In the Literature: March 2010

The patients were mostly Caucasian and overweight. At three years of followup, median HgbA1c was similar in all groups (7.1% biphasic, 6.8% prandial, 6.9% basal); however, more patients who received prandial or basal insulin achieved HgbA1c less than 6.5% (45% and 43%, respectively) than in the biphasic group (32%).

Hypoglycemia was significantly less frequent in the basal insulin group (1.7 per patient per year versus 3.0 and 5.5 with biphasic and prandial, respectively). Patients gained weight in all groups; the greatest gain was with prandial insulin. At three years, there were no significant between-group differences in blood pressure, cholesterol, albuminuria, or quality of life.

Bottom line: Adding insulin to oral diabetic regimens improves glycemic control. Basal or prandial insulin regimens achieve glycemic targets more frequently than biphasic dosing.

Citation: Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.

Advanced Dementia Is a Terminal Illness with High Morbidity and Mortality

Clinical question: Does understanding the expected clinical course of advanced dementia influence end-of-life decisions by proxy decision-makers?

Background: Advanced dementia is a leading cause of death in the United States, but the clinical course of advanced dementia has not been described in a rigorous, prospective manner. The lack of information might cause risk to be underestimated, and patients might receive suboptimal palliative care.

Study design: Multicenter prospective cohort study.

Setting: Twenty-two nursing homes in a single U.S. city.

Synopsis: The survey examined 323 nursing home residents with advanced dementia. The patients were clinically assessed at baseline and quarterly for 18 months through chart reviews, nursing interviews, and physical examinations. Additionally, their proxies were surveyed regarding their understanding of the subjects’ prognoses.

During the survey period, 41.1% of patients developed pneumonia, 52.6% of patients experienced a febrile episode, and 85.8% of patients developed an eating problem; cumulative all-cause mortality was 54.8%. Adjusted for age, sex, and disease duration, the six-month mortality rate for subjects who had pneumonia was 46.7%; a febrile episode, 44.5%; and an eating problem, 38.6%.

Distressing symptoms, including dyspnea (46.0%) and pain (39.1%), were common. In the last three months of life, 40.7% of subjects underwent at least one burdensome intervention (defined as hospitalization, ED visit, parenteral therapy, or tube feeding).

Subjects whose proxies reported an understanding of the poor prognosis and expected clinical complications of advanced dementia underwent significantly fewer burdensome interventions (adjusted odds ratio 0.12).

Bottom line: Advanced dementia is associated with frequent complications, including infections and eating problems, with high six-month mortality and significant associated morbidity. Patients whose healthcare proxies have a good understanding of the expected clinical course and prognosis receive less-aggressive end-of-life care.

Citation: Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529-1538. TH

PEDIATRIC HM LITerature

By Mark Shen, MD

Antibiotic Prophylaxis Might Prevent Recurrent UTIs

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.