Publications

BACKGROUND

The extent of outpatient adverse drug events (ADEs) remains unclear. Trigger tools are used as a screening method to identify care episodes that may be ADEs, but their value in a population with high chronic-illness burden remains unclear.

METHODS

The authors used six abnormal laboratory triggers for detecting ADEs among adults in outpatient care. Eligible patients were included if they were >18 years, sought primary or urgent care between November 2008 and November 2009 and were prescribed at least one medication. The authors then used the clinical / administrative database to identity patients with these triggers. Two physicians conducted in-depth chart review of any medical records with identified triggers.

RESULTS

The authors reviewed 1342 triggers representing 622 unique episodes among 516 patients. The trigger tool identified 91 (15%) ADEs. Of the 91 ADEs included in the analysis, 49 (54%) occurred during medication monitoring, 41 (45%) during patient self-administration, and one could not be determined. 96% of abnormal international normalised ratio triggers were ADEs, followed by 12% of abnormal blood urea nitrogen triggers, 9% of abnormal alanine aminotransferase triggers, 8% of abnormal serum creatinine triggers and 3% of aspartate aminotransferase triggers.

CONCLUSIONS

The findings imply that other tools such as text triggers or more complex automated screening rules, which combine data hierarchically are needed to effectively screen for ADEs in chronically ill adults seen in primary care.

BACKGROUND

Although misdiagnosis in the outpatient setting leads to significant patient harm and wasted resources, it is not well studied. The authors surveyed primary care physicians (PCPs) about barriers to timely diagnosis in the outpatient setting and assessed their perceptions of diagnostic difficulty.

METHODS

Surveys of PCPs practicing in an integrated health system across 10 geographically dispersed states in 2005. The survey elicited information on key cognitive failures (including in clinical knowledge or judgement) for a specific case, and solicited strategies for reducing diagnostic delays. Content analysis was used to categorise cognitive failures and strategies for improvement. The authors examined the extent and predictors of diagnostic difficulty, defined as reporting >5% patients difficult to diagnose.

RESULTS

Of 1817 physicians surveyed, 1054 (58%) responded; 848 (80%) respondents primarily practiced in outpatient settings and had an assigned patient panel (inclusion sample). Inadequate knowledge (19.9%) was the most commonly reported cognitive factor. Half reported >5% of their patients were difficult to diagnose; more experienced physicians reported less diagnostic difficulty. In adjusted analyses, problems with information processing (information availability and time to review it) and the referral process were associated with greater diagnostic difficulty. Strategies for improvement most commonly involved workload issues (panel size, non-visit tasks).

CONCLUSIONS

PCPs report a variety of reasons for diagnostic difficulties in primary care practice. In this study, knowledge gaps appear to be a prominent concern. Interventions that address these gaps as well as practice level issues such as time to process diagnostic information and better subspecialty input may reduce diagnostic difficulties in primary care.

BACKGROUND

Specific isoniazid (INH) resistance conferring mutations have been shown to impact the likelihood of tuberculosis (TB) transmission. However, their role in the clinical presentation and outcomes of TB has not been evaluated.

METHODS

We included all cases of culture-confirmed, INH monoresistant tuberculosis reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005. For cases with stored culture isolates, we used polymerase chain reaction (PCR) testing and gene sequencing to identify INH resistance-conferring mutations, and compared genotypic and phenotypic characteristics.

RESULTS

Among 101 consecutive cases of INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%) had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with other mutations. The katG S315T mutation was independently associated with high-level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07-2.27), and the inhA-15;c-t promoter mutation was inversely associated with high-level INH resistance (RR 0.43, 95% CI 0.21-0.89). However, specific INH resistance-conferring mutations were not associated with the clinical severity or outcomes of INH monoresistant TB cases.

CONCLUSION

These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.

BACKGROUND

Few studies have examined outcomes for children treated for multidrug-resistant tuberculosis (MDR-TB), including those receiving concomitant treatment for MDR-TB and HIV co-infection. In Lesotho, where the adult HIV seroprevalence is estimated to be 24%, we sought to measure outcomes and adverse events in a cohort of children treated for MDR-TB using a community-based treatment delivery model.

METHODS

We reviewed retrospectively the clinical charts of children ≤15 years of age treated for culture-confirmed or suspected MDR-TB between July 2007 and January 2011.

RESULTS

Nineteen children, ages two to 15, received treatment. At baseline, 74% of patients were co-infected with HIV, 63% were malnourished, 84% had severe radiographic findings, and 21% had extrapulmonary disease. Five (26%) children had culture-confirmed MDR-TB, ten (53%) did not have culture results available, and four (21%) subsequently had results indicating drug-susceptible TB. All children with HIV co-infection who were not already on antiretroviral therapy (ART) were initiated on ART a median of two weeks after the start of the MDR-TB regimen. Among the 17 patients with final outcomes, 15 (88%) patients were cured or completed treatment, two (12%) patients died, and none defaulted or were lost to follow-up. The majority of patients (95%) experienced adverse events; only two required permanent discontinuation of the offending agent, and only one required suspension of MDR-TB treatment for more than one week.

CONCLUSIONS

Pediatric MDR-TB and MDR-TB/HIV co-infection can be successfully treated using a combination of social support, close monitoring by community health workers and clinicians, and inpatient care when needed. In this cohort, adverse events were well tolerated and treatment outcomes were comparable to those reported in children with drug-susceptible TB and no HIV infection.

OBJECTIVES

The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection.

BACKGROUND

As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described.

METHODS

The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria.

RESULTS

Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003).

CONCLUSIONS

SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications.

OBJECTIVES

The aim of this study was to investigate whether exposure to a range of relatively low concentrations of aged secondhand smoke (SHS), similar to those encountered commonly in the community, would impair endothelial function in a concentration-dependent manner.

BACKGROUND

Exposure to SHS impairs endothelial function in humans. The concentration-dependent relationship for aged SHS effects on endothelial function after an exposure of short duration is unknown.

METHODS

Thirty-three healthy nonsmokers were exposed to 1 of 2 low levels of aged SHS or to conditioned filtered air for 30 min. The primary end point was change in maximal percent brachial artery flow-mediated dilation after exposure.

RESULTS

In a linear regression model for each increase in SHS exposure by 100 μg/m(3) respirable suspended particles, the absolute maximal percent brachial artery flow-mediated dilation was reduced by 0.67%. We did not find evidence of a threshold for the effect of SHS on flow-mediated dilation.

CONCLUSIONS

Short-term exposure to real-world levels of aged SHS for 30 min resulted in a concentration-dependent decrease in endothelial function as measured by flow-mediated dilation.

BACKGROUND

A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown.

METHODS

In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups -- receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo -- in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period.

RESULTS

When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P=0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here.

CONCLUSIONS

Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.).