Individuals who take cholesterol-lowering statins before being hospitalized with pneumonia appear less likely to die within 90 days afterward, according to a new report.

In the United States and Europe, pneumonia hospitalization rates have increased 20 percent to 50 percent over the past decade, according to background information in the article. About 10 percent to 15 percent of those with pneumonia die from the disease. A recent review article indicated that statins may benefit patients with sepsis (infection of the bloodstream) or bacteremia (presence of bacteria in the bloodstream), possibly due to the medications’ anti-clotting, anti-inflammatory or immune-modifying properties.

Reimar W. Thomsen, M.D., Ph.D., of Aarhus University and Aalborg Hospital, Aalborg, Denmark, and colleagues reviewed data from 29,900 adults hospitalized with pneumonia between 1997 and 2004. Of these, 1,371 (4.6 percent) were taking statins at the time.

“Mortality [death] among statin users was lower than among non-users: 10.3 percent vs. 15.7 percent after 30 days and 16.8 percent vs. 22.4 percent after 90 days,” the authors write. The lowest relative death rate associated with statins was observed in patients older than 80 and in those with bacteremia. “The differences became apparent during the first few weeks of hospitalization, a period associated with a high number of pneumonia-related deaths, and they increased only minimally between 30 and 90 days after admission, which suggests that statin use is beneficial primarily in the early phase of infection.”

Previous statin use, or the use of any other preventive medication for cardiovascular health, was not associated with a reduced death rate from pneumonia.

“Several biological mechanisms may explain our results,” the authors write. Statins change the immune response, beneficially affect processes associated with blood clotting and inflammation and inhibit dysfunction in blood vessels. These effects may especially benefit patients with sepsis and bacteremia, which are associated with early death from pneumonia.

“Our study adds to the accumulating evidence that statin use is associated with improved prognosis after severe infections,” the authors write. “The decrease in mortality associated with statin use seems to be substantial in patients with pneumonia requiring hospital admission. Randomized trials are needed to examine causality of the associations found in observational studies. Given the availability of statins, with their relatively low cost and mild adverse effects, positive results of statin therapy trials in patients with pneumonia would have substantial clinical and public health implications.”

This study was supported by the Western Danish Research Forum for Health Sciences and by the Clinical Epidemiological Research Foundation at Aarhus University Hospital, Aarhus, Denmark.

Editorial: Combining Statins and Antibiotics May Prove Effective Against Infection

“These data suggest a substantial decrease in mortality with statin use,” writes Kasturi Haldar, Ph.D., of the University of Notre Dame, South Bend., Ind., in an accompanying editorial.

The resulting data “raises the question of whether statins should be used to improve anti-infective therapy. They are not optimal for treating acute infection because it takes days to achieve the desirable concentrations in plasma,” Dr. Haldar continues.

“However, because statins target the host, drug resistance, a major problem in treating bacterial infections, is not likely to develop. Thus, it may be useful to consider clinical research testing of combinations of statins with existing antibiotic agents to evaluate whether it is possible to develop optimized combination therapies effective against both acute and persistent infections.”

This editorial was supported by a Department of Veterans Affairs Merit Award, Great Lakes Research Center of Excellence and by the National Institutes of Health.

1. Reimar W. Thomsen; Anders Riis; Jette B. Kornum; Steffen Christensen; Soren P. Johnsen; Henrik T. Sorensen. Preadmission Use of Statins and Outcomes After Hospitalization With Pneumonia: Population-Based Cohort Study of 29 900 Patients. Arch Intern Med., 2008;168(19):2081-2087 [link]

Adapted from materials provided by JAMA and Archives Journals.

Adding corticosteroids to traditional antimicrobial therapy might help people with pneumonia recover more quickly than with antibiotics alone, UT Southwestern Medical Center scientists have found.

Unlike the anabolic steroids used to bulk up muscle, corticosteroids are often used to treat inflammation related to infectious diseases, such as bacterial meningitis. Used against other infectious diseases, however, steroid therapy has been shown to be ineffective or even harmful.

In a study available online and in a future issue of the Journal of Infectious Diseases, researchers at UT Southwestern show that mice infected with a type of severe bacterial pneumonia and subsequently treated with steroids and antibiotics recovered faster and had far less inflammation in their lungs than mice treated with antibiotics alone.

“Some people might think that if you give steroids, it would counteract the effect of the antibiotic,” said Dr. Robert Hardy, associate professor of internal medicine and pediatrics and the study’s senior author. “But it turns out you need the antibiotic to kill the bug and the steroid to make the inflammation in the lung from the infection get better. The steroids don’t kill the bugs, but they do help restore health.”

Pneumonia is a lung infection typically characterized by breathing difficulties and spread by coughing and sneezing. Symptoms include headache, fever, chills, coughs, chest pain, sore throat and nausea. Pneumonia caused by the Mycoplasma pneumoniae bacterium is generally a less severe form of the disease that can occur in any age group. It accounts for 20 percent to 30 percent of all community-acquired pneumonia cases.

In the current study, mice infected with the M pneumoniae bacterium were treated daily with a placebo, an antibiotic, a steroid, or a combination of the antibiotic and steroid in order to investigate the effect on M pneumoniae-induced airway inflammation. The animals were then evaluated after one, three and six days of therapy.

“It turns out that the group that got both the antibiotic and the steroids did the best,” Dr. Hardy said. “The inflammation in their lungs got significantly better.”

Although antimicrobials remain the primary therapy for M pneumoniae infection, there have been several reports in recent years about physicians adding steroids to the treatment regimen of patients with severe cases, Dr. Hardy said. The problem, he said, is that those were individual case reports.

“They never had a control group, so it was impossible to tell what impact the addition of steroids had on recovery,” he said.

The new findings not only suggest that giving antibiotics with steroids can help individuals with pneumonia get better faster, but also suggest a potentially more effective therapy for someone in the midst of an asthma attack due to M pneumoniae infection. Up to 20 percent of asthma attacks in children and adults have been shown to be triggered by this bacterium.

Dr. Hardy said it’s too early to recommend steroids as standard treatment for people with this type of bacterial pneumonia, but the work does support the need for a clinical trial.

“Or if there are very sick patients, this combination treatment doesn’t seem to worsen the disease,” he said. “The good thing about our results is the data alone support moving on to a clinical study.”

Research presented at the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF), found that coronary heart disease (CHD) symptoms presented in the context of a stressful life event were identified as psychogenic in origin when presented by women and organic in origin when presented by men. The study could help explain why there is often a delay in the assessment of women with heart disease.

“We know that there is a delay in diagnosing CHD in women and this is an important step forward in understanding why,” said Alexandra J. Lansky, M.D., director of the Women’s Health Initiative at CRF, director of Clinical Services at the Center for Interventional Vascular Therapy, a cardiologist at NewYork-Presbyterian Hospital/Columbia University Medical Center, and an associate professor of clinical medicine at Columbia University College of Physicians and Surgeons.

The investigation – “Gender Bias in the Diagnosis, Treatment, and Interpretation of CHD Symptoms: Two Experimental Studies with Internists and Family Physicians,” was led by Gabrielle R. Chiaramonte, Ph.D., postdoctoral associate at the Weill Medical College of Cornell University and Clinical Fellow at NewYork-Presbyterian Hospital. The study examined the effects of patients’ gender and the context of how CHD symptoms are presented (with/without mention of life stressors and anxiety) on primary care physicians’ patient evaluations.

“The selection of internists and family physicians was particularly relevant as they are generally the first medical professionals to assess patients’ symptoms and to make treatment recommendations. A greater understanding of factors contributing to gender bias in CHD assessment in this group would thus be especially meaningful,” said Dr. Chiarmonte.

The researchers hypothesized that the presence of life stressors/anxiety would shift the interpretation of women’s – but not men’s – CHD symptoms, so that these would be perceived to have a psychogenic etiology.

“The greater prevalence of anxiety disorders in women, along with the greater likelihood that women will discuss stressors with their physicians, and the overlap of CHD and anxiety symptoms, contribute to this shift in interpretation,” Dr. Chiaramonte said.

In the studies, 87 internists (Study 1) and 143 family physicians (Study 2) read a vignette of a 47-year-old male or a 56-year-old female (by age at equal risk for CHD) presenting a multitude of CHD symptoms and risk factors. Half the vignettes included sentences indicating the patient had recently experienced a life stressor and that they appeared anxious. Each physician read one version of the vignette and then specified a diagnosis, made treatment recommendations, and indicated the etiology of symptoms.

As the investigators predicted, results showed a gender bias when CHD symptoms were presented in the context of stress, with fewer women receiving CHD diagnoses (15% versus 56%), cardiologist referrals (30% versus 62%), and prescriptions of cardiac medication (13% versus 47%) than men. No evidence of a bias was observed when CHD symptoms were presented without the stress. Results also showed that the presence of stress shifted the interpretation of women’s chest pain, shortness of breath and irregular heart rate so that these were thought to have a psychogenic origin. By contrast, men’s symptoms were perceived as organic whether or not stressors were present.

Dr. Chiaramonte stated, “For women, the presence of stress or anxiety drives the interpretation of accompanying symptoms so that symptoms such as chest pain or shortness of breath undergo a ‘meaning shift’ when presented in the context of stress or anxiety and they are perceived as a manifestation of the stress or anxiety and not as CHD symptoms. For men, cardiac symptoms drive the interpretation of accompanying symptoms so that anxiety or stress is perceived (rightly so) as a risk factor for CHD and may in fact augment the CHD assessment. The presence of anxiety or stress in men does not deter from the CHD assessment; for women, it appears to preclude a CHD assessment.”

Dr. Chiaramonte warned that, “Given the overlap of CHD and anxiety symptoms (e.g., chest tightness common in both) and given the higher prevalence of anxiety symptoms or disorders in women, physicians need to be aware of gender differences in symptom presentation and they need to be especially careful to rule out CHD before considering an anxiety diagnosis. In the case of women, anxiety appears to have a pervasive influence on medical judgments regardless of the gender of the health care provider making the evaluations.”

Ronald Friend, Ph.D., co-investigator, Professor of Psychology at Stony Brook University and Oregon Health & Sciences University, School of Nursing, added: “The assessment of women’s CHD is further complicated by evidence that women sometimes present with ‘atypical’ CHD symptoms and that chest pain, a hallmark symptom in men, is less common in women. We recently conducted an additional study with 142 family physicians examining the influence of stress on the assessment of patients presenting atypical CHD symptoms. Results showed a different dynamic in this case: Women were more likely than men to receive a GI rather than a CHD diagnosis regardless of the presence of stress; the addition of stress increased GI diagnoses in both men and women. Given that women are more likely to present with atypical symptoms (and stress), these preliminary results are cause for concern.”

Prior to conducting the two studies reported here, the researchers had tested their hypothesis with 99 first year medical students, 82 third and fourth year medical students, and 122 physician assistant students. The investigators were surprised to find nearly identical results whether the participants surveyed were first year medical students or experienced practicing family physicians and internists.

Dr. Chiaramonte concluded, “The consistent results observed with participants of varying clinical experience attest to the strength of the research and the pervasiveness of the effect. Our results suggest the need for the development of educational initiatives aimed at improving health care providers’ understanding of gender differences in symptom presentation.”

The research team included: Gabrielle R. Chiaramonte, Ph.D., of Weill Medical College of Cornell University/NewYork-Presbyterian Hospital; Ronald Friend, Ph.D., of Stony Brook University and Oregon Health & Sciences University, School of Nursing; Arnold S. Jaffe, Ph.D., and Jeffrey S. Trilling, M.D., of Stony Brook University Medical Center; Gil Weitzman, M.D., B. Robert Meyer, M.D., Susan Evans, Ph.D., and JoAnn Difede, Ph.D., of Weill Medical College of Cornell University/NewYork-Presbyterian Hospital; and Alexandra J. Lansky, M.D., of NewYork-Presbyterian Hospital/Columbia University Medical Center.

About 44 percent of individuals who had bipolar disorder as children continue to have manic episodes as young adults, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals. This rate, along with the severity of the disease at young ages, strongly suggest that bipolar disorder can be continuous from childhood to adulthood, the authors note.

Recent data has demonstrated an enormous increase in the diagnosis of pediatric bipolar disorder, a severe mood disorder involving episodes of mania and depression, according to background information in the article. However, skepticism continues to exist regarding the existence of the condition in children. Given increased media attention to the issue, there is a need to further increase the validity of childhood diagnoses.

Barbara Geller, M.D., and colleagues at Washington University in St. Louis studied 115 children (average age 11.1) diagnosed with bipolar disorder beginning in 1995 to 1998. At the beginning of the study and again during nine follow-up visits conducted over eight years, the children and their parents were interviewed separately about their symptoms, diagnoses, daily cycles of mania and depression and interactions with others.

A total of 108 (93.9 percent) of the children completed the study (average age at follow-up, 18.1 years). During the eight-year follow-up, they spent 60.2 percent of weeks with any mood episodes and 39.6 percent of weeks with episodes of mania. Although 87.8 percent recovered from mania, 73.3 percent relapsed. The researchers also examined the characteristics of children’s second and third episodes of mania and found that like the first episodes, they were characterized by psychosis, daily cycling between mania and depression and a long duration (55.2 weeks for the second and 40 weeks for the third episode).

At the end of the follow-up period, 54 patients were age 18 or older. Of those, 44.4 percent continued to have manic episodes and 35.2 percent had substance use disorders, a rate similar to those diagnosed with bipolar disorder as adults.

“In grown-up subjects with child bipolar disorder I, the 44.4 percent frequency of manic episodes was 13 to 44 times higher than population prevalences, strongly supporting continuity between child and adult bipolar disorder I,” the authors write. “Subjects with child bipolar disorder I who were grown up at the eight-year follow-up constituted approximately half the sample. However, even if all subjects younger than 18 years at the eight-year follow-up never had episodes of bipolar disorder I as adults, the overall significance of the findings would be similar, because the rate would still be six to 22 times higher than population prevalences.”

“In conclusion, mounting data support the existence of child bipolar disorder I, and the severity and chronicity of this disorder argue strongly for large efforts toward understanding the neurobiology and for developing prevention and intervention strategies,” they write.

Editorial: Examination Lays Groundwork for Future Research

“Extending previous seminal work on pediatric bipolar disorder, Geller et al present the first longitudinal study following up a large sample of youth diagnosed with pediatric bipolar disorder into adulthood,” writes Ellen Leibenluft, M.D., of the National Institute of Mental Health, Bethesda, Md., in an accompanying editorial.

“Just as the children in this important study have matured over the last decade, so has research on pediatric bipolar disorder,” Dr. Leibenluft writes. More articles on the condition were published in January 2008 than in the decade between 1986 and 1996.

“This upsurge both results from and contributes to a growing awareness that serious mental illnesses do not emerge de novo when individuals reach adulthood, but rather reflect early developmental processes. This awareness has profound implications for future research, highlighting the need for longitudinal studies such as that of Geller et al as well as pathophysiological research in children, studies comparing adults and youth with bipolar disorder and studies of youth at familial risk for bipolar disorder,” Dr. Leibenluft concludes.

1. Barbara Geller, Rebecca Tillman, Kristine Bolhofner, Betsy Zimerman. Child Bipolar I Disorder: Prospective Continuity With Adult Bipolar I Disorder; Characteristics of Second and Third Episodes; Predictors of 8-Year Outcome. Arch Gen Psychiatry, 2008; 65 (10): 1125-1133 [link]
2. Ellen Leibenluft. Pediatric Bipolar Disorder Comes of Age. Arch Gen Psychiatry, 2008; 65 (10): 1122-1124 [link]

Adapted from materials provided by JAMA and Archives Journals.