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10-06-2012 | Article

Global medical news in review: June 3-9, 2012

MedWire News: A roundup of select stories of interest to US physicians from the univadis Global Medical News wire.

Risk factors for developing overactive bladder identified

Elderly men and people experiencing voiding symptoms or suffering from depression late in life are at an increased risk for developing an overactive bladder (OAB), report researchers.

The three factors independently predicted new-onset OAB in individuals aged 65 years and older who participated in a longitudinal study specifically designed to seek out risk factors for the condition.

Akihide Hirayama (Nara Medical University, Japan) and team conducted a study of 3685 community-based individuals who provided baseline and 1-year follow-up information in response to self-administered questionnaires including the International Prostate Symptom Score (IPSS), the OAB symptoms score (OABSS), and the Geriatric Depression Scale.

The team's data analysis showed that being male, having voiding symptoms at baseline, and having depression at baseline were all significant predictors for developing OAB 1 year later, at odds ratios of 2.0, 1.1, and 1.8, respectively.

The risk for OAB also increased with severity of voiding symptoms, with 24.5% of patients with an OABSS sum of 10 or higher affected by OAB.

Bladder outlet obstruction has previously been shown to induce OAB, notes the team. "Not only bladder outlet obstruction, but also a weak detrusor and low-voided volumes cause deteriorating voiding symptoms."

The researchers say the effect of gender on OAB risk may be due to the difference in anatomy and lifestyle habits between men and women.

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Here's looking at how to help you, kid

US experts have issued recommendations for engaging, assessing, treating, and managing maladaptive aggression in youth.

The Treatment of Maladaptive Aggression in Youth Steering Committee, chaired by Peter Jensen (The Resource for Advancing Children's Health Institute, New York), conducted a literature review identifying studies to help the development of evidence-based management guidelines that take into account the patient's severity and source of symptoms, development, primary diagnosis, coexisting conditions, and family situations.

The findings were presented at a 2-day conference of 90 experts in child, adolescent, and family mental health matters to develop consensus recommendations and the resulting guidelines are published in two papers in Pediatrics.

Recommendations include engaging parents and patients during the initial evaluation, conducting a thorough diagnostic work-up before initiating pharmacologic treatment, and using standardized measures to assess treatment effects and outcomes. They also suggest considering referral to a psychiatrist or emergency department in cases of acute aggression, and the development of an appropriate treatment plan with the patient/family, with the aim of achieving "buy-in."

Psychosocial treatment recommendations include assisting the family in obtaining parent and child skills training, and encouraging the child and family to take an active role in implementing psychosocial strategies.

The group recommends that initial medication should be targeted to the underlying disorder, that antipsychotic medications be considered for severe persistent aggression, and that a mood stabilizer be added in cases of a partial response to a first-line antipsychotic.

Titration scheduling should also be considered, and adequate medication trials should be carried out before switching medication.

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Split course improves palliative radiotherapy in prostate cancer

A split course of high-dose radiotherapy (RT) in men with progressive, hormone-refractory prostate cancer (HRPC) is effective and has an acceptable toxicity profile, report Australian researchers.

The two-phase 45‑60-Gy regimen given in 18‑24 fractions with a 2-week break in between resulted in 91% of the cohort achieving a clinical response within 3 months, they say.

Furthermore, overall survival was 28 months post-treatment, with no reports of high-grade toxicity (grade 3 or 4 on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring criteria).

Nirdosh Kumar Gogna (Mater Centre, Brisbane, Queensland) and colleagues reviewed data for 34 patients with HRPC who had become resistant to androgen deprivation therapy after a median 42 months. The men presented with urinary tract symptoms (61.7%), isolated rectal symptoms (2.9%), or a combination of both symptoms (35.2%), indicating local progression of disease.

Three months after undergoing the two-phase RT regimen to address their presenting symptoms, 19 (56%) patients experienced a major response (defined as significant improvement in all domains to complete resolution of presenting symptoms), and 12 (35%) experienced a partial response (defined as at least a 50% improvement in symptoms).

After an initial period of stabilization, the remaining three patients' disease progressed fairly quickly, write Gogna et al in the International Journal of Radiation Oncology Biology Physics. Further follow up showed the median overall progression-free survival in the cohort was 43 months, and the median overall survival was 28 months.

Sixteen (48%) and 11 (30%) patients experienced grade 1 or 2 urinary and lower gastrointestinal symptoms, respectively, and two (6%) patients underwent temporary catheterization, observes the research team. However, no other acute grade 3 or 4 toxicities were reported, and likewise, no late (post-12 months) grade 3 or 4 toxicities were reported.

The researchers say the "key difference" with their modified high-dose RT schedule compared with others is that "it required fewer treatment visits, an important consideration in administering palliative treatment."

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You're never too young for liver failure

Acute acetaminophen overdose is the most common identifiable cause of acute liver failure in children, warn researchers in the Canadian Medical Association Journal.

They say that infants and children are particularly susceptible to overdose because of dosing errors and call for both patient- and systems-directed interventions to reduce the risk.

Rodrick Lim (London Health Science Center, Ontario, Canada) and team cite a case of a 22-day-old baby boy who was brought to the emergency department because of an acute acetaminophen overdose.

The acetaminophen had been prescribed by a physician who was performing a routine circumcision on the baby; the physician had advised the parents to give the baby 40 mg acetaminophen before bringing him to hospital for the operation. Taking into account the baby's weight, this dose was equivalent to 10 mg/kg.

The label on the acetaminophen bottle stated a concentration of 80 mg/mL, which was misinterpreted by the parents, who thought that it contained 80 mg of acetaminophen in total. They therefore gave the child 10 mL, or about half of the bottle, which was an actual dose of 800 mg (200 mg/kg).

The physician had instructed the parents to give the baby another 40 mg dose of acetaminophen if he seemed uncomfortable after the operation. At that point the parents commented that "it seemed like a lot of medicine," and the error was discovered.

The baby's blood acetaminophen level at 4 hours postoverdose was 1243 µmol/L, far exceeding the upper end of the therapeutic range (66‑199 µmol/L). Other liver indices were normal.

Because the baby had received more than the toxic dose of 150 mg/kg and because 4-hour blood levels were in the "probable toxicity" range, the baby was treated with intravenous N-acetylcysteine, infused over 21 hours. At the end of this infusion, liver indices remained normal and blood acetaminophen levels had become undetectable. The baby was clinically well throughout and showed no evidence of long-term consequences.

Lim et el say that this case illustrates how easily acetaminophen overdoses may arise in pediatric patients, even with intelligent, educated parents. Another common route for overdose is repeated supratherapeutic dosing, which they say has become more common with the advent of combination analgesics and the availability of pediatric liquid formulations in different concentrations.

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Aspirin to prevent heart disease ‑ too risky for the healthy?

A new analysis of aspirin use for primary prevention of cardiovascular disease (CVD) shows the drug is associated with a higher risk for gastrointestinal or cerebral bleeding episodes than previously thought.

However, in patients with diabetes, a high rate of bleeding was seen irrespective of aspirin use. The authors say this might reflect reduced antiplatelet efficacy in patients with diabetes, who may represent "a different population in terms of both expected benefits and risks associated with antiplatelet therapy."

The population-based cohort study, published in JAMA , was conducted by Antonio Nicolucci (Consorzio Mario Negri Sud, Italy) and team. It included 186,425 patients who were treated with low-dose aspirin (≤300 mg) and 186,425 controls who did not use aspirin between January 2003 and December 2008.

During a median follow-up period of 5.7 years, the incidence of hemorrhagic events was 5.58 per 1000 person‑years for aspirin users versus 3.60 per 1000 person‑years for nonaspirin users, corresponding to an incidence rate ratio (IRR) of 1.55. The authors say the increase in bleeding risk is greater than previously reported in randomized clinical trials and estimated in a large meta-analysis ‑ and may mean that the expected benefits of routine aspirin in terms of number of cardiovascular events avoided are not outweighed by the risks, at least for people at relatively low baseline risk.

Aspirin use was associated with a significantly greater risk for major bleeding in most of the subgroups investigated, including gender, age, and hypertension.

However, it was not associated with a significantly increased risk for bleeding in diabetes patients. The baseline risk for bleeding in the absence of aspirin therapy was higher among individuals with diabetes than those without diabetes, at 5.35 versus 3.32 events per 1000 person‑years. But the incidence rate for bleeding events was increased only marginally with aspirin use among diabetes patients (IR=5.83 vs 5.35), whereas it was increased significantly in those without diabetes (IR=5.53 vs 3.32).

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By Neil Osterweil