Richard Platt

Mortality associated with nosocomial urinary-tract infection.

In a prospective study, 131 of 1458 patients acquired 136 urinary-tract infections (defined as greater than 10(5) colony-forming units per milliliter) during 1474 indwelling bladder catheterizations. Seventy-six patients (25 infected and 51 noninfected) died during hospitalization; death rates were 19 per cent in infected patients and 4 per cent in noninfected patients. Multiple logistic regression analysis demonstrated that seven of 21 prospectively monitored variables were associated with mortality among the catheterized patients. The adjusted odds ratio for mortality between those who acquired infection and those who did not was 2.8 (95 per cent confidence limits, 1.5 to 5.1). The acquisition of infection as not associated with the severity of underlying disease; among patients who died, infections occurred in 38 per cent of those classified as having nonfatal underlying disease (15 of 39) and in 27 per cent of those classified as having fatal disease (10 of 37). Twelve deaths may have been caused by acquired urinary-tract infections. Two patients had urinary-tract pathogens in premortem blood cultures. Another 10 died with clinical pictures compatible with serious infection, but no diagnostic cultures were performed. We conclude that the acquisition of urinary-tract infection during indwelling bladder catheterization is associated with nearly a threefold increase in mortality among hospitalized patients, but the reason for this association is not yet clear.

Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy

OBJECTIVES To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. METHODS The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. RESULTS Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. CONCLUSIONS Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.

Targeted versus Universal Decolonization to Prevent ICU Infection

BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital. RESULTS A total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P<0.001 for test of all groups being equal). Universal decolonization resulted in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation. One bloodstream infection was prevented per 54 patients who underwent decolonization. The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections, but the difference was not significant. Adverse events, which occurred in 7 patients, were mild and related to chlorhexidine. CONCLUSIONS In routine ICU practice, universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen. (Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention; REDUCE MRSA ClinicalTrials.gov number, NCT00980980).

Mortality and Costs of Acute Renal Failure Associated with Amphotericin B Therapy

To assess the mortality and resource utilization that results from acute renal failure associated with amphotericin B therapy, 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital. Main outcome measures were mortality, length of stay, and costs; we controlled for potential confounders, including age, sex, insurance status, baseline creatinine level, length of stay before beginning amphotericin B therapy, and severity of illness. Among 707 admissions, there were 212 episodes (30%) of acute renal failure. When renal failure developed, the mortality rate was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal failure occurred, the mean adjusted increase in length of stay was 8.2 days, and the adjusted total cost was

Risk of Methicillin-Resistant Staphylococcus aureus Infection after Previous Infection or Colonization

29,823. Although residual confounding exists despite adjustment, the increases in resource utilization that we found are large and the associated mortality is high when acute renal failure occurs following amphotericin B therapy.

Discontinuation of Antihyperlipidemic Drugs — Do Rates Reported in Clinical Trials Reflect Rates in Primary Care Settings?

Studies evaluating the risk of methicillin-resistant Staphylococcus aureus (MRSA)-associated sequelae in colonized or infected inpatients have not extended follow-up into the period after discharge from the hospital. We determined the 18-month risk of MRSA infection among 209 adult patients newly identified as harboring MRSA. Twenty-nine percent of patients (60 patients) developed subsequent MRSA infections (90 infections). These infections were often severe. Twenty-eight percent of infections (25 of 90) involved bacteremia, and 56% (50 of 90) involved pneumonia, soft tissue infection, osteomyelitis, or septic arthritis. Eighty percent of patients (48 of 60) with subsequent MRSA infection developed the infection at a new site, and 49% of new MRSA infections (44 of 90) first became manifest after discharge from the hospital. Accurate assessment of the risk of MRSA-associated sequelae requires prolonged follow-up after discharge.

Cutaneous Disease and Drug Reactions in HIV Infection

BACKGROUND Discontinuation rates for drugs used to treat chronic conditions may affect the success of therapy. However, the discontinuation rates reported in clinical trials may not reflect those in primary care settings. METHODS We conducted a cohort study using computerized research files and medical records on 2369 new users of antihyperlipidemic therapy at two health maintenance organizations (HMOs) from 1988 through 1990. The rates of drug discontinuation in these primary care settings were compared with the rates reported in clinical trials published from 1975 through 1993, located with the Medline data base. RESULTS In the HMOs, the one-year probability of drug discontinuation was 41 percent for bile acid sequestrants (95 percent confidence interval, 38 to 44 percent), 46 percent for niacin (95 percent confidence interval, 42 to 51 percent), 15 percent for lovastatin (95 percent confidence interval, 11 to 19 percent), and 37 percent for gemfibrozil (95 percent confidence interval, 31 to 43 percent). For the bile acid sequestrants, niacin, and gemfibrozil, the risks of discontinuation were substantially higher in the HMOs than in randomized clinical trials, in which the summary estimates of this risk were 31 percent, 4 percent, and 15 percent, respectively, for trials of one year or longer. The rates of discontinuation in open-label studies were similar to those in the HMOs. CONCLUSIONS The discontinuation rates reported in randomized clinical trials may not reflect the rates actually observed in primary care settings. The effectiveness and tolerability of antihyperlipidemic medications should be studied further in populations that typically use the agents.

Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women

BACKGROUND Skin diseases, including adverse reactions to drugs, are thought to be more common among patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) than among other persons. These skin conditions can be disabling or disfiguring and may require discontinuation of essential drugs. METHODS We identified 684 HIV-infected members of a 265,000-member health maintenance organization and reviewed their medical records to determine the frequency of dermatologic diagnoses from April 1, 1988, through January 15, 1991. We compared the rates of visits per year for skin conditions by HIV-infected men, 20 to 49 years of age, with those by non-HIV-infected men. We used an automated prescription data base to quantify exposures to drugs. RESULTS Of the 684 HIV-infected patients, 540 (79 percent) were given one or more dermatologic diagnoses, for a total of 2281 diagnoses, including 188 cutaneous reactions to drugs. There were 43 hospitalizations for cellulitis (n = 15), cutaneous drug reactions (n = 13), or other skin problems. As compared with non-HIV-infected men, the men with AIDS had visit rates that were at least 5 times higher for 18 of the 20 most common infectious and inflammatory skin conditions and at least 15 times higher for 9 conditions. Drugs with the highest rate of cutaneous reactions (per 1000 courses) included trimethoprim-sulfamethoxazole (149), sulfadiazine (200), trimethoprim-dapsone (156), and aminopenicillins (93). The number of diagnoses of skin conditions increased according to the stage of disease: it was lowest in patients immediately before the documentation of HIV infection and highest in patients with a diagnosis of AIDS. CONCLUSIONS Cutaneous diseases, including drug reactions, are extremely common in patients with HIV infection, and their incidence increases as immune function deteriorates.

Health and economic impact of surgical site infections diagnosed after hospital discharge.

BACKGROUND Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women. METHODS We investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis. FINDINGS There were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs. INTERPRETATION Statins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery

Although surgical site infections (SSIs) are known to cause substantial illness and costs during the index hospitalization, little information exists about the impact of infections diagnosed after discharge, which constitute the majority of SSIs. In this study, using patient questionnaire and administrative databases, we assessed the clinical outcomes and resource utilization in the 8-week postoperative period associated with SSIs recognized after discharge. SSI recognized after discharge was confirmed in 89 (1.9%) of 4,571 procedures from May 1997 to October 1998. Patients with SSI, but not controls, had a significant decline in SF-12 (Medical Outcomes Study 12-Item Short-Form Health Survey) mental health component scores after surgery (p=0.004). Patients required significantly more outpatient visits, emergency room visits, radiology services, readmissions, and home health aide services than did controls. Average total costs during the 8 weeks after discharge were US