Gary Kelsberg, MD

Evidence summary

Two open-label RCTs compared oral and intramuscular (IM) therapy for vitamin B₁₂ deficiency.^1,2 Both studies enrolled patients from hospital-based clinics—not primary care centers. Most patients (63 of 93 total) had conditions associated with intestinal malabsorption, including 7 patients with pernicious anemia and 3 with ileal resection. Both trials excluded patients with celiac and inflammatory bowel disease.

Oral therapy works as well as injections and costs less
One RCT compared the effects of oral B₁₂ with IM therapy in 60 patients (mean age 62 years) with B₁₂ deficiency and megaloblastic anemia.¹ Investigators gave patients in each group equivalent doses of cobalamin: 1000 mcg daily for 10 days, weekly for 4 weeks, and then monthly to complete a 90-day course.

The mean hemoglobin increased significantly in both the oral and IM groups (from 8.4 to 13.8 g/dL, P<.001 for oral therapy; from 8.3 to 13.7 g/dL, P<.001 for IM therapy), as did mean serum B₁₂ levels (from 73 to 214 pg/mL, P<.001, oral; and from 70 to 226 pg/mL, P<.001, IM). Neurologic symptoms (sensitive peripheral neuropathy, alteration of cognitive function, loss of sense of vibration) either cleared or improved markedly in both groups within one month (7 of 9 patients with oral therapy and 9 of 12 patients with IM treatment; P value not given).

Oral therapy cost less ($80 vs $220 per patient) and neither group reported adverse effects.¹

B₁₂ therapy changes hematologic parameters
The second RCT compared oral with IM B₁₂ therapy in 33 patients (mean age 72 years) with newly diagnosed B₁₂ deficiency.² Investigators randomized patients to receive either oral cyanocobalamin (2000 mcg daily) for 120 days or IM cobalamin (1000 mcg) on Days 1, 3, 7, 10, 14, 21, 30, 60, and 90.

At 4 months, both groups had improved significantly from baseline in all metabolite measures and achieved a normal serum cobalamin level. The higher-dose oral therapy raised cobalamin levels more than IM therapy (from 93 to 1005 pg/mL, P<.0005 with oral therapy vs from 95 to 325 pg/mL, P<.0005 with IM treatment). Oral therapy increased cobalamin levels above 300 pg/mL in all patients; only half the patients treated with injections reached that level.

B₁₂ therapy also significantly changed hematologic parameters from baseline even though the patients in the study didn’t have anemia. Mean corpuscular volume, for example, decreased from 100 to 90 fL with oral therapy and 102 to 97 fL with IM therapy (P<.005 for each). Neurologic symptoms (memory loss, paresthesias, ataxia) either cleared or improved markedly in all patients. Investigators compared all parameters against baseline values but didn’t directly compare oral with IM therapy. The trial didn’t assess safety outcomes.²

Recommendations

Canada’s British Columbia Medical Association and Ministry of Health recommend oral replacement of B₁₂ (1000-2000 mcg/d) for most cases of vitamin B₁₂ deficiency, including pernicious anemia. For patients with neurologic symptoms, they recommend an initial B₁₂ injection (1000 mcg IM) followed by oral replacement.³

The US Centers for Disease Control and Prevention recommends either oral (1000 mcg daily) or parenteral B₁₂ replacement. They advise giving parenteral therapy either subcutaneously (to reduce the burning sensation) or IM (1000 mcg per week for 8 weeks, then monthly for life).⁴

Evidence summary

Two open-label RCTs compared oral and intramuscular (IM) therapy for vitamin B₁₂ deficiency.^1,2 Both studies enrolled patients from hospital-based clinics—not primary care centers. Most patients (63 of 93 total) had conditions associated with intestinal malabsorption, including 7 patients with pernicious anemia and 3 with ileal resection. Both trials excluded patients with celiac and inflammatory bowel disease.

Oral therapy works as well as injections and costs less
One RCT compared the effects of oral B₁₂ with IM therapy in 60 patients (mean age 62 years) with B₁₂ deficiency and megaloblastic anemia.¹ Investigators gave patients in each group equivalent doses of cobalamin: 1000 mcg daily for 10 days, weekly for 4 weeks, and then monthly to complete a 90-day course.

The mean hemoglobin increased significantly in both the oral and IM groups (from 8.4 to 13.8 g/dL, P<.001 for oral therapy; from 8.3 to 13.7 g/dL, P<.001 for IM therapy), as did mean serum B₁₂ levels (from 73 to 214 pg/mL, P<.001, oral; and from 70 to 226 pg/mL, P<.001, IM). Neurologic symptoms (sensitive peripheral neuropathy, alteration of cognitive function, loss of sense of vibration) either cleared or improved markedly in both groups within one month (7 of 9 patients with oral therapy and 9 of 12 patients with IM treatment; P value not given).

Oral therapy cost less ($80 vs $220 per patient) and neither group reported adverse effects.¹

B₁₂ therapy changes hematologic parameters
The second RCT compared oral with IM B₁₂ therapy in 33 patients (mean age 72 years) with newly diagnosed B₁₂ deficiency.² Investigators randomized patients to receive either oral cyanocobalamin (2000 mcg daily) for 120 days or IM cobalamin (1000 mcg) on Days 1, 3, 7, 10, 14, 21, 30, 60, and 90.

At 4 months, both groups had improved significantly from baseline in all metabolite measures and achieved a normal serum cobalamin level. The higher-dose oral therapy raised cobalamin levels more than IM therapy (from 93 to 1005 pg/mL, P<.0005 with oral therapy vs from 95 to 325 pg/mL, P<.0005 with IM treatment). Oral therapy increased cobalamin levels above 300 pg/mL in all patients; only half the patients treated with injections reached that level.

B₁₂ therapy also significantly changed hematologic parameters from baseline even though the patients in the study didn’t have anemia. Mean corpuscular volume, for example, decreased from 100 to 90 fL with oral therapy and 102 to 97 fL with IM therapy (P<.005 for each). Neurologic symptoms (memory loss, paresthesias, ataxia) either cleared or improved markedly in all patients. Investigators compared all parameters against baseline values but didn’t directly compare oral with IM therapy. The trial didn’t assess safety outcomes.²

Recommendations

Canada’s British Columbia Medical Association and Ministry of Health recommend oral replacement of B₁₂ (1000-2000 mcg/d) for most cases of vitamin B₁₂ deficiency, including pernicious anemia. For patients with neurologic symptoms, they recommend an initial B₁₂ injection (1000 mcg IM) followed by oral replacement.³

The US Centers for Disease Control and Prevention recommends either oral (1000 mcg daily) or parenteral B₁₂ replacement. They advise giving parenteral therapy either subcutaneously (to reduce the burning sensation) or IM (1000 mcg per week for 8 weeks, then monthly for life).⁴

Evidence summary

Two open-label RCTs compared oral and intramuscular (IM) therapy for vitamin B₁₂ deficiency.^1,2 Both studies enrolled patients from hospital-based clinics—not primary care centers. Most patients (63 of 93 total) had conditions associated with intestinal malabsorption, including 7 patients with pernicious anemia and 3 with ileal resection. Both trials excluded patients with celiac and inflammatory bowel disease.

Oral therapy works as well as injections and costs less
One RCT compared the effects of oral B₁₂ with IM therapy in 60 patients (mean age 62 years) with B₁₂ deficiency and megaloblastic anemia.¹ Investigators gave patients in each group equivalent doses of cobalamin: 1000 mcg daily for 10 days, weekly for 4 weeks, and then monthly to complete a 90-day course.

The mean hemoglobin increased significantly in both the oral and IM groups (from 8.4 to 13.8 g/dL, P<.001 for oral therapy; from 8.3 to 13.7 g/dL, P<.001 for IM therapy), as did mean serum B₁₂ levels (from 73 to 214 pg/mL, P<.001, oral; and from 70 to 226 pg/mL, P<.001, IM). Neurologic symptoms (sensitive peripheral neuropathy, alteration of cognitive function, loss of sense of vibration) either cleared or improved markedly in both groups within one month (7 of 9 patients with oral therapy and 9 of 12 patients with IM treatment; P value not given).

Oral therapy cost less ($80 vs $220 per patient) and neither group reported adverse effects.¹

B₁₂ therapy changes hematologic parameters
The second RCT compared oral with IM B₁₂ therapy in 33 patients (mean age 72 years) with newly diagnosed B₁₂ deficiency.² Investigators randomized patients to receive either oral cyanocobalamin (2000 mcg daily) for 120 days or IM cobalamin (1000 mcg) on Days 1, 3, 7, 10, 14, 21, 30, 60, and 90.

At 4 months, both groups had improved significantly from baseline in all metabolite measures and achieved a normal serum cobalamin level. The higher-dose oral therapy raised cobalamin levels more than IM therapy (from 93 to 1005 pg/mL, P<.0005 with oral therapy vs from 95 to 325 pg/mL, P<.0005 with IM treatment). Oral therapy increased cobalamin levels above 300 pg/mL in all patients; only half the patients treated with injections reached that level.

B₁₂ therapy also significantly changed hematologic parameters from baseline even though the patients in the study didn’t have anemia. Mean corpuscular volume, for example, decreased from 100 to 90 fL with oral therapy and 102 to 97 fL with IM therapy (P<.005 for each). Neurologic symptoms (memory loss, paresthesias, ataxia) either cleared or improved markedly in all patients. Investigators compared all parameters against baseline values but didn’t directly compare oral with IM therapy. The trial didn’t assess safety outcomes.²

Recommendations

Canada’s British Columbia Medical Association and Ministry of Health recommend oral replacement of B₁₂ (1000-2000 mcg/d) for most cases of vitamin B₁₂ deficiency, including pernicious anemia. For patients with neurologic symptoms, they recommend an initial B₁₂ injection (1000 mcg IM) followed by oral replacement.³

The US Centers for Disease Control and Prevention recommends either oral (1000 mcg daily) or parenteral B₁₂ replacement. They advise giving parenteral therapy either subcutaneously (to reduce the burning sensation) or IM (1000 mcg per week for 8 weeks, then monthly for life).⁴

Evidence summary

The TABLE summarizes the results of 6 RCTs that evaluated physician counseling for weight loss. The largest RCT, which included patients with elevated serum low-density lipoprotein levels (>75th percentile), randomized participants to 3 groups: physician counseling plus office support (dietary assessment tools, counseling algorithms, and in-office prompts), physician counseling alone, or usual care.¹

Patients who received physician counseling with office support lost 2.3 kg (P<.001 vs usual care), whereas patients who received physician counseling alone lost 1.0 kg and patients who received usual care didn’t lose any weight.

TABLE
The effectiveness of weight loss counseling by physicians: What the RCTs reveal

Other large studies show mixed results
The second largest RCT randomized participants from community health centers in Colorado to receive either physician counseling (in which physicians reviewed nutritional and physical activity goals generated by a computer in response to a survey) or usual care (patient handouts alone).² Although the physician-counseled group didn’t lose more total weight, more people in this group had lost 2.7 kg or more at the 12-month follow-up (32% vs 19% for usual care; P=.006).

The third largest RCT assigned low-income women from primary care clinics in Louisiana to either a 6-month tailored weight loss intervention or usual care.³ The intervention included monthly 15-minute visits with physician counseling about weight loss, fat intake, physical activity, barriers to weight loss, and weight loss maintenance. Women who received counseling lost 1.5 kg at the 9-month follow-up compared with a loss of 0.6 kg for women who received usual care. Both groups showed no net loss at the 12- and 18-month follow-up.

Counseling with follow-up leads to drop in BMI
Physician counseling in an Italian RCT included a 1-minute, patient-centered assessment of readiness for change, 2 to 5 minutes of exercise counseling by a physician for patients in active and maintenance stages, and phone or mail follow-up at 2 to 3 weeks.⁴ The reported decreases in body mass index (BMI) in the counseling group would translate to 2.4 and 1.0 kg of weight loss for men and women of average height, respectively.

No significant weight loss in a pediatric study
An RCT of children brought to a pediatric clinic for well-child visits recruited children who had either a BMI in the 85th to 95th percentile or obese parents (BMI ≥30 kg/m²).⁵ Parents were randomized to intensive counseling, minimal counseling, or usual care. The intensive intervention group participated in a 10- to 15-minute motivational interview with the pediatrician, followed by 2 45-minute sessions with a dietician at months 1 and 3 of the 6-month program; the minimal intervention group only participated in the motivational interview. No significant weight loss occurred in any of the 3 study groups.

The smallest RCT compared counseling by a family medicine resident with usual care in 30 adult patients.⁶ At 6 months, the counseling group had lost 0.9 kg compared with a gain of 1.3 kg in the usual care group, but follow-up at 12 months found no difference between the groups.

Recommendations

The US Preventive Services Task Force (USPSTF) says that intensive counseling (person-to-person meetings at least monthly, combined with diet, exercise, and behavioral interventions plus longer-term maintenance) can promote modest sustained weight loss and improve clinical outcomes.⁷ They recommend screening adults for obesity and offering intensive counseling and behavioral interventions for obese adults.

USPSTF notes, however, that evidence is insufficient to recommend for or against low- or moderate-intensity counseling and behavioral interventions in obese or overweight adults because the trials showed mixed results, typically had small sample sizes and high dropout rates, and reported average weight change rather than frequency of response.⁸

Evidence summary

The TABLE summarizes the results of 6 RCTs that evaluated physician counseling for weight loss. The largest RCT, which included patients with elevated serum low-density lipoprotein levels (>75th percentile), randomized participants to 3 groups: physician counseling plus office support (dietary assessment tools, counseling algorithms, and in-office prompts), physician counseling alone, or usual care.¹

Patients who received physician counseling with office support lost 2.3 kg (P<.001 vs usual care), whereas patients who received physician counseling alone lost 1.0 kg and patients who received usual care didn’t lose any weight.

TABLE
The effectiveness of weight loss counseling by physicians: What the RCTs reveal

Other large studies show mixed results
The second largest RCT randomized participants from community health centers in Colorado to receive either physician counseling (in which physicians reviewed nutritional and physical activity goals generated by a computer in response to a survey) or usual care (patient handouts alone).² Although the physician-counseled group didn’t lose more total weight, more people in this group had lost 2.7 kg or more at the 12-month follow-up (32% vs 19% for usual care; P=.006).

The third largest RCT assigned low-income women from primary care clinics in Louisiana to either a 6-month tailored weight loss intervention or usual care.³ The intervention included monthly 15-minute visits with physician counseling about weight loss, fat intake, physical activity, barriers to weight loss, and weight loss maintenance. Women who received counseling lost 1.5 kg at the 9-month follow-up compared with a loss of 0.6 kg for women who received usual care. Both groups showed no net loss at the 12- and 18-month follow-up.

Counseling with follow-up leads to drop in BMI
Physician counseling in an Italian RCT included a 1-minute, patient-centered assessment of readiness for change, 2 to 5 minutes of exercise counseling by a physician for patients in active and maintenance stages, and phone or mail follow-up at 2 to 3 weeks.⁴ The reported decreases in body mass index (BMI) in the counseling group would translate to 2.4 and 1.0 kg of weight loss for men and women of average height, respectively.

No significant weight loss in a pediatric study
An RCT of children brought to a pediatric clinic for well-child visits recruited children who had either a BMI in the 85th to 95th percentile or obese parents (BMI ≥30 kg/m²).⁵ Parents were randomized to intensive counseling, minimal counseling, or usual care. The intensive intervention group participated in a 10- to 15-minute motivational interview with the pediatrician, followed by 2 45-minute sessions with a dietician at months 1 and 3 of the 6-month program; the minimal intervention group only participated in the motivational interview. No significant weight loss occurred in any of the 3 study groups.

The smallest RCT compared counseling by a family medicine resident with usual care in 30 adult patients.⁶ At 6 months, the counseling group had lost 0.9 kg compared with a gain of 1.3 kg in the usual care group, but follow-up at 12 months found no difference between the groups.

Recommendations

The US Preventive Services Task Force (USPSTF) says that intensive counseling (person-to-person meetings at least monthly, combined with diet, exercise, and behavioral interventions plus longer-term maintenance) can promote modest sustained weight loss and improve clinical outcomes.⁷ They recommend screening adults for obesity and offering intensive counseling and behavioral interventions for obese adults.

USPSTF notes, however, that evidence is insufficient to recommend for or against low- or moderate-intensity counseling and behavioral interventions in obese or overweight adults because the trials showed mixed results, typically had small sample sizes and high dropout rates, and reported average weight change rather than frequency of response.⁸

Evidence summary

The TABLE summarizes the results of 6 RCTs that evaluated physician counseling for weight loss. The largest RCT, which included patients with elevated serum low-density lipoprotein levels (>75th percentile), randomized participants to 3 groups: physician counseling plus office support (dietary assessment tools, counseling algorithms, and in-office prompts), physician counseling alone, or usual care.¹

Patients who received physician counseling with office support lost 2.3 kg (P<.001 vs usual care), whereas patients who received physician counseling alone lost 1.0 kg and patients who received usual care didn’t lose any weight.

TABLE
The effectiveness of weight loss counseling by physicians: What the RCTs reveal

Other large studies show mixed results
The second largest RCT randomized participants from community health centers in Colorado to receive either physician counseling (in which physicians reviewed nutritional and physical activity goals generated by a computer in response to a survey) or usual care (patient handouts alone).² Although the physician-counseled group didn’t lose more total weight, more people in this group had lost 2.7 kg or more at the 12-month follow-up (32% vs 19% for usual care; P=.006).

The third largest RCT assigned low-income women from primary care clinics in Louisiana to either a 6-month tailored weight loss intervention or usual care.³ The intervention included monthly 15-minute visits with physician counseling about weight loss, fat intake, physical activity, barriers to weight loss, and weight loss maintenance. Women who received counseling lost 1.5 kg at the 9-month follow-up compared with a loss of 0.6 kg for women who received usual care. Both groups showed no net loss at the 12- and 18-month follow-up.

Counseling with follow-up leads to drop in BMI
Physician counseling in an Italian RCT included a 1-minute, patient-centered assessment of readiness for change, 2 to 5 minutes of exercise counseling by a physician for patients in active and maintenance stages, and phone or mail follow-up at 2 to 3 weeks.⁴ The reported decreases in body mass index (BMI) in the counseling group would translate to 2.4 and 1.0 kg of weight loss for men and women of average height, respectively.

No significant weight loss in a pediatric study
An RCT of children brought to a pediatric clinic for well-child visits recruited children who had either a BMI in the 85th to 95th percentile or obese parents (BMI ≥30 kg/m²).⁵ Parents were randomized to intensive counseling, minimal counseling, or usual care. The intensive intervention group participated in a 10- to 15-minute motivational interview with the pediatrician, followed by 2 45-minute sessions with a dietician at months 1 and 3 of the 6-month program; the minimal intervention group only participated in the motivational interview. No significant weight loss occurred in any of the 3 study groups.

The smallest RCT compared counseling by a family medicine resident with usual care in 30 adult patients.⁶ At 6 months, the counseling group had lost 0.9 kg compared with a gain of 1.3 kg in the usual care group, but follow-up at 12 months found no difference between the groups.

Recommendations

The US Preventive Services Task Force (USPSTF) says that intensive counseling (person-to-person meetings at least monthly, combined with diet, exercise, and behavioral interventions plus longer-term maintenance) can promote modest sustained weight loss and improve clinical outcomes.⁷ They recommend screening adults for obesity and offering intensive counseling and behavioral interventions for obese adults.

USPSTF notes, however, that evidence is insufficient to recommend for or against low- or moderate-intensity counseling and behavioral interventions in obese or overweight adults because the trials showed mixed results, typically had small sample sizes and high dropout rates, and reported average weight change rather than frequency of response.⁸

Evidence summary

A prospective cohort study compared educational and employment outcomes among 91 middle-class white boys, 6 to 12 years of age, with ADHD who were referred to a psychiatric clinic with outcomes for 96 matched controls. Investigators used multiple educational achievement tests to evaluate participants when they enrolled in the study, then administered educational and occupational questionnaires 16 years later.

Boys with ADHD completed 2.5 fewer years of school than controls (P=.001). Although rates of employment for the 2 groups were the same at 90%, those with ADHD had a significantly poorer occupational ranking than controls using the Hollingshead and Redlich system, which rates occupations on 7-point scale, with 1 representing top-ranked occupations. Individuals with ADHD scored 4.4 points compared with 3.5 points for the control group (P<.001). However, by the end of the study, more individuals with ADHD owned and operated their own businesses compared with controls (18% vs 5%; P<.01).¹

Fewer degrees but comparable employment rates
A similar prospective cohort study evaluated educational and occupational outcomes among 104 boys with ADHD and 106 controls. Investigators recruited boys 5 to 11 years of age from a psychiatric research clinic and followed them for a mean of 17 years using educational and occupational questionnaires.

Boys with ADHD completed 2 fewer years of school than controls (P=.0001), and more boys in the ADHD group failed to complete high school (25% vs 1%; P value not supplied). Fewer individuals with ADHD than controls obtained a bachelor’s degree (15% vs 50%; P<.001), and fewer enrolled in graduate school (3% vs 16%; P value not given). Employment was comparable in the 2 groups, however (92% vs 93%, P=.07).²

Less success in school and at work
Another prospective case-control study also found that people with ADHD achieved less educational and occupational success than controls. The study compared 224 subjects between 18 and 55 years of age with ADHD from a psychiatric referral clinic with 146 controls matched for age and intelligence quotient (IQ). Investigators correlated predicted educational achievement based on IQ in the controls with that observed in subjects with ADHD.

Five years later, subjects with ADHD didn’t perform as well as predicted. Fewer earned college degrees (29% vs 52%) or graduate degrees (20% vs 33%), and more earned no college or graduate school degrees (50% vs 16%) (P<.001 for comparison of observed compared with expected means using Wilcoxon matched pairs test). Similarly, fewer subjects with ADHD attained a level of 6 on the Hollingshead Socioeconomic Status Scale than controls (58% vs 80%; P<.001).³

Recommendations

We found no statements from national organizations about the long-term educational prognosis for children and adolescents with ADHD. However, the authors of the Multimodal Treatment Study of Children with ADHD have expressed the opinion that prognosis depends on initial presentation (including severity of symptoms and comorbid conduct disorders), intellect, social advantage, and response to treatment.⁴

Evidence summary

A prospective cohort study compared educational and employment outcomes among 91 middle-class white boys, 6 to 12 years of age, with ADHD who were referred to a psychiatric clinic with outcomes for 96 matched controls. Investigators used multiple educational achievement tests to evaluate participants when they enrolled in the study, then administered educational and occupational questionnaires 16 years later.

Boys with ADHD completed 2.5 fewer years of school than controls (P=.001). Although rates of employment for the 2 groups were the same at 90%, those with ADHD had a significantly poorer occupational ranking than controls using the Hollingshead and Redlich system, which rates occupations on 7-point scale, with 1 representing top-ranked occupations. Individuals with ADHD scored 4.4 points compared with 3.5 points for the control group (P<.001). However, by the end of the study, more individuals with ADHD owned and operated their own businesses compared with controls (18% vs 5%; P<.01).¹

Fewer degrees but comparable employment rates
A similar prospective cohort study evaluated educational and occupational outcomes among 104 boys with ADHD and 106 controls. Investigators recruited boys 5 to 11 years of age from a psychiatric research clinic and followed them for a mean of 17 years using educational and occupational questionnaires.

Boys with ADHD completed 2 fewer years of school than controls (P=.0001), and more boys in the ADHD group failed to complete high school (25% vs 1%; P value not supplied). Fewer individuals with ADHD than controls obtained a bachelor’s degree (15% vs 50%; P<.001), and fewer enrolled in graduate school (3% vs 16%; P value not given). Employment was comparable in the 2 groups, however (92% vs 93%, P=.07).²

Less success in school and at work
Another prospective case-control study also found that people with ADHD achieved less educational and occupational success than controls. The study compared 224 subjects between 18 and 55 years of age with ADHD from a psychiatric referral clinic with 146 controls matched for age and intelligence quotient (IQ). Investigators correlated predicted educational achievement based on IQ in the controls with that observed in subjects with ADHD.

Five years later, subjects with ADHD didn’t perform as well as predicted. Fewer earned college degrees (29% vs 52%) or graduate degrees (20% vs 33%), and more earned no college or graduate school degrees (50% vs 16%) (P<.001 for comparison of observed compared with expected means using Wilcoxon matched pairs test). Similarly, fewer subjects with ADHD attained a level of 6 on the Hollingshead Socioeconomic Status Scale than controls (58% vs 80%; P<.001).³

Recommendations

We found no statements from national organizations about the long-term educational prognosis for children and adolescents with ADHD. However, the authors of the Multimodal Treatment Study of Children with ADHD have expressed the opinion that prognosis depends on initial presentation (including severity of symptoms and comorbid conduct disorders), intellect, social advantage, and response to treatment.⁴

Evidence summary

A prospective cohort study compared educational and employment outcomes among 91 middle-class white boys, 6 to 12 years of age, with ADHD who were referred to a psychiatric clinic with outcomes for 96 matched controls. Investigators used multiple educational achievement tests to evaluate participants when they enrolled in the study, then administered educational and occupational questionnaires 16 years later.

Boys with ADHD completed 2.5 fewer years of school than controls (P=.001). Although rates of employment for the 2 groups were the same at 90%, those with ADHD had a significantly poorer occupational ranking than controls using the Hollingshead and Redlich system, which rates occupations on 7-point scale, with 1 representing top-ranked occupations. Individuals with ADHD scored 4.4 points compared with 3.5 points for the control group (P<.001). However, by the end of the study, more individuals with ADHD owned and operated their own businesses compared with controls (18% vs 5%; P<.01).¹

Fewer degrees but comparable employment rates
A similar prospective cohort study evaluated educational and occupational outcomes among 104 boys with ADHD and 106 controls. Investigators recruited boys 5 to 11 years of age from a psychiatric research clinic and followed them for a mean of 17 years using educational and occupational questionnaires.

Boys with ADHD completed 2 fewer years of school than controls (P=.0001), and more boys in the ADHD group failed to complete high school (25% vs 1%; P value not supplied). Fewer individuals with ADHD than controls obtained a bachelor’s degree (15% vs 50%; P<.001), and fewer enrolled in graduate school (3% vs 16%; P value not given). Employment was comparable in the 2 groups, however (92% vs 93%, P=.07).²

Less success in school and at work
Another prospective case-control study also found that people with ADHD achieved less educational and occupational success than controls. The study compared 224 subjects between 18 and 55 years of age with ADHD from a psychiatric referral clinic with 146 controls matched for age and intelligence quotient (IQ). Investigators correlated predicted educational achievement based on IQ in the controls with that observed in subjects with ADHD.

Five years later, subjects with ADHD didn’t perform as well as predicted. Fewer earned college degrees (29% vs 52%) or graduate degrees (20% vs 33%), and more earned no college or graduate school degrees (50% vs 16%) (P<.001 for comparison of observed compared with expected means using Wilcoxon matched pairs test). Similarly, fewer subjects with ADHD attained a level of 6 on the Hollingshead Socioeconomic Status Scale than controls (58% vs 80%; P<.001).³

Recommendations

We found no statements from national organizations about the long-term educational prognosis for children and adolescents with ADHD. However, the authors of the Multimodal Treatment Study of Children with ADHD have expressed the opinion that prognosis depends on initial presentation (including severity of symptoms and comorbid conduct disorders), intellect, social advantage, and response to treatment.⁴

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).¹

Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).²

TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials^1,2

Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.¹ A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.^3,4

Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.^1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)¹

Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.^3,5

Other comparisons that found no significant difference in effectiveness included:

• 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid^1,2
• 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid⁶
• 1 RCT (N=43) that compared topical metronidazole with topical permethrin¹
• 1 RCT (N=40) that compared oral metronidazole with oral tetracycline¹
• 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily⁴
• 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.⁷

Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).¹ Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).⁴

Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).² Another case series with 17 patients reported improvements with photodynamic therapy with red ight.⁸

General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.⁹ Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.^1,2

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.¹⁰

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

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

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

Evidence summary

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

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

Evidence summary

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

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

Evidence summary

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

Evidence summary

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

Evidence summary

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

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

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

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

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

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

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

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

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

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

Recommendations

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

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

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

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

Little evidence directly compares treatments for pyogenic granuloma. Most studies examine multiple treatment methods without comparing results statistically, combine data from adults and children, or comprise case series using a single treatment method. The TABLE summarizes outcomes for different therapies.

TABLE
How treatment outcomes for pyogenic granuloma compare

Surgical excision: Low recurrence, but scarring is common
A retrospective cohort study audited recurrence rates in 408 patients (mean age 41 years, range 5 months to 90 years) whose pyogenic granulomas were treated with either surgical excision or combinations of curettage, shave, and cautery.¹ Investigators identified cases of histopathologically confirmed pyogenic granuloma over a 10-year period from a hospital database. Thirty-six percent of granulomas were located on the head and neck, 33% on the arm, 15% on the trunk, and 8% on the leg.

Of 326 lesions treated with surgical excision, 4 (3.7%) recurred. The overall recurrence rate was 10.3% for 82 lesions removed by combinations of curettage, shave, and cautery (the lesions weren’t differentiated by removal method or location). Investigators didn’t report on residual scarring with any method. However, expert opinion states that surgical excision often results in a conspicuous linear scar.²

Surgery vs laser therapy or no treatment
Another retrospective cohort study described treatment, recurrence rate, residual scarring, and patient satisfaction in 76 patients with pyogenic granuloma (mean age 6 years; range 4 months to 17 years). Outcomes were assessed by telephone follow-up.³

Fifty-eight lesions were removed by surgical excision and cautery with no recurrences (55% of patients had subtle scarring). Nine lesions were treated with pulsed dye laser (33% recurrence, 44% subtle scarring); 3 lesions were removed by CO₂ laser (100% recurrence, 33% subtle scarring). Four patients were followed but not treated (no explanation given); all untreated pyogenic granulomas disappeared spontaneously within 6 to 18 months with no recurrences; 1 patient had subtle scarring.

Cryotherapy may require more treatments than curettage
A prospective trial randomized 89 patients (mean age 34 years; range 11-88 years) with pyogenic granulomas that were 1.5 cm or smaller to receive either curettage or cryotherapy, then evaluated the number of treatments required and whether scarring occurred. Follow-up was 85%.⁴

A single curettage resolved pyogenic granuloma in 35 of 36 patients (97%); 9 of the 36 patients (31%) had residual scarring. Twenty-five of 40 pyogenic granulomas (63%) responded to 1 cryotherapy treatment, 13 lesions (32%) resolved after 2 treatments, and 2 (5%) resolved after 3 treatments; 17 of the 40 patients (42.5%) had a residual scar. Curettage required fewer treatments overall than cryotherapy (P<.001), but no significant difference in residual scarring was noted between the 2 treatments.

A case series reported on 135 patients (mean age 26 years; range 4 months to 70 years) whose pyogenic granulomas were treated with cryotherapy.⁵ Seventy-eight (58%) had complete resolution with 1 session, 30% needed 2 sessions, 8% needed 3 sessions, and 5% needed 4 sessions (mean 1.58 sessions). Ninety-four percent had an excellent cosmetic result (including 12% with a small flat scar); 5% had residual hypopigmentation.

CO₂ laser usually removes lesions in 1 session
Another case series of 100 patients (mean age 27 years; range 6 months to 84 years) treated with CO₂ laser reported that the pyogenic granuloma was removed completely in 1 session in 98 patients. Twelve percent of patients had visible scarring and another 10% had slight textural skin changes. All patients reported satisfaction with the results.⁶

Pulsed dye laser works for small lesions
A case series of 22 patients (mean age 3.4 years; range 6 months to 16 years) treated with pulsed dye laser for mostly small lesions (average diameter 4 mm) on the face reported successful removal in 20 children in 1 to 6 treatment sessions (average 2.25) with no residual scarring. Two children with larger lesions required shave excision with cautery (scarring was not assessed).⁷

Sclerotherapy: No recurrence, inconspicuous scars
A case series reported results in 9 patients (median age 18 years; range 1-57 years) with pyogenic granuloma treated with a single injection of the sclerosing agent monoethanolamine oleate.² All lesions disappeared without recurrence; the authors described remaining scars as inconspicuous. One patient reported residual pain lasting 4 weeks after injection of the sclerosing agent into a 1.5 cm × 1.0 cm pyogenic granuloma that hadn’t responded to previous cryotherapy.

Recommendations

A standard dermatology textbook recommends curettage with cautery, and reports that spontaneous regression is common after 6 months.⁸ A standard pediatric textbook recommends surgical excision with or without cautery, adding that small pyogenic granuloma lesions (<5 mm) may be removed with pulsed dye laser.⁹

An online textbook recommends either excision or shave (with or without curettage), but advises surgical excision with histologic confirmation for pyogenic granuloma lesions that can’t be differentiated with certainty from amelanotic melanoma, which typically grows more slowly.¹⁰

Evidence summary

Little evidence directly compares treatments for pyogenic granuloma. Most studies examine multiple treatment methods without comparing results statistically, combine data from adults and children, or comprise case series using a single treatment method. The TABLE summarizes outcomes for different therapies.

TABLE
How treatment outcomes for pyogenic granuloma compare

Surgical excision: Low recurrence, but scarring is common
A retrospective cohort study audited recurrence rates in 408 patients (mean age 41 years, range 5 months to 90 years) whose pyogenic granulomas were treated with either surgical excision or combinations of curettage, shave, and cautery.¹ Investigators identified cases of histopathologically confirmed pyogenic granuloma over a 10-year period from a hospital database. Thirty-six percent of granulomas were located on the head and neck, 33% on the arm, 15% on the trunk, and 8% on the leg.

Of 326 lesions treated with surgical excision, 4 (3.7%) recurred. The overall recurrence rate was 10.3% for 82 lesions removed by combinations of curettage, shave, and cautery (the lesions weren’t differentiated by removal method or location). Investigators didn’t report on residual scarring with any method. However, expert opinion states that surgical excision often results in a conspicuous linear scar.²

Surgery vs laser therapy or no treatment
Another retrospective cohort study described treatment, recurrence rate, residual scarring, and patient satisfaction in 76 patients with pyogenic granuloma (mean age 6 years; range 4 months to 17 years). Outcomes were assessed by telephone follow-up.³

Fifty-eight lesions were removed by surgical excision and cautery with no recurrences (55% of patients had subtle scarring). Nine lesions were treated with pulsed dye laser (33% recurrence, 44% subtle scarring); 3 lesions were removed by CO₂ laser (100% recurrence, 33% subtle scarring). Four patients were followed but not treated (no explanation given); all untreated pyogenic granulomas disappeared spontaneously within 6 to 18 months with no recurrences; 1 patient had subtle scarring.

Cryotherapy may require more treatments than curettage
A prospective trial randomized 89 patients (mean age 34 years; range 11-88 years) with pyogenic granulomas that were 1.5 cm or smaller to receive either curettage or cryotherapy, then evaluated the number of treatments required and whether scarring occurred. Follow-up was 85%.⁴

A single curettage resolved pyogenic granuloma in 35 of 36 patients (97%); 9 of the 36 patients (31%) had residual scarring. Twenty-five of 40 pyogenic granulomas (63%) responded to 1 cryotherapy treatment, 13 lesions (32%) resolved after 2 treatments, and 2 (5%) resolved after 3 treatments; 17 of the 40 patients (42.5%) had a residual scar. Curettage required fewer treatments overall than cryotherapy (P<.001), but no significant difference in residual scarring was noted between the 2 treatments.

A case series reported on 135 patients (mean age 26 years; range 4 months to 70 years) whose pyogenic granulomas were treated with cryotherapy.⁵ Seventy-eight (58%) had complete resolution with 1 session, 30% needed 2 sessions, 8% needed 3 sessions, and 5% needed 4 sessions (mean 1.58 sessions). Ninety-four percent had an excellent cosmetic result (including 12% with a small flat scar); 5% had residual hypopigmentation.

CO₂ laser usually removes lesions in 1 session
Another case series of 100 patients (mean age 27 years; range 6 months to 84 years) treated with CO₂ laser reported that the pyogenic granuloma was removed completely in 1 session in 98 patients. Twelve percent of patients had visible scarring and another 10% had slight textural skin changes. All patients reported satisfaction with the results.⁶

Pulsed dye laser works for small lesions
A case series of 22 patients (mean age 3.4 years; range 6 months to 16 years) treated with pulsed dye laser for mostly small lesions (average diameter 4 mm) on the face reported successful removal in 20 children in 1 to 6 treatment sessions (average 2.25) with no residual scarring. Two children with larger lesions required shave excision with cautery (scarring was not assessed).⁷

Sclerotherapy: No recurrence, inconspicuous scars
A case series reported results in 9 patients (median age 18 years; range 1-57 years) with pyogenic granuloma treated with a single injection of the sclerosing agent monoethanolamine oleate.² All lesions disappeared without recurrence; the authors described remaining scars as inconspicuous. One patient reported residual pain lasting 4 weeks after injection of the sclerosing agent into a 1.5 cm × 1.0 cm pyogenic granuloma that hadn’t responded to previous cryotherapy.

Recommendations

A standard dermatology textbook recommends curettage with cautery, and reports that spontaneous regression is common after 6 months.⁸ A standard pediatric textbook recommends surgical excision with or without cautery, adding that small pyogenic granuloma lesions (<5 mm) may be removed with pulsed dye laser.⁹

An online textbook recommends either excision or shave (with or without curettage), but advises surgical excision with histologic confirmation for pyogenic granuloma lesions that can’t be differentiated with certainty from amelanotic melanoma, which typically grows more slowly.¹⁰

Evidence summary

Little evidence directly compares treatments for pyogenic granuloma. Most studies examine multiple treatment methods without comparing results statistically, combine data from adults and children, or comprise case series using a single treatment method. The TABLE summarizes outcomes for different therapies.

TABLE
How treatment outcomes for pyogenic granuloma compare

Surgical excision: Low recurrence, but scarring is common
A retrospective cohort study audited recurrence rates in 408 patients (mean age 41 years, range 5 months to 90 years) whose pyogenic granulomas were treated with either surgical excision or combinations of curettage, shave, and cautery.¹ Investigators identified cases of histopathologically confirmed pyogenic granuloma over a 10-year period from a hospital database. Thirty-six percent of granulomas were located on the head and neck, 33% on the arm, 15% on the trunk, and 8% on the leg.

Of 326 lesions treated with surgical excision, 4 (3.7%) recurred. The overall recurrence rate was 10.3% for 82 lesions removed by combinations of curettage, shave, and cautery (the lesions weren’t differentiated by removal method or location). Investigators didn’t report on residual scarring with any method. However, expert opinion states that surgical excision often results in a conspicuous linear scar.²

Surgery vs laser therapy or no treatment
Another retrospective cohort study described treatment, recurrence rate, residual scarring, and patient satisfaction in 76 patients with pyogenic granuloma (mean age 6 years; range 4 months to 17 years). Outcomes were assessed by telephone follow-up.³

Fifty-eight lesions were removed by surgical excision and cautery with no recurrences (55% of patients had subtle scarring). Nine lesions were treated with pulsed dye laser (33% recurrence, 44% subtle scarring); 3 lesions were removed by CO₂ laser (100% recurrence, 33% subtle scarring). Four patients were followed but not treated (no explanation given); all untreated pyogenic granulomas disappeared spontaneously within 6 to 18 months with no recurrences; 1 patient had subtle scarring.

Cryotherapy may require more treatments than curettage
A prospective trial randomized 89 patients (mean age 34 years; range 11-88 years) with pyogenic granulomas that were 1.5 cm or smaller to receive either curettage or cryotherapy, then evaluated the number of treatments required and whether scarring occurred. Follow-up was 85%.⁴

A single curettage resolved pyogenic granuloma in 35 of 36 patients (97%); 9 of the 36 patients (31%) had residual scarring. Twenty-five of 40 pyogenic granulomas (63%) responded to 1 cryotherapy treatment, 13 lesions (32%) resolved after 2 treatments, and 2 (5%) resolved after 3 treatments; 17 of the 40 patients (42.5%) had a residual scar. Curettage required fewer treatments overall than cryotherapy (P<.001), but no significant difference in residual scarring was noted between the 2 treatments.

A case series reported on 135 patients (mean age 26 years; range 4 months to 70 years) whose pyogenic granulomas were treated with cryotherapy.⁵ Seventy-eight (58%) had complete resolution with 1 session, 30% needed 2 sessions, 8% needed 3 sessions, and 5% needed 4 sessions (mean 1.58 sessions). Ninety-four percent had an excellent cosmetic result (including 12% with a small flat scar); 5% had residual hypopigmentation.

CO₂ laser usually removes lesions in 1 session
Another case series of 100 patients (mean age 27 years; range 6 months to 84 years) treated with CO₂ laser reported that the pyogenic granuloma was removed completely in 1 session in 98 patients. Twelve percent of patients had visible scarring and another 10% had slight textural skin changes. All patients reported satisfaction with the results.⁶

Pulsed dye laser works for small lesions
A case series of 22 patients (mean age 3.4 years; range 6 months to 16 years) treated with pulsed dye laser for mostly small lesions (average diameter 4 mm) on the face reported successful removal in 20 children in 1 to 6 treatment sessions (average 2.25) with no residual scarring. Two children with larger lesions required shave excision with cautery (scarring was not assessed).⁷

Sclerotherapy: No recurrence, inconspicuous scars
A case series reported results in 9 patients (median age 18 years; range 1-57 years) with pyogenic granuloma treated with a single injection of the sclerosing agent monoethanolamine oleate.² All lesions disappeared without recurrence; the authors described remaining scars as inconspicuous. One patient reported residual pain lasting 4 weeks after injection of the sclerosing agent into a 1.5 cm × 1.0 cm pyogenic granuloma that hadn’t responded to previous cryotherapy.

Recommendations

A standard dermatology textbook recommends curettage with cautery, and reports that spontaneous regression is common after 6 months.⁸ A standard pediatric textbook recommends surgical excision with or without cautery, adding that small pyogenic granuloma lesions (<5 mm) may be removed with pulsed dye laser.⁹

An online textbook recommends either excision or shave (with or without curettage), but advises surgical excision with histologic confirmation for pyogenic granuloma lesions that can’t be differentiated with certainty from amelanotic melanoma, which typically grows more slowly.¹⁰