Clinical Inquiries

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence summary

A 2-part meta-analysis of 26 studies enrolling men, women, or both, showed a significant inverse association between red wine consumption and fatal and nonfatal cardiovascular events. The first part, encompassing 13 studies (5 prospective cohort and 8 case-control studies with a total of 209,418 participants), compared moderate wine drinkers with non-drinkers and heavy or binge drinkers. Moderate drinkers consumed an average of 1 to 2 drinks per day.¹ This meta-analysis, and other studies described in this summary, defined a drink as 130 mL of wine with 12% ethanol content.

For all 13 studies combined, moderate wine drinking significantly reduced cardiovascular events at 2 to 24 years of follow-up compared with no drinking and heavy drinking (relative risk [RR]=0.68; 95% confidence interval [CI], 0.59-0.77). A pool of the 7 studies that enrolled both male and female participants also found that wine drinking significantly reduced cardiovascular events (RR=0.53; 95% CI, 0.42-0.68). However, pooled results from the 6 studies with exclusively male participants found no difference in cardiovascular events with wine consumption (RR=0.87; 95% CI, 0.68-1.12). Beer drinking, which was also evaluated, produced statistically significant risk reductions in studies of both men and women; the effect was smaller in men-only studies.¹

CV risk decreases with increased wine intake—to a point
The second part of the meta-analysis, 7 prospective cohort and 3 case-control studies with a total of 176,042 participants, found an apparent J-shaped dose-response relationship between wine intake and cardiovascular risk reduction. Daily consumption ranged from 0 to 1738 mL, although most participants had 0 to 3 drinks (390 mL) per day. Data from the 7 prospective studies illustrated a progressive decrease in cardiovascular risk as wine intake increased to 150 mL per day. Consuming larger amounts of wine (as much as 750 mL per day) showed a trend toward further cardiovascular risk reduction, but the trend wasn’t statistically significant.¹

High flavonoid intake is associated with lower CHD mortality

A meta-analysis of 7 prospective cohort studies including 105,000 men and women 30 to 84 years of age indicated that a high dietary intake of flavonoids (present in larger amounts in red wine, chocolate, tea, and other foods) correlated with reduced CHD mortality. Participants whose flavonoid consumption was in the highest third had significantly less CHD mortality than participants in the bottom third (RR=0.80; 95% CI, 0.69-0.93; P<.001). The meta-analysis couldn’t determine whether the flavonoid content of red wine confers additional cardiovascular benefit beyond that of alcohol alone.²

Heavy drinking increases risk of stroke
A meta-analysis of 41 studies (3 cross-sectional, 21 case-control, and 17 cohort studies) enrolling both men and women, correlated heavy alcohol drinking (>4 drinks per day, on average) with increased risk of stroke. Seven of 9 retrospective studies associated heavy drinking with an increase in risk as great as 6.5-fold for hemorrhagic and ischemic stroke, but found no consistent association between stroke and light-to-moderate drinking. Evidence was insufficient to evaluate stroke risks specific to low or moderate wine intake.³

Recommendations

The US Department of Health and Human Services’ Dietary Guidelines for Americans 2005 state that moderate daily wine intake in adults (5 oz for women and 10 oz for men) is associated with the lowest all-cause mortality and CHD. The guidelines warn against drinking by people who are susceptible to the harmful effects of alcohol and participants in activities that require attention, skill, or coordination.⁴

The American Heart Association states that moderate alcohol consumption (1-2 drinks daily) may be considered safe in the absence of contraindications, and recommends consulting a physician first.⁵

The National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health says that moderate drinkers are less likely to die from coronary artery disease than are people who don’t drink any alcohol or who drink more alcohol. It recommends against nondrinkers starting to drink solely to benefit their hearts, however.⁶

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Low back pain, defined as pain between the thoracic cage and proximal thighs, is the fifth most common reason for physician visits in the United States.^1,2 The pain can be characterized by its duration: acute, <4 weeks; subacute, >4 weeks but <3 months; and chronic, >3 months.^1,3

Pharmacologic treatments for low back pain include nonsteroidal anti-inflammatory agents, opioids, and muscle relaxants.^2,3 Nonpharmacologic options comprise exercise, physical therapy, massage, acupuncture, and yoga.^2,3 Self-care includes handouts, books, heat, cognitive-behavioral therapy, and interdisciplinary rehabilitation. Traction, corsets, bed rest, home care, and diathermy are considered harmful.³

How SMT compares with other treatments
A 2004 Cochrane meta-analysis of 39 RCTs with a total of 5486 patients concluded that SMT was superior to placebo and as effective as all other treatments in reducing low back pain.³ SMT wasn’t more helpful than other forms of treatment.^1,3 Neither the professional training of the SMT provider nor the patient’s level of radiating pain was associated with better outcomes.³

Compared with patients who received sham therapy for acute low back pain, SMT-treated patients showed a 10-mm improvement in pain on a visual analog scale (VAS) (95% confidence interval [CI], 2-17 mm) and no statistically significant difference in function on the Roland-Morris Disability Questionnaire (RMDQ).³ No significant clinical or statistical differences were noted between SMT and conventional care/analgesics, physical therapy/exercise, and back school.

SMT patients reported only slightly more pain reduction (4 mm on a 100-mm scale [95% CI, 1-8 mm]) and no significant improvement in function compared with patients treated with nonbeneficial modalities, such as traction, bed rest, or topical gel.

Patients with chronic low back pain showed a 19-mm improvement in pain on the VAS (95% CI, 3-35 mm) and functional gains of 3.3 mm on the RMDQ (95% CI, 0.6-6.0 mm) compared with patients receiving sham therapy.

Complications from SMT are rare
The American Pain Society (APS) and the American College of Physicians (ACP) recently published a comprehensive review of RCTs published from 2000 to 2006 that examined nonpharmacologic treatments for low back pain.² They evaluated 69 trials in 10 systematic reviews of the efficacy of SMT. Five higher-quality reviews reached conclusions consistent with the Cochrane review—there was no difference between SMT and other effective therapies. Two lower-quality reviews (based on 1-3 trials with low numbers) found SMT superior to other effective treatments.^1,2

Based on a review of more than 70 controlled trials, the APS and ACP concluded that the risk of a serious complication from SMT (worsening lumbar disk herniation or cauda equina syndrome) is rare, less than 1 per 1 million patient visits.²

Recommendations

The APS and ACP guidelines recommend adding nonpharmacologic therapies such as SMT for acute, subacute, and chronic low back pain when patients don’t improve with self-care.⁴

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the US air Force medical Service or the US air Force at large.

Evidence summary

Low back pain, defined as pain between the thoracic cage and proximal thighs, is the fifth most common reason for physician visits in the United States.^1,2 The pain can be characterized by its duration: acute, <4 weeks; subacute, >4 weeks but <3 months; and chronic, >3 months.^1,3

Pharmacologic treatments for low back pain include nonsteroidal anti-inflammatory agents, opioids, and muscle relaxants.^2,3 Nonpharmacologic options comprise exercise, physical therapy, massage, acupuncture, and yoga.^2,3 Self-care includes handouts, books, heat, cognitive-behavioral therapy, and interdisciplinary rehabilitation. Traction, corsets, bed rest, home care, and diathermy are considered harmful.³

How SMT compares with other treatments
A 2004 Cochrane meta-analysis of 39 RCTs with a total of 5486 patients concluded that SMT was superior to placebo and as effective as all other treatments in reducing low back pain.³ SMT wasn’t more helpful than other forms of treatment.^1,3 Neither the professional training of the SMT provider nor the patient’s level of radiating pain was associated with better outcomes.³

Compared with patients who received sham therapy for acute low back pain, SMT-treated patients showed a 10-mm improvement in pain on a visual analog scale (VAS) (95% confidence interval [CI], 2-17 mm) and no statistically significant difference in function on the Roland-Morris Disability Questionnaire (RMDQ).³ No significant clinical or statistical differences were noted between SMT and conventional care/analgesics, physical therapy/exercise, and back school.

SMT patients reported only slightly more pain reduction (4 mm on a 100-mm scale [95% CI, 1-8 mm]) and no significant improvement in function compared with patients treated with nonbeneficial modalities, such as traction, bed rest, or topical gel.

Patients with chronic low back pain showed a 19-mm improvement in pain on the VAS (95% CI, 3-35 mm) and functional gains of 3.3 mm on the RMDQ (95% CI, 0.6-6.0 mm) compared with patients receiving sham therapy.

Complications from SMT are rare
The American Pain Society (APS) and the American College of Physicians (ACP) recently published a comprehensive review of RCTs published from 2000 to 2006 that examined nonpharmacologic treatments for low back pain.² They evaluated 69 trials in 10 systematic reviews of the efficacy of SMT. Five higher-quality reviews reached conclusions consistent with the Cochrane review—there was no difference between SMT and other effective therapies. Two lower-quality reviews (based on 1-3 trials with low numbers) found SMT superior to other effective treatments.^1,2

Based on a review of more than 70 controlled trials, the APS and ACP concluded that the risk of a serious complication from SMT (worsening lumbar disk herniation or cauda equina syndrome) is rare, less than 1 per 1 million patient visits.²

Recommendations

The APS and ACP guidelines recommend adding nonpharmacologic therapies such as SMT for acute, subacute, and chronic low back pain when patients don’t improve with self-care.⁴

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the US air Force medical Service or the US air Force at large.

Evidence summary

Low back pain, defined as pain between the thoracic cage and proximal thighs, is the fifth most common reason for physician visits in the United States.^1,2 The pain can be characterized by its duration: acute, <4 weeks; subacute, >4 weeks but <3 months; and chronic, >3 months.^1,3

Pharmacologic treatments for low back pain include nonsteroidal anti-inflammatory agents, opioids, and muscle relaxants.^2,3 Nonpharmacologic options comprise exercise, physical therapy, massage, acupuncture, and yoga.^2,3 Self-care includes handouts, books, heat, cognitive-behavioral therapy, and interdisciplinary rehabilitation. Traction, corsets, bed rest, home care, and diathermy are considered harmful.³

How SMT compares with other treatments
A 2004 Cochrane meta-analysis of 39 RCTs with a total of 5486 patients concluded that SMT was superior to placebo and as effective as all other treatments in reducing low back pain.³ SMT wasn’t more helpful than other forms of treatment.^1,3 Neither the professional training of the SMT provider nor the patient’s level of radiating pain was associated with better outcomes.³

Compared with patients who received sham therapy for acute low back pain, SMT-treated patients showed a 10-mm improvement in pain on a visual analog scale (VAS) (95% confidence interval [CI], 2-17 mm) and no statistically significant difference in function on the Roland-Morris Disability Questionnaire (RMDQ).³ No significant clinical or statistical differences were noted between SMT and conventional care/analgesics, physical therapy/exercise, and back school.

SMT patients reported only slightly more pain reduction (4 mm on a 100-mm scale [95% CI, 1-8 mm]) and no significant improvement in function compared with patients treated with nonbeneficial modalities, such as traction, bed rest, or topical gel.

Patients with chronic low back pain showed a 19-mm improvement in pain on the VAS (95% CI, 3-35 mm) and functional gains of 3.3 mm on the RMDQ (95% CI, 0.6-6.0 mm) compared with patients receiving sham therapy.

Complications from SMT are rare
The American Pain Society (APS) and the American College of Physicians (ACP) recently published a comprehensive review of RCTs published from 2000 to 2006 that examined nonpharmacologic treatments for low back pain.² They evaluated 69 trials in 10 systematic reviews of the efficacy of SMT. Five higher-quality reviews reached conclusions consistent with the Cochrane review—there was no difference between SMT and other effective therapies. Two lower-quality reviews (based on 1-3 trials with low numbers) found SMT superior to other effective treatments.^1,2

Based on a review of more than 70 controlled trials, the APS and ACP concluded that the risk of a serious complication from SMT (worsening lumbar disk herniation or cauda equina syndrome) is rare, less than 1 per 1 million patient visits.²

Recommendations

The APS and ACP guidelines recommend adding nonpharmacologic therapies such as SMT for acute, subacute, and chronic low back pain when patients don’t improve with self-care.⁴

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the US air Force medical Service or the US air Force at large.

Evidence summary

The possible risks and benefits of lowering fever with antipyretics have prompted much discussion in the medical literature. Most evidence supporting the useful effects of fever comes from animal models. A few human studies in special populations (patients with brain trauma) suggest that antipyretics may worsen certain aspects of disease processes.¹ However, many studies show that antipyretics do clinically benefit, and don’t harm, the typical child with an upper respiratory illness.^2-4

Acetaminophen improves some symptoms, but doesn’t shorten fever
A double-blind, randomized, placebo-controlled trial of 210 children with upper respiratory illness showed that giving acetaminophen significantly increased short-term temperature reduction compared with placebo (0.36°F vs 0.09°F/hr; P<.001). Acetaminophen also improved subjective symptoms at 6 hours over placebo: activity (60% vs 16%; P<.001), alertness (58% vs 21%; P<.001), comfort (37% vs 7%; P<.001), mood (36% vs 12%; P<.001), appetite (20% vs 1%; P<0.001), and fluid intake (22% vs 2%; P<.001).² Total time until complete resolution of fever (defined as no fever with or without medication) didn’t differ between treatment and placebo groups (32 hr for acetaminophen vs 36 hr for placebo; P=.23).²

A similar study failed to show a statistically significant difference between acetaminophen and placebo in fever clearance time (34.7 vs 36.1 hr), mood, comfort, or appetite. However, the study did find significant improvement in activity (38% vs 11%; P=.005) and alertness (33% vs 12%; P=.036) based on parents’ reports.³

Ibuprofen is a better antipyretic than acetaminophen
A meta-analysis (N=84,192) comparing acetaminophen with ibuprofen found both drugs to be equally efficacious analgesics; ibuprofen was a more effective antipyretic. Both drugs had the same level of adverse outcomes when compared with each other and placebo.⁵

Lowering fever doesn’t reduce recurrence of febrile seizures
Antipyretics don’t appear to affect the recurrence of febrile seizures. In a well-designed, randomized, double-blind, placebo-controlled trial, 230 patients 1 to 4 years of age with 1 or more risk factors for febrile seizures were randomized to fever reduction with ibuprofen or placebo. The estimated 2-year probability for recurrent febrile seizure was 32% in the ibuprofen group and 39% for the placebo group. The difference between the groups was not significant (relative risk=0.9; 95% confidence interval [CI], 0.6-1.5).⁶

Varicella lesions crust more slowly with acetaminophen
An RCT involving 68 children with varicella found that acetaminophen increased the time for lesions to crust compared with placebo (6.7 days for acetaminophen vs 5.6 days for placebo) and that acetaminophen didn’t alleviate itching or improve appetite. However, patients taking acetaminophen were more active by day 2.⁷

NSAIDs don’t cause necrotizing fasciitis
A case-control study of 48 children with varicella suggested an association between ibuprofen and increased incidence of necrotizing soft tissue infections (odds ratio [OR]=11.5; 95% CI, 1.4-96.9),⁸ but larger reviews haven’t borne out this finding. A review of 5 prospective studies of nonsteroidal anti-inflammatory drugs and invasive soft-tissue infections (N=912; 114 cases of necrotizing fasciitis) failed to show any connection. The largest study (474 cases) suggested a trend that was not statistically significant (OR=3.5; 95% CI, 0.8-16).⁹

Nonpharmacologic measures also lower fever
A Cochrane review showed that cool water sponging caused fever reduction similar to antipyretics at 1 hour; sponging combined with ibuprofen reduced the proportion of patients still febrile at 1 hour. Common side effects of sponging included goose pimples and shivering. The antipyretic effect didn’t last beyond a few hours.¹⁰

Recommendations

Concerning treatment of fever, Nelson’s Pediatrics states, “Fever with temperatures less than 39°C (102.2°F) in healthy children generally does not require treatment. As temperatures become higher, patients tend to become more uncomfortable and administration of antipyretics often makes patients feel better. Other than providing symptomatic relief, antipyretic therapy does not change the course of infectious diseases. Antipyretic therapy is beneficial in high-risk patients who have chronic cardiopulmonary diseases, metabolic disorders, or neurologic diseases and in those who are at risk for febrile seizures. Hyperpyrexia (>41°C [105.8°F]) indicates greater risk for severe infection and should always be treated with antipyretics.”¹¹

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the US Air Force at large.

Evidence summary

The possible risks and benefits of lowering fever with antipyretics have prompted much discussion in the medical literature. Most evidence supporting the useful effects of fever comes from animal models. A few human studies in special populations (patients with brain trauma) suggest that antipyretics may worsen certain aspects of disease processes.¹ However, many studies show that antipyretics do clinically benefit, and don’t harm, the typical child with an upper respiratory illness.^2-4

Acetaminophen improves some symptoms, but doesn’t shorten fever
A double-blind, randomized, placebo-controlled trial of 210 children with upper respiratory illness showed that giving acetaminophen significantly increased short-term temperature reduction compared with placebo (0.36°F vs 0.09°F/hr; P<.001). Acetaminophen also improved subjective symptoms at 6 hours over placebo: activity (60% vs 16%; P<.001), alertness (58% vs 21%; P<.001), comfort (37% vs 7%; P<.001), mood (36% vs 12%; P<.001), appetite (20% vs 1%; P<0.001), and fluid intake (22% vs 2%; P<.001).² Total time until complete resolution of fever (defined as no fever with or without medication) didn’t differ between treatment and placebo groups (32 hr for acetaminophen vs 36 hr for placebo; P=.23).²

A similar study failed to show a statistically significant difference between acetaminophen and placebo in fever clearance time (34.7 vs 36.1 hr), mood, comfort, or appetite. However, the study did find significant improvement in activity (38% vs 11%; P=.005) and alertness (33% vs 12%; P=.036) based on parents’ reports.³

Ibuprofen is a better antipyretic than acetaminophen
A meta-analysis (N=84,192) comparing acetaminophen with ibuprofen found both drugs to be equally efficacious analgesics; ibuprofen was a more effective antipyretic. Both drugs had the same level of adverse outcomes when compared with each other and placebo.⁵

Lowering fever doesn’t reduce recurrence of febrile seizures
Antipyretics don’t appear to affect the recurrence of febrile seizures. In a well-designed, randomized, double-blind, placebo-controlled trial, 230 patients 1 to 4 years of age with 1 or more risk factors for febrile seizures were randomized to fever reduction with ibuprofen or placebo. The estimated 2-year probability for recurrent febrile seizure was 32% in the ibuprofen group and 39% for the placebo group. The difference between the groups was not significant (relative risk=0.9; 95% confidence interval [CI], 0.6-1.5).⁶

Varicella lesions crust more slowly with acetaminophen
An RCT involving 68 children with varicella found that acetaminophen increased the time for lesions to crust compared with placebo (6.7 days for acetaminophen vs 5.6 days for placebo) and that acetaminophen didn’t alleviate itching or improve appetite. However, patients taking acetaminophen were more active by day 2.⁷

NSAIDs don’t cause necrotizing fasciitis
A case-control study of 48 children with varicella suggested an association between ibuprofen and increased incidence of necrotizing soft tissue infections (odds ratio [OR]=11.5; 95% CI, 1.4-96.9),⁸ but larger reviews haven’t borne out this finding. A review of 5 prospective studies of nonsteroidal anti-inflammatory drugs and invasive soft-tissue infections (N=912; 114 cases of necrotizing fasciitis) failed to show any connection. The largest study (474 cases) suggested a trend that was not statistically significant (OR=3.5; 95% CI, 0.8-16).⁹

Nonpharmacologic measures also lower fever
A Cochrane review showed that cool water sponging caused fever reduction similar to antipyretics at 1 hour; sponging combined with ibuprofen reduced the proportion of patients still febrile at 1 hour. Common side effects of sponging included goose pimples and shivering. The antipyretic effect didn’t last beyond a few hours.¹⁰

Recommendations

Concerning treatment of fever, Nelson’s Pediatrics states, “Fever with temperatures less than 39°C (102.2°F) in healthy children generally does not require treatment. As temperatures become higher, patients tend to become more uncomfortable and administration of antipyretics often makes patients feel better. Other than providing symptomatic relief, antipyretic therapy does not change the course of infectious diseases. Antipyretic therapy is beneficial in high-risk patients who have chronic cardiopulmonary diseases, metabolic disorders, or neurologic diseases and in those who are at risk for febrile seizures. Hyperpyrexia (>41°C [105.8°F]) indicates greater risk for severe infection and should always be treated with antipyretics.”¹¹

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the US Air Force at large.

Evidence summary

The possible risks and benefits of lowering fever with antipyretics have prompted much discussion in the medical literature. Most evidence supporting the useful effects of fever comes from animal models. A few human studies in special populations (patients with brain trauma) suggest that antipyretics may worsen certain aspects of disease processes.¹ However, many studies show that antipyretics do clinically benefit, and don’t harm, the typical child with an upper respiratory illness.^2-4

Acetaminophen improves some symptoms, but doesn’t shorten fever
A double-blind, randomized, placebo-controlled trial of 210 children with upper respiratory illness showed that giving acetaminophen significantly increased short-term temperature reduction compared with placebo (0.36°F vs 0.09°F/hr; P<.001). Acetaminophen also improved subjective symptoms at 6 hours over placebo: activity (60% vs 16%; P<.001), alertness (58% vs 21%; P<.001), comfort (37% vs 7%; P<.001), mood (36% vs 12%; P<.001), appetite (20% vs 1%; P<0.001), and fluid intake (22% vs 2%; P<.001).² Total time until complete resolution of fever (defined as no fever with or without medication) didn’t differ between treatment and placebo groups (32 hr for acetaminophen vs 36 hr for placebo; P=.23).²

A similar study failed to show a statistically significant difference between acetaminophen and placebo in fever clearance time (34.7 vs 36.1 hr), mood, comfort, or appetite. However, the study did find significant improvement in activity (38% vs 11%; P=.005) and alertness (33% vs 12%; P=.036) based on parents’ reports.³

Ibuprofen is a better antipyretic than acetaminophen
A meta-analysis (N=84,192) comparing acetaminophen with ibuprofen found both drugs to be equally efficacious analgesics; ibuprofen was a more effective antipyretic. Both drugs had the same level of adverse outcomes when compared with each other and placebo.⁵

Lowering fever doesn’t reduce recurrence of febrile seizures
Antipyretics don’t appear to affect the recurrence of febrile seizures. In a well-designed, randomized, double-blind, placebo-controlled trial, 230 patients 1 to 4 years of age with 1 or more risk factors for febrile seizures were randomized to fever reduction with ibuprofen or placebo. The estimated 2-year probability for recurrent febrile seizure was 32% in the ibuprofen group and 39% for the placebo group. The difference between the groups was not significant (relative risk=0.9; 95% confidence interval [CI], 0.6-1.5).⁶

Varicella lesions crust more slowly with acetaminophen
An RCT involving 68 children with varicella found that acetaminophen increased the time for lesions to crust compared with placebo (6.7 days for acetaminophen vs 5.6 days for placebo) and that acetaminophen didn’t alleviate itching or improve appetite. However, patients taking acetaminophen were more active by day 2.⁷

NSAIDs don’t cause necrotizing fasciitis
A case-control study of 48 children with varicella suggested an association between ibuprofen and increased incidence of necrotizing soft tissue infections (odds ratio [OR]=11.5; 95% CI, 1.4-96.9),⁸ but larger reviews haven’t borne out this finding. A review of 5 prospective studies of nonsteroidal anti-inflammatory drugs and invasive soft-tissue infections (N=912; 114 cases of necrotizing fasciitis) failed to show any connection. The largest study (474 cases) suggested a trend that was not statistically significant (OR=3.5; 95% CI, 0.8-16).⁹

Nonpharmacologic measures also lower fever
A Cochrane review showed that cool water sponging caused fever reduction similar to antipyretics at 1 hour; sponging combined with ibuprofen reduced the proportion of patients still febrile at 1 hour. Common side effects of sponging included goose pimples and shivering. The antipyretic effect didn’t last beyond a few hours.¹⁰

Recommendations

Concerning treatment of fever, Nelson’s Pediatrics states, “Fever with temperatures less than 39°C (102.2°F) in healthy children generally does not require treatment. As temperatures become higher, patients tend to become more uncomfortable and administration of antipyretics often makes patients feel better. Other than providing symptomatic relief, antipyretic therapy does not change the course of infectious diseases. Antipyretic therapy is beneficial in high-risk patients who have chronic cardiopulmonary diseases, metabolic disorders, or neurologic diseases and in those who are at risk for febrile seizures. Hyperpyrexia (>41°C [105.8°F]) indicates greater risk for severe infection and should always be treated with antipyretics.”¹¹

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the US Air Force at large.

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

No epidemiologic data on BPPV in the United States are available, but experts describe increasing incidence with advancing age. A recent German study found a lifetime prevalence of 2.4%, with a cumulative incidence approaching 10% by age 80.¹ Treatments include repositioning maneuvers (regimens of positioning the patient’s head and body) and medication. Evidence about treating BPPV in elderly patients specifically is limited.^2-4

These 2 maneuvers work best
Both Epley’s CRM and Semont’s liberatory maneuver have been shown to treat BPPV effectively. (For descriptions of the maneuvers and video links, see “How the Epley and Semont maneuvers work”.)

An RCT with 124 participants (mean age 58.3 years) demonstrated that either Epley’s or Semont’s maneuver decreased the frequency of vertigo more than a sham maneuver (P=.021 and P=.010, respectively).⁵ Both maneuvers were more effective than the Brandt-Daroff home exercises (P=.033).⁵

Another high-quality, double-blind RCT with 67 participants (median age 59 years) reported an improvement in vertigo and nystagmus at 24 hours among 80% of patients treated with Epley’s CRM, compared with 10% of those who received a sham maneuver (P<.001; number needed to treat [NNT]=1; 95% confidence interval [CI], 1-2).⁶

An RCT that enrolled 80 participants (median age 64 years) found complete resolution of BPPV symptoms and a negative Dix-Hallpike test 1 week after treatment in 88% of patients who received Epley’s CRM plus self-treatment (a modified Epley’s maneuver) compared with 69% who received Epley’s CRM alone (P=.048; NNT=5; 95% CI, 3-124).⁷

Posture restrictions are unnecessary
An RCT involving 50 participants (mean age 60.9 years) demonstrated that postprocedure postural restrictions were unnecessary and didn’t improve BPPV remission rates among patients receiving CRM (P=.97). No differences were noted by age or sex.⁸ Two prospective nonrandomized studies found that the recurrence rate of BPPV symptoms was 15% to 18% at 12 months and 37% to 50% at 40 to 60 months.^9,10

Drug studies are scarce, but CRM appears to work better
Studies of drug treatment among patients with BPPV are extremely limited because BPPV as a cause of vertigo is often an exclusion criterion among medication trials. A small (N=20; age range 32-67 years) double-blinded RCT found no difference in dizziness symptom scores for participants with BPPV who took diazepam (5 mg, 3 times daily), lorazepam (1 mg, 3 times daily), or placebo (1 capsule, 3 times daily) over a period of 4 weeks.¹¹

An RCT of 156 patients (mean age 74 years) with BPPV compared a calcium channel blocker (flunarizine, which isn’t available in the United States) with Semont’s liberatory maneuver or no therapy (observation only). Semont’s maneuver was more effective at the 6-month follow-up than either the calcium channel blocker or no therapy; the rates of asymptomatic patients with a negative Dix-Hallpike test at follow-up were 94%, 58%, and 34%, respectively (P<.001).³

Although meclizine is often used in clinical practice, only 1 double-blind RCT from 1972 (N=31, age range 21-77 years) reported improvement in symptoms and physical findings for meclizine compared with placebo in patients with BPPV.¹²

Recommendations

In a review article, Furman and Cass describe the diagnostic maneuver (Dix-Hallpike) and treatment maneuver (Epley) for BPPV.¹³ They recommend using either Epley’s or Semont’s maneuver for initial treatment.

The authors noted that vestibular suppressant medications may decrease the intensity of symptoms but don’t reduce the frequency of recurrent vertigo attacks. Moreover, medications produce unwanted side effects (somnolence, lethargy, worsened balance) and may prove counterproductive by delaying the central nervous system’s adaptation to a peripheral vestibular abnormality.

Evidence summary

No epidemiologic data on BPPV in the United States are available, but experts describe increasing incidence with advancing age. A recent German study found a lifetime prevalence of 2.4%, with a cumulative incidence approaching 10% by age 80.¹ Treatments include repositioning maneuvers (regimens of positioning the patient’s head and body) and medication. Evidence about treating BPPV in elderly patients specifically is limited.^2-4

These 2 maneuvers work best
Both Epley’s CRM and Semont’s liberatory maneuver have been shown to treat BPPV effectively. (For descriptions of the maneuvers and video links, see “How the Epley and Semont maneuvers work”.)

An RCT with 124 participants (mean age 58.3 years) demonstrated that either Epley’s or Semont’s maneuver decreased the frequency of vertigo more than a sham maneuver (P=.021 and P=.010, respectively).⁵ Both maneuvers were more effective than the Brandt-Daroff home exercises (P=.033).⁵

Another high-quality, double-blind RCT with 67 participants (median age 59 years) reported an improvement in vertigo and nystagmus at 24 hours among 80% of patients treated with Epley’s CRM, compared with 10% of those who received a sham maneuver (P<.001; number needed to treat [NNT]=1; 95% confidence interval [CI], 1-2).⁶

An RCT that enrolled 80 participants (median age 64 years) found complete resolution of BPPV symptoms and a negative Dix-Hallpike test 1 week after treatment in 88% of patients who received Epley’s CRM plus self-treatment (a modified Epley’s maneuver) compared with 69% who received Epley’s CRM alone (P=.048; NNT=5; 95% CI, 3-124).⁷

Posture restrictions are unnecessary
An RCT involving 50 participants (mean age 60.9 years) demonstrated that postprocedure postural restrictions were unnecessary and didn’t improve BPPV remission rates among patients receiving CRM (P=.97). No differences were noted by age or sex.⁸ Two prospective nonrandomized studies found that the recurrence rate of BPPV symptoms was 15% to 18% at 12 months and 37% to 50% at 40 to 60 months.^9,10

Drug studies are scarce, but CRM appears to work better
Studies of drug treatment among patients with BPPV are extremely limited because BPPV as a cause of vertigo is often an exclusion criterion among medication trials. A small (N=20; age range 32-67 years) double-blinded RCT found no difference in dizziness symptom scores for participants with BPPV who took diazepam (5 mg, 3 times daily), lorazepam (1 mg, 3 times daily), or placebo (1 capsule, 3 times daily) over a period of 4 weeks.¹¹

An RCT of 156 patients (mean age 74 years) with BPPV compared a calcium channel blocker (flunarizine, which isn’t available in the United States) with Semont’s liberatory maneuver or no therapy (observation only). Semont’s maneuver was more effective at the 6-month follow-up than either the calcium channel blocker or no therapy; the rates of asymptomatic patients with a negative Dix-Hallpike test at follow-up were 94%, 58%, and 34%, respectively (P<.001).³

Although meclizine is often used in clinical practice, only 1 double-blind RCT from 1972 (N=31, age range 21-77 years) reported improvement in symptoms and physical findings for meclizine compared with placebo in patients with BPPV.¹²

Recommendations

In a review article, Furman and Cass describe the diagnostic maneuver (Dix-Hallpike) and treatment maneuver (Epley) for BPPV.¹³ They recommend using either Epley’s or Semont’s maneuver for initial treatment.

The authors noted that vestibular suppressant medications may decrease the intensity of symptoms but don’t reduce the frequency of recurrent vertigo attacks. Moreover, medications produce unwanted side effects (somnolence, lethargy, worsened balance) and may prove counterproductive by delaying the central nervous system’s adaptation to a peripheral vestibular abnormality.

Evidence summary

No epidemiologic data on BPPV in the United States are available, but experts describe increasing incidence with advancing age. A recent German study found a lifetime prevalence of 2.4%, with a cumulative incidence approaching 10% by age 80.¹ Treatments include repositioning maneuvers (regimens of positioning the patient’s head and body) and medication. Evidence about treating BPPV in elderly patients specifically is limited.^2-4

These 2 maneuvers work best
Both Epley’s CRM and Semont’s liberatory maneuver have been shown to treat BPPV effectively. (For descriptions of the maneuvers and video links, see “How the Epley and Semont maneuvers work”.)

An RCT with 124 participants (mean age 58.3 years) demonstrated that either Epley’s or Semont’s maneuver decreased the frequency of vertigo more than a sham maneuver (P=.021 and P=.010, respectively).⁵ Both maneuvers were more effective than the Brandt-Daroff home exercises (P=.033).⁵

Another high-quality, double-blind RCT with 67 participants (median age 59 years) reported an improvement in vertigo and nystagmus at 24 hours among 80% of patients treated with Epley’s CRM, compared with 10% of those who received a sham maneuver (P<.001; number needed to treat [NNT]=1; 95% confidence interval [CI], 1-2).⁶

An RCT that enrolled 80 participants (median age 64 years) found complete resolution of BPPV symptoms and a negative Dix-Hallpike test 1 week after treatment in 88% of patients who received Epley’s CRM plus self-treatment (a modified Epley’s maneuver) compared with 69% who received Epley’s CRM alone (P=.048; NNT=5; 95% CI, 3-124).⁷

Posture restrictions are unnecessary
An RCT involving 50 participants (mean age 60.9 years) demonstrated that postprocedure postural restrictions were unnecessary and didn’t improve BPPV remission rates among patients receiving CRM (P=.97). No differences were noted by age or sex.⁸ Two prospective nonrandomized studies found that the recurrence rate of BPPV symptoms was 15% to 18% at 12 months and 37% to 50% at 40 to 60 months.^9,10

Drug studies are scarce, but CRM appears to work better
Studies of drug treatment among patients with BPPV are extremely limited because BPPV as a cause of vertigo is often an exclusion criterion among medication trials. A small (N=20; age range 32-67 years) double-blinded RCT found no difference in dizziness symptom scores for participants with BPPV who took diazepam (5 mg, 3 times daily), lorazepam (1 mg, 3 times daily), or placebo (1 capsule, 3 times daily) over a period of 4 weeks.¹¹

An RCT of 156 patients (mean age 74 years) with BPPV compared a calcium channel blocker (flunarizine, which isn’t available in the United States) with Semont’s liberatory maneuver or no therapy (observation only). Semont’s maneuver was more effective at the 6-month follow-up than either the calcium channel blocker or no therapy; the rates of asymptomatic patients with a negative Dix-Hallpike test at follow-up were 94%, 58%, and 34%, respectively (P<.001).³

Although meclizine is often used in clinical practice, only 1 double-blind RCT from 1972 (N=31, age range 21-77 years) reported improvement in symptoms and physical findings for meclizine compared with placebo in patients with BPPV.¹²

Recommendations

In a review article, Furman and Cass describe the diagnostic maneuver (Dix-Hallpike) and treatment maneuver (Epley) for BPPV.¹³ They recommend using either Epley’s or Semont’s maneuver for initial treatment.

The authors noted that vestibular suppressant medications may decrease the intensity of symptoms but don’t reduce the frequency of recurrent vertigo attacks. Moreover, medications produce unwanted side effects (somnolence, lethargy, worsened balance) and may prove counterproductive by delaying the central nervous system’s adaptation to a peripheral vestibular abnormality.

Evidence summary

For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.

Testing doesn’t predict risk more accurately than clinical history

Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).^1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.^1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.^5-7

TABLE
Thrombophilic conditions that increase the risk of DVT

Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.⁸ Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.

Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.⁴ After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.

A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.⁹ Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.

Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.⁸

Recommendations

A consensus opinion from the British Society for Haematology concludes that:

• thrombophilia testing of unselected patients is inappropriate
• initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
• identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.¹⁰

The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.

Evidence summary

For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.

Testing doesn’t predict risk more accurately than clinical history

Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).^1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.^1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.^5-7

TABLE
Thrombophilic conditions that increase the risk of DVT

Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.⁸ Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.

Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.⁴ After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.

A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.⁹ Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.

Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.⁸

Recommendations

A consensus opinion from the British Society for Haematology concludes that:

• thrombophilia testing of unselected patients is inappropriate
• initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
• identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.¹⁰

The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.

Evidence summary

For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.

Testing doesn’t predict risk more accurately than clinical history

Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).^1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.^1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.^5-7

TABLE
Thrombophilic conditions that increase the risk of DVT

Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.⁸ Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.

Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.⁴ After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.

A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.⁹ Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.

Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.⁸

Recommendations

A consensus opinion from the British Society for Haematology concludes that:

• thrombophilia testing of unselected patients is inappropriate
• initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
• identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.¹⁰

The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.

Evidence summary

Perinatal transmission of HCV is rare. It occurs only when serum HCV RNA is detectable; transmission rates may be related to higher levels (>106 copies/mL).¹ HCV is transmitted to 2% of infants of anti-HCV seropositive women and 4% to 7% of infants born to mothers who are HCV RNA-positive at delivery.¹

Spontaneous clearance of the virus occurs in approximately 20% of infants. Most remain asymptomatic if HCV persists, but have mild elevation of liver function tests.²

Routine screening for HCV in mothers is not recommended, but pregnant women at high risk for HCV infection should be screened for anti-HCV.

Route of delivery: Only a concern for HIV-positive mothers
The mode of delivery doesn’t influence the rate of HCV transmission, except in mothers with HIV. Retrospective analysis of 503 HCV-positive mothers coinfected with HIV showed a decreased risk of transmission during cesarean delivery (odds ratio [OR]=0.36; P=.01; number needed to treat [NNT]=10).³

One study suggested an increased rate of vertical HCV transmission during vaginal delivery compared with cesarean delivery (32% vs 6%; P<.05). The study didn’t account for the percent of mothers coinfected with HIV, however.⁴

A meta-analysis of 11 studies showed similar rates of transmission for vaginal and cesarean delivery: adjusted rates were 4.3% and 3%, respectively.¹

Internal monitoring is an issue
Avoid internal fetal monitoring to minimize HCV transmission, based on a single retrospective cohort of 244 infants born to HCV-positive mothers (relative risk [RR]= 7.7; 95% confidence interval [CI], 1.9-31.⁶; number needed to harm [NNH]=6).⁷ The same study showed an increased risk with membrane rupture longer than 6 hours (RR=9.9; 95% CI, 1.2-81; NNH=13).⁵

Breastfeeding doesn’t significantly affect HCV transmission. Transmission rates for breastfed and nonbreastfed infants are 3.7% and 3.9%, respectively.¹

Defer postpartum lab testing
Because about 20% of infants exposed to HCV clear the virus spontaneously, and maternal antibodies can confound laboratory results, deferring postpartum diagnostic testing is appropriate. A study of 1104 children in whom vertical transmission didn’t occur after exposure to HCV showed that 95% of the children were anti-HCV antibody negative by 12 months age.⁶ A prospective study of 23 infants documented spontaneous clearance of HCV RNA by 6 months in all patients.⁷

Recommendations

The National Institutes of Health 2002 Consensus Statement recommends:⁸

• avoiding fetal scalp electrodes and prolonged rupture of membranes
• serum testing for HCV RNA at 2 months and 6 months of age
• anti-HCV antibody testing after 15 months of age.

The American College of Obstetricians and Gynecologists supports breastfeeding, recommends against routine HCV screening, and recommends that cesarean delivery be reserved for obstetric indications.⁹

The American Association for the Study of Liver Diseases recommends serum testing and liver biopsy on the same schedule as adult patients and endorses considering treatment after 3 years of age.⁶

The US Food and Drug Administration has approved treatment after 3 years of age for children with detectable HCV RNA levels higher than 50 IU/mL and who have had a liver biopsy with portal or bridging fibrosis and at least moderate inflammation and necrosis.

The American Gastroenterological Association recommends considering treatment with PEG-interferon and ribavirin after 3 years of age.¹⁰

Acknowledgements
The opinions and assertions contained herein are the private view of the authors and not to be construed as official, or as reflecting the view of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Perinatal transmission of HCV is rare. It occurs only when serum HCV RNA is detectable; transmission rates may be related to higher levels (>106 copies/mL).¹ HCV is transmitted to 2% of infants of anti-HCV seropositive women and 4% to 7% of infants born to mothers who are HCV RNA-positive at delivery.¹

Spontaneous clearance of the virus occurs in approximately 20% of infants. Most remain asymptomatic if HCV persists, but have mild elevation of liver function tests.²

Routine screening for HCV in mothers is not recommended, but pregnant women at high risk for HCV infection should be screened for anti-HCV.

Route of delivery: Only a concern for HIV-positive mothers
The mode of delivery doesn’t influence the rate of HCV transmission, except in mothers with HIV. Retrospective analysis of 503 HCV-positive mothers coinfected with HIV showed a decreased risk of transmission during cesarean delivery (odds ratio [OR]=0.36; P=.01; number needed to treat [NNT]=10).³

One study suggested an increased rate of vertical HCV transmission during vaginal delivery compared with cesarean delivery (32% vs 6%; P<.05). The study didn’t account for the percent of mothers coinfected with HIV, however.⁴

A meta-analysis of 11 studies showed similar rates of transmission for vaginal and cesarean delivery: adjusted rates were 4.3% and 3%, respectively.¹

Internal monitoring is an issue
Avoid internal fetal monitoring to minimize HCV transmission, based on a single retrospective cohort of 244 infants born to HCV-positive mothers (relative risk [RR]= 7.7; 95% confidence interval [CI], 1.9-31.⁶; number needed to harm [NNH]=6).⁷ The same study showed an increased risk with membrane rupture longer than 6 hours (RR=9.9; 95% CI, 1.2-81; NNH=13).⁵

Breastfeeding doesn’t significantly affect HCV transmission. Transmission rates for breastfed and nonbreastfed infants are 3.7% and 3.9%, respectively.¹

Defer postpartum lab testing
Because about 20% of infants exposed to HCV clear the virus spontaneously, and maternal antibodies can confound laboratory results, deferring postpartum diagnostic testing is appropriate. A study of 1104 children in whom vertical transmission didn’t occur after exposure to HCV showed that 95% of the children were anti-HCV antibody negative by 12 months age.⁶ A prospective study of 23 infants documented spontaneous clearance of HCV RNA by 6 months in all patients.⁷

Recommendations

The National Institutes of Health 2002 Consensus Statement recommends:⁸

• avoiding fetal scalp electrodes and prolonged rupture of membranes
• serum testing for HCV RNA at 2 months and 6 months of age
• anti-HCV antibody testing after 15 months of age.

The American College of Obstetricians and Gynecologists supports breastfeeding, recommends against routine HCV screening, and recommends that cesarean delivery be reserved for obstetric indications.⁹

The American Association for the Study of Liver Diseases recommends serum testing and liver biopsy on the same schedule as adult patients and endorses considering treatment after 3 years of age.⁶

The US Food and Drug Administration has approved treatment after 3 years of age for children with detectable HCV RNA levels higher than 50 IU/mL and who have had a liver biopsy with portal or bridging fibrosis and at least moderate inflammation and necrosis.

The American Gastroenterological Association recommends considering treatment with PEG-interferon and ribavirin after 3 years of age.¹⁰

Acknowledgements
The opinions and assertions contained herein are the private view of the authors and not to be construed as official, or as reflecting the view of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Perinatal transmission of HCV is rare. It occurs only when serum HCV RNA is detectable; transmission rates may be related to higher levels (>106 copies/mL).¹ HCV is transmitted to 2% of infants of anti-HCV seropositive women and 4% to 7% of infants born to mothers who are HCV RNA-positive at delivery.¹

Spontaneous clearance of the virus occurs in approximately 20% of infants. Most remain asymptomatic if HCV persists, but have mild elevation of liver function tests.²

Routine screening for HCV in mothers is not recommended, but pregnant women at high risk for HCV infection should be screened for anti-HCV.

Route of delivery: Only a concern for HIV-positive mothers
The mode of delivery doesn’t influence the rate of HCV transmission, except in mothers with HIV. Retrospective analysis of 503 HCV-positive mothers coinfected with HIV showed a decreased risk of transmission during cesarean delivery (odds ratio [OR]=0.36; P=.01; number needed to treat [NNT]=10).³

One study suggested an increased rate of vertical HCV transmission during vaginal delivery compared with cesarean delivery (32% vs 6%; P<.05). The study didn’t account for the percent of mothers coinfected with HIV, however.⁴

A meta-analysis of 11 studies showed similar rates of transmission for vaginal and cesarean delivery: adjusted rates were 4.3% and 3%, respectively.¹

Internal monitoring is an issue
Avoid internal fetal monitoring to minimize HCV transmission, based on a single retrospective cohort of 244 infants born to HCV-positive mothers (relative risk [RR]= 7.7; 95% confidence interval [CI], 1.9-31.⁶; number needed to harm [NNH]=6).⁷ The same study showed an increased risk with membrane rupture longer than 6 hours (RR=9.9; 95% CI, 1.2-81; NNH=13).⁵

Breastfeeding doesn’t significantly affect HCV transmission. Transmission rates for breastfed and nonbreastfed infants are 3.7% and 3.9%, respectively.¹

Defer postpartum lab testing
Because about 20% of infants exposed to HCV clear the virus spontaneously, and maternal antibodies can confound laboratory results, deferring postpartum diagnostic testing is appropriate. A study of 1104 children in whom vertical transmission didn’t occur after exposure to HCV showed that 95% of the children were anti-HCV antibody negative by 12 months age.⁶ A prospective study of 23 infants documented spontaneous clearance of HCV RNA by 6 months in all patients.⁷

Recommendations

The National Institutes of Health 2002 Consensus Statement recommends:⁸

• avoiding fetal scalp electrodes and prolonged rupture of membranes
• serum testing for HCV RNA at 2 months and 6 months of age
• anti-HCV antibody testing after 15 months of age.

The American College of Obstetricians and Gynecologists supports breastfeeding, recommends against routine HCV screening, and recommends that cesarean delivery be reserved for obstetric indications.⁹

The American Association for the Study of Liver Diseases recommends serum testing and liver biopsy on the same schedule as adult patients and endorses considering treatment after 3 years of age.⁶

The US Food and Drug Administration has approved treatment after 3 years of age for children with detectable HCV RNA levels higher than 50 IU/mL and who have had a liver biopsy with portal or bridging fibrosis and at least moderate inflammation and necrosis.

The American Gastroenterological Association recommends considering treatment with PEG-interferon and ribavirin after 3 years of age.¹⁰

Acknowledgements
The opinions and assertions contained herein are the private view of the authors and not to be construed as official, or as reflecting the view of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

ADHD affects 7% to 8% of school-age children, and the prevalence is increasing.¹ The quality of studies investigating the link between diet and ADHD is limited by small sample sizes, subjective outcome measures, and nonstandardized intervention protocols.

Elimination diets show little or no effect
Studies of elimination diets for ADHD have investigated the effects of withholding sugar and artificial food colorings (AFCs).

Sugar. A 1995 meta-analysis of 16 double-blind, randomized, placebo-controlled trials evaluated the effect of dietary sugar in the form of sucrose, glucose, and fructose on behavior or cognition of children. Outcomes included subjective measurements from teachers, parents, and researchers, as well as objective scoring of activities.

No significant differences in the summary effect size were noted for any measured variable. A weakness of the analysis was that not all of the trials studied children who had been specifically diagnosed with ADHD.²

AFCs. A 2004 meta-analysis of 15 double-blind, placebo-controlled trials (total 219 children) evaluated the effect of AFCs on hyperactivity. Outcomes were measured by behavioral rating scales that ranged from standardized forms such as the Conners Parent-Teacher Questionnaire (12 trials) to nonvalidated author-developed scales (3 trials). Analysis revealed a small summary effect size (0.283; 95% confidence interval, 0.079-0.488), and the authors concluded that AFCs do have a small effect on hyperactivity.³

A secondary analysis of children who previously showed worsening of hyperactivity with AFCs (either by parental report or in an earlier study) found a larger effect size (0.53). This finding implies that a subset of children whose parents notice an increase in hyperactivity with AFCs may benefit from exclusion. However, because the quality of the meta-analysis is limited by the heterogeneity of the studies, publication bias, unvalidated outcome measures, and variety of diagnoses in the participants, no recommendation can be made for AFC exclusion diets.³

Supplementation with fatty acids doesn’t improve symptoms
Because polyunsaturated fatty acids (PUFAs) are essential for brain development and function, a deficiency theoretically may contribute to a range of developmental disorders, including ADHD. An RCT of 63 children 6 to 12 years of age with ADHD randomly assigned the children to supplementation with the most abundant PUFA, docosahexanoic (DHA), or placebo for 4 months. Measured outcomes included objective attention evaluation by computer and written tests and standardized objective measures such as the Conners Rating Scales.⁴ The study found no significant improvement in any ADHD symptom.⁴

The findings of this trial were confirmed by another double-blinded RCT of 40 children with ADHD who were randomized to DHA or placebo. The second trial found no significant differences in ADHD symptoms after 2 months.⁵

Recommendations

The American Academy of Pediatrics states that there is a need for well-designed, rigorous studies of currently promoted but less well-established therapies for ADHD, such as occupational therapy, biofeedback, herbs, vitamins, and food supplements. These interventions aren’t supported by evidence-based studies at present.⁶

The American Academy of Child and Adolescent Psychiatry’s guidelines on managing ADHD don’t mention dietary interventions.⁷

Investigators from the Cincinnati Children’s Hospital report that elimination diets and food supplements have little or no quality evidence to support their effectiveness.⁸

Evidence summary

ADHD affects 7% to 8% of school-age children, and the prevalence is increasing.¹ The quality of studies investigating the link between diet and ADHD is limited by small sample sizes, subjective outcome measures, and nonstandardized intervention protocols.

Elimination diets show little or no effect
Studies of elimination diets for ADHD have investigated the effects of withholding sugar and artificial food colorings (AFCs).

Sugar. A 1995 meta-analysis of 16 double-blind, randomized, placebo-controlled trials evaluated the effect of dietary sugar in the form of sucrose, glucose, and fructose on behavior or cognition of children. Outcomes included subjective measurements from teachers, parents, and researchers, as well as objective scoring of activities.

No significant differences in the summary effect size were noted for any measured variable. A weakness of the analysis was that not all of the trials studied children who had been specifically diagnosed with ADHD.²

AFCs. A 2004 meta-analysis of 15 double-blind, placebo-controlled trials (total 219 children) evaluated the effect of AFCs on hyperactivity. Outcomes were measured by behavioral rating scales that ranged from standardized forms such as the Conners Parent-Teacher Questionnaire (12 trials) to nonvalidated author-developed scales (3 trials). Analysis revealed a small summary effect size (0.283; 95% confidence interval, 0.079-0.488), and the authors concluded that AFCs do have a small effect on hyperactivity.³

A secondary analysis of children who previously showed worsening of hyperactivity with AFCs (either by parental report or in an earlier study) found a larger effect size (0.53). This finding implies that a subset of children whose parents notice an increase in hyperactivity with AFCs may benefit from exclusion. However, because the quality of the meta-analysis is limited by the heterogeneity of the studies, publication bias, unvalidated outcome measures, and variety of diagnoses in the participants, no recommendation can be made for AFC exclusion diets.³

Supplementation with fatty acids doesn’t improve symptoms
Because polyunsaturated fatty acids (PUFAs) are essential for brain development and function, a deficiency theoretically may contribute to a range of developmental disorders, including ADHD. An RCT of 63 children 6 to 12 years of age with ADHD randomly assigned the children to supplementation with the most abundant PUFA, docosahexanoic (DHA), or placebo for 4 months. Measured outcomes included objective attention evaluation by computer and written tests and standardized objective measures such as the Conners Rating Scales.⁴ The study found no significant improvement in any ADHD symptom.⁴

The findings of this trial were confirmed by another double-blinded RCT of 40 children with ADHD who were randomized to DHA or placebo. The second trial found no significant differences in ADHD symptoms after 2 months.⁵

Recommendations

The American Academy of Pediatrics states that there is a need for well-designed, rigorous studies of currently promoted but less well-established therapies for ADHD, such as occupational therapy, biofeedback, herbs, vitamins, and food supplements. These interventions aren’t supported by evidence-based studies at present.⁶

The American Academy of Child and Adolescent Psychiatry’s guidelines on managing ADHD don’t mention dietary interventions.⁷

Investigators from the Cincinnati Children’s Hospital report that elimination diets and food supplements have little or no quality evidence to support their effectiveness.⁸

Evidence summary

ADHD affects 7% to 8% of school-age children, and the prevalence is increasing.¹ The quality of studies investigating the link between diet and ADHD is limited by small sample sizes, subjective outcome measures, and nonstandardized intervention protocols.

Elimination diets show little or no effect
Studies of elimination diets for ADHD have investigated the effects of withholding sugar and artificial food colorings (AFCs).

Sugar. A 1995 meta-analysis of 16 double-blind, randomized, placebo-controlled trials evaluated the effect of dietary sugar in the form of sucrose, glucose, and fructose on behavior or cognition of children. Outcomes included subjective measurements from teachers, parents, and researchers, as well as objective scoring of activities.

No significant differences in the summary effect size were noted for any measured variable. A weakness of the analysis was that not all of the trials studied children who had been specifically diagnosed with ADHD.²

AFCs. A 2004 meta-analysis of 15 double-blind, placebo-controlled trials (total 219 children) evaluated the effect of AFCs on hyperactivity. Outcomes were measured by behavioral rating scales that ranged from standardized forms such as the Conners Parent-Teacher Questionnaire (12 trials) to nonvalidated author-developed scales (3 trials). Analysis revealed a small summary effect size (0.283; 95% confidence interval, 0.079-0.488), and the authors concluded that AFCs do have a small effect on hyperactivity.³

A secondary analysis of children who previously showed worsening of hyperactivity with AFCs (either by parental report or in an earlier study) found a larger effect size (0.53). This finding implies that a subset of children whose parents notice an increase in hyperactivity with AFCs may benefit from exclusion. However, because the quality of the meta-analysis is limited by the heterogeneity of the studies, publication bias, unvalidated outcome measures, and variety of diagnoses in the participants, no recommendation can be made for AFC exclusion diets.³

Supplementation with fatty acids doesn’t improve symptoms
Because polyunsaturated fatty acids (PUFAs) are essential for brain development and function, a deficiency theoretically may contribute to a range of developmental disorders, including ADHD. An RCT of 63 children 6 to 12 years of age with ADHD randomly assigned the children to supplementation with the most abundant PUFA, docosahexanoic (DHA), or placebo for 4 months. Measured outcomes included objective attention evaluation by computer and written tests and standardized objective measures such as the Conners Rating Scales.⁴ The study found no significant improvement in any ADHD symptom.⁴

The findings of this trial were confirmed by another double-blinded RCT of 40 children with ADHD who were randomized to DHA or placebo. The second trial found no significant differences in ADHD symptoms after 2 months.⁵

Recommendations

The American Academy of Pediatrics states that there is a need for well-designed, rigorous studies of currently promoted but less well-established therapies for ADHD, such as occupational therapy, biofeedback, herbs, vitamins, and food supplements. These interventions aren’t supported by evidence-based studies at present.⁶

The American Academy of Child and Adolescent Psychiatry’s guidelines on managing ADHD don’t mention dietary interventions.⁷

Investigators from the Cincinnati Children’s Hospital report that elimination diets and food supplements have little or no quality evidence to support their effectiveness.⁸

Evidence summary

Disc herniation is defined as any protrusion of the disc nucleus, cartilage, or other associated tissues from the normal disc space. Lumbar disc herniations (LDHs) are most likely to occur in the L4 to L5 and L5 to S1 levels, causing low back pain and sciatica. Many LDHs occur without symptoms, however, so it’s important to correlate level and side of herniation before assuming causality. Expert opinion recommends early surgical intervention for patients with cauda equina syndrome or progressive neurologic deficits.¹

Surgery provides short-term gains
A search identified 4 RCTs that compared surgical intervention with conservative management. The first, published in 1983, evaluated 126 patients with radicular pain and confirmed LDH who did not improve after 2 weeks of conservative therapy. The study assigned patients to either open discectomy or back school.² Patients rated their results as good, fair, poor, or bad; a good or fair rating was considered a positive outcome.

At 1 year, significantly more patients in the surgery group reported positive results (P<.001), based on working capacity, neurological deficits, pain, and lumbar spine mobility. At 4 years, no significant difference was found between the groups.

The study showed significant crossover, with 26% of conservatively managed patients receiving surgery within the first year. Evaluators weren’t blinded, and outcome measurements weren’t based on standardized evaluation tools.

Crossover complicates comparison of relative treatment effects
The Spine Patient Outcomes Research Trial (SPORT), published in 2006, compared 501 patients with confirmed LDH and persistent symptoms after 6 weeks.³ Patients were randomized to open discectomy or nonoperative “usual care.” Both groups showed improvement in pain scores and no significant differences in standardized pain scales at 3 months, 1 year, or 2 years.

Crossover for the study was high: 40% of the surgical group didn’t have surgery, and 45% of the nonoperative group underwent surgery. Although the pattern of care in the SPORT study resembles common clinical situations,⁴ the high degree of crossover makes it difficult to draw inferences about relative treatment effects.⁵

Greater patient satisfaction with surgery
Another RCT followed 56 patients with confirmed LDH and symptoms for 6 to 12 weeks.⁶ Patients were randomized to receive microdiscectomy within 2 weeks of randomization or nonoperative care. Outcomes were based on standardized pain scales for leg and back pain. The surgical group had significantly better leg pain relief (P<.01) at the 6-week evaluation. At 12 weeks, neither back pain nor leg pain differed between the groups.

Although pain didn’t differ significantly, patients in the surgical group were more satisfied with their care, and physicians were more likely to believe that surgery would improve outcomes. Crossover from the nonoperative group was high, with 39% of that group undergoing surgery.

Surgery improves leg pain, not disability, more than conservative therapy
Another RCT also directly compared microdiscectomy to conservative treatment in 283 patients with confirmed LDH and symptoms lasting 6 to 12 weeks.⁷ The surgical group underwent microdiscectomy within 2 weeks of randomization. Pain and disability measurements, based on standardized scales, showed significant improvement in leg pain (P<.001) for the surgical group, but no significant difference in disability.

Patient perception of recovery on a Likert-type scale showed a median recovery time of 4 weeks for the surgical group and 12 weeks for the conservative therapy group. No significant differences in perceived degree of recovery were noted between the groups at 1 year; 95% of participants had a satisfactory recovery.

Again, significant crossover occurred: 11% of patients allocated to surgery recovered before surgery, and 39% of the conservative therapy group experienced worsening symptoms or intractable pain that led them to undergo microdiscectomy.

Open discectomy, microdiscectomy produce similar results
A Cochrane review of interventions for LDH included only the Weber² and SPORT³ RCTs. The review also included 3 RCTs that compared open discectomy and microdiscectomy. These studies found no difference in pain relief or complications between the 2 interventions.⁸

Recommendations

The Institute for Clinical Systems Improvement guidelines for adult low back pain list cauda equina, progressive neurologic deficits, or uncontrolled pain as reasons for direct referral to a spine specialist.¹ Patients can be treated conservatively for 6 weeks without imaging, unless other symptoms or concerns are present.

The guidelines recommend that patients with chronic sciatica (lasting >6 weeks) receive further imaging or referral to a specialist if the patient is a potential candidate for surgery.

Evidence summary

Disc herniation is defined as any protrusion of the disc nucleus, cartilage, or other associated tissues from the normal disc space. Lumbar disc herniations (LDHs) are most likely to occur in the L4 to L5 and L5 to S1 levels, causing low back pain and sciatica. Many LDHs occur without symptoms, however, so it’s important to correlate level and side of herniation before assuming causality. Expert opinion recommends early surgical intervention for patients with cauda equina syndrome or progressive neurologic deficits.¹

Surgery provides short-term gains
A search identified 4 RCTs that compared surgical intervention with conservative management. The first, published in 1983, evaluated 126 patients with radicular pain and confirmed LDH who did not improve after 2 weeks of conservative therapy. The study assigned patients to either open discectomy or back school.² Patients rated their results as good, fair, poor, or bad; a good or fair rating was considered a positive outcome.

At 1 year, significantly more patients in the surgery group reported positive results (P<.001), based on working capacity, neurological deficits, pain, and lumbar spine mobility. At 4 years, no significant difference was found between the groups.

The study showed significant crossover, with 26% of conservatively managed patients receiving surgery within the first year. Evaluators weren’t blinded, and outcome measurements weren’t based on standardized evaluation tools.

Crossover complicates comparison of relative treatment effects
The Spine Patient Outcomes Research Trial (SPORT), published in 2006, compared 501 patients with confirmed LDH and persistent symptoms after 6 weeks.³ Patients were randomized to open discectomy or nonoperative “usual care.” Both groups showed improvement in pain scores and no significant differences in standardized pain scales at 3 months, 1 year, or 2 years.

Crossover for the study was high: 40% of the surgical group didn’t have surgery, and 45% of the nonoperative group underwent surgery. Although the pattern of care in the SPORT study resembles common clinical situations,⁴ the high degree of crossover makes it difficult to draw inferences about relative treatment effects.⁵

Greater patient satisfaction with surgery
Another RCT followed 56 patients with confirmed LDH and symptoms for 6 to 12 weeks.⁶ Patients were randomized to receive microdiscectomy within 2 weeks of randomization or nonoperative care. Outcomes were based on standardized pain scales for leg and back pain. The surgical group had significantly better leg pain relief (P<.01) at the 6-week evaluation. At 12 weeks, neither back pain nor leg pain differed between the groups.

Although pain didn’t differ significantly, patients in the surgical group were more satisfied with their care, and physicians were more likely to believe that surgery would improve outcomes. Crossover from the nonoperative group was high, with 39% of that group undergoing surgery.

Surgery improves leg pain, not disability, more than conservative therapy
Another RCT also directly compared microdiscectomy to conservative treatment in 283 patients with confirmed LDH and symptoms lasting 6 to 12 weeks.⁷ The surgical group underwent microdiscectomy within 2 weeks of randomization. Pain and disability measurements, based on standardized scales, showed significant improvement in leg pain (P<.001) for the surgical group, but no significant difference in disability.

Patient perception of recovery on a Likert-type scale showed a median recovery time of 4 weeks for the surgical group and 12 weeks for the conservative therapy group. No significant differences in perceived degree of recovery were noted between the groups at 1 year; 95% of participants had a satisfactory recovery.

Again, significant crossover occurred: 11% of patients allocated to surgery recovered before surgery, and 39% of the conservative therapy group experienced worsening symptoms or intractable pain that led them to undergo microdiscectomy.

Open discectomy, microdiscectomy produce similar results
A Cochrane review of interventions for LDH included only the Weber² and SPORT³ RCTs. The review also included 3 RCTs that compared open discectomy and microdiscectomy. These studies found no difference in pain relief or complications between the 2 interventions.⁸

Recommendations

The Institute for Clinical Systems Improvement guidelines for adult low back pain list cauda equina, progressive neurologic deficits, or uncontrolled pain as reasons for direct referral to a spine specialist.¹ Patients can be treated conservatively for 6 weeks without imaging, unless other symptoms or concerns are present.

The guidelines recommend that patients with chronic sciatica (lasting >6 weeks) receive further imaging or referral to a specialist if the patient is a potential candidate for surgery.

Evidence summary

Disc herniation is defined as any protrusion of the disc nucleus, cartilage, or other associated tissues from the normal disc space. Lumbar disc herniations (LDHs) are most likely to occur in the L4 to L5 and L5 to S1 levels, causing low back pain and sciatica. Many LDHs occur without symptoms, however, so it’s important to correlate level and side of herniation before assuming causality. Expert opinion recommends early surgical intervention for patients with cauda equina syndrome or progressive neurologic deficits.¹

Surgery provides short-term gains
A search identified 4 RCTs that compared surgical intervention with conservative management. The first, published in 1983, evaluated 126 patients with radicular pain and confirmed LDH who did not improve after 2 weeks of conservative therapy. The study assigned patients to either open discectomy or back school.² Patients rated their results as good, fair, poor, or bad; a good or fair rating was considered a positive outcome.

At 1 year, significantly more patients in the surgery group reported positive results (P<.001), based on working capacity, neurological deficits, pain, and lumbar spine mobility. At 4 years, no significant difference was found between the groups.

The study showed significant crossover, with 26% of conservatively managed patients receiving surgery within the first year. Evaluators weren’t blinded, and outcome measurements weren’t based on standardized evaluation tools.

Crossover complicates comparison of relative treatment effects
The Spine Patient Outcomes Research Trial (SPORT), published in 2006, compared 501 patients with confirmed LDH and persistent symptoms after 6 weeks.³ Patients were randomized to open discectomy or nonoperative “usual care.” Both groups showed improvement in pain scores and no significant differences in standardized pain scales at 3 months, 1 year, or 2 years.

Crossover for the study was high: 40% of the surgical group didn’t have surgery, and 45% of the nonoperative group underwent surgery. Although the pattern of care in the SPORT study resembles common clinical situations,⁴ the high degree of crossover makes it difficult to draw inferences about relative treatment effects.⁵

Greater patient satisfaction with surgery
Another RCT followed 56 patients with confirmed LDH and symptoms for 6 to 12 weeks.⁶ Patients were randomized to receive microdiscectomy within 2 weeks of randomization or nonoperative care. Outcomes were based on standardized pain scales for leg and back pain. The surgical group had significantly better leg pain relief (P<.01) at the 6-week evaluation. At 12 weeks, neither back pain nor leg pain differed between the groups.

Although pain didn’t differ significantly, patients in the surgical group were more satisfied with their care, and physicians were more likely to believe that surgery would improve outcomes. Crossover from the nonoperative group was high, with 39% of that group undergoing surgery.

Surgery improves leg pain, not disability, more than conservative therapy
Another RCT also directly compared microdiscectomy to conservative treatment in 283 patients with confirmed LDH and symptoms lasting 6 to 12 weeks.⁷ The surgical group underwent microdiscectomy within 2 weeks of randomization. Pain and disability measurements, based on standardized scales, showed significant improvement in leg pain (P<.001) for the surgical group, but no significant difference in disability.

Patient perception of recovery on a Likert-type scale showed a median recovery time of 4 weeks for the surgical group and 12 weeks for the conservative therapy group. No significant differences in perceived degree of recovery were noted between the groups at 1 year; 95% of participants had a satisfactory recovery.

Again, significant crossover occurred: 11% of patients allocated to surgery recovered before surgery, and 39% of the conservative therapy group experienced worsening symptoms or intractable pain that led them to undergo microdiscectomy.

Open discectomy, microdiscectomy produce similar results
A Cochrane review of interventions for LDH included only the Weber² and SPORT³ RCTs. The review also included 3 RCTs that compared open discectomy and microdiscectomy. These studies found no difference in pain relief or complications between the 2 interventions.⁸

Recommendations

The Institute for Clinical Systems Improvement guidelines for adult low back pain list cauda equina, progressive neurologic deficits, or uncontrolled pain as reasons for direct referral to a spine specialist.¹ Patients can be treated conservatively for 6 weeks without imaging, unless other symptoms or concerns are present.

The guidelines recommend that patients with chronic sciatica (lasting >6 weeks) receive further imaging or referral to a specialist if the patient is a potential candidate for surgery.