Recent Research

Acid suppression benefits and harms, updated guidelines on uncomplicated UTIs, and more.


Acid suppression benefits don't outweigh harms

Acid-suppressive medication does reduce patients' risk of nosocomial gastrointestinal tract bleeding, but the incidence is so low in non-critically ill hospitalized patients that prophylactic treatment should not be used routinely in patients outside of the intensive care unit, a recent study concluded.

The cohort study used the records of more than 78,000 admissions to one academic medical center between 2004 and 2007. All patients were hospitalized for three or more days, and 59% of them were prescribed acid-suppressive medications. Overall, nosocomial gastrointestinal (GI) bleeding occurred in 224 or 0.29% of admissions. After adjustment, use of acid-suppressive medications was associated with decreased odds of bleeding (odds ratio, 0.63; 95% CI, 0.42 to 0.93). However, given the rarity of GI bleeding, the number needed to treat with medication to prevent one episode of bleeding was 770. The results were published online by Archives of Internal Medicine on Feb. 14.

This study did not quantify the potential harms of acid-suppressive medication. However, other studies have found numbers needed to harm of 533 (for hospital-acquired Clostridium difficile) and 111 (for hospital-acquired pneumonia), the authors noted. The finding that the number needed to treat is greater than the number needed to harm lends support to current guidelines, which recommend against prophylactic acid-suppressive medication for patients outside of the intensive care unit, the study authors concluded. Clinicians should balance the potential benefits against the risks and costs in deciding whether to use acid-suppressive medications, they recommended.

The study was not sufficiently powered to investigate the effects of histamine-2 receptor antagonists compared to proton-pump inhibitors. However, since the former drugs are less potent than the latter, it's unlikely that the number needed to treat would be more favorable, the authors concluded. An accompanying commentary noted that patients who are prescribed acid-suppressive medications in the hospital often remain on them after discharge, and thus, inpatient use of the drugs could also lead to later adverse events.

IDSA updates guidelines for uncomplicated UTIs in premenopausal, non-pregnant women

The Infectious Diseases Society of America recently updated its clinical practice guidelines for treating women with acute uncomplicated cystitis and pyelonephritis.

The guidelines are limited to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. Full recommendations and an executive summary are in the March 1 Clinical Infectious Diseases.

IDSA published its previous guidelines in 1999. Since then, antimicrobial resistance, collateral damage (referring to the adverse effects of antimicrobial therapy, including the selection of drug-resistant organisms associated with broad-spectrum cephalosporins and fluoroquinolones), newer agents and different durations of therapy have been studied. Women with drug-resistant uropathogens have been included in some studies, allowing for estimations of expected response rates in real-life clinical settings.

Recommendations for acute uncomplicated cystitis include the following:

  • Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) has minimal resistance and collateral damage, with efficacy comparable to 3 days of trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole (160/800 mg [1 double-strength tablet] twice-daily for 3 days) is appropriate if local resistance rates do not exceed 20%, or if the infecting strain is susceptible. Ofloxacin, ciprofloxacin and levofloxacin are highly efficacious in 3-day regimens, but have a propensity for collateral damage and should be reserved for important uses other than acute cystitis.
  • β-Lactam agents in 3- to 7-day regimens are appropriate when other recommended agents cannot be used. Amoxicillin or ampicillin should not be used because of poor efficacy and very high antimicrobial resistance.

Recommendations for acute pyelonephritis include the following:

  • A urine culture and susceptibility test should always be performed, and initial empirical therapy should be tailored to the infecting uropathogen.
  • Cases requiring hospitalization should be initially treated with an intravenous antimicrobial regimen, such as a fluoroquinolone; an aminoglycoside with or without ampicillin; an extended-spectrum cephalosporin or extended-spectrum penicillin with or without an aminoglycoside; or a carbapenem. The choice among these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.
  • Oral trimethoprim-sulfamethoxazole (160/800 mg [1 double-strength tablet] twice-daily for 14 days) is appropriate if the uropathogen is known to be susceptible (good evidence from one or more randomized, controlled trials). If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone (moderate evidence from one or more nonrandomized trials), or a consolidated 24-hour dose of an aminoglycoside is recommended.
  • Oral β-lactam agents are less effective than other agents (moderate evidence from expert consensus). If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone (moderate evidence from one or more nonrandomized trials), or a consolidated 24-hour dose of an aminoglycoside is recommended.

Automatic prompts, clinician discussions boost cardiac rehab referral, enrollment

Automatic referral combined with a clinician discussion can increase patients' use of cardiac rehabilitation after hospital discharge, recent research suggests.

In a prospective, observational study of 2,635 inpatients with coronary artery disease, clinicians from 11 community and academic hospitals in Ontario, Canada used one of four referral strategies: automatic referral via electronic records or standard discharge orders as a prompt before discharge; referral via a personal discussion with a clinician, like a nurse or physiotherapist; a combination of the two; or “usual” referral at the clinician's discretion. Patients completed a sociodemographic survey, and clinical data were extracted from their medical charts. A year later, 1,809 patients completed a survey that assessed their cardiac rehabilitation (CR) referral, enrollment and participation. Results were published in the Feb. 14 Archives of Internal Medicine.

CR referral was significantly greater for all intervention strategies compared to usual care (P<0.001). The greatest use of CR came from combining automatic referral and personal discussion (85.8% referral, 73.5% enrollment; odds ratio [OR], 8.41), then automatic referral alone (70.2% referral, 60% enrollment; OR, 3.27), then personal discussion alone (59% referral, 50.6% enrollment; OR, 3.35). Usual care resulted in 32.2% referral and 29% enrollment. Enrollment (P=0.34) and degree of participation once enrolled (P=0.88) didn't differ by referral strategy, with patients attending a mean of 82.87% of classes (standard deviation was 27.2%).

All centers with CR referral strategies had had them in place for a couple of years, on average, before the study started, but the time varied by ward and wasn't controlled, which may have biased results, the authors noted. CR referral and usage rates were also self-reported by patients, which may have biased results as well, though self-reports have been shown to be congruent with CR-site report data in the past, the authors noted. Also, CR coverage in this geographic area is fully covered; results may differ in areas where patients pay out-of-pocket for CR, they noted. Still, the results suggest that combined automatic and personal discussion referral strategies should be more widely adopted, as this strategy could raise CR use by 45%, the authors concluded. The combination approach may be most effective because it involves both the clinician and the patient, with the discussion aspect facilitating clinician endorsement and the chance to clear up potential misconceptions or barriers to CR use, they said.

Acute heart failure outcomes don't differ by furosemide dose level, interval of administration

Outcomes for patients with acute decompensated heart failure don't differ when furosemide is delivered via continuous infusion versus bolus, or at a high dose versus a low dose, a study found.

In a prospective, double-blind trial, researchers randomized 308 patients with acute decompensated heart failure to intravenous furosemide given every 12 hours (bolus) or continuously, and at a dose equal to the patient's previous oral dose (low dose) or 2.5 times the previous dose (high dose). Treatment was continued for up to 72 hours. At 48 hours, the treating physician could, based on clinical response, maintain the current strategy, increase the dose by 50%, or stop intravenous treatment and use open-label oral diuretics instead. The primary end points were change in serum creatinine level from baseline to 72 hours and the patients' global assessment of symptoms. Results were published in the March 3 New England Journal of Medicine.

There was no significant difference in patients' global assessment of symptoms whether they had received bolus or continuous infusion (mean area under the curve [AUC], 4,236 ± 1,440 and 4,373 ± 1,404, respectively; P=0.47) or in the mean change in creatinine level (0.05 ± 0.3 mg/dL and 0.07 ± 0.3 mg/dL, respectively; P=0.45). There was also no significant difference between the high- and low-dose strategy, though there was a trend toward the high dose improving symptoms (mean AUC, 4,430 ± 1,401 vs. 4,171 ± 1,436; P=0.06). High and low doses didn't yield a significant difference in mean creatinine level, either (0.08 ± 0.3 mg/dL vs. 0.04 ± 0.3 mg/dL, respectively; P=0.21). The high-dose approach was associated with transient worsening of renal function, but greater diuresis, greater relief of dyspnea and fewer serious adverse events.

While prior, smaller studies have suggested that continuous infusion leads to less renal dysfunction and greater diuresis than bolus, the current study found no difference. This may be because bolus patients used continuous placebo infusion, which increased the time the patients were supine—a position that has been shown to increase diuresis, the authors noted. Separately, they cautioned that the patients in this study had a history of chronic heart failure and required moderate to high doses of loop diuretics as outpatients; the results may not apply to patients with more modest diuretic requirements or newly diagnosed heart failure. The dose and interval findings should change practice, according to an editorialist. “Since a high-dose regimen may relieve dyspnea more quickly without adverse effects on renal function, that regimen is preferable,” he wrote. “Administration of boluses may be more convenient than continuous infusion and equally effective,” he added.

Clopidogrel may improve outcomes after CABG in patients with MI

Clopidogrel may improve outcomes after coronary artery bypass grafting (CABG) for myocardial infarction (MI), a recent study reported.

To evaluate the effect of clopidogrel on death and recurrent MI after CABG, Danish researchers examined data on patients admitted to the hospital with a first MI between 2002 and 2006 who underwent CABG within 180 days. They determined which patients received clopidogrel after discharge by looking at filled prescriptions. The main outcome measures were risk for death, recurrent MI or both. The study results appeared in the March 8 Journal of the American College of Cardiology.

Study patients were followed for a mean of 466 ± 144 days. A total of 3,545 patients were included, 957 (27.0%) of whom received clopidogrel after CABG. Thirty-nine (4.1%) of those who received clopidogrel died or had a recurrent MI compared with 203 (7.8%) of those who did not receive clopidogrel (log-rank P=0.0003; hazard ratio, 0.59; 95% CI, 0.42 to 0.85). In a subgroup analysis of 945 patients matched by propensity score, 38 (4.0%) of those treated with clopidogrel died or had recurrent MI compared with 57 (6.0%) of those not treated with clopidogrel (log-rank P=0.05; hazard ratio, 0.67; 95% CI, 0.44 to 1.00). Rates of bleeding events after hospital discharge did not differ between groups.

The study was limited by its observational design, which did not allow the authors to definitively establish a causal relationship between clopidogrel and the primary outcomes. The authors also could not rule out selection bias. However, they concluded that clopidogrel treatment helped improve outcomes in patients with MI after CABG, but that the percentage of eligible patients who received clopidogrel treatment was low. They said that a randomized, controlled trial is warranted to clarify the relationship between postoperative clopidogrel treatment and outcomes, and that more attention should be paid to prescribing clopidogrel at discharge in this group of patients.

Transient cognitive impairment at discharge may impede elderly patients' self-care

It may be worthwhile to screen patients for low cognition at hospital discharge and to offer care instructions after—rather than at the time of—discharge for those who score poorly, a study recently suggested.

To determine the frequency of low cognition at hospital discharge, researchers conducted face-to-face surveys at the time of discharge and one month later in the homes of 200 community-dwelling seniors. The subjects had been admitted for more than 24 hours to the acute medicine service of Northwestern Memorial Hospital in Chicago. Their mean age was 79.6 years (range, 70 to 100 years) and 58% were women. Patients were excluded if they were unable to consent to their own procedures (which implies known cognitive dysfunction), had previously documented cognitive loss, or were admitted for cognitive changes. Results appeared online March 4 in the Journal of General Internal Medicine.

Researchers applied the Folstein Mini-Mental Status Examination (MMSE), Backward Digit Span, and 15 Word Immediate and Delayed Recall Tests to evaluate cognition. Upon hospital discharge, 31.5% of subjects (n=60) had previously unrecognized low cognition. One month later, only 13.5% (n=27) had low cognition (P<0.001). Patients with low cognition had a mean score on the MMSE of 20.56 (range, 14 to 24) at discharge, which improved to a mean of 24.57 (range, 18 to 29) by one month (P<0.001). Orientation, task completion, registration, repetition, naming, reading, writing and calculation improved significantly. At discharge, only 54% of low-cognition subjects were able to correctly complete a three-step task of folding paper, placing it in their left hands, and handing the pieces to an interviewer. One month later, 98.4% were able to perform the task correctly.

According to assessment by the Backward Digit Span test, low cognition in working memory was present at discharge in 35.5% of the subjects, and declined to 31.5% one month later (P=0.014). With the 15 Word Immediate and Delayed Recall Tests, 50% of subjects had low cognition and were not able to remember more than one word from the 15-word list after eight minutes. One month post-discharge, significant improvements were seen, but 34.5% of subjects still had trouble (P<0.001).

Transient cognitive impairment threatens the comprehension and fulfillment of discharge instructions for seniors, over half of whom lived alone and almost 85% of whom managed their own medications in this study, the authors said. Screening for low cognition at discharge and educating caregivers to provide more attention to those who score poorly would help seniors transition back into their home environments, the authors wrote. “This tailoring of discharge interventions would decrease the costs to the hospital of initiating sweeping interventions to all discharged seniors,” they wrote. “These seniors may also benefit from closer follow-up with their primary care physician to ensure that the discharge plan is being followed and to monitor the cognitive impairment.”

Secondary benefit seen for early tracheotomy in cardiac patients with prolonged mechanical ventilation

Mechanically ventilated patients who had early tracheotomy or prolonged intubation after cardiac surgery didn't differ in number of ventilator-free days or infection rates, but the former required less sedation, a study found.

In a prospective, randomized controlled trial, 216 mechanically ventilated patients were assigned to early percutaneous tracheotomy or prolonged intubation. Patients, who came from a single academic center in France, were eligible if they had undergone cardiac surgery and were still on mechanical ventilation four days afterwards; hadn't passed a weaning screening test or spontaneous breathing trial; and were expected to require mechanical ventilation for a week or more. The primary end point was number of days alive and breathing without assistance (i.e., ventilator-free days) during the first 60 days after randomization. Secondary end points included number of ventilator-free days at 28 and 90 days; mortality rates at 28, 60 and 90 days; duration of mechanical ventilation; length of ICU and hospital stays; ventilator-associated pneumonia rate; unscheduled extubations; sedative, analgesic and neuroleptic use; patient comfort and ease of care; and long-term quality of life and psychosocial status. Results were published in the March 15 Annals of Internal Medicine.

There was no difference in ventilator-free days in the first 60 days after randomization between the tracheotomy and prolonged intubation groups (mean, 30.4 days vs. 28.3 days, respectively; P=0.50), nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, 30% vs. 30%, respectively). Frequency of ventilator-associated pneumonia was similar in the tracheotomy and intubation groups (50% vs. 47%, respectively; P=0.77), as were duration of mechanical ventilation (17.9 days vs. 19.3 days; P=0.55) and hospitalization (39 days vs. 37.5 days; P=0.56). Early tracheotomy patients had significantly shorter duration of intravenous sedation (6.4 days vs. 9.6 days; P=0.007) and more sedation-free days in the first 28 days (19 days vs. 15.5 days; P=0.005); lower cumulative haloperidol dose for agitation and/or delirium during days 1 to 15 (0.26 mg/kg vs. 0.57 mg/kg; P=0.002); fewer unscheduled extubations (3 vs. 17; P<0.001); more days nurse-assessed as comfortable (11.8 vs. 10.4; P=0.01); and earlier resumption of oral nutrition (91% resumed at 15 days vs. 57%; P<0.001).

Although previous studies have linked decreased sedation with shorter duration on mechanical ventilation, there was no such indication in this study, the authors noted. This may be because polyneuropathy acquired in the ICU prolonged ventilation for both groups, or because the strict weaning protocol that was applied to the intubation group compensated for higher sedative use, they said. Only 29% of patients required tracheotomy at day 15 or later—far fewer than was found in a previous study, editorialists noted. It's possible this is because the cardiac population only requires mechanical ventilation for one or two weeks after surgery, or that clinicians don't predict clinical course well for these patients, they wrote. The finding that sedation and other medication needs are lower in patients with early tracheotomy raises the question of whether the procedure can facilitate an earlier return to independence (eating, mobility), when paired with an aggressive mobilization protocol, the editorialists wrote.

Depression management program helps cardiac inpatients

A depression management program begun during hospitalization helped improve mental and physical health outcomes months later, a recent study found.

In a randomized, prospective trial, researchers assigned 175 depressed inpatients with acute coronary syndrome, arrhythmia or heart failure to usual care or a collaborative depression care management program. The patients—who were admitted to one of three cardiac units at an urban academic hospital—were defined as depressed if they had a score of 10 or higher on the Patient Health Questionnaire-9 (PHQ-9), with five or more symptoms present more than half the days for the preceding two weeks. For the usual care patients, a care manager informed the inpatient treatment team of the patient's depression and recommended treatment. For the collaborative care patients, the care manager provided patient education about depression and its impact on cardiac disease; helped the patient schedule enjoyable activities after discharge; and described treatment options (drugs or therapy). For the latter patients, the manager also consulted with the study psychiatrist, who developed individualized treatment recommendations that the care manager then worked to implement with in- and outpatient health professionals. The study was published in the March Circulation: Cardiovascular Quality and Outcomes.

Post-discharge interventions lasted 12 weeks, during which subjects received three separate phone assessments of depression symptoms. If a usual-care subject still scored as depressed, his or her primary care physician was informed. If a collaborative care subject was depressed, a multi-component intervention similar to the one in the hospital was enacted. Study outcomes were measured at six and 12 weeks and six months. Collaborative care subjects had significantly greater improvement of depression symptoms at six weeks (between-group difference in PHQ-9 improvement of −3.03 points; 95% CI, −4.97 to −1.10; P=0.002) and 12 weeks (−3.43-point difference; 95% CI, −5.41 to −1.45; P<0.001) after discharge. There was a nonsignificant trend toward improvement at six months (P=0.081).

Depression response on the PHQ-9 was also greater at six weeks for intervention subjects (59.7% vs. 33.7% for usual care; odds ratio [OR], 2.91; P=0.003) and 12 weeks (51.5% vs. 34.4%; OR, 2.02; P=0.04), but not significantly different at six months. Intervention subjects had greater improvement in number of cardiac symptoms (improvement greater by 0.80 symptom; P=0.047) and intensity of symptoms (2.15 points; P=0.011) at six months, but there was no difference at six or 12 weeks. Self-reported adherence to medical recommendations was also greater in the collaborative care arm at six months (15.9 mean adherence score vs. 14.6 for usual care; P=0.027), but not at six and 12 weeks.

The waning of psychiatric benefit from the intervention by six months is not surprising, the authors wrote, given that subjects received only three telephone contacts in a 12-week discharge period, and no contact after. This is a “much less intense follow-up intervention than most successful collaborative care programs,” they noted. The improvement in adherence and cardiac symptoms at six months suggests patients may first need improvement in mental health before they can improve cardiac health behaviors, the authors wrote. This study extended prior work in that it addressed patients with several cardiac conditions for which collaborative depression care hadn't been used before. It also used phone rather than in-person interventions, and social workers instead of nurses as care workers; both of these allowed the intervention to be more feasible, the authors wrote. Limitations include that it was performed at a single center, most patients were white, and unit staff members were aware a depression study was ongoing.