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DERMATOLOGIC CARE

Investigational Psoriasis Drug Shows Promise

Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 moniclonal antibody, in patients with psoriasis: 76-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665-1674.

 

Papp K, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675-1684.

 

Bartlett B, Tyring SK. Ustekinumab for chronic plaque psoriasis. Lancet. 2008;371:1639-1640.

 

Ustekinumab is a biologic trial for plaque psoriasis. It is a human monoclonal antibody that binds to the interleukin molecules IL-12 and IL-23, and is administered via subcutaneous injection. Two double-blind, placebo-controlled trials, PHOENIX 1 and PHOENIX 2, showed notable symptom relief in psoriasis patients over 52 or 76 weeks.

  
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Both studies started the participants on 45 or 90 mg of ustekinumab or placebo, given at weeks 0 and 4. The participants were rerandomized at week 12 to either 45 or 90 mg of ustekinumab. After 12 weeks, 66.4% to 75.7% of the ustekinumab recipients experienced at least a 75% reduction in their symptoms. Only 3.1% to 3.7% of the placebo recipients experienced any relief.

 

Both studies continued the ustekinumab in two doses at 16 weeks. At 28 weeks, fewer than 7% of all participants experienced less than a 50% reduction in symptoms. Some participants' symptoms disappeared completely, while others achieved at least a 90% reduction in symptoms.

 

After the 28th week, the studies separated into different drug reassignment scenarios. PHOENIX 1 lasted 76 weeks, while PHOENIX 2 lasted 52 weeks.

 

Adverse effects were minimal in both the placebo-controlled and ustekinumab phases of the studies. The results do not reveal any major safety concerns in the 52 to 76 week duration of the studies. Overall, ustekinumab compares favorably with the best current treatments for psoriasis. It also offers a more convenient treatment schedule than those presently available.

 

The long-term safety of the drug is still unknown. It is also not known whether the drug will benefit those with psoriatic arthritis.

 

Ustekinumab is currently awaiting FDA approval.

 

Women's Health Care

Women Who Breastfeed Have Lower Risk for RA

Pikwer M, Bergstrom U, Nilsson JA, et al. Breast-feeding, but not oral contraceptives, is associated with a reduced risk of rheumatoid arthritis. Ann Rheum Dis. 2008:1-5.

 

Breastfeeding has long been known to offer protective health benefits to both children and their mothers, including stronger immune systems for children and a lower risk of breast and ovarian cancer for mothers. Now, current research findings show that women who nurse their children for at least a year reduce their risk of developing rheumatoid arthritis (RA) by 54%. Even short-term breastfeeding offered some protective benefits; women who nursed for at least 1 month reduced their risk of developing RA by 26%.

  
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This study isolated breastfeeding-not giving birth or taking oral contraceptives-as being responsible for lowering the risk. However, women who gave birth to more than one child tended to have a lower RA risk, with a 13% reduction for each subsequent child they had. Overall, breastfeeding was a much more significant factor in lowering RA risk than was the number of children the women had.

 

Psychiatric Care

Short-Term Antipsychotics Not for Dementia Patients

Rochon PA, Normand SL, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168:1090-1096.

 

Antipsychotic drugs are often used in clinical practice for short interludes to treat behavioral and psychological symptoms of dementia. However, recent research shows that administering short-term antipsychotics to older adults with dementia is very risky. It is likely to cause a serious adverse event leading to hospitalization or death.

  
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This research indicates that the newer atypical antipsychotics, such as olanzapine (Zyprexa), quetiapine fumarate (Seroquel), and risperidone (Risperdal), cause less of a risk than the older antipsychotics. The older drugs, including haloperidol (Haldol) and loxapine (Loxitane), caused four times more risk than the newer drugs.

 

The Ontario study included dementia patients over 65 years of age who had been given a prescription for an antipsychotic from April 1997 to March 2004. Of the total study population, 20,682 lived in the community and 20,559 lived in a nursing home. The populations were divided into three study groups: the control group, the group that was administered the atypical drugs, and the group that was administered conventional antipsychotics.

 

In the community-dwelling group, those given the atypical antipsychotics were 3.2 times more likely to develop a serious event within 30 days of follow-up. Those who received the conventional antipsychotics were 3.8 times more likely to experience a serious event. These numbers were similar, but not as high for the nursing home residents.

 

Pediatric Care

Possible Link Between Cigarette Smoke and SIDS

Pendlebury JD, Wilson RJ, Bano S, et al. Respiratory control in neonatal rats exposed to prenatal cigarette smoke. Am J Respir Crit Care Med. 2008;177:1255-1261.

 

A new investigation has uncovered evocative substantiation in rats that prenatal exposure to cigarette smoke may lead to impaired breathing in pups.

  
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In this investigation, 11 pregnant rats were exposed to amounts of smoke equivalent to what a moderate-to-heavy human smoker smokes-about a pack a day. Ten pregnant rats were exposed to clean air.

 

The pups born to the smoke-exposed mothers weighed significantly less than those born to the control group. Under normal temperature conditions, 25% of the smoke-exposed rats started gasping in response to low oxygen, while none of the control group rat pups gasped. When the temperature was raised, both groups started to struggle for breath in a hypoxic state. However, the control group recovered to normal breathing much faster than the smoke-exposed group.

 

This investigation concluded that although moderate hypoxia and increased ambient temperature upset normal breathing patterns without the presence of cigarette smoke, prenatal smoke exposure further increases the failure of eupneic breathing. These results offer the first actual evidence that prenatal smoking could increase risk of sudden infant death syndrome.

 

Cardiovascular Care

Life Expectancy Discrepancy in HF Patients

Allen LA, Yager JE, Funk MJ, et al. Discordance between patient-predicted and model-predicted life expectancy among ambulatory patients with heart failure. JAMA. 2008;299:2533-2542.

 

Research shows that most chronic heart failure patients have an unrealistic view of their life expectancies. The June 4 issue of the Journal of the American Medical Association reports that 63% of these patients misjudged their likely survival, compared with the Seattle Heart Failure Model's estimates.

  
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This study included 122 ambulatory chronic heart failure patients with a mean age of 62 years, with 42% in New York Heart Association class III or IV. In this group, the patients predicted that they had a median of 13 years to live, while The Seattle Heart Failure Model predicted a mean of only 10 years. During a median follow-up of 3.1 years, 29% of these patients had died.

 

The reason for this confusion is unknown, but may reflect a misunderstanding between the healthcare providers and their patients stemming from poor communication skills, patient-specific factors, and language/cultural barriers.

 

It is imperative that chronic heart failure patients have an accurate understanding of the reality of their situations so that they may make the appropriate decisions about quality-of-life and end-of-life care issues. Proper communication between the healthcare provider and the patient in this circumstance is of utmost importance.

 

Gastrointestinal Care

Family History Predicts Recurrence of Colorectal Cancer

Chan JA, Meyerhardt JA, Niedzwiecki D, et al. Association of family history with cancer recurrence and survival among patients with stage III colon cancer. JAMA. 2008;299:2515-2523.

 

The latest research on colorectal cancer shows that family history not only predicts one's risk of developing the disease, but also predicts one's chance of cancer recurrence and survival after diagnosis.

  
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The researchers followed 1,087 stage III colorectal cancer patients through a randomized trial of adjuvant chemotherapy. One hundred ninety-five of those patients had at least one first-degree relative with a history of the disease, and 30 had two or more relatives with a history of the disease.

 

Among these patients, the adjusted hazard ratio for disease-free survival was 0.72, compared with those without a family history. The adjusted hazard ratio for recurrence-free survival was 0.74, and for overall survival it was 0.75.

 

Though these findings are promising, they should not change the treatment of individual colorectal cancer patients. More studies are needed to identify germline and tumor-specific hereditary features coupled with a family history of the disease, as well as favorable outcome as a result of adjuvant chemotherapy.

 

Respiratory Care

Likelihood to Quit Smoking Could Be Hereditary

Uhl GR, Liu QR, Drgon T, et al. Molecular genetics of successful smoking cessation: convergent genome-wide association study results. Arch Gen Psychiatry. 2008;65(6):683-693.

 

Research articles recently published in the June issue of Archives of General Psychiatry uncovers that one's heredity might be a determining factor on whether or not he or she will be able to successfully cease smoking.

  
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Researchers performed a genome-wide association study of 550 smokers who were taking part in trials that tested either nicotine replacement therapy or bupropion (Zyban). The results revealed that 99 autosomal genes are differently expressed in successful quitters than in people who cannot cease smoking. These genes are likely to modify cell adhesion, enzymatic, transcriptional, constitutional, and protein handling operations.

 

Of these genes, 41 were exclusive to bupropion and 26 for nicotine replacement therapy. The findings of this research are significant because knowing this information would help healthcare providers to customize smoking cessation plans according to each individual patient. In the future, a simple blood test could make this information readily available to healthcare providers, and help these patients more easily achieve their smoking cessation goal.

 

Pediatric Care

Infants and Toddlers May Lack Vitamin D

Gordon CM, Feldman HA, Sinclair L, et al. Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med. 2008;162:505-512.

 

Taylor JA. Defining vitamin D deficiency in infants and toddlers. Arch Pediatr Adolesc Med. 2008;162:583-584.

 

Poor diet and lack of outdoor activity have led to concern about a rebirth of vitamin D deficiency and rickets among infants and toddlers. A recent study, published in the June issue of Archives of Pediatrics & Adolescent Medicine, examined 365 children aged 8 months to 2 years. Of these otherwise healthy children, 40% had insufficient levels of vitamin D, while 12.1% had a vitamin D deficiency.

  
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Those with deficiencies underwent bilateral wrist and knee computed radiography. Forty of them showed demineralization, and three had changes that suggested rickets.

 

The cause of these lower vitamin D levels is thought to be breastfeeding without supplementation among infants and insufficient milk consumption among toddlers. The vitamin D levels increased by 2.9 ng/mL, with each cup of milk consumed daily by the toddlers. Additionally, the levels increased with exposure to sunlight.

 

These findings indicate that vitamin D supplementation should be given to all infants and toddlers, and that the current amount of 200 international units recommended by the American Academy of Pediatrics may not be enough.

 

St. John's Wort Not a Viable Treatment for ADHD

Weber W, Vander SA, McCarty RL, et al. Hypericum perforatum (St. John's Wort) for attention deficit/hyperactivity disorder in children and adolescents-a randomized controlled trial. JAMA. 2008;299:2633-2631.

 

Chan E. Quality of efficacy research in complementary and alternative medicine. JAMA. 2008;299(22):2685-2686.

 

Following a diagnosis of attention deficit-hyperactivity disorder (ADHD), many parents seek out alternative treatments instead of putting their children on conventional medication. St. John's Wort (Hypericum perforatum), commonly used to treat depression and many other disorders, is one of the most repeatedly used botanical agents.

 

St. John's Wort has been shown to inhibit reuptake of serotonin, norepinephrine, and dopamine. As one of the newer medications for ADHD, atomoxetine (Strattera) is a norepinephrine reuptake inhibitor, a study was warranted to test the efficacy of St. John's Wort as a treatment option for ADHD.

 

Fifty-four pediatric and adolescent ADHD patients were randomized to either placebo or St. John's Wort. Other ADHD medications were not allowed during the trial, which lasted 8 weeks.

 

At the end of the 8 weeks, the improvement of the St. John's Wort group nearly equaled that of the placebo group. Therefore, St. John's Wort is ineffective in treating ADHD.

 

These results emphasize that more studies of this kind are needed to assess complementary and alternative therapies.

 

Emergency Care

Injuries and Deaths After Repealed Helmet Law

Mertz KJ, Weiss HB. Changes in motorcycle-related head injury deaths, hospitalizations, and hospital charges following repeal of Pennsylvania's mandatory motorcycle helmet law. Am J Pub Health. 2008;98:8-11.

 

Pennsylvania repealed its mandatory motorcycle universal helmet law in 2003. Instead, a new law was instituted to require helmets only for motorcycle riders younger than 21 years, and for riders with less than 2 years of riding experience who have not completed a motorcycle safety program.

  
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In the first 2 years of the new legislation, head injury hospitalizations increased by nearly 80%, and head injury deaths increased by 66%. This corresponded with a 30% reduction of helmet use among motorcycle riders who were in accidents.

 

Additionally, researchers evaluated state databases on motorcycle crashes and associated hospital admissions and deaths. They compared motorcycle-related injuries and deaths in 2001-2002 with those in 2004-2005 and noted the following dramatic increases:

 

* injuries, 40%

 

* head-injury deaths, 66%

 

* nonhead-injury deaths, 25%

 

* acute-care hospitalizations, 43%

 

* head-injury hospitalizations, 78%

 

* acute-care charges for head injuries, 132%

 

* acute-care charges for nonhead injuries, 69%

 

* need for rehabilitation and long-term care, 87% for head injuries and 16% for nonhead injuries.

 

 

Voluntary helmet use programs should be developed and encouraged until mandatory helmet laws are restored.