Heidi Splete

Nearly one-third of adults with stable schizophrenia also met independent clinical criteria for depression, findings from an analysis of 90 patients have shown.

Overall, 28 of the 90 patients (31%) had scores of 5 or more on the Calgary Depression Scale for Schizophrenia (CDSS), which is highly correlated with other measures of depression, said Dr. Susana Majadas of the Universidad de Salamanca (Spain) and her colleagues.

Data from previous studies have shown depressive symptoms in many patients with schizophrenia, but some clinicians maintain that these symptoms are secondary to schizophrenia or a side effect of treatment, the researchers noted.

In this study, the researchers analyzed 90 stable schizophrenia outpatients aged 18-50 years across five centers in Spain; 75 had a diagnosis of schizophrenia and 15 had a schizoaffective disorder. The mean age of the patients was 35 years, and 59% were men (Comp. Psychiatry 2012;53:145-51).

The prevalence of depression was 33% in patients with schizophrenia and 20% in those with a schizoaffective disorder. The prevalence of depression was not significantly different in men vs. women (34% vs. 27%).

The patients’ treatments included risperidone (32 patients), quetiapine (21 patients), olanzapine (9 patients), fluphenazine (6 patients), amisulpride (6 patients), and other antipsychotics (14 patients).

When the presence of depression was analyzed according to antipsychotic treatment, the criteria for depression (a CDSS score below 5) were not met in 90% of patients on quetiapine, 67% of patients on fluphenazine, 56% of those on risperidone, and 44% of those on olanzapine, the researchers noted.

"Depression appears to be associated with a greater severity of disease, and in part, overlaps with negative symptoms," the researchers said.

The study is the first to use the CDSS to assess depression in schizophrenia patients, and the prevalence rates are similar to those found in other studies, they noted. Although the study was limited by its cross-sectional design, which did not permit the evaluation of symptoms over time, the findings suggest that clinical depression is often present in stable schizophrenia patients. The findings also suggest that depressive symptoms are not secondary to schizophrenia symptoms or the effects of medication, Dr. Majadas and her colleagues added.

The researchers said they had no relevant financial disclosures.

Nearly one-third of adults with stable schizophrenia also met independent clinical criteria for depression, findings from an analysis of 90 patients have shown.

Overall, 28 of the 90 patients (31%) had scores of 5 or more on the Calgary Depression Scale for Schizophrenia (CDSS), which is highly correlated with other measures of depression, said Dr. Susana Majadas of the Universidad de Salamanca (Spain) and her colleagues.

Data from previous studies have shown depressive symptoms in many patients with schizophrenia, but some clinicians maintain that these symptoms are secondary to schizophrenia or a side effect of treatment, the researchers noted.

In this study, the researchers analyzed 90 stable schizophrenia outpatients aged 18-50 years across five centers in Spain; 75 had a diagnosis of schizophrenia and 15 had a schizoaffective disorder. The mean age of the patients was 35 years, and 59% were men (Comp. Psychiatry 2012;53:145-51).

The prevalence of depression was 33% in patients with schizophrenia and 20% in those with a schizoaffective disorder. The prevalence of depression was not significantly different in men vs. women (34% vs. 27%).

The patients’ treatments included risperidone (32 patients), quetiapine (21 patients), olanzapine (9 patients), fluphenazine (6 patients), amisulpride (6 patients), and other antipsychotics (14 patients).

When the presence of depression was analyzed according to antipsychotic treatment, the criteria for depression (a CDSS score below 5) were not met in 90% of patients on quetiapine, 67% of patients on fluphenazine, 56% of those on risperidone, and 44% of those on olanzapine, the researchers noted.

"Depression appears to be associated with a greater severity of disease, and in part, overlaps with negative symptoms," the researchers said.

The study is the first to use the CDSS to assess depression in schizophrenia patients, and the prevalence rates are similar to those found in other studies, they noted. Although the study was limited by its cross-sectional design, which did not permit the evaluation of symptoms over time, the findings suggest that clinical depression is often present in stable schizophrenia patients. The findings also suggest that depressive symptoms are not secondary to schizophrenia symptoms or the effects of medication, Dr. Majadas and her colleagues added.

The researchers said they had no relevant financial disclosures.

Nearly one-third of adults with stable schizophrenia also met independent clinical criteria for depression, findings from an analysis of 90 patients have shown.

Overall, 28 of the 90 patients (31%) had scores of 5 or more on the Calgary Depression Scale for Schizophrenia (CDSS), which is highly correlated with other measures of depression, said Dr. Susana Majadas of the Universidad de Salamanca (Spain) and her colleagues.

Data from previous studies have shown depressive symptoms in many patients with schizophrenia, but some clinicians maintain that these symptoms are secondary to schizophrenia or a side effect of treatment, the researchers noted.

In this study, the researchers analyzed 90 stable schizophrenia outpatients aged 18-50 years across five centers in Spain; 75 had a diagnosis of schizophrenia and 15 had a schizoaffective disorder. The mean age of the patients was 35 years, and 59% were men (Comp. Psychiatry 2012;53:145-51).

The prevalence of depression was 33% in patients with schizophrenia and 20% in those with a schizoaffective disorder. The prevalence of depression was not significantly different in men vs. women (34% vs. 27%).

The patients’ treatments included risperidone (32 patients), quetiapine (21 patients), olanzapine (9 patients), fluphenazine (6 patients), amisulpride (6 patients), and other antipsychotics (14 patients).

When the presence of depression was analyzed according to antipsychotic treatment, the criteria for depression (a CDSS score below 5) were not met in 90% of patients on quetiapine, 67% of patients on fluphenazine, 56% of those on risperidone, and 44% of those on olanzapine, the researchers noted.

"Depression appears to be associated with a greater severity of disease, and in part, overlaps with negative symptoms," the researchers said.

The study is the first to use the CDSS to assess depression in schizophrenia patients, and the prevalence rates are similar to those found in other studies, they noted. Although the study was limited by its cross-sectional design, which did not permit the evaluation of symptoms over time, the findings suggest that clinical depression is often present in stable schizophrenia patients. The findings also suggest that depressive symptoms are not secondary to schizophrenia symptoms or the effects of medication, Dr. Majadas and her colleagues added.

The researchers said they had no relevant financial disclosures.

Federal legislation has improved the safety and design of drug studies in children, but there is room for improvement, particularly in conducting long-term follow-up studies of approved products, and in studies of newborns.

That was the finding of an Institute of Medicine review committee that examined studies of drugs and biologic products in children that have be conducted since the 1997 enactment of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA).

The BPCA provides economic incentives for drug companies to respond to Food and Drug Administration requests for studies in children, while the PREA allows the FDA to require pediatric studies in certain situations. Both laws are scheduled to be reauthorized this year.

© Louis-Paul St-Onge/iStockphoto

Since the two laws went into effect, the FDA has approved 400 labeling changes for drugs related to their use in children, according to the report. The report did not address the impact of BPCA and PREA on clinical practice or on the off-label use of medication in children.

Planning, initiating, and completing studies in a timelier manner would increase the benefits for children, the report authors noted. But they added that not all studies under BPCA and PREA succeed for many reasons, including insufficient numbers, weak study designs, and reluctance of doctors and parents to enroll children in clinical trials of approved adult drugs.

Although public access to information from pediatric drug studies has greatly improved under the two laws, such studies remain limited in several key areas, namely the lack of long-term safety data on drugs that children take for chronic conditions and on the long-term side effects on growth and development in children who take medications for short periods during infancy and early childhood.

In addition, there remains a lack of data on the use of drugs in infants aged 28 days and younger, and in premature or sick newborns, according to the report.

In 2010, Congress extended BPCA incentives to include biologics; therefore, it is too soon to evaluate any impact in this area, the authors noted.

The IOM review committee made suggestions for further improvements to pediatric drug studies, including:

• Improved public access to study findings.

• Improved timeliness of pediatric studies.

• Added emphasis on areas with insufficient research, including drug studies in newborns and long-term safety studies of children using medication for short-term and chronic conditions.

• Improved design and execution of pediatric studies.

• Added encouragement for the study of biologics in children.

• Improved clarity and understanding of the expected health benefits of pediatric studies requested under BPCA.

Federal legislation has improved the safety and design of drug studies in children, but there is room for improvement, particularly in conducting long-term follow-up studies of approved products, and in studies of newborns.

That was the finding of an Institute of Medicine review committee that examined studies of drugs and biologic products in children that have be conducted since the 1997 enactment of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA).

The BPCA provides economic incentives for drug companies to respond to Food and Drug Administration requests for studies in children, while the PREA allows the FDA to require pediatric studies in certain situations. Both laws are scheduled to be reauthorized this year.

© Louis-Paul St-Onge/iStockphoto

Since the two laws went into effect, the FDA has approved 400 labeling changes for drugs related to their use in children, according to the report. The report did not address the impact of BPCA and PREA on clinical practice or on the off-label use of medication in children.

Planning, initiating, and completing studies in a timelier manner would increase the benefits for children, the report authors noted. But they added that not all studies under BPCA and PREA succeed for many reasons, including insufficient numbers, weak study designs, and reluctance of doctors and parents to enroll children in clinical trials of approved adult drugs.

Although public access to information from pediatric drug studies has greatly improved under the two laws, such studies remain limited in several key areas, namely the lack of long-term safety data on drugs that children take for chronic conditions and on the long-term side effects on growth and development in children who take medications for short periods during infancy and early childhood.

In addition, there remains a lack of data on the use of drugs in infants aged 28 days and younger, and in premature or sick newborns, according to the report.

In 2010, Congress extended BPCA incentives to include biologics; therefore, it is too soon to evaluate any impact in this area, the authors noted.

The IOM review committee made suggestions for further improvements to pediatric drug studies, including:

• Improved public access to study findings.

• Improved timeliness of pediatric studies.

• Added emphasis on areas with insufficient research, including drug studies in newborns and long-term safety studies of children using medication for short-term and chronic conditions.

• Improved design and execution of pediatric studies.

• Added encouragement for the study of biologics in children.

• Improved clarity and understanding of the expected health benefits of pediatric studies requested under BPCA.

Federal legislation has improved the safety and design of drug studies in children, but there is room for improvement, particularly in conducting long-term follow-up studies of approved products, and in studies of newborns.

That was the finding of an Institute of Medicine review committee that examined studies of drugs and biologic products in children that have be conducted since the 1997 enactment of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA).

The BPCA provides economic incentives for drug companies to respond to Food and Drug Administration requests for studies in children, while the PREA allows the FDA to require pediatric studies in certain situations. Both laws are scheduled to be reauthorized this year.

© Louis-Paul St-Onge/iStockphoto

Since the two laws went into effect, the FDA has approved 400 labeling changes for drugs related to their use in children, according to the report. The report did not address the impact of BPCA and PREA on clinical practice or on the off-label use of medication in children.

Planning, initiating, and completing studies in a timelier manner would increase the benefits for children, the report authors noted. But they added that not all studies under BPCA and PREA succeed for many reasons, including insufficient numbers, weak study designs, and reluctance of doctors and parents to enroll children in clinical trials of approved adult drugs.

Although public access to information from pediatric drug studies has greatly improved under the two laws, such studies remain limited in several key areas, namely the lack of long-term safety data on drugs that children take for chronic conditions and on the long-term side effects on growth and development in children who take medications for short periods during infancy and early childhood.

In addition, there remains a lack of data on the use of drugs in infants aged 28 days and younger, and in premature or sick newborns, according to the report.

In 2010, Congress extended BPCA incentives to include biologics; therefore, it is too soon to evaluate any impact in this area, the authors noted.

The IOM review committee made suggestions for further improvements to pediatric drug studies, including:

• Improved public access to study findings.

• Improved timeliness of pediatric studies.

• Added emphasis on areas with insufficient research, including drug studies in newborns and long-term safety studies of children using medication for short-term and chronic conditions.

• Improved design and execution of pediatric studies.

• Added encouragement for the study of biologics in children.

• Improved clarity and understanding of the expected health benefits of pediatric studies requested under BPCA.

Skin conditions in cancer patients can lead to a decreased quality of life because of the psychosocial impact, financial burden, poor health, and disruption of anticancer treatments, said Dr. Mario E. Lacouture at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Clinical trials are underway to address management, cost, and quality of life, but in the meantime, "an early and proactive approach toward toxicities is advisable," he said.

Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed common cancer-associated dermatology at the seminar.

• Rashes. A RAF inhibitor–induced rash can occur within 1-2 weeks of starting treatment, Dr. Lacouture noted. This rash is associated with sensations of burning or itching in photo-exposed areas. In most cases, the rash can be managed with topical steroids and oral GABA agonists. Vemurafenib use also has been associated with rashes, as well as with photosensitivity, itching, and alopecia, he said.

In addition, mTOR inhibitor–induced rashes involving erythematous pruritic papules and ulcerlike lesions have been observed in patients on everolimus and temsirolimus.

• Skin cancers. Data from several studies suggest that the incidence of squamous cell carcinomas in patients on RAF inhibitors is 7%, and the incidence of actinic keratoses in these patients is 4%, according to Dr. Lacouture. These conditions usually develop after approximately 6 months of treatment. They can be managed by surgery or destruction; and there have been no reports of metastases.

Photo courtesy Dr. Peter W. Heald

• Hand-foot syndrome. Hand-Foot Syndrome (HFSR) is a common side effect in cancer patients that usually occurs within 45 days of starting treatment, said Dr. Lacouture. HFSR is often associated with the use of sorafenib, sunitinib, and pazopanib, and the histology of these patients shows epidermal necrosis, he noted. Patients who develop HFSR may need to temporarily reduce their medications. Additional management of HFSR includes avoiding excess pressure on the affected areas and keeping them cool and moist to reduce patient discomfort.

• Hair and nail changes. Changes in hair can occur in patients being treated with epidermal growth factor receptor inhibitors (EGFRIs), including a slower hair growth rate and alopecia, Dr. Lacouture said. Changes in hair texture such as increased brittleness and hair curling also have been observed, he said. Other hair-related adverse events can include hirsutism on the face and eyelash trichomegaly. In addition, paronychia has been observed in patients on EGFRIs for more than 6 months.

• Radiation dermatitis. Approximately 50% of cancer patients develop radiation dermatitis, including 87% of breast cancer patients, reported Dr. Lacouture. However, the treatment of radiation dermatitis remains challenging, he said. In several studies, patients who used a nonsteroidal topical, including aloe vera and trolamine, showed no significant improvement in radiation dermatitis, compared with controls. However, studies are ongoing, and significant improvements in radiation dermatitis in breast cancer patients have been seen with topical corticosteroids including mometasone, beclomethasone, and betamethasone.

Dr. Lacouture disclosed financial relationships with multiple companies including Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche. SDEF and this news organization are owned by Elsevier.

Skin conditions in cancer patients can lead to a decreased quality of life because of the psychosocial impact, financial burden, poor health, and disruption of anticancer treatments, said Dr. Mario E. Lacouture at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Clinical trials are underway to address management, cost, and quality of life, but in the meantime, "an early and proactive approach toward toxicities is advisable," he said.

Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed common cancer-associated dermatology at the seminar.

• Rashes. A RAF inhibitor–induced rash can occur within 1-2 weeks of starting treatment, Dr. Lacouture noted. This rash is associated with sensations of burning or itching in photo-exposed areas. In most cases, the rash can be managed with topical steroids and oral GABA agonists. Vemurafenib use also has been associated with rashes, as well as with photosensitivity, itching, and alopecia, he said.

In addition, mTOR inhibitor–induced rashes involving erythematous pruritic papules and ulcerlike lesions have been observed in patients on everolimus and temsirolimus.

• Skin cancers. Data from several studies suggest that the incidence of squamous cell carcinomas in patients on RAF inhibitors is 7%, and the incidence of actinic keratoses in these patients is 4%, according to Dr. Lacouture. These conditions usually develop after approximately 6 months of treatment. They can be managed by surgery or destruction; and there have been no reports of metastases.

Photo courtesy Dr. Peter W. Heald

• Hand-foot syndrome. Hand-Foot Syndrome (HFSR) is a common side effect in cancer patients that usually occurs within 45 days of starting treatment, said Dr. Lacouture. HFSR is often associated with the use of sorafenib, sunitinib, and pazopanib, and the histology of these patients shows epidermal necrosis, he noted. Patients who develop HFSR may need to temporarily reduce their medications. Additional management of HFSR includes avoiding excess pressure on the affected areas and keeping them cool and moist to reduce patient discomfort.

• Hair and nail changes. Changes in hair can occur in patients being treated with epidermal growth factor receptor inhibitors (EGFRIs), including a slower hair growth rate and alopecia, Dr. Lacouture said. Changes in hair texture such as increased brittleness and hair curling also have been observed, he said. Other hair-related adverse events can include hirsutism on the face and eyelash trichomegaly. In addition, paronychia has been observed in patients on EGFRIs for more than 6 months.

• Radiation dermatitis. Approximately 50% of cancer patients develop radiation dermatitis, including 87% of breast cancer patients, reported Dr. Lacouture. However, the treatment of radiation dermatitis remains challenging, he said. In several studies, patients who used a nonsteroidal topical, including aloe vera and trolamine, showed no significant improvement in radiation dermatitis, compared with controls. However, studies are ongoing, and significant improvements in radiation dermatitis in breast cancer patients have been seen with topical corticosteroids including mometasone, beclomethasone, and betamethasone.

Dr. Lacouture disclosed financial relationships with multiple companies including Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche. SDEF and this news organization are owned by Elsevier.

Skin conditions in cancer patients can lead to a decreased quality of life because of the psychosocial impact, financial burden, poor health, and disruption of anticancer treatments, said Dr. Mario E. Lacouture at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Clinical trials are underway to address management, cost, and quality of life, but in the meantime, "an early and proactive approach toward toxicities is advisable," he said.

Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed common cancer-associated dermatology at the seminar.

• Rashes. A RAF inhibitor–induced rash can occur within 1-2 weeks of starting treatment, Dr. Lacouture noted. This rash is associated with sensations of burning or itching in photo-exposed areas. In most cases, the rash can be managed with topical steroids and oral GABA agonists. Vemurafenib use also has been associated with rashes, as well as with photosensitivity, itching, and alopecia, he said.

In addition, mTOR inhibitor–induced rashes involving erythematous pruritic papules and ulcerlike lesions have been observed in patients on everolimus and temsirolimus.

• Skin cancers. Data from several studies suggest that the incidence of squamous cell carcinomas in patients on RAF inhibitors is 7%, and the incidence of actinic keratoses in these patients is 4%, according to Dr. Lacouture. These conditions usually develop after approximately 6 months of treatment. They can be managed by surgery or destruction; and there have been no reports of metastases.

Photo courtesy Dr. Peter W. Heald

• Hand-foot syndrome. Hand-Foot Syndrome (HFSR) is a common side effect in cancer patients that usually occurs within 45 days of starting treatment, said Dr. Lacouture. HFSR is often associated with the use of sorafenib, sunitinib, and pazopanib, and the histology of these patients shows epidermal necrosis, he noted. Patients who develop HFSR may need to temporarily reduce their medications. Additional management of HFSR includes avoiding excess pressure on the affected areas and keeping them cool and moist to reduce patient discomfort.

• Hair and nail changes. Changes in hair can occur in patients being treated with epidermal growth factor receptor inhibitors (EGFRIs), including a slower hair growth rate and alopecia, Dr. Lacouture said. Changes in hair texture such as increased brittleness and hair curling also have been observed, he said. Other hair-related adverse events can include hirsutism on the face and eyelash trichomegaly. In addition, paronychia has been observed in patients on EGFRIs for more than 6 months.

• Radiation dermatitis. Approximately 50% of cancer patients develop radiation dermatitis, including 87% of breast cancer patients, reported Dr. Lacouture. However, the treatment of radiation dermatitis remains challenging, he said. In several studies, patients who used a nonsteroidal topical, including aloe vera and trolamine, showed no significant improvement in radiation dermatitis, compared with controls. However, studies are ongoing, and significant improvements in radiation dermatitis in breast cancer patients have been seen with topical corticosteroids including mometasone, beclomethasone, and betamethasone.

Dr. Lacouture disclosed financial relationships with multiple companies including Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche. SDEF and this news organization are owned by Elsevier.

Adalimumab therapy was associated with a significant decrease in sperm count in a 35-year-old man who had taken the biologic for 3 years as treatment for ankylosing spondylitis, according to a case report presented in the March issue of Annals of the Rheumatic Diseases.

Anti-tumor necrosis factor (anti-TNF) agents have been used in rheumatology for more than a decade, and few new side effects have been observed, wrote Dr. Lukas M. Wildi and Dr. Boulos Haraoui of the University of Montreal.

The patient was the father of a healthy 4-year-old, but after 3 years of adalimumab treatment he was tested for infertility. A sperm analysis showed a combination of decreased sperm motility and an unusually low sperm count (0.9 million/mL), which led to a diagnosis of oligoasthenozoospermia (Ann. Rheum. Dis. 2012;71:473-4).

No other cause of the problem was identified, and the patient discontinued adalimumab. After 3 months of no treatment, the patient’s sperm count increased to 6 million/mL, but only 1% of the sperm were normal. However, after 6 months, the sperm count increased to 12 million/mL and the sperm morphology reached the normal range (15%), but sperm motility remained below normal (motile concentration of 3.5 million/mL).

The patient’s symptoms of ankylosing spondylitis recurred, and he opted to resume adalimumab therapy after freezing some sperm, the researchers said.

Previous case series have shown similar reductions in sperm count and quality in men taking infliximab, the researchers said, but no impact on fertility was reported.

Additional studies have shown decreased sperm motility in ankylosing spondylitis patients on conventional treatment compared with those on TNF-alpha blockers, the researchers said. "However, in general, male patients also seem to remain fertile under anti-TNF alpha therapy," they said.

"Imbalances in TNF-alpha level, either too high or too low, seem to influence spermatogenesis and may sometimes lead to infertility," the researchers noted. "The present case demonstrates the reversibility of this adverse event after cessation of therapy and raises an issue not frequently discussed with male patients," they said.

The authors had no financial conflicts to disclose.

Adalimumab therapy was associated with a significant decrease in sperm count in a 35-year-old man who had taken the biologic for 3 years as treatment for ankylosing spondylitis, according to a case report presented in the March issue of Annals of the Rheumatic Diseases.

Anti-tumor necrosis factor (anti-TNF) agents have been used in rheumatology for more than a decade, and few new side effects have been observed, wrote Dr. Lukas M. Wildi and Dr. Boulos Haraoui of the University of Montreal.

The patient was the father of a healthy 4-year-old, but after 3 years of adalimumab treatment he was tested for infertility. A sperm analysis showed a combination of decreased sperm motility and an unusually low sperm count (0.9 million/mL), which led to a diagnosis of oligoasthenozoospermia (Ann. Rheum. Dis. 2012;71:473-4).

No other cause of the problem was identified, and the patient discontinued adalimumab. After 3 months of no treatment, the patient’s sperm count increased to 6 million/mL, but only 1% of the sperm were normal. However, after 6 months, the sperm count increased to 12 million/mL and the sperm morphology reached the normal range (15%), but sperm motility remained below normal (motile concentration of 3.5 million/mL).

The patient’s symptoms of ankylosing spondylitis recurred, and he opted to resume adalimumab therapy after freezing some sperm, the researchers said.

Previous case series have shown similar reductions in sperm count and quality in men taking infliximab, the researchers said, but no impact on fertility was reported.

Additional studies have shown decreased sperm motility in ankylosing spondylitis patients on conventional treatment compared with those on TNF-alpha blockers, the researchers said. "However, in general, male patients also seem to remain fertile under anti-TNF alpha therapy," they said.

"Imbalances in TNF-alpha level, either too high or too low, seem to influence spermatogenesis and may sometimes lead to infertility," the researchers noted. "The present case demonstrates the reversibility of this adverse event after cessation of therapy and raises an issue not frequently discussed with male patients," they said.

The authors had no financial conflicts to disclose.

Adalimumab therapy was associated with a significant decrease in sperm count in a 35-year-old man who had taken the biologic for 3 years as treatment for ankylosing spondylitis, according to a case report presented in the March issue of Annals of the Rheumatic Diseases.

Anti-tumor necrosis factor (anti-TNF) agents have been used in rheumatology for more than a decade, and few new side effects have been observed, wrote Dr. Lukas M. Wildi and Dr. Boulos Haraoui of the University of Montreal.

The patient was the father of a healthy 4-year-old, but after 3 years of adalimumab treatment he was tested for infertility. A sperm analysis showed a combination of decreased sperm motility and an unusually low sperm count (0.9 million/mL), which led to a diagnosis of oligoasthenozoospermia (Ann. Rheum. Dis. 2012;71:473-4).

No other cause of the problem was identified, and the patient discontinued adalimumab. After 3 months of no treatment, the patient’s sperm count increased to 6 million/mL, but only 1% of the sperm were normal. However, after 6 months, the sperm count increased to 12 million/mL and the sperm morphology reached the normal range (15%), but sperm motility remained below normal (motile concentration of 3.5 million/mL).

The patient’s symptoms of ankylosing spondylitis recurred, and he opted to resume adalimumab therapy after freezing some sperm, the researchers said.

Previous case series have shown similar reductions in sperm count and quality in men taking infliximab, the researchers said, but no impact on fertility was reported.

Additional studies have shown decreased sperm motility in ankylosing spondylitis patients on conventional treatment compared with those on TNF-alpha blockers, the researchers said. "However, in general, male patients also seem to remain fertile under anti-TNF alpha therapy," they said.

"Imbalances in TNF-alpha level, either too high or too low, seem to influence spermatogenesis and may sometimes lead to infertility," the researchers noted. "The present case demonstrates the reversibility of this adverse event after cessation of therapy and raises an issue not frequently discussed with male patients," they said.

The authors had no financial conflicts to disclose.

RIO GRANDE, P.R. – In patients with chronic recurrent candida, "the first thing to do is culture," Dr. Ted Rosen said at the Caribbean Dermatology Symposium.

"Make sure that it is really fungal," said Dr. Rosen, a professor of dermatology at Baylor College of Medicine, Houston. About 70%-80% of so-called candida infections aren’t yeast infections at all. Be sure to consider other diagnoses before proceeding with treatment.

If culture confirms the chronic candida diagnosis, fluconazole is the traditional treatment.

In case of vulvovaginal candidiasis, data from several studies now suggest that probiotics also are effective in patients who are not immunocompromised, said Dr. Rosen.

"I’m not really a New Age kind of person, but it turns out that probiotics have shown effectiveness against chronic candida, thrush, and vulvovaginal candida" in otherwise healthy individuals, he said.

Probiotics administered over a fairly long time seem to make those infections stop. As to how this works, "the probiotics secrete a surfactant" that keeps the candida from adhering to tissues. In addition, "the probiotic bacteria act as competition for the yeast forms," Dr. Rosen said. "They [the probiotics] also secrete antibacterial substances because they want to get rid of their competition [the yeast]," he added.

Dr. Rosen cited a recent review of data supporting the impact of probiotics on healthy vaginal flora and their effectiveness for treating and preventing candidiasis. The review was published in the journal Mycoses (2012;55:17-26).

In a randomized, double-blind, placebo-controlled trial of 64 women with vulvovaginal candidiasis, those who took capsules containing Lactobacillus rhamnosus and L. fermentum showed significantly decreased yeast and coliforms after 4 weeks compared with women who took a calcium carbonate placebo. The probiotics group also showed a significant increase in healthy vaginal lactobacilli.

Courtesy CDC/Dr. Stuart Brown

In another randomized, double-blind, placebo controlled trial, women with vulvovaginal candidiasis received a standard dose of fluconazole plus probiotics (L. reuteri and L. rhamnosus) or fluconazole plus placebo once daily for 28 days. At day 28, significantly more women who took probiotics were cured of vulvovaginal candidiasis, based on negative cultures and symptom resolution.

The findings suggest that probiotics may be useful therapeutic interventions for candida, in part because of the nearly nonexistent adverse effects on patients and the lack of resistance developed by the pathogens, the researchers wrote.

Based on the available data, a standard oral probiotic with lactobacillus and bifidobacteria is worth trying in a patient with chronic candida, Dr. Rosen said.

Dr. Rosen had no relevant financial conflicts to disclose. The authors of the study published in Mycoses had no financial conflicts to disclose.

RIO GRANDE, P.R. – In patients with chronic recurrent candida, "the first thing to do is culture," Dr. Ted Rosen said at the Caribbean Dermatology Symposium.

"Make sure that it is really fungal," said Dr. Rosen, a professor of dermatology at Baylor College of Medicine, Houston. About 70%-80% of so-called candida infections aren’t yeast infections at all. Be sure to consider other diagnoses before proceeding with treatment.

If culture confirms the chronic candida diagnosis, fluconazole is the traditional treatment.

In case of vulvovaginal candidiasis, data from several studies now suggest that probiotics also are effective in patients who are not immunocompromised, said Dr. Rosen.

"I’m not really a New Age kind of person, but it turns out that probiotics have shown effectiveness against chronic candida, thrush, and vulvovaginal candida" in otherwise healthy individuals, he said.

Probiotics administered over a fairly long time seem to make those infections stop. As to how this works, "the probiotics secrete a surfactant" that keeps the candida from adhering to tissues. In addition, "the probiotic bacteria act as competition for the yeast forms," Dr. Rosen said. "They [the probiotics] also secrete antibacterial substances because they want to get rid of their competition [the yeast]," he added.

Dr. Rosen cited a recent review of data supporting the impact of probiotics on healthy vaginal flora and their effectiveness for treating and preventing candidiasis. The review was published in the journal Mycoses (2012;55:17-26).

In a randomized, double-blind, placebo-controlled trial of 64 women with vulvovaginal candidiasis, those who took capsules containing Lactobacillus rhamnosus and L. fermentum showed significantly decreased yeast and coliforms after 4 weeks compared with women who took a calcium carbonate placebo. The probiotics group also showed a significant increase in healthy vaginal lactobacilli.

Courtesy CDC/Dr. Stuart Brown

In another randomized, double-blind, placebo controlled trial, women with vulvovaginal candidiasis received a standard dose of fluconazole plus probiotics (L. reuteri and L. rhamnosus) or fluconazole plus placebo once daily for 28 days. At day 28, significantly more women who took probiotics were cured of vulvovaginal candidiasis, based on negative cultures and symptom resolution.

The findings suggest that probiotics may be useful therapeutic interventions for candida, in part because of the nearly nonexistent adverse effects on patients and the lack of resistance developed by the pathogens, the researchers wrote.

Based on the available data, a standard oral probiotic with lactobacillus and bifidobacteria is worth trying in a patient with chronic candida, Dr. Rosen said.

Dr. Rosen had no relevant financial conflicts to disclose. The authors of the study published in Mycoses had no financial conflicts to disclose.

RIO GRANDE, P.R. – In patients with chronic recurrent candida, "the first thing to do is culture," Dr. Ted Rosen said at the Caribbean Dermatology Symposium.

"Make sure that it is really fungal," said Dr. Rosen, a professor of dermatology at Baylor College of Medicine, Houston. About 70%-80% of so-called candida infections aren’t yeast infections at all. Be sure to consider other diagnoses before proceeding with treatment.

If culture confirms the chronic candida diagnosis, fluconazole is the traditional treatment.

In case of vulvovaginal candidiasis, data from several studies now suggest that probiotics also are effective in patients who are not immunocompromised, said Dr. Rosen.

"I’m not really a New Age kind of person, but it turns out that probiotics have shown effectiveness against chronic candida, thrush, and vulvovaginal candida" in otherwise healthy individuals, he said.

Probiotics administered over a fairly long time seem to make those infections stop. As to how this works, "the probiotics secrete a surfactant" that keeps the candida from adhering to tissues. In addition, "the probiotic bacteria act as competition for the yeast forms," Dr. Rosen said. "They [the probiotics] also secrete antibacterial substances because they want to get rid of their competition [the yeast]," he added.

Dr. Rosen cited a recent review of data supporting the impact of probiotics on healthy vaginal flora and their effectiveness for treating and preventing candidiasis. The review was published in the journal Mycoses (2012;55:17-26).

In a randomized, double-blind, placebo-controlled trial of 64 women with vulvovaginal candidiasis, those who took capsules containing Lactobacillus rhamnosus and L. fermentum showed significantly decreased yeast and coliforms after 4 weeks compared with women who took a calcium carbonate placebo. The probiotics group also showed a significant increase in healthy vaginal lactobacilli.

Courtesy CDC/Dr. Stuart Brown

In another randomized, double-blind, placebo controlled trial, women with vulvovaginal candidiasis received a standard dose of fluconazole plus probiotics (L. reuteri and L. rhamnosus) or fluconazole plus placebo once daily for 28 days. At day 28, significantly more women who took probiotics were cured of vulvovaginal candidiasis, based on negative cultures and symptom resolution.

The findings suggest that probiotics may be useful therapeutic interventions for candida, in part because of the nearly nonexistent adverse effects on patients and the lack of resistance developed by the pathogens, the researchers wrote.

Based on the available data, a standard oral probiotic with lactobacillus and bifidobacteria is worth trying in a patient with chronic candida, Dr. Rosen said.

Dr. Rosen had no relevant financial conflicts to disclose. The authors of the study published in Mycoses had no financial conflicts to disclose.

Despite the advances in biologics, classic therapies still have a large role to play in treating moderate to severe psoriasis, according to Dr. Jeffrey M. Sobell.

"Biologics have expanded our treatment options, not replaced them," said Dr. Sobell at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Dr. Sobell of Tufts Medical Center in Boston discussed how he uses three classic psoriasis therapies.

Methotrexate

The efficacy of methotrexate is quite respectable, with a PASI 75 (that is, an improvement of 75% on the baseline Psoriasis Area and Severity Index) of 40% at 16 weeks, said Dr. Sobell. He said that he uses the drug for patients as a monotherapy for concomitant psoriatic arthritis and for life-impacting nail psoriasis. For some patients, he uses methotrexate in combination with anti–tumor necrosis factor therapy both for the synergistic effects on the skin and to reduce potential antibody formation.

The clinical dose of methotrexate is 7.5-25 mg/week (averaging 10-15 mg/week). Clinical effects should be seen by week 8, and doses greater than 20 mg/week are rarely necessary, he noted.

Clinicians who want to use methotrexate for psoriasis do need to be mindful of the possible side effects, which include hepatotoxicity, bone marrow suppression, gastrointestinal intolerance, pulmonary toxicity, and induction of malignancy. Also, methotrexate is teratogenic and is contraindicated during pregnancy, he said.

Cyclosporine

"Cyclosporine is an indispensable therapy in my clinic," said Dr. Sobell. He said that he uses it mostly for psoriasis in crisis situations, but also as a transitional therapy. "Clinicians have concerns about potential nephrotoxicity, but at low doses for short treatment periods, cyclosporine is extremely safe as long as serum creatinine levels are followed," he said.

A standard clinical dose of cyclosporine for psoriasis is 2.5-4.0 mg/kg per day. Other side effects to watch for include hypertension, paresthesias, and gastrointestinal intolerance.

Acitretin

Dr. Sobell said he uses acitretin in psoriasis patients as a monotherapy and in conjunction with phototherapy, biologics, and other oral medications.

His standard clinical dose is 10-25 mg/day. Follow-up lab tests should be done monthly for the first 3 months of acitretin use, and then every 3 months, he said. Acitretin is teratogenic, and other possible side effects include ocular or musculoskeletal problems, hyperlipidemia, and hepatotoxicity.

Dr. Sobell disclosed financial relationships with Abbott, Amgen, Celgene, Eli Lilly, and Janssen. SDEF and this news organization are owned by Elsevier.

Despite the advances in biologics, classic therapies still have a large role to play in treating moderate to severe psoriasis, according to Dr. Jeffrey M. Sobell.

"Biologics have expanded our treatment options, not replaced them," said Dr. Sobell at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Dr. Sobell of Tufts Medical Center in Boston discussed how he uses three classic psoriasis therapies.

Methotrexate

The efficacy of methotrexate is quite respectable, with a PASI 75 (that is, an improvement of 75% on the baseline Psoriasis Area and Severity Index) of 40% at 16 weeks, said Dr. Sobell. He said that he uses the drug for patients as a monotherapy for concomitant psoriatic arthritis and for life-impacting nail psoriasis. For some patients, he uses methotrexate in combination with anti–tumor necrosis factor therapy both for the synergistic effects on the skin and to reduce potential antibody formation.

The clinical dose of methotrexate is 7.5-25 mg/week (averaging 10-15 mg/week). Clinical effects should be seen by week 8, and doses greater than 20 mg/week are rarely necessary, he noted.

Clinicians who want to use methotrexate for psoriasis do need to be mindful of the possible side effects, which include hepatotoxicity, bone marrow suppression, gastrointestinal intolerance, pulmonary toxicity, and induction of malignancy. Also, methotrexate is teratogenic and is contraindicated during pregnancy, he said.

Cyclosporine

"Cyclosporine is an indispensable therapy in my clinic," said Dr. Sobell. He said that he uses it mostly for psoriasis in crisis situations, but also as a transitional therapy. "Clinicians have concerns about potential nephrotoxicity, but at low doses for short treatment periods, cyclosporine is extremely safe as long as serum creatinine levels are followed," he said.

A standard clinical dose of cyclosporine for psoriasis is 2.5-4.0 mg/kg per day. Other side effects to watch for include hypertension, paresthesias, and gastrointestinal intolerance.

Acitretin

Dr. Sobell said he uses acitretin in psoriasis patients as a monotherapy and in conjunction with phototherapy, biologics, and other oral medications.

His standard clinical dose is 10-25 mg/day. Follow-up lab tests should be done monthly for the first 3 months of acitretin use, and then every 3 months, he said. Acitretin is teratogenic, and other possible side effects include ocular or musculoskeletal problems, hyperlipidemia, and hepatotoxicity.

Dr. Sobell disclosed financial relationships with Abbott, Amgen, Celgene, Eli Lilly, and Janssen. SDEF and this news organization are owned by Elsevier.

Despite the advances in biologics, classic therapies still have a large role to play in treating moderate to severe psoriasis, according to Dr. Jeffrey M. Sobell.

"Biologics have expanded our treatment options, not replaced them," said Dr. Sobell at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Dr. Sobell of Tufts Medical Center in Boston discussed how he uses three classic psoriasis therapies.

Methotrexate

The efficacy of methotrexate is quite respectable, with a PASI 75 (that is, an improvement of 75% on the baseline Psoriasis Area and Severity Index) of 40% at 16 weeks, said Dr. Sobell. He said that he uses the drug for patients as a monotherapy for concomitant psoriatic arthritis and for life-impacting nail psoriasis. For some patients, he uses methotrexate in combination with anti–tumor necrosis factor therapy both for the synergistic effects on the skin and to reduce potential antibody formation.

The clinical dose of methotrexate is 7.5-25 mg/week (averaging 10-15 mg/week). Clinical effects should be seen by week 8, and doses greater than 20 mg/week are rarely necessary, he noted.

Clinicians who want to use methotrexate for psoriasis do need to be mindful of the possible side effects, which include hepatotoxicity, bone marrow suppression, gastrointestinal intolerance, pulmonary toxicity, and induction of malignancy. Also, methotrexate is teratogenic and is contraindicated during pregnancy, he said.

Cyclosporine

"Cyclosporine is an indispensable therapy in my clinic," said Dr. Sobell. He said that he uses it mostly for psoriasis in crisis situations, but also as a transitional therapy. "Clinicians have concerns about potential nephrotoxicity, but at low doses for short treatment periods, cyclosporine is extremely safe as long as serum creatinine levels are followed," he said.

A standard clinical dose of cyclosporine for psoriasis is 2.5-4.0 mg/kg per day. Other side effects to watch for include hypertension, paresthesias, and gastrointestinal intolerance.

Acitretin

Dr. Sobell said he uses acitretin in psoriasis patients as a monotherapy and in conjunction with phototherapy, biologics, and other oral medications.

His standard clinical dose is 10-25 mg/day. Follow-up lab tests should be done monthly for the first 3 months of acitretin use, and then every 3 months, he said. Acitretin is teratogenic, and other possible side effects include ocular or musculoskeletal problems, hyperlipidemia, and hepatotoxicity.

Dr. Sobell disclosed financial relationships with Abbott, Amgen, Celgene, Eli Lilly, and Janssen. SDEF and this news organization are owned by Elsevier.

An immediate access clinic significantly reduced the wait times for patients seeking rheumatology assessments, based on data from 660 patients seen between February and December 2009. The findings were published in the March issue of Annals of the Rheumatic Diseases.

"The delay from symptom onset to the first visit with a rheumatologist or start of therapy ranges from several months up to more than 1 year," said Dr. Miriam Gärtner of the Medical University of Vienna and her colleagues.

One reason for the delay in care is the lack of rheumatologists, the researchers said. To help get patients started on therapy sooner, an immediate access clinic (IAC) was established, in which patients could be seen within 1 day to 2 weeks of their referral, or seen immediately for a brief evaluation without a referral.

Of 1,036 patients who were assessed in the clinic during the study period, 660 patients were reevaluated 6-12 months after visiting the clinic. The patients were divided into those who were referred for further care in the clinic (331 patients) and those referred for further care outside of the clinic (329 patients). The average age of the patients was 50 years, and the average duration of symptoms was 24 years; the average pain rating on the visual analog scale of 0-100 mm was 54 mm (Ann. Rheum. Dis. 2012;71:363-8).

At a 6- to 12-month follow-up visit, 75% of the initial diagnoses that had been made at the clinic proved to be correct, the researchers said. "This indicates high reliability of these initial categorizations by an experienced rheumatologist, which often have to be made within only a few minutes, compared with a later and mostly ‘criteria-based’ classification," they said.

Of the patients who were referred for follow-up in the clinic, 213 returned for additional care and 118 did not return. Overall, 90% of those who returned for additional care received treatment depending on their diagnoses, with 25%-73% receiving disease-modifying antirheumatic drugs, 1%-25% receiving biologics, *5%-56% receiving glucocorticoids, and 2%-17% receiving physiotherapy. Of those who did not return for additional care (but were contacted later by phone), 38% said they received additional therapy at their initial visit. Of these, 42% received NSAIDs, 16% received biologics, 13% received synthetic DMARDs or physiotherapy, and 4% received glucocorticoids.

Of the 329 who were reached for follow-up after 6-12 months, 60% reported that their medical problems were "fully resolved," whereas approximately 40% said they were receiving additional medical care.

Approximately one-third of the patients were referred to the clinic because of suspected RA, but their median symptom duration of 9 months was beyond the ideal window of opportunity for effective early treatment (which should be within the first 3 months), the researchers noted.

Men were diagnosed with spondyloarthropathy more often than women, whereas women were more often diagnosed with osteoarthritis.

Also, "no difference in the frequency of final diagnosis of an inflammatory rheumatic disease between physician and self-referred individuals was apparent," the researchers said.

The study findings were limited by the potential unreliability of telephone interviews. But the results suggest that the IAC model is effective for reducing wait times for seeing a rheumatologist, and that the majority of the diagnoses made in this setting were accurate, the researchers said.

"Despite the short time of interaction between patient and rheumatologist at the time of the visit to the IAC, complaints about insufficient attention were very rare," the researchers added. "Apparently, patients appreciated the fact that they had an immediate opportunity to discuss their problems with a specialist, albeit for a short time, and to receive an initial diagnostic assessment and therapeutic recommendations," they said.

Dr. Gärtner and colleagues had no financial conflicts to disclose.

* Correction, 3/2/2012: An earlier version of this story incorrectly reported the percentages of returning patients who received glucocorticoids.

An immediate access clinic significantly reduced the wait times for patients seeking rheumatology assessments, based on data from 660 patients seen between February and December 2009. The findings were published in the March issue of Annals of the Rheumatic Diseases.

"The delay from symptom onset to the first visit with a rheumatologist or start of therapy ranges from several months up to more than 1 year," said Dr. Miriam Gärtner of the Medical University of Vienna and her colleagues.

One reason for the delay in care is the lack of rheumatologists, the researchers said. To help get patients started on therapy sooner, an immediate access clinic (IAC) was established, in which patients could be seen within 1 day to 2 weeks of their referral, or seen immediately for a brief evaluation without a referral.

Of 1,036 patients who were assessed in the clinic during the study period, 660 patients were reevaluated 6-12 months after visiting the clinic. The patients were divided into those who were referred for further care in the clinic (331 patients) and those referred for further care outside of the clinic (329 patients). The average age of the patients was 50 years, and the average duration of symptoms was 24 years; the average pain rating on the visual analog scale of 0-100 mm was 54 mm (Ann. Rheum. Dis. 2012;71:363-8).

At a 6- to 12-month follow-up visit, 75% of the initial diagnoses that had been made at the clinic proved to be correct, the researchers said. "This indicates high reliability of these initial categorizations by an experienced rheumatologist, which often have to be made within only a few minutes, compared with a later and mostly ‘criteria-based’ classification," they said.

Of the patients who were referred for follow-up in the clinic, 213 returned for additional care and 118 did not return. Overall, 90% of those who returned for additional care received treatment depending on their diagnoses, with 25%-73% receiving disease-modifying antirheumatic drugs, 1%-25% receiving biologics, *5%-56% receiving glucocorticoids, and 2%-17% receiving physiotherapy. Of those who did not return for additional care (but were contacted later by phone), 38% said they received additional therapy at their initial visit. Of these, 42% received NSAIDs, 16% received biologics, 13% received synthetic DMARDs or physiotherapy, and 4% received glucocorticoids.

Of the 329 who were reached for follow-up after 6-12 months, 60% reported that their medical problems were "fully resolved," whereas approximately 40% said they were receiving additional medical care.

Approximately one-third of the patients were referred to the clinic because of suspected RA, but their median symptom duration of 9 months was beyond the ideal window of opportunity for effective early treatment (which should be within the first 3 months), the researchers noted.

Men were diagnosed with spondyloarthropathy more often than women, whereas women were more often diagnosed with osteoarthritis.

Also, "no difference in the frequency of final diagnosis of an inflammatory rheumatic disease between physician and self-referred individuals was apparent," the researchers said.

The study findings were limited by the potential unreliability of telephone interviews. But the results suggest that the IAC model is effective for reducing wait times for seeing a rheumatologist, and that the majority of the diagnoses made in this setting were accurate, the researchers said.

"Despite the short time of interaction between patient and rheumatologist at the time of the visit to the IAC, complaints about insufficient attention were very rare," the researchers added. "Apparently, patients appreciated the fact that they had an immediate opportunity to discuss their problems with a specialist, albeit for a short time, and to receive an initial diagnostic assessment and therapeutic recommendations," they said.

Dr. Gärtner and colleagues had no financial conflicts to disclose.

* Correction, 3/2/2012: An earlier version of this story incorrectly reported the percentages of returning patients who received glucocorticoids.

An immediate access clinic significantly reduced the wait times for patients seeking rheumatology assessments, based on data from 660 patients seen between February and December 2009. The findings were published in the March issue of Annals of the Rheumatic Diseases.

"The delay from symptom onset to the first visit with a rheumatologist or start of therapy ranges from several months up to more than 1 year," said Dr. Miriam Gärtner of the Medical University of Vienna and her colleagues.

One reason for the delay in care is the lack of rheumatologists, the researchers said. To help get patients started on therapy sooner, an immediate access clinic (IAC) was established, in which patients could be seen within 1 day to 2 weeks of their referral, or seen immediately for a brief evaluation without a referral.

Of 1,036 patients who were assessed in the clinic during the study period, 660 patients were reevaluated 6-12 months after visiting the clinic. The patients were divided into those who were referred for further care in the clinic (331 patients) and those referred for further care outside of the clinic (329 patients). The average age of the patients was 50 years, and the average duration of symptoms was 24 years; the average pain rating on the visual analog scale of 0-100 mm was 54 mm (Ann. Rheum. Dis. 2012;71:363-8).

At a 6- to 12-month follow-up visit, 75% of the initial diagnoses that had been made at the clinic proved to be correct, the researchers said. "This indicates high reliability of these initial categorizations by an experienced rheumatologist, which often have to be made within only a few minutes, compared with a later and mostly ‘criteria-based’ classification," they said.

Of the patients who were referred for follow-up in the clinic, 213 returned for additional care and 118 did not return. Overall, 90% of those who returned for additional care received treatment depending on their diagnoses, with 25%-73% receiving disease-modifying antirheumatic drugs, 1%-25% receiving biologics, *5%-56% receiving glucocorticoids, and 2%-17% receiving physiotherapy. Of those who did not return for additional care (but were contacted later by phone), 38% said they received additional therapy at their initial visit. Of these, 42% received NSAIDs, 16% received biologics, 13% received synthetic DMARDs or physiotherapy, and 4% received glucocorticoids.

Of the 329 who were reached for follow-up after 6-12 months, 60% reported that their medical problems were "fully resolved," whereas approximately 40% said they were receiving additional medical care.

Approximately one-third of the patients were referred to the clinic because of suspected RA, but their median symptom duration of 9 months was beyond the ideal window of opportunity for effective early treatment (which should be within the first 3 months), the researchers noted.

Men were diagnosed with spondyloarthropathy more often than women, whereas women were more often diagnosed with osteoarthritis.

Also, "no difference in the frequency of final diagnosis of an inflammatory rheumatic disease between physician and self-referred individuals was apparent," the researchers said.

The study findings were limited by the potential unreliability of telephone interviews. But the results suggest that the IAC model is effective for reducing wait times for seeing a rheumatologist, and that the majority of the diagnoses made in this setting were accurate, the researchers said.

"Despite the short time of interaction between patient and rheumatologist at the time of the visit to the IAC, complaints about insufficient attention were very rare," the researchers added. "Apparently, patients appreciated the fact that they had an immediate opportunity to discuss their problems with a specialist, albeit for a short time, and to receive an initial diagnostic assessment and therapeutic recommendations," they said.

Dr. Gärtner and colleagues had no financial conflicts to disclose.

* Correction, 3/2/2012: An earlier version of this story incorrectly reported the percentages of returning patients who received glucocorticoids.

RIO GRANDE, P.R. – Langerhans cell histiocytosis can be benign and self-limited, or a disseminated disease with the potential for significant morbidity and death, said Dr. Anthony J. Mancini.

The mortality risk depends on whether high-risk organs such as the liver or spleen are involved, as well as the early response to treatment, said Dr. Mancini, professor of pediatrics and dermatology at Northwestern University and Children’s Memorial Hospital in Chicago.

Photos courtesy Dr. Anthony Mancini

Langerhans cell histiocytosis (LCH) was one of five pediatric dermatology diagnoses Dr. Mancini urged dermatologists at the annual Caribbean Dermatology Symposium not to miss. Prompt identification of these conditions can improve young patients’ outcomes and reduce the risk for complications later, he said.

The clinical diagnosis of LCH in infants and children includes scaly erythematous seborrheic-like dermatitis, brown or red papules that may be lichenoid, and erythema in skin fold areas including the groin and the anterior neck folds, often with punctate erosions, he noted. Petechiae may be present, and crusted papules on the palms and soles are occasionally seen in young children.

Histopathology of LCH shows a granulomatous infiltrate that is epidermotropic, and the presence of positive CD1a or CD207 staining confirms the diagnosis, he said. An important distinction between LCH and streptococcal intertrigo: The strep responds rapidly to antibiotics and the erosive changes are more diffuse rather than focal.

Kawasaki Disease

"The most feared complication of Kawasaki disease (KD) is that of coronary artery aneurysm," said Dr. Mancini. "So it is very important to think about this disorder and get a rapid diagnosis," he said. The diagnosis is purely clinical, he noted, without the availability of a confirmatory diagnostic test at this time. Therefore, "have a high index of suspicion" for this disorder, he said.

Clinical criteria for KD include oropharyngeal changes, extremity changes, and a polymorphous skin eruption. Common prodromal symptoms may include irritability, vomiting, anorexia, cough, diarrhea, abdominal pain, and joint pain. "These kids appear sick," Dr. Mancini said.

Skin findings in KD may take on several morphologies, including morbilliform, urticarial, serum sickness-like, or even pustular.

One key finding that is suggestive of KD: Accentuation of erythema in skin folds, especially in the form of perineal desquamation, he said. However, blisters and purpura are not typically associated with the disorder.

Congenital Immunodeficiency

"In many patients, skin manifestations may be the presenting finding" of congenital immunodeficiency, Dr. Mancini said. In a recent study of 128 patients with primary immunodeficiency, 48% had skin manifestations, and these were the presenting feature in 39% with total PID and 82% of those with skin lesions (Pediatr. Dermatol. 2011;28;494-501).

Consider congenital immunodeficiency (CID) in cases of severe atopic or seborrheic dermatitis, intertrigo, or erythroderma that are resistant to therapy, said Dr. Mancini. Growth failure, alopecia, and recurrent infections (especially with unusual organisms) also can be signs of CID.

Graft vs. host disease (GVHD) in a skin biopsy increases suspicion for CID, he added.

An initial evaluation for suspected CID should include a complete blood count, quantitative immunoglobulins, mitogen stimulation assay, tetanus titer, T- and B-cell flow cytometry, and nitroblue tetrazolium or chronic granulomatous disease flow assay, said Dr. Mancini.

There are many congenital immunodeficiencies that may present with skin findings, including Wiskott-Aldrich syndrome, chronic mucocutaneous candidiasis, severe combined immunodeficiency, and leukocyte adhesion deficiency.

Drug Hypersensitivity Syndrome (DRESS)

Also known as Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS), drug hypersensitivity tends to occur from 3-8 weeks after starting a particular medication, said Dr. Mancini. A skin rash is one of the most common findings, occurring in 77% to 100% of patients, he said. Facial edema is common, especially in the periorbital area. DRESS also can include fever, lymph node enlargement, and internal organ involvement.

Other clinical symptoms include conjunctivitis, pharyngitis, vomiting, and diarrhea. Telltale hematology findings indicative of DRESS include atypical lymphocytes and eosinophilia; pancytopenia occasionally appears.

The first line of defense is recognition and withdrawal from the drug. Serial monitoring of liver function studies is vital, given the fulminant hepatitis that can ensue, Dr. Mancini said. Treatment with systemic steroids and/or intravenous immunoglobulin is occasionally used, albeit controversially, he noted. Complete resolution of symptoms may take as long as 6 months.

Neonatal Herpes

The risk for neonatal infection with herpes simplex virus (HSV) is highest when the mother has active genital herpes at the time of delivery, Dr. Mancini said. If left untreated, the mortality rate for central nervous system or disseminated neonatal herpes is estimated at 50%-90%, so rapid recognition and diagnosis is vital, he said. The central nervous system, liver, lungs, adrenal glands, and bone marrow are important sites of potential involvement when the process disseminates, he added.

The classic skin presentation of neonatal HSV infection is vesicles and vesiculopustules that may be grouped on a red base or may become hemorrhagic. Bullae, widespread skin erosions, and polycyclic patches occasionally may be seen, and scarring may be present. Prompt evaluation is important, and intravenous acyclovir should be immediately instituted if the diagnosis of neonatal HSV is being considered.

Dr. Mancini said he had no financial conflicts to disclose.

RIO GRANDE, P.R. – Langerhans cell histiocytosis can be benign and self-limited, or a disseminated disease with the potential for significant morbidity and death, said Dr. Anthony J. Mancini.

The mortality risk depends on whether high-risk organs such as the liver or spleen are involved, as well as the early response to treatment, said Dr. Mancini, professor of pediatrics and dermatology at Northwestern University and Children’s Memorial Hospital in Chicago.

Photos courtesy Dr. Anthony Mancini

Langerhans cell histiocytosis (LCH) was one of five pediatric dermatology diagnoses Dr. Mancini urged dermatologists at the annual Caribbean Dermatology Symposium not to miss. Prompt identification of these conditions can improve young patients’ outcomes and reduce the risk for complications later, he said.

The clinical diagnosis of LCH in infants and children includes scaly erythematous seborrheic-like dermatitis, brown or red papules that may be lichenoid, and erythema in skin fold areas including the groin and the anterior neck folds, often with punctate erosions, he noted. Petechiae may be present, and crusted papules on the palms and soles are occasionally seen in young children.

Histopathology of LCH shows a granulomatous infiltrate that is epidermotropic, and the presence of positive CD1a or CD207 staining confirms the diagnosis, he said. An important distinction between LCH and streptococcal intertrigo: The strep responds rapidly to antibiotics and the erosive changes are more diffuse rather than focal.

Kawasaki Disease

"The most feared complication of Kawasaki disease (KD) is that of coronary artery aneurysm," said Dr. Mancini. "So it is very important to think about this disorder and get a rapid diagnosis," he said. The diagnosis is purely clinical, he noted, without the availability of a confirmatory diagnostic test at this time. Therefore, "have a high index of suspicion" for this disorder, he said.

Clinical criteria for KD include oropharyngeal changes, extremity changes, and a polymorphous skin eruption. Common prodromal symptoms may include irritability, vomiting, anorexia, cough, diarrhea, abdominal pain, and joint pain. "These kids appear sick," Dr. Mancini said.

Skin findings in KD may take on several morphologies, including morbilliform, urticarial, serum sickness-like, or even pustular.

One key finding that is suggestive of KD: Accentuation of erythema in skin folds, especially in the form of perineal desquamation, he said. However, blisters and purpura are not typically associated with the disorder.

Congenital Immunodeficiency

"In many patients, skin manifestations may be the presenting finding" of congenital immunodeficiency, Dr. Mancini said. In a recent study of 128 patients with primary immunodeficiency, 48% had skin manifestations, and these were the presenting feature in 39% with total PID and 82% of those with skin lesions (Pediatr. Dermatol. 2011;28;494-501).

Consider congenital immunodeficiency (CID) in cases of severe atopic or seborrheic dermatitis, intertrigo, or erythroderma that are resistant to therapy, said Dr. Mancini. Growth failure, alopecia, and recurrent infections (especially with unusual organisms) also can be signs of CID.

Graft vs. host disease (GVHD) in a skin biopsy increases suspicion for CID, he added.

An initial evaluation for suspected CID should include a complete blood count, quantitative immunoglobulins, mitogen stimulation assay, tetanus titer, T- and B-cell flow cytometry, and nitroblue tetrazolium or chronic granulomatous disease flow assay, said Dr. Mancini.

There are many congenital immunodeficiencies that may present with skin findings, including Wiskott-Aldrich syndrome, chronic mucocutaneous candidiasis, severe combined immunodeficiency, and leukocyte adhesion deficiency.

Drug Hypersensitivity Syndrome (DRESS)

Also known as Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS), drug hypersensitivity tends to occur from 3-8 weeks after starting a particular medication, said Dr. Mancini. A skin rash is one of the most common findings, occurring in 77% to 100% of patients, he said. Facial edema is common, especially in the periorbital area. DRESS also can include fever, lymph node enlargement, and internal organ involvement.

Other clinical symptoms include conjunctivitis, pharyngitis, vomiting, and diarrhea. Telltale hematology findings indicative of DRESS include atypical lymphocytes and eosinophilia; pancytopenia occasionally appears.

The first line of defense is recognition and withdrawal from the drug. Serial monitoring of liver function studies is vital, given the fulminant hepatitis that can ensue, Dr. Mancini said. Treatment with systemic steroids and/or intravenous immunoglobulin is occasionally used, albeit controversially, he noted. Complete resolution of symptoms may take as long as 6 months.

Neonatal Herpes

The risk for neonatal infection with herpes simplex virus (HSV) is highest when the mother has active genital herpes at the time of delivery, Dr. Mancini said. If left untreated, the mortality rate for central nervous system or disseminated neonatal herpes is estimated at 50%-90%, so rapid recognition and diagnosis is vital, he said. The central nervous system, liver, lungs, adrenal glands, and bone marrow are important sites of potential involvement when the process disseminates, he added.

The classic skin presentation of neonatal HSV infection is vesicles and vesiculopustules that may be grouped on a red base or may become hemorrhagic. Bullae, widespread skin erosions, and polycyclic patches occasionally may be seen, and scarring may be present. Prompt evaluation is important, and intravenous acyclovir should be immediately instituted if the diagnosis of neonatal HSV is being considered.

Dr. Mancini said he had no financial conflicts to disclose.

RIO GRANDE, P.R. – Langerhans cell histiocytosis can be benign and self-limited, or a disseminated disease with the potential for significant morbidity and death, said Dr. Anthony J. Mancini.

The mortality risk depends on whether high-risk organs such as the liver or spleen are involved, as well as the early response to treatment, said Dr. Mancini, professor of pediatrics and dermatology at Northwestern University and Children’s Memorial Hospital in Chicago.

Photos courtesy Dr. Anthony Mancini

Langerhans cell histiocytosis (LCH) was one of five pediatric dermatology diagnoses Dr. Mancini urged dermatologists at the annual Caribbean Dermatology Symposium not to miss. Prompt identification of these conditions can improve young patients’ outcomes and reduce the risk for complications later, he said.

The clinical diagnosis of LCH in infants and children includes scaly erythematous seborrheic-like dermatitis, brown or red papules that may be lichenoid, and erythema in skin fold areas including the groin and the anterior neck folds, often with punctate erosions, he noted. Petechiae may be present, and crusted papules on the palms and soles are occasionally seen in young children.

Histopathology of LCH shows a granulomatous infiltrate that is epidermotropic, and the presence of positive CD1a or CD207 staining confirms the diagnosis, he said. An important distinction between LCH and streptococcal intertrigo: The strep responds rapidly to antibiotics and the erosive changes are more diffuse rather than focal.

Kawasaki Disease

"The most feared complication of Kawasaki disease (KD) is that of coronary artery aneurysm," said Dr. Mancini. "So it is very important to think about this disorder and get a rapid diagnosis," he said. The diagnosis is purely clinical, he noted, without the availability of a confirmatory diagnostic test at this time. Therefore, "have a high index of suspicion" for this disorder, he said.

Clinical criteria for KD include oropharyngeal changes, extremity changes, and a polymorphous skin eruption. Common prodromal symptoms may include irritability, vomiting, anorexia, cough, diarrhea, abdominal pain, and joint pain. "These kids appear sick," Dr. Mancini said.

Skin findings in KD may take on several morphologies, including morbilliform, urticarial, serum sickness-like, or even pustular.

One key finding that is suggestive of KD: Accentuation of erythema in skin folds, especially in the form of perineal desquamation, he said. However, blisters and purpura are not typically associated with the disorder.

Congenital Immunodeficiency

"In many patients, skin manifestations may be the presenting finding" of congenital immunodeficiency, Dr. Mancini said. In a recent study of 128 patients with primary immunodeficiency, 48% had skin manifestations, and these were the presenting feature in 39% with total PID and 82% of those with skin lesions (Pediatr. Dermatol. 2011;28;494-501).

Consider congenital immunodeficiency (CID) in cases of severe atopic or seborrheic dermatitis, intertrigo, or erythroderma that are resistant to therapy, said Dr. Mancini. Growth failure, alopecia, and recurrent infections (especially with unusual organisms) also can be signs of CID.

Graft vs. host disease (GVHD) in a skin biopsy increases suspicion for CID, he added.

An initial evaluation for suspected CID should include a complete blood count, quantitative immunoglobulins, mitogen stimulation assay, tetanus titer, T- and B-cell flow cytometry, and nitroblue tetrazolium or chronic granulomatous disease flow assay, said Dr. Mancini.

There are many congenital immunodeficiencies that may present with skin findings, including Wiskott-Aldrich syndrome, chronic mucocutaneous candidiasis, severe combined immunodeficiency, and leukocyte adhesion deficiency.

Drug Hypersensitivity Syndrome (DRESS)

Also known as Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS), drug hypersensitivity tends to occur from 3-8 weeks after starting a particular medication, said Dr. Mancini. A skin rash is one of the most common findings, occurring in 77% to 100% of patients, he said. Facial edema is common, especially in the periorbital area. DRESS also can include fever, lymph node enlargement, and internal organ involvement.

Other clinical symptoms include conjunctivitis, pharyngitis, vomiting, and diarrhea. Telltale hematology findings indicative of DRESS include atypical lymphocytes and eosinophilia; pancytopenia occasionally appears.

The first line of defense is recognition and withdrawal from the drug. Serial monitoring of liver function studies is vital, given the fulminant hepatitis that can ensue, Dr. Mancini said. Treatment with systemic steroids and/or intravenous immunoglobulin is occasionally used, albeit controversially, he noted. Complete resolution of symptoms may take as long as 6 months.

Neonatal Herpes

The risk for neonatal infection with herpes simplex virus (HSV) is highest when the mother has active genital herpes at the time of delivery, Dr. Mancini said. If left untreated, the mortality rate for central nervous system or disseminated neonatal herpes is estimated at 50%-90%, so rapid recognition and diagnosis is vital, he said. The central nervous system, liver, lungs, adrenal glands, and bone marrow are important sites of potential involvement when the process disseminates, he added.

The classic skin presentation of neonatal HSV infection is vesicles and vesiculopustules that may be grouped on a red base or may become hemorrhagic. Bullae, widespread skin erosions, and polycyclic patches occasionally may be seen, and scarring may be present. Prompt evaluation is important, and intravenous acyclovir should be immediately instituted if the diagnosis of neonatal HSV is being considered.

Dr. Mancini said he had no financial conflicts to disclose.

Levels of air pollution that fall within the amounts deemed safe in current U.S. standards for air quality were associated with a significant increase the risk for acute ischemic stroke after short-term exposure and accelerated cognitive decline after long-term exposure in two separate studies.

Previous studies of the effects of ambient fine particulate matter air pollution, defined as particulate matter less than 2.5 mcm in diameter (PM_2.5), on ischemic stroke risk have not provided unequivocal results and have not adequately examined the etiology of such strokes. Studies of the effects of air pollution on cognitive decline are even rarer, and none have assessed the longitudinal effects of PM_2.5 on cognition, according to the authors of the reports, which were published online Feb. 13 in Archives of Internal Medicine.

©Sergiy Serdyuk/istockphoto.com

Gregory Wellenius, Sc.D., of Brown University, Providence, R.I., and his colleagues reviewed data from patients admitted to Beth Israel Deaconess Hospital, Boston, with ischemic stroke between 1999 and 2008. They used a time-stratified case-crossover study design to examine the association between ischemic stroke risk and PM_2.5 levels in the hours and days before each stroke (Arch. Intern. Med. 2012;172:229-34).

Overall, a 24-hour period of exposure to "moderate" air quality (as defined by the Environmental Protection Agency Air Quality Index) raised the odds of having a stroke by 34%, compared with a 24-hour period of "good" air quality. The estimated odds ratio of ischemic stroke was 1.11 for each interquartile range increase in pollution levels (defined as 6.4 mcg/m³).

The increased stroke risk was highest within 12-14 hours of exposure to PM_2.5 and was most strongly associated with traffic-related pollution, the researchers noted.

The mean age of the patients was 73 years; 55% were white, and 68% were women. The most common determined causes of the strokes were small-vessel strokes (26%), cardioembolism (25%), and large-artery atherosclerosis (20%).

When the patients were examined by clinical subgroups, increased pollution levels were associated with stroke in patients with large-artery atherosclerosis (odds ratio 1.24) and small-vessel strokes (1.19), but not in patients with strokes due to cardioembolism. There was no evidence that comorbid diabetes, hypertension, atrial fibrillation, or a history of stroke increased susceptibility to pollution-related strokes, the researchers noted.

Although the observed relative risk of stroke was modest, the findings suggest that "if the association between stroke and pollution is causal and a linear dose-response occurs, a 2-microgram/m³ reduction in mean PM_2.5 levels (approximately 20%) during this time period might have averted approximately 6,100 of the 184,000 stroke hospitalizations observed in the U.S. Northeast region in 2007 alone," the researchers said.

If pollution levels decline, further data on stroke timing and patient demographics can be used to show whether pollution control impacts stroke risk, they added.

In a related finding, Jennifer Weuve, Sc.D., of Rush University Medical Center, Chicago, and colleagues found that long-term exposure to both coarse and fine PM was significantly associated with faster cognitive decline in older adults. They reviewed data from 19,409 women aged 70-81 years in the Nurses’ Health Study Cognitive Cohort and used geographic information to estimate short-term exposure (1 month) and long-term exposure (7-14 years) before the women underwent baseline cognitive testing.

Overall, the 2-year cognitive decline as measured by a global score was 0.020 standard units worse per 10 mcg/m³ increment of exposure to coarse PM, defined as particles from 2.5-10 mcm in diameter (PM_2.5-10), and 0.018 standard units worse per 10 microgram/m³ increment of exposure to PM_2.5, the researchers said. The average age at the time of baseline cognitive assessment was 74 years (Arch. Intern. Med. 2012;172:219-27).

The trend of cognitive decline across quintiles of pollution exposure bordered on statistical significance. But when air pollution exposure was treated as a continuous variable, both the long-term PM_2.5 exposure and PM_2.5 exposure in the 5 years before the initial cognitive assessment were associated with significantly worse decline in global cognition. "Decline in the individual cognitive domains generally was more strongly predicted by long-term than recent exposure to PM_2.5," the investigators wrote.

The results were limited by indirect estimates of pollution exposure. But the findings support data from previous studies showing that ambient particles in the air may have a negative effect on cognition, they said.

The associations with cognitive decline were observed in women with levels of PM exposure typical in many areas of the United States, the researchers said. "Therefore, if our findings are confirmed in other research, air pollution reduction is a potential means for reducing the future population burden of age-related cognitive decline, and eventually, dementia."

Dr. Wellenius’s study was funded by the National Institutes of Health and the Environmental Protection Agency. Dr. Weuve’s study was funded by the National Institute of Environmental Health Sciences and the EPA. The Nurses Health Study is separately funded by the National Cancer Institute. None of the authors of either study had relevant financial disclosures.

Levels of air pollution that fall within the amounts deemed safe in current U.S. standards for air quality were associated with a significant increase the risk for acute ischemic stroke after short-term exposure and accelerated cognitive decline after long-term exposure in two separate studies.

Previous studies of the effects of ambient fine particulate matter air pollution, defined as particulate matter less than 2.5 mcm in diameter (PM_2.5), on ischemic stroke risk have not provided unequivocal results and have not adequately examined the etiology of such strokes. Studies of the effects of air pollution on cognitive decline are even rarer, and none have assessed the longitudinal effects of PM_2.5 on cognition, according to the authors of the reports, which were published online Feb. 13 in Archives of Internal Medicine.

©Sergiy Serdyuk/istockphoto.com

Gregory Wellenius, Sc.D., of Brown University, Providence, R.I., and his colleagues reviewed data from patients admitted to Beth Israel Deaconess Hospital, Boston, with ischemic stroke between 1999 and 2008. They used a time-stratified case-crossover study design to examine the association between ischemic stroke risk and PM_2.5 levels in the hours and days before each stroke (Arch. Intern. Med. 2012;172:229-34).

Overall, a 24-hour period of exposure to "moderate" air quality (as defined by the Environmental Protection Agency Air Quality Index) raised the odds of having a stroke by 34%, compared with a 24-hour period of "good" air quality. The estimated odds ratio of ischemic stroke was 1.11 for each interquartile range increase in pollution levels (defined as 6.4 mcg/m³).

The increased stroke risk was highest within 12-14 hours of exposure to PM_2.5 and was most strongly associated with traffic-related pollution, the researchers noted.

The mean age of the patients was 73 years; 55% were white, and 68% were women. The most common determined causes of the strokes were small-vessel strokes (26%), cardioembolism (25%), and large-artery atherosclerosis (20%).

When the patients were examined by clinical subgroups, increased pollution levels were associated with stroke in patients with large-artery atherosclerosis (odds ratio 1.24) and small-vessel strokes (1.19), but not in patients with strokes due to cardioembolism. There was no evidence that comorbid diabetes, hypertension, atrial fibrillation, or a history of stroke increased susceptibility to pollution-related strokes, the researchers noted.

Although the observed relative risk of stroke was modest, the findings suggest that "if the association between stroke and pollution is causal and a linear dose-response occurs, a 2-microgram/m³ reduction in mean PM_2.5 levels (approximately 20%) during this time period might have averted approximately 6,100 of the 184,000 stroke hospitalizations observed in the U.S. Northeast region in 2007 alone," the researchers said.

If pollution levels decline, further data on stroke timing and patient demographics can be used to show whether pollution control impacts stroke risk, they added.

In a related finding, Jennifer Weuve, Sc.D., of Rush University Medical Center, Chicago, and colleagues found that long-term exposure to both coarse and fine PM was significantly associated with faster cognitive decline in older adults. They reviewed data from 19,409 women aged 70-81 years in the Nurses’ Health Study Cognitive Cohort and used geographic information to estimate short-term exposure (1 month) and long-term exposure (7-14 years) before the women underwent baseline cognitive testing.

Overall, the 2-year cognitive decline as measured by a global score was 0.020 standard units worse per 10 mcg/m³ increment of exposure to coarse PM, defined as particles from 2.5-10 mcm in diameter (PM_2.5-10), and 0.018 standard units worse per 10 microgram/m³ increment of exposure to PM_2.5, the researchers said. The average age at the time of baseline cognitive assessment was 74 years (Arch. Intern. Med. 2012;172:219-27).

The trend of cognitive decline across quintiles of pollution exposure bordered on statistical significance. But when air pollution exposure was treated as a continuous variable, both the long-term PM_2.5 exposure and PM_2.5 exposure in the 5 years before the initial cognitive assessment were associated with significantly worse decline in global cognition. "Decline in the individual cognitive domains generally was more strongly predicted by long-term than recent exposure to PM_2.5," the investigators wrote.

The results were limited by indirect estimates of pollution exposure. But the findings support data from previous studies showing that ambient particles in the air may have a negative effect on cognition, they said.

The associations with cognitive decline were observed in women with levels of PM exposure typical in many areas of the United States, the researchers said. "Therefore, if our findings are confirmed in other research, air pollution reduction is a potential means for reducing the future population burden of age-related cognitive decline, and eventually, dementia."

Dr. Wellenius’s study was funded by the National Institutes of Health and the Environmental Protection Agency. Dr. Weuve’s study was funded by the National Institute of Environmental Health Sciences and the EPA. The Nurses Health Study is separately funded by the National Cancer Institute. None of the authors of either study had relevant financial disclosures.

Levels of air pollution that fall within the amounts deemed safe in current U.S. standards for air quality were associated with a significant increase the risk for acute ischemic stroke after short-term exposure and accelerated cognitive decline after long-term exposure in two separate studies.

Previous studies of the effects of ambient fine particulate matter air pollution, defined as particulate matter less than 2.5 mcm in diameter (PM_2.5), on ischemic stroke risk have not provided unequivocal results and have not adequately examined the etiology of such strokes. Studies of the effects of air pollution on cognitive decline are even rarer, and none have assessed the longitudinal effects of PM_2.5 on cognition, according to the authors of the reports, which were published online Feb. 13 in Archives of Internal Medicine.

©Sergiy Serdyuk/istockphoto.com

Gregory Wellenius, Sc.D., of Brown University, Providence, R.I., and his colleagues reviewed data from patients admitted to Beth Israel Deaconess Hospital, Boston, with ischemic stroke between 1999 and 2008. They used a time-stratified case-crossover study design to examine the association between ischemic stroke risk and PM_2.5 levels in the hours and days before each stroke (Arch. Intern. Med. 2012;172:229-34).

Overall, a 24-hour period of exposure to "moderate" air quality (as defined by the Environmental Protection Agency Air Quality Index) raised the odds of having a stroke by 34%, compared with a 24-hour period of "good" air quality. The estimated odds ratio of ischemic stroke was 1.11 for each interquartile range increase in pollution levels (defined as 6.4 mcg/m³).

The increased stroke risk was highest within 12-14 hours of exposure to PM_2.5 and was most strongly associated with traffic-related pollution, the researchers noted.

The mean age of the patients was 73 years; 55% were white, and 68% were women. The most common determined causes of the strokes were small-vessel strokes (26%), cardioembolism (25%), and large-artery atherosclerosis (20%).

When the patients were examined by clinical subgroups, increased pollution levels were associated with stroke in patients with large-artery atherosclerosis (odds ratio 1.24) and small-vessel strokes (1.19), but not in patients with strokes due to cardioembolism. There was no evidence that comorbid diabetes, hypertension, atrial fibrillation, or a history of stroke increased susceptibility to pollution-related strokes, the researchers noted.

Although the observed relative risk of stroke was modest, the findings suggest that "if the association between stroke and pollution is causal and a linear dose-response occurs, a 2-microgram/m³ reduction in mean PM_2.5 levels (approximately 20%) during this time period might have averted approximately 6,100 of the 184,000 stroke hospitalizations observed in the U.S. Northeast region in 2007 alone," the researchers said.

If pollution levels decline, further data on stroke timing and patient demographics can be used to show whether pollution control impacts stroke risk, they added.

In a related finding, Jennifer Weuve, Sc.D., of Rush University Medical Center, Chicago, and colleagues found that long-term exposure to both coarse and fine PM was significantly associated with faster cognitive decline in older adults. They reviewed data from 19,409 women aged 70-81 years in the Nurses’ Health Study Cognitive Cohort and used geographic information to estimate short-term exposure (1 month) and long-term exposure (7-14 years) before the women underwent baseline cognitive testing.

Overall, the 2-year cognitive decline as measured by a global score was 0.020 standard units worse per 10 mcg/m³ increment of exposure to coarse PM, defined as particles from 2.5-10 mcm in diameter (PM_2.5-10), and 0.018 standard units worse per 10 microgram/m³ increment of exposure to PM_2.5, the researchers said. The average age at the time of baseline cognitive assessment was 74 years (Arch. Intern. Med. 2012;172:219-27).

The trend of cognitive decline across quintiles of pollution exposure bordered on statistical significance. But when air pollution exposure was treated as a continuous variable, both the long-term PM_2.5 exposure and PM_2.5 exposure in the 5 years before the initial cognitive assessment were associated with significantly worse decline in global cognition. "Decline in the individual cognitive domains generally was more strongly predicted by long-term than recent exposure to PM_2.5," the investigators wrote.

The results were limited by indirect estimates of pollution exposure. But the findings support data from previous studies showing that ambient particles in the air may have a negative effect on cognition, they said.

The associations with cognitive decline were observed in women with levels of PM exposure typical in many areas of the United States, the researchers said. "Therefore, if our findings are confirmed in other research, air pollution reduction is a potential means for reducing the future population burden of age-related cognitive decline, and eventually, dementia."

Dr. Wellenius’s study was funded by the National Institutes of Health and the Environmental Protection Agency. Dr. Weuve’s study was funded by the National Institute of Environmental Health Sciences and the EPA. The Nurses Health Study is separately funded by the National Cancer Institute. None of the authors of either study had relevant financial disclosures.