Diana Mahoney

BOSTON — Successful pregnancies in women with systemic lupus erythematosus depend on a combination of factors, including disease activity at the time of conception, maternal renal function, the presence of lupus-related autoantibodies, and medication use, according to Dr. Lisa Sammaritano of Cornell University, Ithaca, N.Y.

In terms of disease activity, “it has been shown time and again that patients with inactive disease for 6 or more months prior to conception have a substantially reduced risk of experiencing a disease flare during pregnancy than women with active disease,” Dr. Sammaritano reported at a meeting on rheumatology sponsored by Harvard Medical School. “[Physicians] should have this in mind during prepregnancy consultations and advise patients to wait for periods of stable disease before trying to conceive.”

Maternal renal function should also be evaluated prior to conception, said Dr. Sammaritano. In women with renal insufficiency, pregnancy can accelerate a decline in renal function and worsen hypertension and proteinuria, thus increasing the risk of maternal and fetal complications, such as preeclampsia, intrauterine growth restriction, and intrauterine death.

Additionally, “it's essential to assess renal function before pregnancy in women with renal insufficiency in order to better differentiate worsening lupus-related renal disease from superimposed preeclampsia during pregnancy,” Dr. Sammaritano said. Kidney problems during pregnancy are more likely to be related to systemic lupus erythematosus (SLE) renal disease than to preeclampsia if the patient exhibits clinical symptoms of active SLE, has an elevated anti-double-stranded DNA antibody, or has detectable red blood cell casts in the urine, she said.

The presence and levels of certain lupus-related autoantibodies can also affect pregnancy outcome, Dr. Sammaritano noted. The antiphospholipid antibodies as well as lupus anticoagulant and medium to high anticardiolipin antibodies have been associated with recurrent pregnancy losses, poor fetal growth, preeclampsia, and stillbirths in women with lupus. Identifying the antibodies ahead of time “is critical, because studies have shown that treatment with medication, such as aspirin or heparin, during pregnancy can improve the viability of the fetus,” she added.

Two other lupus-related autoantibodies—anti-SS-A and anti-SS-B—can have an effect on the babies born to mothers with lupus. The presence of one or both of these IgG autoantibodies in the mother increases the risk of neonatal lupus erythematosus (NLE), which can cause rash or changes in blood counts or liver function and, in severe cases, can affect the conduction system of the heart, Dr. Sammaritano said.

For pregnant women who test positive for anti-SS-A or anti-SS-B, current management guidelines recommend weekly fetal echocardiographic monitoring between gestational weeks 16 and 26 and biweekly monitoring between weeks 27 and 34 to look for congenital heart block, she said.

In terms of medication during pregnancy for women with lupus, corticosteroids should be used for active disease only.

“If a patient is on a dose of steroid, in general we will continue at a low dose during the course of the pregnancy. However, we do not recommend prophylactic steroids in patients without active disease in an effort to prevent a flare,” Dr. Sammaritano said.

BOSTON — Successful pregnancies in women with systemic lupus erythematosus depend on a combination of factors, including disease activity at the time of conception, maternal renal function, the presence of lupus-related autoantibodies, and medication use, according to Dr. Lisa Sammaritano of Cornell University, Ithaca, N.Y.

In terms of disease activity, “it has been shown time and again that patients with inactive disease for 6 or more months prior to conception have a substantially reduced risk of experiencing a disease flare during pregnancy than women with active disease,” Dr. Sammaritano reported at a meeting on rheumatology sponsored by Harvard Medical School. “[Physicians] should have this in mind during prepregnancy consultations and advise patients to wait for periods of stable disease before trying to conceive.”

Maternal renal function should also be evaluated prior to conception, said Dr. Sammaritano. In women with renal insufficiency, pregnancy can accelerate a decline in renal function and worsen hypertension and proteinuria, thus increasing the risk of maternal and fetal complications, such as preeclampsia, intrauterine growth restriction, and intrauterine death.

Additionally, “it's essential to assess renal function before pregnancy in women with renal insufficiency in order to better differentiate worsening lupus-related renal disease from superimposed preeclampsia during pregnancy,” Dr. Sammaritano said. Kidney problems during pregnancy are more likely to be related to systemic lupus erythematosus (SLE) renal disease than to preeclampsia if the patient exhibits clinical symptoms of active SLE, has an elevated anti-double-stranded DNA antibody, or has detectable red blood cell casts in the urine, she said.

The presence and levels of certain lupus-related autoantibodies can also affect pregnancy outcome, Dr. Sammaritano noted. The antiphospholipid antibodies as well as lupus anticoagulant and medium to high anticardiolipin antibodies have been associated with recurrent pregnancy losses, poor fetal growth, preeclampsia, and stillbirths in women with lupus. Identifying the antibodies ahead of time “is critical, because studies have shown that treatment with medication, such as aspirin or heparin, during pregnancy can improve the viability of the fetus,” she added.

Two other lupus-related autoantibodies—anti-SS-A and anti-SS-B—can have an effect on the babies born to mothers with lupus. The presence of one or both of these IgG autoantibodies in the mother increases the risk of neonatal lupus erythematosus (NLE), which can cause rash or changes in blood counts or liver function and, in severe cases, can affect the conduction system of the heart, Dr. Sammaritano said.

For pregnant women who test positive for anti-SS-A or anti-SS-B, current management guidelines recommend weekly fetal echocardiographic monitoring between gestational weeks 16 and 26 and biweekly monitoring between weeks 27 and 34 to look for congenital heart block, she said.

In terms of medication during pregnancy for women with lupus, corticosteroids should be used for active disease only.

“If a patient is on a dose of steroid, in general we will continue at a low dose during the course of the pregnancy. However, we do not recommend prophylactic steroids in patients without active disease in an effort to prevent a flare,” Dr. Sammaritano said.

BOSTON — Successful pregnancies in women with systemic lupus erythematosus depend on a combination of factors, including disease activity at the time of conception, maternal renal function, the presence of lupus-related autoantibodies, and medication use, according to Dr. Lisa Sammaritano of Cornell University, Ithaca, N.Y.

In terms of disease activity, “it has been shown time and again that patients with inactive disease for 6 or more months prior to conception have a substantially reduced risk of experiencing a disease flare during pregnancy than women with active disease,” Dr. Sammaritano reported at a meeting on rheumatology sponsored by Harvard Medical School. “[Physicians] should have this in mind during prepregnancy consultations and advise patients to wait for periods of stable disease before trying to conceive.”

Maternal renal function should also be evaluated prior to conception, said Dr. Sammaritano. In women with renal insufficiency, pregnancy can accelerate a decline in renal function and worsen hypertension and proteinuria, thus increasing the risk of maternal and fetal complications, such as preeclampsia, intrauterine growth restriction, and intrauterine death.

Additionally, “it's essential to assess renal function before pregnancy in women with renal insufficiency in order to better differentiate worsening lupus-related renal disease from superimposed preeclampsia during pregnancy,” Dr. Sammaritano said. Kidney problems during pregnancy are more likely to be related to systemic lupus erythematosus (SLE) renal disease than to preeclampsia if the patient exhibits clinical symptoms of active SLE, has an elevated anti-double-stranded DNA antibody, or has detectable red blood cell casts in the urine, she said.

The presence and levels of certain lupus-related autoantibodies can also affect pregnancy outcome, Dr. Sammaritano noted. The antiphospholipid antibodies as well as lupus anticoagulant and medium to high anticardiolipin antibodies have been associated with recurrent pregnancy losses, poor fetal growth, preeclampsia, and stillbirths in women with lupus. Identifying the antibodies ahead of time “is critical, because studies have shown that treatment with medication, such as aspirin or heparin, during pregnancy can improve the viability of the fetus,” she added.

Two other lupus-related autoantibodies—anti-SS-A and anti-SS-B—can have an effect on the babies born to mothers with lupus. The presence of one or both of these IgG autoantibodies in the mother increases the risk of neonatal lupus erythematosus (NLE), which can cause rash or changes in blood counts or liver function and, in severe cases, can affect the conduction system of the heart, Dr. Sammaritano said.

For pregnant women who test positive for anti-SS-A or anti-SS-B, current management guidelines recommend weekly fetal echocardiographic monitoring between gestational weeks 16 and 26 and biweekly monitoring between weeks 27 and 34 to look for congenital heart block, she said.

In terms of medication during pregnancy for women with lupus, corticosteroids should be used for active disease only.

“If a patient is on a dose of steroid, in general we will continue at a low dose during the course of the pregnancy. However, we do not recommend prophylactic steroids in patients without active disease in an effort to prevent a flare,” Dr. Sammaritano said.

Rituximab is a safe and effective treatment for the systemic complications of primary Sjögren's syndrome, judging from the findings of a small retrospective study.

Recent investigations have linked high levels of B-cell autoreactivity with high levels of disease activity and the development of a range of systemic complications, including arthritis; vasculitis; lymph node enlargement; thyroid, lung, kidney, nerve, and muscle problems; and an increased risk of developing B-cell lymphoma.

To assess the safety and efficacy of rituximab (Rituxan), an anti-CD20 antibody that targets B cells, for treating the systemic manifestations of primary Sjögren's syndrome (pSS), Dr. Raphaéle Seror of Bicetre Hospital, Paris, and colleagues obtained records from six referral centers in France for 16 female patients (median age 59 years) diagnosed with the condition who had been treated with rituximab for either lymphoma or other complications (Ann. Rheum. Dis. 2006 Sept. 1 [Epub doi:10:1136/ard.2006.057919]).

All of the patients included in the evaluation received a 100-mg pulse of methylprednisone and either 20 mg of oral cetirizine or an intravenous pulse of 5-mg dexchlorpheniramine before each rituximab infusion, and four of the patients received concomitant immunosuppressants.

Rituximab therapy induced complete remission in four of the five lymphoma patients but was not effective in one patient with salivary lymphoma. Among the 11 patients with systemic features, rituximab was effective in 9, including 4 with cryoglobulinemia, 2 with pulmonary involvement and polysynovitis, 2 with polysynovitis, and 1 with mononeuritis multiplex. Despite rituximab therapy, one patient with cryoglobulinemia experienced a worsening of peripheral nerve involvement, and the platelet counts of the patient with thrombocytopenia remained below 10,000/mm

The investigators also assessed laboratory outcomes, including changes in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, cryoglobulinemia, B-cell biomarkers, and, for some patients, serum B-cell activating factor of the tumor necrosis factor family (BAFF) levels from retrospective ELISA assessment of frozen samples. B-cell depletion was achieved in 14 of the 15 patients, and median ESR and CRP levels decreased from 60 to 20 mm/h and from 11.4 to 4 mg/L, respectively.

Median rheumatoid factor decreased from 124 to 7.5 IU/mL, disappearing completely in five patients. Median gammaglobulin, IgG, and beta-2 microglobulin levels also decreased, while median BAFF levels increased, possibly as a consequence of B-cell depletion, the authors hypothesized.

During the median 14.5-month follow-up, five patients relapsed, four experienced a flare of pSS, and lymphoma was diagnosed in one patient treated initially for cryoglobulinemia. Clinical relapse was associated with the reappearance within 3 months prior to relapse of peripheral blood B cells and an increase in B-cell biomarkers. Rituximab was effective in all but four of five patients treated for relapse. Only three of the patients experienced moderate adverse events, including delayed, infusion-related flulike reactions, the authors wrote.

Rituximab is a safe and effective treatment for the systemic complications of primary Sjögren's syndrome, judging from the findings of a small retrospective study.

Recent investigations have linked high levels of B-cell autoreactivity with high levels of disease activity and the development of a range of systemic complications, including arthritis; vasculitis; lymph node enlargement; thyroid, lung, kidney, nerve, and muscle problems; and an increased risk of developing B-cell lymphoma.

To assess the safety and efficacy of rituximab (Rituxan), an anti-CD20 antibody that targets B cells, for treating the systemic manifestations of primary Sjögren's syndrome (pSS), Dr. Raphaéle Seror of Bicetre Hospital, Paris, and colleagues obtained records from six referral centers in France for 16 female patients (median age 59 years) diagnosed with the condition who had been treated with rituximab for either lymphoma or other complications (Ann. Rheum. Dis. 2006 Sept. 1 [Epub doi:10:1136/ard.2006.057919]).

All of the patients included in the evaluation received a 100-mg pulse of methylprednisone and either 20 mg of oral cetirizine or an intravenous pulse of 5-mg dexchlorpheniramine before each rituximab infusion, and four of the patients received concomitant immunosuppressants.

Rituximab therapy induced complete remission in four of the five lymphoma patients but was not effective in one patient with salivary lymphoma. Among the 11 patients with systemic features, rituximab was effective in 9, including 4 with cryoglobulinemia, 2 with pulmonary involvement and polysynovitis, 2 with polysynovitis, and 1 with mononeuritis multiplex. Despite rituximab therapy, one patient with cryoglobulinemia experienced a worsening of peripheral nerve involvement, and the platelet counts of the patient with thrombocytopenia remained below 10,000/mm

The investigators also assessed laboratory outcomes, including changes in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, cryoglobulinemia, B-cell biomarkers, and, for some patients, serum B-cell activating factor of the tumor necrosis factor family (BAFF) levels from retrospective ELISA assessment of frozen samples. B-cell depletion was achieved in 14 of the 15 patients, and median ESR and CRP levels decreased from 60 to 20 mm/h and from 11.4 to 4 mg/L, respectively.

Median rheumatoid factor decreased from 124 to 7.5 IU/mL, disappearing completely in five patients. Median gammaglobulin, IgG, and beta-2 microglobulin levels also decreased, while median BAFF levels increased, possibly as a consequence of B-cell depletion, the authors hypothesized.

During the median 14.5-month follow-up, five patients relapsed, four experienced a flare of pSS, and lymphoma was diagnosed in one patient treated initially for cryoglobulinemia. Clinical relapse was associated with the reappearance within 3 months prior to relapse of peripheral blood B cells and an increase in B-cell biomarkers. Rituximab was effective in all but four of five patients treated for relapse. Only three of the patients experienced moderate adverse events, including delayed, infusion-related flulike reactions, the authors wrote.

Rituximab is a safe and effective treatment for the systemic complications of primary Sjögren's syndrome, judging from the findings of a small retrospective study.

Recent investigations have linked high levels of B-cell autoreactivity with high levels of disease activity and the development of a range of systemic complications, including arthritis; vasculitis; lymph node enlargement; thyroid, lung, kidney, nerve, and muscle problems; and an increased risk of developing B-cell lymphoma.

To assess the safety and efficacy of rituximab (Rituxan), an anti-CD20 antibody that targets B cells, for treating the systemic manifestations of primary Sjögren's syndrome (pSS), Dr. Raphaéle Seror of Bicetre Hospital, Paris, and colleagues obtained records from six referral centers in France for 16 female patients (median age 59 years) diagnosed with the condition who had been treated with rituximab for either lymphoma or other complications (Ann. Rheum. Dis. 2006 Sept. 1 [Epub doi:10:1136/ard.2006.057919]).

All of the patients included in the evaluation received a 100-mg pulse of methylprednisone and either 20 mg of oral cetirizine or an intravenous pulse of 5-mg dexchlorpheniramine before each rituximab infusion, and four of the patients received concomitant immunosuppressants.

Rituximab therapy induced complete remission in four of the five lymphoma patients but was not effective in one patient with salivary lymphoma. Among the 11 patients with systemic features, rituximab was effective in 9, including 4 with cryoglobulinemia, 2 with pulmonary involvement and polysynovitis, 2 with polysynovitis, and 1 with mononeuritis multiplex. Despite rituximab therapy, one patient with cryoglobulinemia experienced a worsening of peripheral nerve involvement, and the platelet counts of the patient with thrombocytopenia remained below 10,000/mm

The investigators also assessed laboratory outcomes, including changes in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, cryoglobulinemia, B-cell biomarkers, and, for some patients, serum B-cell activating factor of the tumor necrosis factor family (BAFF) levels from retrospective ELISA assessment of frozen samples. B-cell depletion was achieved in 14 of the 15 patients, and median ESR and CRP levels decreased from 60 to 20 mm/h and from 11.4 to 4 mg/L, respectively.

Median rheumatoid factor decreased from 124 to 7.5 IU/mL, disappearing completely in five patients. Median gammaglobulin, IgG, and beta-2 microglobulin levels also decreased, while median BAFF levels increased, possibly as a consequence of B-cell depletion, the authors hypothesized.

During the median 14.5-month follow-up, five patients relapsed, four experienced a flare of pSS, and lymphoma was diagnosed in one patient treated initially for cryoglobulinemia. Clinical relapse was associated with the reappearance within 3 months prior to relapse of peripheral blood B cells and an increase in B-cell biomarkers. Rituximab was effective in all but four of five patients treated for relapse. Only three of the patients experienced moderate adverse events, including delayed, infusion-related flulike reactions, the authors wrote.

BOSTON — Antibiotic therapy decreases the duration of persistent joint inflammation in Lyme arthritis, and disease-modifying antirheumatic drugs can reduce its severity in individuals with antibiotic-refractory disease, reported Dr. Alan Steere at a rheumatology conference sponsored by Harvard Medical School, Boston.

Antibiotics continue to be the cornerstone of treatment for Lyme arthritis, with the majority of patients responding to a 1-month course of oral doxycycline or amoxicillin, said Dr. Steere of Massachusetts General Hospital, Boston. In patients with mild, residual joint swelling, the oral antibiotic regimen is repeated for an additional 30 days. When joint swelling is moderate to severe, an additional month of intravenous antibiotic therapy with ceftriaxone, cefotaxime, or penicillin is a standard course, he said.

Management options have been less clear-cut, however, for patients with proliferative synovitis that persists for months or years despite antibiotic treatment, he said.

According to Infectious Diseases Society of America practice guidelines, patients with persistent postantibiotic joint swelling—whose joint fluid test results are negative for Borrelia burgdorferi, the spirochete implicated in Lyme arthritis—should be treated with nonsteroidal anti-inflammatory agents, intra-articular corticosteroid injections, or disease-modifying antirheumatic drugs (DMARDs). The guidelines also state that arthroscopic synovectomy should be considered for swelling that persists longer than 12 months (Clin. Infect. Dis. 2000;31:S1–14).

To evaluate postantibiotic treatment strategies in refractory patients and to compare treatment and disease course in antibiotic-responsive and -refractory patients, Dr. Steere and his colleagues reviewed the outcomes of 117 patients seen from November 1987 through May 2004. Of those, 50 were antibiotic responsive, and 67 had antibiotic-refractory Lyme arthritis.

All of the patients in the study met the Centers for Disease Control and Prevention criteria for Lyme arthritis as well as the Infectious Diseases Society of America guidelines for antibiotic treatment. The groups did not differ in age, sex, clinical presentation, duration of arthritis prior to diagnosis, or standard lab testing, according to Dr. Steere. Although the antibiotic-refractory patients tended to receive intra-articular steroids more often than the antibiotic-responsive patients did, “the majority of the refractory patients were not given this medication,” he said.

Comparisons between the responsive and refractory groups identified potential risk factors for antibiotic-refractory arthritis, including specific human histocompatibility leukocyte antigen-DR alleles, greater immune reactivity with the outer-surface protein A epitope, and treatment with intra-articular steroids prior to antibiotic therapy, Dr. Steere said.

In terms of treatment course, “in patients with antibiotic-responsive arthritis, a 1-month course of oral doxycycline was usually successful, while patients with refractory arthritis tended to have persistent disease even after 2 months of oral antibiotics and 1 month of IV ceftriaxone,” Dr. Steere said, adding that type of therapy (oral antibiotics alone or combined with intravenous antibiotics) did not correlate with the postantibiotic duration of arthritis.

Patients in the refractory group underwent one of two different postantibiotic treatment strategies. Of the 67 patients, 22 were treated with NSAIDs or intra-articular corticosteroids. If their arthritis persisted for 12–24 months, they underwent arthroscopic synovectomy. In the remaining 45 patients, DMARD treatment (primarily hydroxychloroquine) was added to the previous regimen if polymerase chain reaction (PCR) testing was negative for B. burgdorferi. If the arthritis persisted, patients were given oral methotrexate for 3–4 months or two to four infusions of intravenous inifliximab, after which arthroscopic synovectomy was offered, if needed.

At follow-up, data for 20 of the 22 patients treated with NSAIDs or intraarticular corticosteroids showed that 11 patients had complete resolution of arthritis within a median of 11 months after the start of antibiotic therapy, whereas 9 patients underwent arthroscopic synovectomies. “Arthritis resolved in the all of the patients within a median of 14 months,” Dr. Steere said.

Of the 42 patients treated with DMARDs for whom follow-up was available, 34 had resolution of arthritis within a median of 8 months after the start of antibiotic therapy. Three of the remaining eight patients who did not respond to treatment with hydroxychloroquine elected to have arthroscopic synovectomies, which was successful in only one patient, Dr. Steere said.

The two patients in whom the synovectomies failed, along with the remaining five with unresolved arthritis, received methotrexate or intravenous inifliximab, he said. Although both of the drugs induced responses, he said, “inifliximab resulted in particularly marked reductions in joint inflammation.”

Overall, arthritis persisted in the group of 42 patients who received DMARDs for a median of 9 months, Dr. Steere said. One patient in this group experienced a breakthrough case of persistent infection.

Based on these findings, a “reasonable management plan” for Lyme arthritis that persists after 60 days of antibiotics (including 30 days of intravenous therapy) should include an additional month of oral antibiotic therapy if PCR testing for B. burgdorferi DNA is still positive; treatment with NSAIDs if PCR results for B. burgdorferi DNA are negative; and the addition of 200 mg oral hydroxychloroquine twice daily if arthritis still persists, Dr. Steere said. If arthritis persists for 3–6 more months, arthroscopic synovectomy should be considered, he added.

Although DMARDs stronger than hydroxychloroquine were used in the investigation, “we're reluctant to recommend them, both because our limited experience with them doesn't prove efficacy and because of the possibility that they may be given to patients in whom the infection is still active,” Dr. Steere noted.

Because Lyme arthritis eventually resolves even without antibiotic therapy, Dr. Steere and colleagues also sought to determine whether antibiotic treatment altered the natural course of the disease in patients with antibiotic-refractory arthritis.

To do this, they compared the current findings to those of 21 patients treated for Lyme arthritis in the late 1970s “before the etiologic agent of Lyme disease was known,” Dr. Steere said. That group of patients received NSAIDs and intra-articular steroids, but not antibiotics, and experienced episodes of arthritis for a median period of 43 months.

In contrast, the median total time of arthritis episodes for the antibiotic-responsive patients and the antibiotic-refractory patients in the current study was 4 and 16 months, respectively. The finding suggests “antibiotic therapy decreases the period of joint inflammation, even in patients with antibiotic-refractory arthritis,” he said.

BOSTON — Antibiotic therapy decreases the duration of persistent joint inflammation in Lyme arthritis, and disease-modifying antirheumatic drugs can reduce its severity in individuals with antibiotic-refractory disease, reported Dr. Alan Steere at a rheumatology conference sponsored by Harvard Medical School, Boston.

Antibiotics continue to be the cornerstone of treatment for Lyme arthritis, with the majority of patients responding to a 1-month course of oral doxycycline or amoxicillin, said Dr. Steere of Massachusetts General Hospital, Boston. In patients with mild, residual joint swelling, the oral antibiotic regimen is repeated for an additional 30 days. When joint swelling is moderate to severe, an additional month of intravenous antibiotic therapy with ceftriaxone, cefotaxime, or penicillin is a standard course, he said.

Management options have been less clear-cut, however, for patients with proliferative synovitis that persists for months or years despite antibiotic treatment, he said.

According to Infectious Diseases Society of America practice guidelines, patients with persistent postantibiotic joint swelling—whose joint fluid test results are negative for Borrelia burgdorferi, the spirochete implicated in Lyme arthritis—should be treated with nonsteroidal anti-inflammatory agents, intra-articular corticosteroid injections, or disease-modifying antirheumatic drugs (DMARDs). The guidelines also state that arthroscopic synovectomy should be considered for swelling that persists longer than 12 months (Clin. Infect. Dis. 2000;31:S1–14).

To evaluate postantibiotic treatment strategies in refractory patients and to compare treatment and disease course in antibiotic-responsive and -refractory patients, Dr. Steere and his colleagues reviewed the outcomes of 117 patients seen from November 1987 through May 2004. Of those, 50 were antibiotic responsive, and 67 had antibiotic-refractory Lyme arthritis.

All of the patients in the study met the Centers for Disease Control and Prevention criteria for Lyme arthritis as well as the Infectious Diseases Society of America guidelines for antibiotic treatment. The groups did not differ in age, sex, clinical presentation, duration of arthritis prior to diagnosis, or standard lab testing, according to Dr. Steere. Although the antibiotic-refractory patients tended to receive intra-articular steroids more often than the antibiotic-responsive patients did, “the majority of the refractory patients were not given this medication,” he said.

Comparisons between the responsive and refractory groups identified potential risk factors for antibiotic-refractory arthritis, including specific human histocompatibility leukocyte antigen-DR alleles, greater immune reactivity with the outer-surface protein A epitope, and treatment with intra-articular steroids prior to antibiotic therapy, Dr. Steere said.

In terms of treatment course, “in patients with antibiotic-responsive arthritis, a 1-month course of oral doxycycline was usually successful, while patients with refractory arthritis tended to have persistent disease even after 2 months of oral antibiotics and 1 month of IV ceftriaxone,” Dr. Steere said, adding that type of therapy (oral antibiotics alone or combined with intravenous antibiotics) did not correlate with the postantibiotic duration of arthritis.

Patients in the refractory group underwent one of two different postantibiotic treatment strategies. Of the 67 patients, 22 were treated with NSAIDs or intra-articular corticosteroids. If their arthritis persisted for 12–24 months, they underwent arthroscopic synovectomy. In the remaining 45 patients, DMARD treatment (primarily hydroxychloroquine) was added to the previous regimen if polymerase chain reaction (PCR) testing was negative for B. burgdorferi. If the arthritis persisted, patients were given oral methotrexate for 3–4 months or two to four infusions of intravenous inifliximab, after which arthroscopic synovectomy was offered, if needed.

At follow-up, data for 20 of the 22 patients treated with NSAIDs or intraarticular corticosteroids showed that 11 patients had complete resolution of arthritis within a median of 11 months after the start of antibiotic therapy, whereas 9 patients underwent arthroscopic synovectomies. “Arthritis resolved in the all of the patients within a median of 14 months,” Dr. Steere said.

Of the 42 patients treated with DMARDs for whom follow-up was available, 34 had resolution of arthritis within a median of 8 months after the start of antibiotic therapy. Three of the remaining eight patients who did not respond to treatment with hydroxychloroquine elected to have arthroscopic synovectomies, which was successful in only one patient, Dr. Steere said.

The two patients in whom the synovectomies failed, along with the remaining five with unresolved arthritis, received methotrexate or intravenous inifliximab, he said. Although both of the drugs induced responses, he said, “inifliximab resulted in particularly marked reductions in joint inflammation.”

Overall, arthritis persisted in the group of 42 patients who received DMARDs for a median of 9 months, Dr. Steere said. One patient in this group experienced a breakthrough case of persistent infection.

Based on these findings, a “reasonable management plan” for Lyme arthritis that persists after 60 days of antibiotics (including 30 days of intravenous therapy) should include an additional month of oral antibiotic therapy if PCR testing for B. burgdorferi DNA is still positive; treatment with NSAIDs if PCR results for B. burgdorferi DNA are negative; and the addition of 200 mg oral hydroxychloroquine twice daily if arthritis still persists, Dr. Steere said. If arthritis persists for 3–6 more months, arthroscopic synovectomy should be considered, he added.

Although DMARDs stronger than hydroxychloroquine were used in the investigation, “we're reluctant to recommend them, both because our limited experience with them doesn't prove efficacy and because of the possibility that they may be given to patients in whom the infection is still active,” Dr. Steere noted.

Because Lyme arthritis eventually resolves even without antibiotic therapy, Dr. Steere and colleagues also sought to determine whether antibiotic treatment altered the natural course of the disease in patients with antibiotic-refractory arthritis.

To do this, they compared the current findings to those of 21 patients treated for Lyme arthritis in the late 1970s “before the etiologic agent of Lyme disease was known,” Dr. Steere said. That group of patients received NSAIDs and intra-articular steroids, but not antibiotics, and experienced episodes of arthritis for a median period of 43 months.

In contrast, the median total time of arthritis episodes for the antibiotic-responsive patients and the antibiotic-refractory patients in the current study was 4 and 16 months, respectively. The finding suggests “antibiotic therapy decreases the period of joint inflammation, even in patients with antibiotic-refractory arthritis,” he said.

BOSTON — Antibiotic therapy decreases the duration of persistent joint inflammation in Lyme arthritis, and disease-modifying antirheumatic drugs can reduce its severity in individuals with antibiotic-refractory disease, reported Dr. Alan Steere at a rheumatology conference sponsored by Harvard Medical School, Boston.

Antibiotics continue to be the cornerstone of treatment for Lyme arthritis, with the majority of patients responding to a 1-month course of oral doxycycline or amoxicillin, said Dr. Steere of Massachusetts General Hospital, Boston. In patients with mild, residual joint swelling, the oral antibiotic regimen is repeated for an additional 30 days. When joint swelling is moderate to severe, an additional month of intravenous antibiotic therapy with ceftriaxone, cefotaxime, or penicillin is a standard course, he said.

Management options have been less clear-cut, however, for patients with proliferative synovitis that persists for months or years despite antibiotic treatment, he said.

According to Infectious Diseases Society of America practice guidelines, patients with persistent postantibiotic joint swelling—whose joint fluid test results are negative for Borrelia burgdorferi, the spirochete implicated in Lyme arthritis—should be treated with nonsteroidal anti-inflammatory agents, intra-articular corticosteroid injections, or disease-modifying antirheumatic drugs (DMARDs). The guidelines also state that arthroscopic synovectomy should be considered for swelling that persists longer than 12 months (Clin. Infect. Dis. 2000;31:S1–14).

To evaluate postantibiotic treatment strategies in refractory patients and to compare treatment and disease course in antibiotic-responsive and -refractory patients, Dr. Steere and his colleagues reviewed the outcomes of 117 patients seen from November 1987 through May 2004. Of those, 50 were antibiotic responsive, and 67 had antibiotic-refractory Lyme arthritis.

All of the patients in the study met the Centers for Disease Control and Prevention criteria for Lyme arthritis as well as the Infectious Diseases Society of America guidelines for antibiotic treatment. The groups did not differ in age, sex, clinical presentation, duration of arthritis prior to diagnosis, or standard lab testing, according to Dr. Steere. Although the antibiotic-refractory patients tended to receive intra-articular steroids more often than the antibiotic-responsive patients did, “the majority of the refractory patients were not given this medication,” he said.

Comparisons between the responsive and refractory groups identified potential risk factors for antibiotic-refractory arthritis, including specific human histocompatibility leukocyte antigen-DR alleles, greater immune reactivity with the outer-surface protein A epitope, and treatment with intra-articular steroids prior to antibiotic therapy, Dr. Steere said.

In terms of treatment course, “in patients with antibiotic-responsive arthritis, a 1-month course of oral doxycycline was usually successful, while patients with refractory arthritis tended to have persistent disease even after 2 months of oral antibiotics and 1 month of IV ceftriaxone,” Dr. Steere said, adding that type of therapy (oral antibiotics alone or combined with intravenous antibiotics) did not correlate with the postantibiotic duration of arthritis.

Patients in the refractory group underwent one of two different postantibiotic treatment strategies. Of the 67 patients, 22 were treated with NSAIDs or intra-articular corticosteroids. If their arthritis persisted for 12–24 months, they underwent arthroscopic synovectomy. In the remaining 45 patients, DMARD treatment (primarily hydroxychloroquine) was added to the previous regimen if polymerase chain reaction (PCR) testing was negative for B. burgdorferi. If the arthritis persisted, patients were given oral methotrexate for 3–4 months or two to four infusions of intravenous inifliximab, after which arthroscopic synovectomy was offered, if needed.

At follow-up, data for 20 of the 22 patients treated with NSAIDs or intraarticular corticosteroids showed that 11 patients had complete resolution of arthritis within a median of 11 months after the start of antibiotic therapy, whereas 9 patients underwent arthroscopic synovectomies. “Arthritis resolved in the all of the patients within a median of 14 months,” Dr. Steere said.

Of the 42 patients treated with DMARDs for whom follow-up was available, 34 had resolution of arthritis within a median of 8 months after the start of antibiotic therapy. Three of the remaining eight patients who did not respond to treatment with hydroxychloroquine elected to have arthroscopic synovectomies, which was successful in only one patient, Dr. Steere said.

The two patients in whom the synovectomies failed, along with the remaining five with unresolved arthritis, received methotrexate or intravenous inifliximab, he said. Although both of the drugs induced responses, he said, “inifliximab resulted in particularly marked reductions in joint inflammation.”

Overall, arthritis persisted in the group of 42 patients who received DMARDs for a median of 9 months, Dr. Steere said. One patient in this group experienced a breakthrough case of persistent infection.

Based on these findings, a “reasonable management plan” for Lyme arthritis that persists after 60 days of antibiotics (including 30 days of intravenous therapy) should include an additional month of oral antibiotic therapy if PCR testing for B. burgdorferi DNA is still positive; treatment with NSAIDs if PCR results for B. burgdorferi DNA are negative; and the addition of 200 mg oral hydroxychloroquine twice daily if arthritis still persists, Dr. Steere said. If arthritis persists for 3–6 more months, arthroscopic synovectomy should be considered, he added.

Although DMARDs stronger than hydroxychloroquine were used in the investigation, “we're reluctant to recommend them, both because our limited experience with them doesn't prove efficacy and because of the possibility that they may be given to patients in whom the infection is still active,” Dr. Steere noted.

Because Lyme arthritis eventually resolves even without antibiotic therapy, Dr. Steere and colleagues also sought to determine whether antibiotic treatment altered the natural course of the disease in patients with antibiotic-refractory arthritis.

To do this, they compared the current findings to those of 21 patients treated for Lyme arthritis in the late 1970s “before the etiologic agent of Lyme disease was known,” Dr. Steere said. That group of patients received NSAIDs and intra-articular steroids, but not antibiotics, and experienced episodes of arthritis for a median period of 43 months.

In contrast, the median total time of arthritis episodes for the antibiotic-responsive patients and the antibiotic-refractory patients in the current study was 4 and 16 months, respectively. The finding suggests “antibiotic therapy decreases the period of joint inflammation, even in patients with antibiotic-refractory arthritis,” he said.

BOSTON — Adults with juvenile-onset rheumatoid arthritis have greater accumulated morbidity than do those with adult-onset rheumatoid arthritis, and failing to take that into account can lead to suboptimal outcomes, Dr. Peter A. Nigrovic reported at a rheumatology conference sponsored by Harvard Medical School, Boston.

“This may include structural bony deformity related to disturbed growth, premature osteoporosis, uveitis, and rarely amyloidosis,” said Dr. Nigrovic, director of the Center for Adults with Pediatric Rheumatic Illness at Brigham and Women's Hospital in Boston. In addition, impaired development of life goals, excess anxiety, and impaired social and vocational functioning can lead to psychosocial morbidity.

In terms of the medical management of JRA in adulthood, “a substantial proportion of these patients will have ongoing synovitis. Therefore, aggressive treatment to prevent further injury is a major priority,” Dr. Nigrovic said. Appropriate anti-inflammatory management can be challenging, however, as it is relatively difficult to assess disease activity using conventional measures. Inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein level, are often unreliable indicators of active disease in this population, and biomechanical joint pain is common despite clinical remission.

Drug therapy for adult JRA patients is similar to that for adult RA, with some exceptions, Dr. Nigrovic said. Medications used to control inflammation include NSAIDs, intra-articular and/or oral steroids, disease-modifying antirheumatic drugs, anti-tumor necrosis factor-α (anti-TNF-α) agents, and occasionally anakinra and thalidomide.

Two drugs—sulfasalazine and gold injections—are usually avoided in patients with systemic-onset JRA because of evidence linking their use for this condition with the rare but potentially fatal macrophage activation syndrome, he said.

Because inflammation in JRA affects the growing skeleton, adults in whom the disease persists often have a range of unique orthopedic complications that can be the source of pain and disability, including shortened upper extremities, small femoral heads, and deformed ankles and feet.

The temporomandibular joint (TMJ) and the cervical spine are both sites of hallmark growth abnormalities, according to Dr. Nigrovic. Involvement of the [TMJ] correlates strongly with cervical spine disease, and as such, clinicians should pay close attention to adult JRA patients with micrognathia for signs of spinal problems.

Because of the unique orthopedic considerations of adult JRA patients, joint replacement surgery can involve numerous obstacles, including the need for custom prosthetics to compensate for growth-related contractures, osteopenia, and abnormal bone morphology.

For optimal patient care, physicians also need to be cognizant of the extra-articular complications associated with JRA, because they may have an impact on clinical management. For example, patients with a history of uveitis should receive continued specialist follow-up into adulthood, and those without a history of the eye condition should be watched carefully for symptoms of the disease.

Peak bone mass attained during adolescence is lower in affected teens than in their healthy peers. Given their increased risk for osteoporosis, patient education on nutritional and lifestyle issues pertinent to building and maintaining bone strength, along with drug therapy as warranted, should be a priority in adults, he said.

Ongoing systemic inflammation associated with JRA can lead to amyloidosis, and potentially renal failure, in a small percentage of patients. Symptoms of the condition, which is diagnosed by fat pad biopsy, include proteinuria with or without hypertension, splenomegaly, hepatomegaly, and abdominal pain. Treatment of this condition has focused on suppressing the underlying inflammation with drugs such as cyclophosphamide and chlorambucil. More recently, anti-TNF-α therapy has proved to be an effective treatment option.

The psychosocial consequences of the disease, including low self-esteem, difficulty with social interactions, and increased risk of depression, can lead to diminished quality of life and social/vocational failure, said Dr. Nigrovic. The transition from juvenile to adult care should be facilitated in stages to best meet the patients' developmental needs.

BOSTON — Adults with juvenile-onset rheumatoid arthritis have greater accumulated morbidity than do those with adult-onset rheumatoid arthritis, and failing to take that into account can lead to suboptimal outcomes, Dr. Peter A. Nigrovic reported at a rheumatology conference sponsored by Harvard Medical School, Boston.

“This may include structural bony deformity related to disturbed growth, premature osteoporosis, uveitis, and rarely amyloidosis,” said Dr. Nigrovic, director of the Center for Adults with Pediatric Rheumatic Illness at Brigham and Women's Hospital in Boston. In addition, impaired development of life goals, excess anxiety, and impaired social and vocational functioning can lead to psychosocial morbidity.

In terms of the medical management of JRA in adulthood, “a substantial proportion of these patients will have ongoing synovitis. Therefore, aggressive treatment to prevent further injury is a major priority,” Dr. Nigrovic said. Appropriate anti-inflammatory management can be challenging, however, as it is relatively difficult to assess disease activity using conventional measures. Inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein level, are often unreliable indicators of active disease in this population, and biomechanical joint pain is common despite clinical remission.

Drug therapy for adult JRA patients is similar to that for adult RA, with some exceptions, Dr. Nigrovic said. Medications used to control inflammation include NSAIDs, intra-articular and/or oral steroids, disease-modifying antirheumatic drugs, anti-tumor necrosis factor-α (anti-TNF-α) agents, and occasionally anakinra and thalidomide.

Two drugs—sulfasalazine and gold injections—are usually avoided in patients with systemic-onset JRA because of evidence linking their use for this condition with the rare but potentially fatal macrophage activation syndrome, he said.

Because inflammation in JRA affects the growing skeleton, adults in whom the disease persists often have a range of unique orthopedic complications that can be the source of pain and disability, including shortened upper extremities, small femoral heads, and deformed ankles and feet.

The temporomandibular joint (TMJ) and the cervical spine are both sites of hallmark growth abnormalities, according to Dr. Nigrovic. Involvement of the [TMJ] correlates strongly with cervical spine disease, and as such, clinicians should pay close attention to adult JRA patients with micrognathia for signs of spinal problems.

Because of the unique orthopedic considerations of adult JRA patients, joint replacement surgery can involve numerous obstacles, including the need for custom prosthetics to compensate for growth-related contractures, osteopenia, and abnormal bone morphology.

For optimal patient care, physicians also need to be cognizant of the extra-articular complications associated with JRA, because they may have an impact on clinical management. For example, patients with a history of uveitis should receive continued specialist follow-up into adulthood, and those without a history of the eye condition should be watched carefully for symptoms of the disease.

Peak bone mass attained during adolescence is lower in affected teens than in their healthy peers. Given their increased risk for osteoporosis, patient education on nutritional and lifestyle issues pertinent to building and maintaining bone strength, along with drug therapy as warranted, should be a priority in adults, he said.

Ongoing systemic inflammation associated with JRA can lead to amyloidosis, and potentially renal failure, in a small percentage of patients. Symptoms of the condition, which is diagnosed by fat pad biopsy, include proteinuria with or without hypertension, splenomegaly, hepatomegaly, and abdominal pain. Treatment of this condition has focused on suppressing the underlying inflammation with drugs such as cyclophosphamide and chlorambucil. More recently, anti-TNF-α therapy has proved to be an effective treatment option.

The psychosocial consequences of the disease, including low self-esteem, difficulty with social interactions, and increased risk of depression, can lead to diminished quality of life and social/vocational failure, said Dr. Nigrovic. The transition from juvenile to adult care should be facilitated in stages to best meet the patients' developmental needs.

BOSTON — Adults with juvenile-onset rheumatoid arthritis have greater accumulated morbidity than do those with adult-onset rheumatoid arthritis, and failing to take that into account can lead to suboptimal outcomes, Dr. Peter A. Nigrovic reported at a rheumatology conference sponsored by Harvard Medical School, Boston.

“This may include structural bony deformity related to disturbed growth, premature osteoporosis, uveitis, and rarely amyloidosis,” said Dr. Nigrovic, director of the Center for Adults with Pediatric Rheumatic Illness at Brigham and Women's Hospital in Boston. In addition, impaired development of life goals, excess anxiety, and impaired social and vocational functioning can lead to psychosocial morbidity.

In terms of the medical management of JRA in adulthood, “a substantial proportion of these patients will have ongoing synovitis. Therefore, aggressive treatment to prevent further injury is a major priority,” Dr. Nigrovic said. Appropriate anti-inflammatory management can be challenging, however, as it is relatively difficult to assess disease activity using conventional measures. Inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein level, are often unreliable indicators of active disease in this population, and biomechanical joint pain is common despite clinical remission.

Drug therapy for adult JRA patients is similar to that for adult RA, with some exceptions, Dr. Nigrovic said. Medications used to control inflammation include NSAIDs, intra-articular and/or oral steroids, disease-modifying antirheumatic drugs, anti-tumor necrosis factor-α (anti-TNF-α) agents, and occasionally anakinra and thalidomide.

Two drugs—sulfasalazine and gold injections—are usually avoided in patients with systemic-onset JRA because of evidence linking their use for this condition with the rare but potentially fatal macrophage activation syndrome, he said.

Because inflammation in JRA affects the growing skeleton, adults in whom the disease persists often have a range of unique orthopedic complications that can be the source of pain and disability, including shortened upper extremities, small femoral heads, and deformed ankles and feet.

The temporomandibular joint (TMJ) and the cervical spine are both sites of hallmark growth abnormalities, according to Dr. Nigrovic. Involvement of the [TMJ] correlates strongly with cervical spine disease, and as such, clinicians should pay close attention to adult JRA patients with micrognathia for signs of spinal problems.

Because of the unique orthopedic considerations of adult JRA patients, joint replacement surgery can involve numerous obstacles, including the need for custom prosthetics to compensate for growth-related contractures, osteopenia, and abnormal bone morphology.

For optimal patient care, physicians also need to be cognizant of the extra-articular complications associated with JRA, because they may have an impact on clinical management. For example, patients with a history of uveitis should receive continued specialist follow-up into adulthood, and those without a history of the eye condition should be watched carefully for symptoms of the disease.

Peak bone mass attained during adolescence is lower in affected teens than in their healthy peers. Given their increased risk for osteoporosis, patient education on nutritional and lifestyle issues pertinent to building and maintaining bone strength, along with drug therapy as warranted, should be a priority in adults, he said.

Ongoing systemic inflammation associated with JRA can lead to amyloidosis, and potentially renal failure, in a small percentage of patients. Symptoms of the condition, which is diagnosed by fat pad biopsy, include proteinuria with or without hypertension, splenomegaly, hepatomegaly, and abdominal pain. Treatment of this condition has focused on suppressing the underlying inflammation with drugs such as cyclophosphamide and chlorambucil. More recently, anti-TNF-α therapy has proved to be an effective treatment option.

The psychosocial consequences of the disease, including low self-esteem, difficulty with social interactions, and increased risk of depression, can lead to diminished quality of life and social/vocational failure, said Dr. Nigrovic. The transition from juvenile to adult care should be facilitated in stages to best meet the patients' developmental needs.

BOSTON – Adolescent boys and girls with symptoms of depression are more likely than their nondepressed peers to engage in high-risk sexual behavior, results of a recent study have shown.

These findings fuel arguments in favor of expanding depression prevention, screening, and treatment efforts in this vulnerable population, Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

The results were based on home interview data from a sample of 4,152 sexually active, unmarried high school students who participated in Waves I and II of the National Longitudinal Study of Adolescent Health at 1-year intervals between 1995 and 1996.

Dr. Lehrer of the University of California, San Francisco, and her colleagues at the Harvard School of Public Health and Children's Hospital Boston examined associations between baseline depressive symptoms (measured as both trichotomous and continuous variables) and sexual risk behaviors over the course of the year between the first and second interviews.

The researchers conducted separate analyses for boys and girls and adjusted for demographic variables, religious practices, same-sex attraction and behaviors, sexual intercourse before age 10, and baseline sexual risk behaviors.

Depressive symptoms were assessed using a 19-item modified Center for Epidemiological Studies-Depression Scale. Among the sexual risk behaviors examined were condom nonuse, birth control nonuse, and substance use–all at last sexual encounter–as well as participation with multiple sexual partners.

“In the adjusted models for both the boys and the girls, adolescents with high levels of depressive symptoms at baseline were significantly more likely than those with low or no symptom levels [to have engaged in] at least one of the sexual risk behaviors over the course of the year,” Dr. Lehrer said.

Among boys, high levels of depressive symptoms predicted condom nonuse, birth control nonuse, and substance use in both the trichotomous (low, moderate, and high symptom levels) and continuous depression measure analyses, she said.

Among girls, analysis with the continuous depression measure showed significant associations between depressive symptoms and condom nonuse, birth control nonuse, participation with three or more sexual partners, and any other sexual risk behavior. In the parallel analysis with the trichotomous depression measures, moderate depressive symptoms predicted substance use at last sexual encounter. No link was seen between high depressive symptom levels and individual sexual risk behaviors, Dr. Lehrer said.

“The findings of this study suggest that elevated depressive symptom levels during adolescence may, at the very least, serve as a red flag for an increased likelihood of sexual risk behaviors,” Dr. Lehrer said.

“This has important implications both for depression screening and sexual health counseling by primary care providers and mental health providers.”

Additionally, because of the increased risk of STDs associated with sexual risk behaviors, the content of population-based STD and HIV prevention programs should include educational information on the signs and symptoms of depression and resources for getting help, Dr. Lehrer said.

BOSTON – Adolescent boys and girls with symptoms of depression are more likely than their nondepressed peers to engage in high-risk sexual behavior, results of a recent study have shown.

These findings fuel arguments in favor of expanding depression prevention, screening, and treatment efforts in this vulnerable population, Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

The results were based on home interview data from a sample of 4,152 sexually active, unmarried high school students who participated in Waves I and II of the National Longitudinal Study of Adolescent Health at 1-year intervals between 1995 and 1996.

Dr. Lehrer of the University of California, San Francisco, and her colleagues at the Harvard School of Public Health and Children's Hospital Boston examined associations between baseline depressive symptoms (measured as both trichotomous and continuous variables) and sexual risk behaviors over the course of the year between the first and second interviews.

The researchers conducted separate analyses for boys and girls and adjusted for demographic variables, religious practices, same-sex attraction and behaviors, sexual intercourse before age 10, and baseline sexual risk behaviors.

Depressive symptoms were assessed using a 19-item modified Center for Epidemiological Studies-Depression Scale. Among the sexual risk behaviors examined were condom nonuse, birth control nonuse, and substance use–all at last sexual encounter–as well as participation with multiple sexual partners.

“In the adjusted models for both the boys and the girls, adolescents with high levels of depressive symptoms at baseline were significantly more likely than those with low or no symptom levels [to have engaged in] at least one of the sexual risk behaviors over the course of the year,” Dr. Lehrer said.

Among boys, high levels of depressive symptoms predicted condom nonuse, birth control nonuse, and substance use in both the trichotomous (low, moderate, and high symptom levels) and continuous depression measure analyses, she said.

Among girls, analysis with the continuous depression measure showed significant associations between depressive symptoms and condom nonuse, birth control nonuse, participation with three or more sexual partners, and any other sexual risk behavior. In the parallel analysis with the trichotomous depression measures, moderate depressive symptoms predicted substance use at last sexual encounter. No link was seen between high depressive symptom levels and individual sexual risk behaviors, Dr. Lehrer said.

“The findings of this study suggest that elevated depressive symptom levels during adolescence may, at the very least, serve as a red flag for an increased likelihood of sexual risk behaviors,” Dr. Lehrer said.

“This has important implications both for depression screening and sexual health counseling by primary care providers and mental health providers.”

Additionally, because of the increased risk of STDs associated with sexual risk behaviors, the content of population-based STD and HIV prevention programs should include educational information on the signs and symptoms of depression and resources for getting help, Dr. Lehrer said.

BOSTON – Adolescent boys and girls with symptoms of depression are more likely than their nondepressed peers to engage in high-risk sexual behavior, results of a recent study have shown.

These findings fuel arguments in favor of expanding depression prevention, screening, and treatment efforts in this vulnerable population, Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

The results were based on home interview data from a sample of 4,152 sexually active, unmarried high school students who participated in Waves I and II of the National Longitudinal Study of Adolescent Health at 1-year intervals between 1995 and 1996.

Dr. Lehrer of the University of California, San Francisco, and her colleagues at the Harvard School of Public Health and Children's Hospital Boston examined associations between baseline depressive symptoms (measured as both trichotomous and continuous variables) and sexual risk behaviors over the course of the year between the first and second interviews.

The researchers conducted separate analyses for boys and girls and adjusted for demographic variables, religious practices, same-sex attraction and behaviors, sexual intercourse before age 10, and baseline sexual risk behaviors.

Depressive symptoms were assessed using a 19-item modified Center for Epidemiological Studies-Depression Scale. Among the sexual risk behaviors examined were condom nonuse, birth control nonuse, and substance use–all at last sexual encounter–as well as participation with multiple sexual partners.

“In the adjusted models for both the boys and the girls, adolescents with high levels of depressive symptoms at baseline were significantly more likely than those with low or no symptom levels [to have engaged in] at least one of the sexual risk behaviors over the course of the year,” Dr. Lehrer said.

Among boys, high levels of depressive symptoms predicted condom nonuse, birth control nonuse, and substance use in both the trichotomous (low, moderate, and high symptom levels) and continuous depression measure analyses, she said.

Among girls, analysis with the continuous depression measure showed significant associations between depressive symptoms and condom nonuse, birth control nonuse, participation with three or more sexual partners, and any other sexual risk behavior. In the parallel analysis with the trichotomous depression measures, moderate depressive symptoms predicted substance use at last sexual encounter. No link was seen between high depressive symptom levels and individual sexual risk behaviors, Dr. Lehrer said.

“The findings of this study suggest that elevated depressive symptom levels during adolescence may, at the very least, serve as a red flag for an increased likelihood of sexual risk behaviors,” Dr. Lehrer said.

“This has important implications both for depression screening and sexual health counseling by primary care providers and mental health providers.”

Additionally, because of the increased risk of STDs associated with sexual risk behaviors, the content of population-based STD and HIV prevention programs should include educational information on the signs and symptoms of depression and resources for getting help, Dr. Lehrer said.

BOSTON – Adolescent girls who exhibit symptoms of depression are at greater risk for subsequent intimate partner violence than their nondepressed peers, a study has shown.

The findings suggest that preventing, identifying, and treating depression in this population, as well as preemptive counseling of high-risk adolescent girls about their peer choices and romantic relationships, “could reduce the likelihood of subsequent victimization,” lead author Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

Dr. Lehrer of the University of California, San Francisco and her colleagues from the Harvard School of Public Health and Children's Hospital in Boston reviewed home interview data from a sample of 1,659 young women ages 15–24 who participated in Waves II and III of the National Longitudinal Study of Adolescent Health. They examined the incidence and prevalence of past-week depressive symptoms measured in the Wave II data using a 19-item modified Center for Epidemiologic Studies-Depression scale (CES-D).

The investigators correlated the baseline depression information with data regarding past-year physical partner abuse from the Wave III surveys conducted about 5 years later, controlling for age, race, ethnicity, parental education, retrospective childhood and physical sexual abuse, and baseline dating violence and forced sex.

Depression symptoms were measured as both dichotomous and continuous variables, and exposure to partner violence was classified as mild (threats of violence, pushing, and/or shoving) or moderate to severe (hitting, slapping, kicking, or an injury causing action), Dr. Lehrer noted.

All of the girls in the study were in a current, opposite-sex relationship at follow-up at the time of the Wave III interview. The average age of the participants was 15.9 years at baseline and 21.3 years at follow-up.

Baseline depression measures showed that 10.2% of the young women in the sample had high levels of depressive symptoms. “In adjusted models [using the dichotomous depressive symptoms variable], high baseline symptoms were associated with 1.86 times the odds of subsequent exposure to moderate to severe partner violence,” Dr. Lehrer said. With use of the continuous depressive symptoms variable, “each standard deviation increase in baseline symptom level increased the odds of exposure to both mild partner violence and moderate to severe partner violence by 24%,” she said.

The National Longitudinal Study of Adolescent Health explores the causes of health-related behaviors of adolescents in grades 7–12 and their outcomes in young adulthood. The Wave I survey was completed in 1994. Waves II and III were completed in 1996 and 2002, respectively.

BOSTON – Adolescent girls who exhibit symptoms of depression are at greater risk for subsequent intimate partner violence than their nondepressed peers, a study has shown.

The findings suggest that preventing, identifying, and treating depression in this population, as well as preemptive counseling of high-risk adolescent girls about their peer choices and romantic relationships, “could reduce the likelihood of subsequent victimization,” lead author Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

Dr. Lehrer of the University of California, San Francisco and her colleagues from the Harvard School of Public Health and Children's Hospital in Boston reviewed home interview data from a sample of 1,659 young women ages 15–24 who participated in Waves II and III of the National Longitudinal Study of Adolescent Health. They examined the incidence and prevalence of past-week depressive symptoms measured in the Wave II data using a 19-item modified Center for Epidemiologic Studies-Depression scale (CES-D).

The investigators correlated the baseline depression information with data regarding past-year physical partner abuse from the Wave III surveys conducted about 5 years later, controlling for age, race, ethnicity, parental education, retrospective childhood and physical sexual abuse, and baseline dating violence and forced sex.

Depression symptoms were measured as both dichotomous and continuous variables, and exposure to partner violence was classified as mild (threats of violence, pushing, and/or shoving) or moderate to severe (hitting, slapping, kicking, or an injury causing action), Dr. Lehrer noted.

All of the girls in the study were in a current, opposite-sex relationship at follow-up at the time of the Wave III interview. The average age of the participants was 15.9 years at baseline and 21.3 years at follow-up.

Baseline depression measures showed that 10.2% of the young women in the sample had high levels of depressive symptoms. “In adjusted models [using the dichotomous depressive symptoms variable], high baseline symptoms were associated with 1.86 times the odds of subsequent exposure to moderate to severe partner violence,” Dr. Lehrer said. With use of the continuous depressive symptoms variable, “each standard deviation increase in baseline symptom level increased the odds of exposure to both mild partner violence and moderate to severe partner violence by 24%,” she said.

The National Longitudinal Study of Adolescent Health explores the causes of health-related behaviors of adolescents in grades 7–12 and their outcomes in young adulthood. The Wave I survey was completed in 1994. Waves II and III were completed in 1996 and 2002, respectively.

BOSTON – Adolescent girls who exhibit symptoms of depression are at greater risk for subsequent intimate partner violence than their nondepressed peers, a study has shown.

The findings suggest that preventing, identifying, and treating depression in this population, as well as preemptive counseling of high-risk adolescent girls about their peer choices and romantic relationships, “could reduce the likelihood of subsequent victimization,” lead author Jocelyn A. Lehrer, Sc.D., said at the annual meeting of the Society for Adolescent Medicine.

Dr. Lehrer of the University of California, San Francisco and her colleagues from the Harvard School of Public Health and Children's Hospital in Boston reviewed home interview data from a sample of 1,659 young women ages 15–24 who participated in Waves II and III of the National Longitudinal Study of Adolescent Health. They examined the incidence and prevalence of past-week depressive symptoms measured in the Wave II data using a 19-item modified Center for Epidemiologic Studies-Depression scale (CES-D).

The investigators correlated the baseline depression information with data regarding past-year physical partner abuse from the Wave III surveys conducted about 5 years later, controlling for age, race, ethnicity, parental education, retrospective childhood and physical sexual abuse, and baseline dating violence and forced sex.

Depression symptoms were measured as both dichotomous and continuous variables, and exposure to partner violence was classified as mild (threats of violence, pushing, and/or shoving) or moderate to severe (hitting, slapping, kicking, or an injury causing action), Dr. Lehrer noted.

All of the girls in the study were in a current, opposite-sex relationship at follow-up at the time of the Wave III interview. The average age of the participants was 15.9 years at baseline and 21.3 years at follow-up.

Baseline depression measures showed that 10.2% of the young women in the sample had high levels of depressive symptoms. “In adjusted models [using the dichotomous depressive symptoms variable], high baseline symptoms were associated with 1.86 times the odds of subsequent exposure to moderate to severe partner violence,” Dr. Lehrer said. With use of the continuous depressive symptoms variable, “each standard deviation increase in baseline symptom level increased the odds of exposure to both mild partner violence and moderate to severe partner violence by 24%,” she said.

The National Longitudinal Study of Adolescent Health explores the causes of health-related behaviors of adolescents in grades 7–12 and their outcomes in young adulthood. The Wave I survey was completed in 1994. Waves II and III were completed in 1996 and 2002, respectively.

Efforts to prevent childhood obesity should begin in the womb and infancy to turn the tide on the startling increase in the number of overweight and obese children in this country, according to Dr. Matthew W. Gillman.

In a study of more than 120,000 children enrolled in a Massachusetts health maintenance organization, Dr. Gillman and his colleagues at Harvard Medical School in Boston showed that the prevalence of overweight and obesity among healthy, middle- class children younger than 6 years increased by 59% between 1980 and 2001. The increase in the number of overweight infants younger than 6 months during the same time period was 74% (Obesity 2006;14:1107–12).

Results of another study found that children who were overweight very young were not likely to outgrow that “baby fat” when they were older.

In fact, the definition of “overweight” is coming into question with the introduction of new growth standards by the World Health Organization (WHO), which differ fundamentally from the Centers for Disease Control and Prevention (CDC) standards and classify more American infants and young children as overweight. It is unclear whether the U. S. medical community will adopt or adapt these new growth charts.

Back to the Data

Children in the Harvard study were deemed overweight if their weight for body length/height was in the 95th percentile or higher. If that measure fell between the 85th and 95th percentile, children were considered at risk for overweight. With these cutoffs, 10% of the study population was overweight and 14% was at risk for overweight. For infants younger than 6 months, 6% were overweight and 11% were at risk for becoming overweight.

Although the Harvard study represented a regional population, the findings are consistent with those of two recent national nutritional surveillance systems—the National Health and Nutrition Examination Survey and the Pediatric Nutrition Surveillance System—that have documented significant increases in the prevalence of overweight children younger than 5 years old, Dr. Gillman noted.

The excessive weight trend does not stop in young children. In fact, that is where it starts. Children who are overweight as babies and preschoolers are at increased risk for being overweight or obese adolescents, according to data from another recent study that followed the growth and development of 1,000 U.S. infants over 10 years.

Using height and weight information collected at frequent intervals starting at age 2 years, Dr. Philip R. Nader of the University of California at San Diego and his colleagues showed that children who met the criteria for being overweight—defined as having a body mass index at or above the 85th percentile, compared with national statistics—at least once between the ages of 2 and 4.5 years—were five times more likely than their average weight peers to be overweight at age 12. And the risk of becoming an overweight adolescent increased by an order of magnitude relative to the number of times the child met the overweight criteria during the elementary school years (Pediatrics 2006;118:594–601).

The Health Consequences

The public health consequences of early excess weight gain are substantial. Epidemiologic studies over the past 15 years have demonstrated short- and long-term problems associated with overweight and obesity in childhood.

In the short term, overweight children are at risk for high blood pressure, respiratory problems, cardiovascular conditions, and early onset of type 2 diabetes. In the longer term, overweight children and adolescents are significantly more likely than their peers to become overweight adults, placing them at further risk for developing associated endocrine and cardiovascular comorbidities, as well as certain types of cancer, arthritis, and other serious problems later in life.

The rising rates of obesity and overweight in very young children that have set the stage for this unhealthy developmental cascade also have led to a shift in prevention efforts toward the identification of early factors that predict risk of subsequent obesity, which may allow for early targeted interventions.

Early Intervention

“Excessive weight at birth and excessive weight gain in the early weeks and months appear to be particularly harmful,” according to Dr. Gillman. And they also seem to be associated with certain prenatal factors. “Most evidence points to the fact that women are coming into pregnancy heavier than ever before and they are more likely to get gestational diabetes, which is a risk factor for child overweight. Also, women are gaining weight excessively during pregnancy, which is another risk factor,” he said in an interview.

Efforts to mitigate the risk of overweight in babies should include interventions targeted at parents that focus on avoiding excessive weight gain during pregnancy, preventing gestational diabetes, and promoting breast-feeding, which tends to be associated with leaner babies, according to Dr. Gillman.

For babies and young children who are above the percentile curves, talk of intervention should focus squarely on the development of healthful habits. “We are not talking about weight loss in younger or even older children. We want kids to grow in a healthy manner, without putting on too much fat,” said Dr. Gillman.

Toward this end, actively monitoring children's weight status is an important component of obesity prevention, although there is a lack of data available on infants in this realm. “We don't yet know the optimal weight gain during infancy for short- and long-term outcomes, so for now [physicians] and parents should aim for growth in weight for length along the percentile curves in the growth charts that doctors use,” he said.

Growth Charts

The use of growth charts has been the subject of some controversy in recent years. In the United States, most physicians rely on the CDC 2000 growth reference in which the development of an individual child is plotted against the rate of growth of the “average” American child, as determined from a limited sample.

The problem with this approach, according to Dr. Cutberto Garza, provost and dean of faculties at Boston College, is that the measure does not provide a scientific assessment of healthy growth based on a large sample of infants and children whose feeding habits and environment are consistent with good health outcomes.

A growth chart should be an assessment tool that shows not only how a child is growing but also whether the child is growing as he or she should, Dr. Garza, who chaired the WHO Multicenter Growth Reference Study from which the new standards were generated, said in an interview.

New growth standards introduced by WHO in April of this year were designed to fit this bill, he said. The goal of the study was to develop standards based on the growth and development of healthy infants and children up to 5 years old from around the world.

In total, the investigators compiled primary growth data for 8,500 children from six ethnically and culturally diverse countries (Brazil, Ghana, India, Norway, Oman, and the United States). The children were selected based on predefined criteria for feeding practices, nutrition, and health care that have been previously associated with good health outcomes.

For the purposes of the study, breast-feeding—including exclusive/predominant breast-feeding for at least the first 4–6 months of life and continued complementary breast-feeding for at least 1 year—was considered the normative behavior for infant feeding.

The study showed that, despite individual differences among the children, the average growth across the board was similar, indicating the important influence of healthy growth conditions in early life, Dr. Garza said.

The resulting standards are representative of physiologic growth and include charts based on longitudinal data for infants from birth to 2 years and charts based on cross-sectional data for children from 2 to 5 years. Separate curves for boys and girls include a variety of growth indicators such as weight for age, length/height for age, and weight for length/height, as well as a body mass index standard for children up to age 5.

Eventually, velocity standards as well as attained head circumference, skin-fold thickness, and mid-arm circumference standards will be incorporated, according to Dr. Garza (

www.who.int/childgrowth/en

With the WHO curves, more babies and young children in the United States fall into an overweight category, compared with the CDC growth chart, possibly because a smaller percentage of U.S. babies are breast-fed, and breast-fed babies tend to be leaner than formula-fed babies.

This does not diminish the relevance of the growth curves in the United States, according to Dr. Garza. Rather, “it highlights the fact that breast-feeding is an important early risk reduction factor and should be promoted as such.”

It has yet to be determined whether the United States will adopt the new WHO standard or adapt existing standards to include some of the important changes, but the possibility was put on the table in late June at a meeting of the CDC, the National Institutes of Health, and the American Academy of Pediatrics, according to Dr. Frank R. Greer, chairman of the AAP Committee on Nutrition. Any new recommendations would need to be accompanied by guidance for clinicians on how to interpret the changes, he said in an interview.

In terms of clinical application, the role of the new standards is basically unchanged, Dr. Garza stated. “It's a mistake to use anthropometric data for diagnostic purposes. The clinical uses are to assess risk to either excessive or inadequate growth and to assess responses to treatments designed to positively impact growth.”

Dr. Nader said growth curves raise the idea of prevention as not such a daunting endeavor because one has time over the entire preschool and school age period to be sure that family has healthy nutrition and active play opportunities for their child.

Whether using the CDC or WHO standards, routine monitoring and assessment of a child's growth and development is an important step in the battle against childhood obesity, but simply identifying children at risk during well child visits and recommending more healthful eating and activity habits will not win the war.

“The medical system can play a big role, but it's only one site of potentially effective interventions for preventing obesity,” according to Dr. Gillman. “Broader, population-based initiatives are also needed.”

With the WHO growth curves, more American babies and young children fall into an overweight category. Denise Fulton/Elsevier Global Medical News

Efforts to prevent childhood obesity should begin in the womb and infancy to turn the tide on the startling increase in the number of overweight and obese children in this country, according to Dr. Matthew W. Gillman.

In a study of more than 120,000 children enrolled in a Massachusetts health maintenance organization, Dr. Gillman and his colleagues at Harvard Medical School in Boston showed that the prevalence of overweight and obesity among healthy, middle- class children younger than 6 years increased by 59% between 1980 and 2001. The increase in the number of overweight infants younger than 6 months during the same time period was 74% (Obesity 2006;14:1107–12).

Results of another study found that children who were overweight very young were not likely to outgrow that “baby fat” when they were older.

In fact, the definition of “overweight” is coming into question with the introduction of new growth standards by the World Health Organization (WHO), which differ fundamentally from the Centers for Disease Control and Prevention (CDC) standards and classify more American infants and young children as overweight. It is unclear whether the U. S. medical community will adopt or adapt these new growth charts.

Back to the Data

Children in the Harvard study were deemed overweight if their weight for body length/height was in the 95th percentile or higher. If that measure fell between the 85th and 95th percentile, children were considered at risk for overweight. With these cutoffs, 10% of the study population was overweight and 14% was at risk for overweight. For infants younger than 6 months, 6% were overweight and 11% were at risk for becoming overweight.

Although the Harvard study represented a regional population, the findings are consistent with those of two recent national nutritional surveillance systems—the National Health and Nutrition Examination Survey and the Pediatric Nutrition Surveillance System—that have documented significant increases in the prevalence of overweight children younger than 5 years old, Dr. Gillman noted.

The excessive weight trend does not stop in young children. In fact, that is where it starts. Children who are overweight as babies and preschoolers are at increased risk for being overweight or obese adolescents, according to data from another recent study that followed the growth and development of 1,000 U.S. infants over 10 years.

Using height and weight information collected at frequent intervals starting at age 2 years, Dr. Philip R. Nader of the University of California at San Diego and his colleagues showed that children who met the criteria for being overweight—defined as having a body mass index at or above the 85th percentile, compared with national statistics—at least once between the ages of 2 and 4.5 years—were five times more likely than their average weight peers to be overweight at age 12. And the risk of becoming an overweight adolescent increased by an order of magnitude relative to the number of times the child met the overweight criteria during the elementary school years (Pediatrics 2006;118:594–601).

The Health Consequences

The public health consequences of early excess weight gain are substantial. Epidemiologic studies over the past 15 years have demonstrated short- and long-term problems associated with overweight and obesity in childhood.

In the short term, overweight children are at risk for high blood pressure, respiratory problems, cardiovascular conditions, and early onset of type 2 diabetes. In the longer term, overweight children and adolescents are significantly more likely than their peers to become overweight adults, placing them at further risk for developing associated endocrine and cardiovascular comorbidities, as well as certain types of cancer, arthritis, and other serious problems later in life.

The rising rates of obesity and overweight in very young children that have set the stage for this unhealthy developmental cascade also have led to a shift in prevention efforts toward the identification of early factors that predict risk of subsequent obesity, which may allow for early targeted interventions.

Early Intervention

“Excessive weight at birth and excessive weight gain in the early weeks and months appear to be particularly harmful,” according to Dr. Gillman. And they also seem to be associated with certain prenatal factors. “Most evidence points to the fact that women are coming into pregnancy heavier than ever before and they are more likely to get gestational diabetes, which is a risk factor for child overweight. Also, women are gaining weight excessively during pregnancy, which is another risk factor,” he said in an interview.

Efforts to mitigate the risk of overweight in babies should include interventions targeted at parents that focus on avoiding excessive weight gain during pregnancy, preventing gestational diabetes, and promoting breast-feeding, which tends to be associated with leaner babies, according to Dr. Gillman.

For babies and young children who are above the percentile curves, talk of intervention should focus squarely on the development of healthful habits. “We are not talking about weight loss in younger or even older children. We want kids to grow in a healthy manner, without putting on too much fat,” said Dr. Gillman.

Toward this end, actively monitoring children's weight status is an important component of obesity prevention, although there is a lack of data available on infants in this realm. “We don't yet know the optimal weight gain during infancy for short- and long-term outcomes, so for now [physicians] and parents should aim for growth in weight for length along the percentile curves in the growth charts that doctors use,” he said.

Growth Charts

The use of growth charts has been the subject of some controversy in recent years. In the United States, most physicians rely on the CDC 2000 growth reference in which the development of an individual child is plotted against the rate of growth of the “average” American child, as determined from a limited sample.

The problem with this approach, according to Dr. Cutberto Garza, provost and dean of faculties at Boston College, is that the measure does not provide a scientific assessment of healthy growth based on a large sample of infants and children whose feeding habits and environment are consistent with good health outcomes.

A growth chart should be an assessment tool that shows not only how a child is growing but also whether the child is growing as he or she should, Dr. Garza, who chaired the WHO Multicenter Growth Reference Study from which the new standards were generated, said in an interview.

New growth standards introduced by WHO in April of this year were designed to fit this bill, he said. The goal of the study was to develop standards based on the growth and development of healthy infants and children up to 5 years old from around the world.

In total, the investigators compiled primary growth data for 8,500 children from six ethnically and culturally diverse countries (Brazil, Ghana, India, Norway, Oman, and the United States). The children were selected based on predefined criteria for feeding practices, nutrition, and health care that have been previously associated with good health outcomes.

For the purposes of the study, breast-feeding—including exclusive/predominant breast-feeding for at least the first 4–6 months of life and continued complementary breast-feeding for at least 1 year—was considered the normative behavior for infant feeding.

The study showed that, despite individual differences among the children, the average growth across the board was similar, indicating the important influence of healthy growth conditions in early life, Dr. Garza said.

The resulting standards are representative of physiologic growth and include charts based on longitudinal data for infants from birth to 2 years and charts based on cross-sectional data for children from 2 to 5 years. Separate curves for boys and girls include a variety of growth indicators such as weight for age, length/height for age, and weight for length/height, as well as a body mass index standard for children up to age 5.

Eventually, velocity standards as well as attained head circumference, skin-fold thickness, and mid-arm circumference standards will be incorporated, according to Dr. Garza (

www.who.int/childgrowth/en

With the WHO curves, more babies and young children in the United States fall into an overweight category, compared with the CDC growth chart, possibly because a smaller percentage of U.S. babies are breast-fed, and breast-fed babies tend to be leaner than formula-fed babies.

This does not diminish the relevance of the growth curves in the United States, according to Dr. Garza. Rather, “it highlights the fact that breast-feeding is an important early risk reduction factor and should be promoted as such.”

It has yet to be determined whether the United States will adopt the new WHO standard or adapt existing standards to include some of the important changes, but the possibility was put on the table in late June at a meeting of the CDC, the National Institutes of Health, and the American Academy of Pediatrics, according to Dr. Frank R. Greer, chairman of the AAP Committee on Nutrition. Any new recommendations would need to be accompanied by guidance for clinicians on how to interpret the changes, he said in an interview.

In terms of clinical application, the role of the new standards is basically unchanged, Dr. Garza stated. “It's a mistake to use anthropometric data for diagnostic purposes. The clinical uses are to assess risk to either excessive or inadequate growth and to assess responses to treatments designed to positively impact growth.”

Dr. Nader said growth curves raise the idea of prevention as not such a daunting endeavor because one has time over the entire preschool and school age period to be sure that family has healthy nutrition and active play opportunities for their child.

Whether using the CDC or WHO standards, routine monitoring and assessment of a child's growth and development is an important step in the battle against childhood obesity, but simply identifying children at risk during well child visits and recommending more healthful eating and activity habits will not win the war.

“The medical system can play a big role, but it's only one site of potentially effective interventions for preventing obesity,” according to Dr. Gillman. “Broader, population-based initiatives are also needed.”

With the WHO growth curves, more American babies and young children fall into an overweight category. Denise Fulton/Elsevier Global Medical News

Efforts to prevent childhood obesity should begin in the womb and infancy to turn the tide on the startling increase in the number of overweight and obese children in this country, according to Dr. Matthew W. Gillman.

In a study of more than 120,000 children enrolled in a Massachusetts health maintenance organization, Dr. Gillman and his colleagues at Harvard Medical School in Boston showed that the prevalence of overweight and obesity among healthy, middle- class children younger than 6 years increased by 59% between 1980 and 2001. The increase in the number of overweight infants younger than 6 months during the same time period was 74% (Obesity 2006;14:1107–12).

Results of another study found that children who were overweight very young were not likely to outgrow that “baby fat” when they were older.

In fact, the definition of “overweight” is coming into question with the introduction of new growth standards by the World Health Organization (WHO), which differ fundamentally from the Centers for Disease Control and Prevention (CDC) standards and classify more American infants and young children as overweight. It is unclear whether the U. S. medical community will adopt or adapt these new growth charts.

Back to the Data

Children in the Harvard study were deemed overweight if their weight for body length/height was in the 95th percentile or higher. If that measure fell between the 85th and 95th percentile, children were considered at risk for overweight. With these cutoffs, 10% of the study population was overweight and 14% was at risk for overweight. For infants younger than 6 months, 6% were overweight and 11% were at risk for becoming overweight.

Although the Harvard study represented a regional population, the findings are consistent with those of two recent national nutritional surveillance systems—the National Health and Nutrition Examination Survey and the Pediatric Nutrition Surveillance System—that have documented significant increases in the prevalence of overweight children younger than 5 years old, Dr. Gillman noted.

The excessive weight trend does not stop in young children. In fact, that is where it starts. Children who are overweight as babies and preschoolers are at increased risk for being overweight or obese adolescents, according to data from another recent study that followed the growth and development of 1,000 U.S. infants over 10 years.

Using height and weight information collected at frequent intervals starting at age 2 years, Dr. Philip R. Nader of the University of California at San Diego and his colleagues showed that children who met the criteria for being overweight—defined as having a body mass index at or above the 85th percentile, compared with national statistics—at least once between the ages of 2 and 4.5 years—were five times more likely than their average weight peers to be overweight at age 12. And the risk of becoming an overweight adolescent increased by an order of magnitude relative to the number of times the child met the overweight criteria during the elementary school years (Pediatrics 2006;118:594–601).

The Health Consequences

The public health consequences of early excess weight gain are substantial. Epidemiologic studies over the past 15 years have demonstrated short- and long-term problems associated with overweight and obesity in childhood.

In the short term, overweight children are at risk for high blood pressure, respiratory problems, cardiovascular conditions, and early onset of type 2 diabetes. In the longer term, overweight children and adolescents are significantly more likely than their peers to become overweight adults, placing them at further risk for developing associated endocrine and cardiovascular comorbidities, as well as certain types of cancer, arthritis, and other serious problems later in life.

The rising rates of obesity and overweight in very young children that have set the stage for this unhealthy developmental cascade also have led to a shift in prevention efforts toward the identification of early factors that predict risk of subsequent obesity, which may allow for early targeted interventions.

Early Intervention

“Excessive weight at birth and excessive weight gain in the early weeks and months appear to be particularly harmful,” according to Dr. Gillman. And they also seem to be associated with certain prenatal factors. “Most evidence points to the fact that women are coming into pregnancy heavier than ever before and they are more likely to get gestational diabetes, which is a risk factor for child overweight. Also, women are gaining weight excessively during pregnancy, which is another risk factor,” he said in an interview.

Efforts to mitigate the risk of overweight in babies should include interventions targeted at parents that focus on avoiding excessive weight gain during pregnancy, preventing gestational diabetes, and promoting breast-feeding, which tends to be associated with leaner babies, according to Dr. Gillman.

For babies and young children who are above the percentile curves, talk of intervention should focus squarely on the development of healthful habits. “We are not talking about weight loss in younger or even older children. We want kids to grow in a healthy manner, without putting on too much fat,” said Dr. Gillman.

Toward this end, actively monitoring children's weight status is an important component of obesity prevention, although there is a lack of data available on infants in this realm. “We don't yet know the optimal weight gain during infancy for short- and long-term outcomes, so for now [physicians] and parents should aim for growth in weight for length along the percentile curves in the growth charts that doctors use,” he said.

Growth Charts

The use of growth charts has been the subject of some controversy in recent years. In the United States, most physicians rely on the CDC 2000 growth reference in which the development of an individual child is plotted against the rate of growth of the “average” American child, as determined from a limited sample.

The problem with this approach, according to Dr. Cutberto Garza, provost and dean of faculties at Boston College, is that the measure does not provide a scientific assessment of healthy growth based on a large sample of infants and children whose feeding habits and environment are consistent with good health outcomes.

A growth chart should be an assessment tool that shows not only how a child is growing but also whether the child is growing as he or she should, Dr. Garza, who chaired the WHO Multicenter Growth Reference Study from which the new standards were generated, said in an interview.

New growth standards introduced by WHO in April of this year were designed to fit this bill, he said. The goal of the study was to develop standards based on the growth and development of healthy infants and children up to 5 years old from around the world.

In total, the investigators compiled primary growth data for 8,500 children from six ethnically and culturally diverse countries (Brazil, Ghana, India, Norway, Oman, and the United States). The children were selected based on predefined criteria for feeding practices, nutrition, and health care that have been previously associated with good health outcomes.

For the purposes of the study, breast-feeding—including exclusive/predominant breast-feeding for at least the first 4–6 months of life and continued complementary breast-feeding for at least 1 year—was considered the normative behavior for infant feeding.

The study showed that, despite individual differences among the children, the average growth across the board was similar, indicating the important influence of healthy growth conditions in early life, Dr. Garza said.

The resulting standards are representative of physiologic growth and include charts based on longitudinal data for infants from birth to 2 years and charts based on cross-sectional data for children from 2 to 5 years. Separate curves for boys and girls include a variety of growth indicators such as weight for age, length/height for age, and weight for length/height, as well as a body mass index standard for children up to age 5.

Eventually, velocity standards as well as attained head circumference, skin-fold thickness, and mid-arm circumference standards will be incorporated, according to Dr. Garza (

www.who.int/childgrowth/en

With the WHO curves, more babies and young children in the United States fall into an overweight category, compared with the CDC growth chart, possibly because a smaller percentage of U.S. babies are breast-fed, and breast-fed babies tend to be leaner than formula-fed babies.

This does not diminish the relevance of the growth curves in the United States, according to Dr. Garza. Rather, “it highlights the fact that breast-feeding is an important early risk reduction factor and should be promoted as such.”

It has yet to be determined whether the United States will adopt the new WHO standard or adapt existing standards to include some of the important changes, but the possibility was put on the table in late June at a meeting of the CDC, the National Institutes of Health, and the American Academy of Pediatrics, according to Dr. Frank R. Greer, chairman of the AAP Committee on Nutrition. Any new recommendations would need to be accompanied by guidance for clinicians on how to interpret the changes, he said in an interview.

In terms of clinical application, the role of the new standards is basically unchanged, Dr. Garza stated. “It's a mistake to use anthropometric data for diagnostic purposes. The clinical uses are to assess risk to either excessive or inadequate growth and to assess responses to treatments designed to positively impact growth.”

Dr. Nader said growth curves raise the idea of prevention as not such a daunting endeavor because one has time over the entire preschool and school age period to be sure that family has healthy nutrition and active play opportunities for their child.

Whether using the CDC or WHO standards, routine monitoring and assessment of a child's growth and development is an important step in the battle against childhood obesity, but simply identifying children at risk during well child visits and recommending more healthful eating and activity habits will not win the war.

“The medical system can play a big role, but it's only one site of potentially effective interventions for preventing obesity,” according to Dr. Gillman. “Broader, population-based initiatives are also needed.”

With the WHO growth curves, more American babies and young children fall into an overweight category. Denise Fulton/Elsevier Global Medical News

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex. In total, about 12% reported any sexual activity. Of those students who reported having had intercourse, 36% were aged 11 or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. Additionally, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said earlier this year at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory?

In reality, the “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex. In total, about 12% reported any sexual activity. Of those students who reported having had intercourse, 36% were aged 11 or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. Additionally, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said earlier this year at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory?

In reality, the “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex. In total, about 12% reported any sexual activity. Of those students who reported having had intercourse, 36% were aged 11 or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. Additionally, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said earlier this year at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory?

In reality, the “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Daily injections of the interleukin-1β antagonist anakinra significantly improved the peripheral and central nervous system manifestations of neonatal-onset multisystem inflammatory disease in patients with and without the genetic mutation that is associated with the rare systemic disease, a study found.

Neonatal-onset multisystem inflammatory disease (NOMID) often develops in patients who have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that is associated with regulating inflammation.

Previous studies have linked interleukin-1β pathways to NOMID, and isolated case reports have suggested that by inhibiting interleukin-1β, anakinra (Kineret) may be effective in the treatment of rash and the constitutional symptoms of disease.

To assess anakinra efficacy on these manifestations, as well as those that affect the central nervous system, Dr. Raphaela Goldbach-Mansky of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., and colleagues enrolled 18 patients with active disease, including 12 with identifiable CIAS1 mutations, into an open-label investigation (N. Engl. J. Med. 2006;355:581-92).

All of the patients were between the ages of 4 and 32 years old (mean age 11 years) and presented with at least two of the following clinical manifestations of NOMID: urticarial rash, central nervous system involvement, or epiphyseal or patellar overgrowth on radiography. Additionally, all of the patients had undergone previous treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and/or corticosteroids.

Each patient received daily subcutaneous anakinra injections of 1-2 mg/kg of body weight and underwent efficacy assessments at 1, 3, and 6 months.

The primary end points of the study were changes in symptom scores for fever, rash, headache, joint pain, and vomiting as measured in a daily diary, changes in acute-phase reactants, including serum amyloid A, C-reactive protein, and erythrocyte sedimentation rate from baseline to 3 months and from 3 months until a flare. Secondary end points were childhood health assessment questionnaire scores, audiography and vision assessments, MRI of the brain, and lumbar puncture results.

The initial study design included an inpatient withdrawal phase at 3 months for patients who responded to anakinra treatment in order to induce a clinical flare, followed by a reintroduction of therapy and continuation in an ongoing extension period. The withdrawal phase was discontinued after the first 11 patients because of the severity of the flares, which included pericarditis in 1 patient, corneal infiltrates in 3 patients, and uveitis in 2 patients, according to the authors.

In all of the patients, anakinra treatment produced an immediate clinical response, including disappearance of rash and conjunctivitis within 3 days, significantly decreased diary scores at 3 months, and significant decreases in C-reactive protein, serum amyloid A, and erythrocyte sedimentation rates. Of the 11 patients who underwent an inpatient withdrawal period for up to 7 days, 10 experienced a flare that met prespecified criteria at a median of 5 days. All of the patients responded to resumed anakinra therapy promptly, and the improvements were sustained at the 6-month follow-up.

Additional findings included improved hearing in six patients and stable hearing in patients relative to baseline, stable vision in all patients, and significant improvements on the pain, parent, and physician global assessment, and Childhood Health Assessment Questionnaire scores.

With respect to central nervous system manifestations, median daily headache scores decreased significantly in all patients, with complete resolution of headaches in eight patients at 3 months. Intracranial pressures, protein levels, and white cell counts decreased significantly in the 12 patients for whom cerebrospinal fluid was evaluated. Additionally, MRI showed significant improvement from baseline in cochlear and leptomeningeal lesions, the authors wrote.

Overall, anakinra was well tolerated in the patients. Eight experienced a localized, erythematous, sometimes painful injection-site skin reaction that disappeared by 6 weeks, 15 had upper respiratory events during treatment, 3 had urinary tract infections, and 1 was hospitalized for dehydration from nonbacterial diarrhea. No patients withdrew from the study because of adverse events, according to the authors.

Dr. Goldbach-Mansky reported no conflicts of interest with respect to this study. Some coinvestigators reported having received consulting fees, lecture fees, and/or research support from Amgen (maker of anakinra), Genentech, and Abbott.

Daily injections of the interleukin-1β antagonist anakinra significantly improved the peripheral and central nervous system manifestations of neonatal-onset multisystem inflammatory disease in patients with and without the genetic mutation that is associated with the rare systemic disease, a study found.

Neonatal-onset multisystem inflammatory disease (NOMID) often develops in patients who have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that is associated with regulating inflammation.

Previous studies have linked interleukin-1β pathways to NOMID, and isolated case reports have suggested that by inhibiting interleukin-1β, anakinra (Kineret) may be effective in the treatment of rash and the constitutional symptoms of disease.

To assess anakinra efficacy on these manifestations, as well as those that affect the central nervous system, Dr. Raphaela Goldbach-Mansky of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., and colleagues enrolled 18 patients with active disease, including 12 with identifiable CIAS1 mutations, into an open-label investigation (N. Engl. J. Med. 2006;355:581-92).

All of the patients were between the ages of 4 and 32 years old (mean age 11 years) and presented with at least two of the following clinical manifestations of NOMID: urticarial rash, central nervous system involvement, or epiphyseal or patellar overgrowth on radiography. Additionally, all of the patients had undergone previous treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and/or corticosteroids.

Each patient received daily subcutaneous anakinra injections of 1-2 mg/kg of body weight and underwent efficacy assessments at 1, 3, and 6 months.

The primary end points of the study were changes in symptom scores for fever, rash, headache, joint pain, and vomiting as measured in a daily diary, changes in acute-phase reactants, including serum amyloid A, C-reactive protein, and erythrocyte sedimentation rate from baseline to 3 months and from 3 months until a flare. Secondary end points were childhood health assessment questionnaire scores, audiography and vision assessments, MRI of the brain, and lumbar puncture results.

The initial study design included an inpatient withdrawal phase at 3 months for patients who responded to anakinra treatment in order to induce a clinical flare, followed by a reintroduction of therapy and continuation in an ongoing extension period. The withdrawal phase was discontinued after the first 11 patients because of the severity of the flares, which included pericarditis in 1 patient, corneal infiltrates in 3 patients, and uveitis in 2 patients, according to the authors.

In all of the patients, anakinra treatment produced an immediate clinical response, including disappearance of rash and conjunctivitis within 3 days, significantly decreased diary scores at 3 months, and significant decreases in C-reactive protein, serum amyloid A, and erythrocyte sedimentation rates. Of the 11 patients who underwent an inpatient withdrawal period for up to 7 days, 10 experienced a flare that met prespecified criteria at a median of 5 days. All of the patients responded to resumed anakinra therapy promptly, and the improvements were sustained at the 6-month follow-up.

Additional findings included improved hearing in six patients and stable hearing in patients relative to baseline, stable vision in all patients, and significant improvements on the pain, parent, and physician global assessment, and Childhood Health Assessment Questionnaire scores.

With respect to central nervous system manifestations, median daily headache scores decreased significantly in all patients, with complete resolution of headaches in eight patients at 3 months. Intracranial pressures, protein levels, and white cell counts decreased significantly in the 12 patients for whom cerebrospinal fluid was evaluated. Additionally, MRI showed significant improvement from baseline in cochlear and leptomeningeal lesions, the authors wrote.

Overall, anakinra was well tolerated in the patients. Eight experienced a localized, erythematous, sometimes painful injection-site skin reaction that disappeared by 6 weeks, 15 had upper respiratory events during treatment, 3 had urinary tract infections, and 1 was hospitalized for dehydration from nonbacterial diarrhea. No patients withdrew from the study because of adverse events, according to the authors.

Dr. Goldbach-Mansky reported no conflicts of interest with respect to this study. Some coinvestigators reported having received consulting fees, lecture fees, and/or research support from Amgen (maker of anakinra), Genentech, and Abbott.

Daily injections of the interleukin-1β antagonist anakinra significantly improved the peripheral and central nervous system manifestations of neonatal-onset multisystem inflammatory disease in patients with and without the genetic mutation that is associated with the rare systemic disease, a study found.

Neonatal-onset multisystem inflammatory disease (NOMID) often develops in patients who have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that is associated with regulating inflammation.

Previous studies have linked interleukin-1β pathways to NOMID, and isolated case reports have suggested that by inhibiting interleukin-1β, anakinra (Kineret) may be effective in the treatment of rash and the constitutional symptoms of disease.

To assess anakinra efficacy on these manifestations, as well as those that affect the central nervous system, Dr. Raphaela Goldbach-Mansky of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., and colleagues enrolled 18 patients with active disease, including 12 with identifiable CIAS1 mutations, into an open-label investigation (N. Engl. J. Med. 2006;355:581-92).

All of the patients were between the ages of 4 and 32 years old (mean age 11 years) and presented with at least two of the following clinical manifestations of NOMID: urticarial rash, central nervous system involvement, or epiphyseal or patellar overgrowth on radiography. Additionally, all of the patients had undergone previous treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and/or corticosteroids.

Each patient received daily subcutaneous anakinra injections of 1-2 mg/kg of body weight and underwent efficacy assessments at 1, 3, and 6 months.

The primary end points of the study were changes in symptom scores for fever, rash, headache, joint pain, and vomiting as measured in a daily diary, changes in acute-phase reactants, including serum amyloid A, C-reactive protein, and erythrocyte sedimentation rate from baseline to 3 months and from 3 months until a flare. Secondary end points were childhood health assessment questionnaire scores, audiography and vision assessments, MRI of the brain, and lumbar puncture results.

The initial study design included an inpatient withdrawal phase at 3 months for patients who responded to anakinra treatment in order to induce a clinical flare, followed by a reintroduction of therapy and continuation in an ongoing extension period. The withdrawal phase was discontinued after the first 11 patients because of the severity of the flares, which included pericarditis in 1 patient, corneal infiltrates in 3 patients, and uveitis in 2 patients, according to the authors.

In all of the patients, anakinra treatment produced an immediate clinical response, including disappearance of rash and conjunctivitis within 3 days, significantly decreased diary scores at 3 months, and significant decreases in C-reactive protein, serum amyloid A, and erythrocyte sedimentation rates. Of the 11 patients who underwent an inpatient withdrawal period for up to 7 days, 10 experienced a flare that met prespecified criteria at a median of 5 days. All of the patients responded to resumed anakinra therapy promptly, and the improvements were sustained at the 6-month follow-up.

Additional findings included improved hearing in six patients and stable hearing in patients relative to baseline, stable vision in all patients, and significant improvements on the pain, parent, and physician global assessment, and Childhood Health Assessment Questionnaire scores.

With respect to central nervous system manifestations, median daily headache scores decreased significantly in all patients, with complete resolution of headaches in eight patients at 3 months. Intracranial pressures, protein levels, and white cell counts decreased significantly in the 12 patients for whom cerebrospinal fluid was evaluated. Additionally, MRI showed significant improvement from baseline in cochlear and leptomeningeal lesions, the authors wrote.

Overall, anakinra was well tolerated in the patients. Eight experienced a localized, erythematous, sometimes painful injection-site skin reaction that disappeared by 6 weeks, 15 had upper respiratory events during treatment, 3 had urinary tract infections, and 1 was hospitalized for dehydration from nonbacterial diarrhea. No patients withdrew from the study because of adverse events, according to the authors.

Dr. Goldbach-Mansky reported no conflicts of interest with respect to this study. Some coinvestigators reported having received consulting fees, lecture fees, and/or research support from Amgen (maker of anakinra), Genentech, and Abbott.

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex.

In total, about 12% reported any sexual activity. Of those who reported having had intercourse, 36% were aged 11 years or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. In addition, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory? The “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Some identified protective and risk factors that don't easily fall within the norm/connectedness framework, such as community opportunity and poverty, hormone levels, self-efficacy, and emotional well-being, are also important intervention targets that must be considered “if we are to dramatically reduce sexual risk taking [in adolescents],” Dr. Kirby said.

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex.

In total, about 12% reported any sexual activity. Of those who reported having had intercourse, 36% were aged 11 years or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. In addition, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory? The “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Some identified protective and risk factors that don't easily fall within the norm/connectedness framework, such as community opportunity and poverty, hormone levels, self-efficacy, and emotional well-being, are also important intervention targets that must be considered “if we are to dramatically reduce sexual risk taking [in adolescents],” Dr. Kirby said.

Sexually risky behaviors on the part of adolescents is nothing new, but the age at which these behaviors begin is. In fact, new data suggest that sexual risk taking often begins in middle school.

Baseline data collected in spring 2005 from 4,457 middle school students aged 11–14 years at 14 urban schools participating in Project Connect, an 8-year multilevel intervention study, showed that more than 9% of the students surveyed reported ever having sexual intercourse, and 8% reported ever having oral sex.

In total, about 12% reported any sexual activity. Of those who reported having had intercourse, 36% were aged 11 years or younger at first sex, 27% were 12 years old, 28% were 13 years old, and 9% were aged 14 or older. In addition, of those who reported having had intercourse, 43% reported having had multiple sex partners.

Given their young age at sexual onset, “these youth are at very high risk for adverse health outcomes,” Project Connect investigator Christine J. DeRosa, Ph.D., said at the annual meeting of the Society for Adolescent Medicine in Boston. As such, “behavioral and health education are imperative for all youth beginning early in middle school, and the involvement of parents, health care providers, and community leaders is also critical.”

The goal of such interventions should be to assist those youth who have already engaged in some sexual activity to return to abstinence, said Dr. DeRosa of Health Research Association Inc., a University of Southern California affiliate that is facilitating the Centers for Disease Control-sponsored project. “For the majority of youth who have not engaged in sexual activities, the goal should be to further delay the onset of sexual initiation.”

How the interventions should look and be implemented is a matter of much debate. Should they focus on abstinence or contraception? Should they be school or clinic based? Should they be voluntary or mandatory? The “best” intervention is one that identifies and targets the range of risk and protective factors that influence initiation of sex, number of partners, condom use, and contraception use, and this will vary depending on the individuals or populations being served, according to Douglas Kirby, Ph.D., a senior research scientist with ETR Associates in Scotts Valley, Calif.

In a 2001 report for the National Campaign to Prevent Teen Pregnancy called “Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy” (www.teenpregnancy.org/resources/data/pdf/emeranswsum.pdf

At the community level, education, employment, income, and crime rate are important predictive factors. At the family level, family structure, dynamics, and values play a role. And at the individual level, age, hormones, peers, emotional well-being, relationship history, sexual abuse history, and attachment to school, religious groups, and proactive community organizations have an impact.

In the review, Dr. Kirby identified four groups of effective intervention programs. These included sex and HIV education programs that not only stated the target norm—whether abstinence or contraception—clearly and frequently with factual information to support it, but also engaged the youth in activities, such as role playing, to model, practice, and personalize the norm. Also effective were some programs within health, family planning, or STD clinics that similarly expressed clear norms, as well as focusing on perceived barriers, providing backup information, and offering structured follow-up.

Certain service-learning programs that include both intensive voluntary service in various capacities (tutors, teachers' aides, nursing home assistants) and ongoing small group discussions about the service, with or without discussion about sexual or contraceptive behavior, also had a demonstrable impact. The last group was long-term intensive programs with multiple components—including family life support, sexuality education, academic guidance, employment, opportunity for self-expression, and health care—in which norms were clearly stated and supported and staff consciously developed close relationships with the adolescents.

Although diverse in their focus and implementation, most of the effective intervention strategies share a conceptual framework built on social norms and an adolescent's sense of connection to those expressing the norms, Dr. Kirby said. “If a group has clear norms for or against sex or contraceptive use, then adolescents associated with this group will be more or less likely to have sex and use contraceptives depending on the norm,” he said. The more closely an adolescent feels connected to the group, the greater the impact the group's norms will have.

Some identified protective and risk factors that don't easily fall within the norm/connectedness framework, such as community opportunity and poverty, hormone levels, self-efficacy, and emotional well-being, are also important intervention targets that must be considered “if we are to dramatically reduce sexual risk taking [in adolescents],” Dr. Kirby said.