risk patients (TABLE).^1,3

The K/DOQI recommends that patients with stage 5 kidney disease be treated according to the NCEP guidelines for high-risk patients.² The expected release date for the NCEP Adult Treatment Panel IV guidelines is fall 2011.¹³

Acknowledgement
The authors gratefully acknowledge the work of Dr. Marguerite Elliott, who co-authored this Clinical Inquiry, and who passed away on February 15, 2010.

Evidence summary

The National Cholesterol Expert Panel (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults defines high-risk patients as having known CHD, diabetes, noncoronary atherosclerotic disease, or multiple risk factors for CHD.¹ (Moderate-or low-risk patients are defined as having a 10-year risk of CHD <20%.) The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) also includes in the high-risk group patients with stage 5 kidney disease (glomerular filtration rate <15 mL/min or on dialysis).²

The NCEP goes on to define very-high-risk patients as those with known CHD and multiple risk factors. These risks include acute coronary syndrome, diabetes, metabolic syndrome, or poorly controlled or severe risk factors, especially cigarette smoking.¹

An LDL target of <100 mg/dL for high-risk patients and an optional target of <70 mg/dL for very-high-risk patients were determined by expert interpretation of evidence from large trials and meta-analyses of a log-linear relationship between LDL levels and CHD risk (TABLE).^3,4

TABLE
Target LDL measurements for high-risk and very-high-risk patients^1,2,7,8

Lowering LDL reduces first coronary events in high-risk patients
A large 2005 meta-analysis pooled 90,056 high-risk patients in 14 trials of statin use compared with placebo (11 studies), no treatment (1 study), very-low-dose statin use (1 study), or usual care (1 study). Primary outcomes were a change in LDL cholesterol, all-cause mortality, CHD mortality, and non-CHD mortality.⁵

The meta-analysis showed that high-risk patients had a 21% reduction in the 5-year incidence of first major coronary events for every 39 mg/dL decrease in LDL cholesterol (relative risk [RR]=0.79; 95% confidence interval [CI], 0.77-0.81; number needed to treat [NNT]=27). A subanalysis of 447 high-risk patients with LDL levels <100 mg/dL at baseline found that the risk of major coronary events decreased with statin therapy, but the 99% CI included 1 (RR=0.75; 99% CI, 0.56-1.01).⁵

Simvastatin decreases MI and stroke regardless of baseline LDL
One RCT included in the meta-analysis warrants special attention. This study evaluated the use of simvastatin 40 mg daily compared with placebo for 5 years in 20,536 high-risk patients who were grouped according to initial LDL level (<115 mg/dL, 115-135 mg/dL, and >135 mg/dL). Simvastatin lowered the average patient’s LDL by 39 mg/dL (no CIs provided).⁶

Regardless of the baseline LDL, simvastatin decreased the rate of first myocardial infarction (MI), stroke, or need for revascularization compared with placebo (RR=0.76; 95% CI, 0.72-0.81; NNT=18). Subgroup analysis of 3421 high-risk patients with LDL levels <100 mg/dL at baseline showed fewer major coronary events with simvastatin than with placebo (RR=0.78; 95% CI, 0.68-0.90).⁶

High-dose statins decrease MI more than standard doses
A 2008 meta-analysis of 29,395 high-risk patients in 7 trials examined high-dose compared with standard statin use for secondary prevention. Six trials used atorvastatin 80 mg daily as the high-dose regimen; 1 trial used simvastatin 80 mg daily. The standard regimens were 5 to 40 mg of pravastatin, simvastatin, atorvastatin, or lovastatin.

The weighted mean difference of LDL lowering between the 2 groups was 28 mg/dL (95% CI, 23-32 mg/dL), and fewer than 50% of patients achieved the treatment target (LDL <80 mg/dL). Nevertheless, intensive statin use decreased MIs compared with standard dosing (RR=0.83; 95% CI, 0.77-0.91).⁷

This meta-analysis included a key RCT, which enrolled 4162 high-risk patients and compared pravastatin 40 mg (standard therapy) with atorvastatin 80 mg (intensive therapy) over an average of 24 months. The pravastatin group achieved a median LDL of 95 mg/dL and the atorvastatin group achieved a median LDL of 62 mg/dL. The atorvastatin group had fewer deaths from any cause or a major cardiovascular event (RR=0.85; 95% CI, 0.76-0.95; NNT=25).⁸

Does benefit result from lower LDL, or some other statin effect?
Since most lipid studies have been done using a statin as the sole treatment agent, it is unclear whether patients benefit more from a lower LDL or from some effect of the statin medication class.⁹ Statins reduce the risk of cardiovascular events in patients with an elevated C-reactive protein,¹⁰ perhaps indicating an anti-inflammatory effect. However, fibrates and niacin have also been shown to decrease coronary events in high-risk patients in a few studies.^11,12

Recommendations

The NCEP Adult Treatment Panel III guidelines recommend treating high-risk patients to a target LDL of <100 mg/dL.¹ A target LDL of <70 mg/dL is optional for very-high-risk patients (TABLE).^1,3

The K/DOQI recommends that patients with stage 5 kidney disease be treated according to the NCEP guidelines for high-risk patients.² The expected release date for the NCEP Adult Treatment Panel IV guidelines is fall 2011.¹³

Acknowledgement
The authors gratefully acknowledge the work of Dr. Marguerite Elliott, who co-authored this Clinical Inquiry, and who passed away on February 15, 2010.

Evidence summary

Continuous EFM is designed to detect early fetal hypoxia and thereby decrease neonatal morbidity and mortality compared with IA. IA is defined as auscultation of the fetal heart rate for at least 60 seconds every 15 minutes during the first stage of labor and every 5 minutes during the second stage of labor.

A decrease in seizures, but not deaths or cerebral palsy
A 2006 Cochrane systematic review examined 12 RCTs (with >37,000 women) that compared continuous EFM with IA.¹ Continuous EFM reduced the risk of neonatal seizure by 50% (relative risk [RR]=0.50; 95% confidence interval [CI], 0.31-0.80), but had no effect on the rate of neonatal death (RR=0.85; 95% CI, 0.59-1.23) or development of cerebral palsy (RR=1.74; 95% CI, 0.97-3.11).

Reduction of seizures was consistent across all trials. However, a subgroup analysis of high-risk pregnancies (advanced maternal age, diabetes mellitus, chronic hypertension, renal disease, preeclampsia, cardiac disease, renal disease, previous delivery of a low-birth-weight infant) didn’t find a statistically significant decrease in seizures.

Cesarean deliveries rise, regardless of patient risk status
Continuous EFM raised the rates of cesarean delivery (RR=1.66; 95% CI, 1.30-2.13) and instrumental vaginal deliveries (RR=1.16; 95% CI, 1.01-1.32). The increased rate of cesarean section in the EFM group was consistent regardless of clinical risk status (low- vs high-risk women). One additional cesarean section was performed for every 58 women monitored continuously. For “high-risk” women, 1 additional cesarean section was performed for every 12 women monitored continuously.¹

Cesarean section rates varied widely among the individual trials (2.3%-35%). Analysis suggested that studies with higher baseline rates showed the greatest increases with continuous EFM. The rate for all studies combined was just 4.3%; 69% of patients included in the meta-analysis were contributed by the Dublin trial, which had an average cesarean rate of 2.3%.¹ By comparison, the US Division of Vital Statistics reported a cesarean rate of 32.3% in 2008.²

EFM reduces death from fetal hypoxia
A 1995 meta-analysis, including 9 of the Cochrane review studies with a total of 18,561 women, evaluated the additional outcome of death resulting from fetal hypoxia.³ Compared with IA, EFM was associated with a 59% reduction in death from fetal hypoxia (RR=0.41; 95% CI, 0.17-0.98). Continuous EFM prevented 1 perinatal death per 1000 births. The reduction in perinatal mortality was offset by a 53% increase in cesarean deliveries and a 23% increase in operative vaginal deliveries.³

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) doesn’t recommend for or against continuous fetal heart rate monitoring in uncomplicated labor, recognizing either EFM or IA as acceptable in uncomplicated patients.⁴ ACOG does recommend continuous EFM for women with high-risk conditions (suspected fetal growth restriction, preeclampsia, and type 1 diabetes mellitus).

The US Preventive Services Task Force doesn’t support routine intrapartum EFM for low-risk woman. The Task Force found insufficient evidence for using EFM in high-risk pregnancies.⁵

The Royal College of Obstetricians and Gynaecologists and the Royal Australian and New Zealand College of Obstetricians and Gynecologists both recommend continuous EFM for high-risk women and IA for low-risk patients.^6,7

Acknowledgements
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army Medical Department or the US Army at large.

Evidence summary

Continuous EFM is designed to detect early fetal hypoxia and thereby decrease neonatal morbidity and mortality compared with IA. IA is defined as auscultation of the fetal heart rate for at least 60 seconds every 15 minutes during the first stage of labor and every 5 minutes during the second stage of labor.

A decrease in seizures, but not deaths or cerebral palsy
A 2006 Cochrane systematic review examined 12 RCTs (with >37,000 women) that compared continuous EFM with IA.¹ Continuous EFM reduced the risk of neonatal seizure by 50% (relative risk [RR]=0.50; 95% confidence interval [CI], 0.31-0.80), but had no effect on the rate of neonatal death (RR=0.85; 95% CI, 0.59-1.23) or development of cerebral palsy (RR=1.74; 95% CI, 0.97-3.11).

Reduction of seizures was consistent across all trials. However, a subgroup analysis of high-risk pregnancies (advanced maternal age, diabetes mellitus, chronic hypertension, renal disease, preeclampsia, cardiac disease, renal disease, previous delivery of a low-birth-weight infant) didn’t find a statistically significant decrease in seizures.

Cesarean deliveries rise, regardless of patient risk status
Continuous EFM raised the rates of cesarean delivery (RR=1.66; 95% CI, 1.30-2.13) and instrumental vaginal deliveries (RR=1.16; 95% CI, 1.01-1.32). The increased rate of cesarean section in the EFM group was consistent regardless of clinical risk status (low- vs high-risk women). One additional cesarean section was performed for every 58 women monitored continuously. For “high-risk” women, 1 additional cesarean section was performed for every 12 women monitored continuously.¹

Cesarean section rates varied widely among the individual trials (2.3%-35%). Analysis suggested that studies with higher baseline rates showed the greatest increases with continuous EFM. The rate for all studies combined was just 4.3%; 69% of patients included in the meta-analysis were contributed by the Dublin trial, which had an average cesarean rate of 2.3%.¹ By comparison, the US Division of Vital Statistics reported a cesarean rate of 32.3% in 2008.²

EFM reduces death from fetal hypoxia
A 1995 meta-analysis, including 9 of the Cochrane review studies with a total of 18,561 women, evaluated the additional outcome of death resulting from fetal hypoxia.³ Compared with IA, EFM was associated with a 59% reduction in death from fetal hypoxia (RR=0.41; 95% CI, 0.17-0.98). Continuous EFM prevented 1 perinatal death per 1000 births. The reduction in perinatal mortality was offset by a 53% increase in cesarean deliveries and a 23% increase in operative vaginal deliveries.³

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) doesn’t recommend for or against continuous fetal heart rate monitoring in uncomplicated labor, recognizing either EFM or IA as acceptable in uncomplicated patients.⁴ ACOG does recommend continuous EFM for women with high-risk conditions (suspected fetal growth restriction, preeclampsia, and type 1 diabetes mellitus).

The US Preventive Services Task Force doesn’t support routine intrapartum EFM for low-risk woman. The Task Force found insufficient evidence for using EFM in high-risk pregnancies.⁵

The Royal College of Obstetricians and Gynaecologists and the Royal Australian and New Zealand College of Obstetricians and Gynecologists both recommend continuous EFM for high-risk women and IA for low-risk patients.^6,7

Acknowledgements
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army Medical Department or the US Army at large.

Evidence summary

Continuous EFM is designed to detect early fetal hypoxia and thereby decrease neonatal morbidity and mortality compared with IA. IA is defined as auscultation of the fetal heart rate for at least 60 seconds every 15 minutes during the first stage of labor and every 5 minutes during the second stage of labor.

A decrease in seizures, but not deaths or cerebral palsy
A 2006 Cochrane systematic review examined 12 RCTs (with >37,000 women) that compared continuous EFM with IA.¹ Continuous EFM reduced the risk of neonatal seizure by 50% (relative risk [RR]=0.50; 95% confidence interval [CI], 0.31-0.80), but had no effect on the rate of neonatal death (RR=0.85; 95% CI, 0.59-1.23) or development of cerebral palsy (RR=1.74; 95% CI, 0.97-3.11).

Reduction of seizures was consistent across all trials. However, a subgroup analysis of high-risk pregnancies (advanced maternal age, diabetes mellitus, chronic hypertension, renal disease, preeclampsia, cardiac disease, renal disease, previous delivery of a low-birth-weight infant) didn’t find a statistically significant decrease in seizures.

Cesarean deliveries rise, regardless of patient risk status
Continuous EFM raised the rates of cesarean delivery (RR=1.66; 95% CI, 1.30-2.13) and instrumental vaginal deliveries (RR=1.16; 95% CI, 1.01-1.32). The increased rate of cesarean section in the EFM group was consistent regardless of clinical risk status (low- vs high-risk women). One additional cesarean section was performed for every 58 women monitored continuously. For “high-risk” women, 1 additional cesarean section was performed for every 12 women monitored continuously.¹

Cesarean section rates varied widely among the individual trials (2.3%-35%). Analysis suggested that studies with higher baseline rates showed the greatest increases with continuous EFM. The rate for all studies combined was just 4.3%; 69% of patients included in the meta-analysis were contributed by the Dublin trial, which had an average cesarean rate of 2.3%.¹ By comparison, the US Division of Vital Statistics reported a cesarean rate of 32.3% in 2008.²

EFM reduces death from fetal hypoxia
A 1995 meta-analysis, including 9 of the Cochrane review studies with a total of 18,561 women, evaluated the additional outcome of death resulting from fetal hypoxia.³ Compared with IA, EFM was associated with a 59% reduction in death from fetal hypoxia (RR=0.41; 95% CI, 0.17-0.98). Continuous EFM prevented 1 perinatal death per 1000 births. The reduction in perinatal mortality was offset by a 53% increase in cesarean deliveries and a 23% increase in operative vaginal deliveries.³

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) doesn’t recommend for or against continuous fetal heart rate monitoring in uncomplicated labor, recognizing either EFM or IA as acceptable in uncomplicated patients.⁴ ACOG does recommend continuous EFM for women with high-risk conditions (suspected fetal growth restriction, preeclampsia, and type 1 diabetes mellitus).

The US Preventive Services Task Force doesn’t support routine intrapartum EFM for low-risk woman. The Task Force found insufficient evidence for using EFM in high-risk pregnancies.⁵

The Royal College of Obstetricians and Gynaecologists and the Royal Australian and New Zealand College of Obstetricians and Gynecologists both recommend continuous EFM for high-risk women and IA for low-risk patients.^6,7

Acknowledgements
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army Medical Department or the US Army at large.

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

Psychotic symptoms, including aggression, in patients with dementia are a leading cause of nursing home placement and pharmacologic treatment. RCTs have demonstrated the efficacy of atypical antipsychotics in aggressive nursing home patients.

Risperidone significantly reduces aggression
An RCT comparing risperidone with placebo in 345 patients found that low-dose risperidone (mean 0.95 mg/d) significantly improved aggression scores (number needed to treat [NNT][H11005]4; P<.001). Serious adverse events included injury, cerebrovascular events, pneumonia, and accidental overdose (number needed to harm [NNH][H11005]13).¹ Other RCTs also have found risperidone to be effective in reducing aggressive behavior.^2,3

Olanzapine is effective and well tolerated
Researchers have also studied olanzapine, another atypical antipsychotic. A 6-week RCT of 206 elderly nursing home patients with Alzheimer’s disease and psychotic or behavioral symptoms found that low-dose olanzapine (5 or 10 mg/d) decreased agitation and aggression scores (olanzapine 5 mg: NNT=5; olanzapine 10 mg: NNT=6) compared with placebo. Commonly reported adverse effects included somnolence (5 mg: NNH=5; 10 mg: NNH=5) and gait disturbance (5 mg: NNH=6; 10 mg: NNH=8).⁴ An open-label follow-up study also found low-dose olanzapine to be well tolerated and effective in decreasing agitation and aggression scores.⁵

Weigh the benefits against the risks
The US Food and Drug Administration issued a public health advisory regarding increased mortality risk after reviewing RCTs that evaluated atypical antipsychotics in patients with dementia.⁶ A meta-analysis of 15 RCTs (N=5110) that studied olanzapine, aripiprazole, risperidone, and quetiapine in patients with dementia demonstrated a small, but increased risk of death associated with their use when compared with placebo (3.5% vs 2.3%; odds ratio=1.54; 95% confidence interval [CI], 1.06-2.23; P=.02; NNH= 83).⁷

A population-based (community and long-term care facilities), retrospective cohort study of atypical and conventional antipsychotics involving 27,259 matched pairs also suggested an increased risk of death. Thirty days after beginning an atypical antipsychotic medication, increased mortality was noted when compared with no antipsychotic use in both the community cohort (adjusted hazard ratio [AHR]=1.31 [95% CI, 1.02-1.70]; NNH=500) and the long-term care cohort (AHR=1.55 [95% CI, 1.15-2.07]; absolute risk difference=1.2 percentage points; NNH=83). Conventional antipsychotics were associated with higher rates of death than atypical antipsychotics (absolute risk difference=2.6 percentage points in the community group [NNH=38] and 2.2 percentage points in the long-term care groups [NNH=45]).⁸

SSRIs may be an alternative
An RCT comparing citalopram and risperidone over 12 weeks in 103 patients with dementia demonstrated similar efficacy for the 2 drugs in treating agitation. Patients receiving citalopram experienced fewer adverse effects than those receiving risperidone.⁹ The study suggests that SSRIs may be an alternative to atypical antipsychotics.

Carbamazepine helps, valproate doesn’t
Evidence regarding the use of antiepileptic medications is conflicting. One RCT of 51 patients found carbamazepine 300 mg daily to be efficacious for short-term control of agitation with good safety and tolerability. Six weeks after beginning the study, Overt Aggression Scale scores decreased 6.7 points for carbamazepine compared with 1.9 points for placebo (P=.008). Adverse effects, including ataxia, drowsiness, postural instability, rash, weakness, and disorientation, were more common in the carbamazepine group than the placebo group (absolute risk increase=30%; NNH=3).¹⁰

When compared with placebo, 480 mg daily of sodium valproate for 8 weeks showed no differences in controlling aggressive behavior.¹¹ In an open-label follow-up study, aggressive behavior improved from 10.52 on the Social Dysfunction and Aggression Scale to 6.31 (P<.001), but no improvement was observed using the Clinical Global Impression Scale for aggressive behavior. Seven deaths that authors couldn’t attribute to the drug occurred. Three patients experienced drowsiness. No other adverse events were noted.¹²

A very small, double-blind crossover RCT (N=14) evaluated 250 to 1500 mg sodium valproate daily for 6 weeks compared with placebo. A 2-week period separated the valproate and placebo regimens. Neuropsychiatric Inventory agitation and aggression scores worsened significantly with valproate (increase of 1.43 points compared with a decrease of 2.08 points with placebo; P=.04). Adverse events related to valproate included falls, sedation, loss of appetite, thrombocytopenia, and loose stools (NNH=3).¹³

Recommendations

The Expert Consensus Guideline for the Treatment of Agitation in Older Persons with Dementia¹⁴ and treatment guidelines for Alzheimer’s disease and other dementias from the American Psychiatric Association (APA)¹⁵ offer different recommendations for first-line treatment.

The Expert Consensus Guideline recommends divalproate, risperidone, and conventional high-potency antipsychotics for patients with severe anger and physical aggression. Alternative treatments include olanzapine, carbamazepine, trazodone, and SSRIs.¹⁴

The APA recommends antipsychotics to treat agitation based on available evidence. If treatment fails, consider anticonvulsants, lithium, or beta-blockers. The APA notes that although evidence for SSRIs is limited, they may be appropriate for agitated nonpsychotic patients.¹⁵

Evidence summary

Psychotic symptoms, including aggression, in patients with dementia are a leading cause of nursing home placement and pharmacologic treatment. RCTs have demonstrated the efficacy of atypical antipsychotics in aggressive nursing home patients.

Risperidone significantly reduces aggression
An RCT comparing risperidone with placebo in 345 patients found that low-dose risperidone (mean 0.95 mg/d) significantly improved aggression scores (number needed to treat [NNT][H11005]4; P<.001). Serious adverse events included injury, cerebrovascular events, pneumonia, and accidental overdose (number needed to harm [NNH][H11005]13).¹ Other RCTs also have found risperidone to be effective in reducing aggressive behavior.^2,3

Olanzapine is effective and well tolerated
Researchers have also studied olanzapine, another atypical antipsychotic. A 6-week RCT of 206 elderly nursing home patients with Alzheimer’s disease and psychotic or behavioral symptoms found that low-dose olanzapine (5 or 10 mg/d) decreased agitation and aggression scores (olanzapine 5 mg: NNT=5; olanzapine 10 mg: NNT=6) compared with placebo. Commonly reported adverse effects included somnolence (5 mg: NNH=5; 10 mg: NNH=5) and gait disturbance (5 mg: NNH=6; 10 mg: NNH=8).⁴ An open-label follow-up study also found low-dose olanzapine to be well tolerated and effective in decreasing agitation and aggression scores.⁵

Weigh the benefits against the risks
The US Food and Drug Administration issued a public health advisory regarding increased mortality risk after reviewing RCTs that evaluated atypical antipsychotics in patients with dementia.⁶ A meta-analysis of 15 RCTs (N=5110) that studied olanzapine, aripiprazole, risperidone, and quetiapine in patients with dementia demonstrated a small, but increased risk of death associated with their use when compared with placebo (3.5% vs 2.3%; odds ratio=1.54; 95% confidence interval [CI], 1.06-2.23; P=.02; NNH= 83).⁷

A population-based (community and long-term care facilities), retrospective cohort study of atypical and conventional antipsychotics involving 27,259 matched pairs also suggested an increased risk of death. Thirty days after beginning an atypical antipsychotic medication, increased mortality was noted when compared with no antipsychotic use in both the community cohort (adjusted hazard ratio [AHR]=1.31 [95% CI, 1.02-1.70]; NNH=500) and the long-term care cohort (AHR=1.55 [95% CI, 1.15-2.07]; absolute risk difference=1.2 percentage points; NNH=83). Conventional antipsychotics were associated with higher rates of death than atypical antipsychotics (absolute risk difference=2.6 percentage points in the community group [NNH=38] and 2.2 percentage points in the long-term care groups [NNH=45]).⁸

SSRIs may be an alternative
An RCT comparing citalopram and risperidone over 12 weeks in 103 patients with dementia demonstrated similar efficacy for the 2 drugs in treating agitation. Patients receiving citalopram experienced fewer adverse effects than those receiving risperidone.⁹ The study suggests that SSRIs may be an alternative to atypical antipsychotics.

Carbamazepine helps, valproate doesn’t
Evidence regarding the use of antiepileptic medications is conflicting. One RCT of 51 patients found carbamazepine 300 mg daily to be efficacious for short-term control of agitation with good safety and tolerability. Six weeks after beginning the study, Overt Aggression Scale scores decreased 6.7 points for carbamazepine compared with 1.9 points for placebo (P=.008). Adverse effects, including ataxia, drowsiness, postural instability, rash, weakness, and disorientation, were more common in the carbamazepine group than the placebo group (absolute risk increase=30%; NNH=3).¹⁰

When compared with placebo, 480 mg daily of sodium valproate for 8 weeks showed no differences in controlling aggressive behavior.¹¹ In an open-label follow-up study, aggressive behavior improved from 10.52 on the Social Dysfunction and Aggression Scale to 6.31 (P<.001), but no improvement was observed using the Clinical Global Impression Scale for aggressive behavior. Seven deaths that authors couldn’t attribute to the drug occurred. Three patients experienced drowsiness. No other adverse events were noted.¹²

A very small, double-blind crossover RCT (N=14) evaluated 250 to 1500 mg sodium valproate daily for 6 weeks compared with placebo. A 2-week period separated the valproate and placebo regimens. Neuropsychiatric Inventory agitation and aggression scores worsened significantly with valproate (increase of 1.43 points compared with a decrease of 2.08 points with placebo; P=.04). Adverse events related to valproate included falls, sedation, loss of appetite, thrombocytopenia, and loose stools (NNH=3).¹³

Recommendations

The Expert Consensus Guideline for the Treatment of Agitation in Older Persons with Dementia¹⁴ and treatment guidelines for Alzheimer’s disease and other dementias from the American Psychiatric Association (APA)¹⁵ offer different recommendations for first-line treatment.

The Expert Consensus Guideline recommends divalproate, risperidone, and conventional high-potency antipsychotics for patients with severe anger and physical aggression. Alternative treatments include olanzapine, carbamazepine, trazodone, and SSRIs.¹⁴

The APA recommends antipsychotics to treat agitation based on available evidence. If treatment fails, consider anticonvulsants, lithium, or beta-blockers. The APA notes that although evidence for SSRIs is limited, they may be appropriate for agitated nonpsychotic patients.¹⁵

Evidence summary

Psychotic symptoms, including aggression, in patients with dementia are a leading cause of nursing home placement and pharmacologic treatment. RCTs have demonstrated the efficacy of atypical antipsychotics in aggressive nursing home patients.

Risperidone significantly reduces aggression
An RCT comparing risperidone with placebo in 345 patients found that low-dose risperidone (mean 0.95 mg/d) significantly improved aggression scores (number needed to treat [NNT][H11005]4; P<.001). Serious adverse events included injury, cerebrovascular events, pneumonia, and accidental overdose (number needed to harm [NNH][H11005]13).¹ Other RCTs also have found risperidone to be effective in reducing aggressive behavior.^2,3

Olanzapine is effective and well tolerated
Researchers have also studied olanzapine, another atypical antipsychotic. A 6-week RCT of 206 elderly nursing home patients with Alzheimer’s disease and psychotic or behavioral symptoms found that low-dose olanzapine (5 or 10 mg/d) decreased agitation and aggression scores (olanzapine 5 mg: NNT=5; olanzapine 10 mg: NNT=6) compared with placebo. Commonly reported adverse effects included somnolence (5 mg: NNH=5; 10 mg: NNH=5) and gait disturbance (5 mg: NNH=6; 10 mg: NNH=8).⁴ An open-label follow-up study also found low-dose olanzapine to be well tolerated and effective in decreasing agitation and aggression scores.⁵

Weigh the benefits against the risks
The US Food and Drug Administration issued a public health advisory regarding increased mortality risk after reviewing RCTs that evaluated atypical antipsychotics in patients with dementia.⁶ A meta-analysis of 15 RCTs (N=5110) that studied olanzapine, aripiprazole, risperidone, and quetiapine in patients with dementia demonstrated a small, but increased risk of death associated with their use when compared with placebo (3.5% vs 2.3%; odds ratio=1.54; 95% confidence interval [CI], 1.06-2.23; P=.02; NNH= 83).⁷

A population-based (community and long-term care facilities), retrospective cohort study of atypical and conventional antipsychotics involving 27,259 matched pairs also suggested an increased risk of death. Thirty days after beginning an atypical antipsychotic medication, increased mortality was noted when compared with no antipsychotic use in both the community cohort (adjusted hazard ratio [AHR]=1.31 [95% CI, 1.02-1.70]; NNH=500) and the long-term care cohort (AHR=1.55 [95% CI, 1.15-2.07]; absolute risk difference=1.2 percentage points; NNH=83). Conventional antipsychotics were associated with higher rates of death than atypical antipsychotics (absolute risk difference=2.6 percentage points in the community group [NNH=38] and 2.2 percentage points in the long-term care groups [NNH=45]).⁸

SSRIs may be an alternative
An RCT comparing citalopram and risperidone over 12 weeks in 103 patients with dementia demonstrated similar efficacy for the 2 drugs in treating agitation. Patients receiving citalopram experienced fewer adverse effects than those receiving risperidone.⁹ The study suggests that SSRIs may be an alternative to atypical antipsychotics.

Carbamazepine helps, valproate doesn’t
Evidence regarding the use of antiepileptic medications is conflicting. One RCT of 51 patients found carbamazepine 300 mg daily to be efficacious for short-term control of agitation with good safety and tolerability. Six weeks after beginning the study, Overt Aggression Scale scores decreased 6.7 points for carbamazepine compared with 1.9 points for placebo (P=.008). Adverse effects, including ataxia, drowsiness, postural instability, rash, weakness, and disorientation, were more common in the carbamazepine group than the placebo group (absolute risk increase=30%; NNH=3).¹⁰

When compared with placebo, 480 mg daily of sodium valproate for 8 weeks showed no differences in controlling aggressive behavior.¹¹ In an open-label follow-up study, aggressive behavior improved from 10.52 on the Social Dysfunction and Aggression Scale to 6.31 (P<.001), but no improvement was observed using the Clinical Global Impression Scale for aggressive behavior. Seven deaths that authors couldn’t attribute to the drug occurred. Three patients experienced drowsiness. No other adverse events were noted.¹²

A very small, double-blind crossover RCT (N=14) evaluated 250 to 1500 mg sodium valproate daily for 6 weeks compared with placebo. A 2-week period separated the valproate and placebo regimens. Neuropsychiatric Inventory agitation and aggression scores worsened significantly with valproate (increase of 1.43 points compared with a decrease of 2.08 points with placebo; P=.04). Adverse events related to valproate included falls, sedation, loss of appetite, thrombocytopenia, and loose stools (NNH=3).¹³

Recommendations

The Expert Consensus Guideline for the Treatment of Agitation in Older Persons with Dementia¹⁴ and treatment guidelines for Alzheimer’s disease and other dementias from the American Psychiatric Association (APA)¹⁵ offer different recommendations for first-line treatment.

The Expert Consensus Guideline recommends divalproate, risperidone, and conventional high-potency antipsychotics for patients with severe anger and physical aggression. Alternative treatments include olanzapine, carbamazepine, trazodone, and SSRIs.¹⁴

The APA recommends antipsychotics to treat agitation based on available evidence. If treatment fails, consider anticonvulsants, lithium, or beta-blockers. The APA notes that although evidence for SSRIs is limited, they may be appropriate for agitated nonpsychotic patients.¹⁵

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸

Evidence summary

A systematic review of 3 RCTs with a total of 649 participants evaluated office spirometry as a motivational tool to improve quit rates by comparing spirometry plus cessation advice with cessation advice alone. All participants were men and women 19 to 75 years of age recruited from outpatient clinics.¹

In 1 trial, the intervention group received repeated counseling at 4 visits and underwent spirometry; the control group had 1 counseling session and was given a brochure. In the other 2 trials, the intervention group had both carbon monoxide measurements and spirometry, and all participants received more extensive counseling, including cessation skills training.

At 9 to 12 months’ follow-up, quit rates ranged from 6% to 24% in the intervention groups vs 5% to 14% in the control groups (not significantly different).¹

A subsequent study randomized 221 smokers to receive either spirometry plus brief cessation advice or advice alone. Researchers recruited patients 15 to 80 years of age who were willing to quit smoking from 16 general practice clinics in Belgium. Fifty-one percent of patients in both groups used nicotine replacement therapy (a larger percentage than is typical in studies done in the United States). At 6, 12, and 24 months, 5%, 2%, and 5% more smokers, respectively, from the spirometry group quit smoking compared with the control group, but this difference was not significant.²

Reporting spirometry results in terms of lung age may spur quitting
One RCT found significantly improved quit rates when patients who smoked were given their office spirometry results in terms of “lung age” (the age of an average healthy person with similar spirometry results) rather than as forced expiratory volume in 1 second (FEV1). Investigators performed office spirometry and gave smoking cessation advice to 561 smokers older than 35 years who were recruited from 5 general practices. They randomized patients to receive their spirometry results as either lung age or FEV1 and recorded quit rates at 12 months (smoking cessation was verified by measuring blood levels of carbon monoxide).

Patients whose spirometry results were reported as lung age were significantly more likely to quit than smokers whose results were given as FEV1 (13.6% vs 6.4%; P=.005; number needed to treat [NNT]=14 smokers counseled using lung age to cause 1 more patient to quit). Smokers with normal lung ages were no more likely to quit than smokers with abnormal results.³

Abnormal results also may be a motivator
However, 3 prospective cohort studies demonstrated that patients with abnormal spirometry results were more likely to quit than patients with normal spirometry. In the first study, 4494 patients with at least 10 pack-years of smoking from 10 outpatient chest clinics in Poland underwent spirometry and were counseled to quit smoking; 1177 had abnormal spirometry results.

One year later, 16.3% of smokers with abnormal results had quit smoking, compared with 12% in the group with normal spirometry (P=.0003; NNT=23).⁴

The second study, also at outpatient chest clinics in Poland, evaluated spirometry plus cessation advice among 558 smokers, 297 of whom had abnormal spirometry results. At 1 year, 10.6% of patients with abnormal results had quit, compared with 8.4% of patients with normal lung function. A subgroup of 109 patients with moderate to severe airflow limitation showed significantly higher quit rates when compared with patients with mildly abnormal spirometry (16.5% vs 6.4%; P<.0001; NNT=10).⁵

In the third study, 6 primary care sites in Sweden provided spirometry and brief cessation advice to 445 smokers, 119 of whom were found to have abnormal lung function. At 3-year follow-up, 29% of patients with abnormal lung function had quit smoking, compared with 14% of patients with normal lung function (P=.001; NNT=7). Forty-five smokers with mildly abnormal lung function were recruited from this study to participate in another study, which may have biased the results toward higher quit rates among smokers with worse spirometry results.⁶

Recommendations

The US Preventive Services Task Force recommends against using spirometry to screen for chronic obstructive pulmonary disease, but advocates screening all adults for tobacco use and encouraging cessation.⁷

The authors of a Cochrane review found insufficient evidence to recommend using biomedical risk assessment (carbon monoxide blood levels, spirometry, genetic testing for alpha-1 antitrypsin deficiency) as a smoking cessation aid.⁸