Susan E. Puumala

Prospective study of survival outcomes in Non-Hodgkin's lymphoma patients with rheumatoid arthritis.

PURPOSE Although preliminary studies suggest that non-Hodgkins lymphoma (NHL) complicating rheumatoid arthritis (RA) may be a clinically distinct entity compared with that occurring in the general population, studies examining the impact of antecedent RA on survival are limited. In this prospective study, we examined the association of RA with survival in patients with NHL. PATIENTS AND METHODS Using two large lymphoma registries, we identified patients with evidence of RA preceding NHL. Survival in RA patients was compared with that of controls using proportional hazards regression, adjusting for the effects of age, sex, lymphoma diagnosis-to-treatment lag time, calendar year, International Prognostic Index score, and NHL grade. RESULTS The frequency of NHL subtypes was similar in RA patients (n = 65) and controls (n = 1,530). Compared with controls, RA patients with NHL had similar overall survival (hazard ratio [HR] = 0.95; 95% CI, 0.70 to 1.30) but were at lower risk of lymphoma progression or relapse (HR = 0.41; 95% CI, 0.25 to 0.68) or death related to lymphoma or its treatment (HR = 0.60; 95% CI, 0.37 to 0.98), but were more than twice as likely to die from causes unrelated to lymphoma (HR = 2.16; 95% CI, 1.33 to 3.50). CONCLUSION RA is associated with improved NHL-related outcomes, including a 40% reduced risk of death occurring as a result of lymphoma or its treatment and approximately a 60% lower risk of lymphoma relapse or progression compared with non-RA controls. However, the survival advantage gained in RA from the acquisition of lymphomas with favorable prognoses is negated through an increased mortality from other comorbid conditions.

Pharmacist Monitoring of QTc Interval–Prolonging Medications in Critically Ill Medical Patients: A Pilot Study

BACKGROUND: No data exist regarding the value of pharmacist monitoring of drugs associated with QTc interval prolongation. OBJECTIVE: To assess the capability, clinical impact, and economic impact of pharmacists monitoring for drug-induced QTc interval prolongation in critically ill medical adult patients. METHODS: In a prospective, parallel-group study, 149 consecutive medical intensive care unit (ICU) patients prescribed a QTc interval–prolonging drug at the Los Angeles County + University of Southern California Medical Center were assigned on alternating days to an intervention group (clinical pharmacist on physician team monitored drugs using a standardized algorithm) or a standard care group (team without pharmacist using an algorithm). The monitoring algorithm used daily assessments of electrocardiograms and laboratory data to generate pharmacotherapeutic recommendations. The primary endpoint was the frequency of QTc interval prolongation (>500 msec at any time or an increase ≥60 msec over baseline). Secondary endpoints included QTc interval greater than 470 msec in women or greater than 450 msec in men, mean increase in QTc interval at 48 hours, recommendation acceptance rate, and cost of care. RESULTS: QTc interval prolongation occurred less frequently in the intervention group compared with the standard care group (19% vs 39%, respectively; p = 0.006). Incidence of QTc interval greater than 500 msec (13% vs 33%, respectively; p = 0.003) was also lower in the intervention group. Incidence of QTc interval increase of 60 msec or more over baseline (12% vs 21%, respectively; p = 0.12) and increase in QTc interval at 48 hours over baseline (mean ± SD; 6.4 ± 40.8 vs 18.2 ± 42.3 msec, respectively; p = 0.097) were not significantly different between the groups. Algorithm-generated recommendations were accepted 70% of the time by the intervention group physician team. Total cost and cost per day were not significantly different between groups. CONCLUSIONS: In this preliminary study, pharmacist monitoring of QTc interval–prolonging drugs using a simple algorithm was feasible and reduced the risk of QTc interval prolongation. Further studies that monitor other proarrhythmic medications are warranted.

Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery

The risk factors for nonalcoholic fatty liver disease in patients undergoing bariatric surgery are under study. We wanted to determine the correlation between nonalcoholic fatty liver disease and patient factors such as obesity and liver function tests. A retrospective analysis was performed on 177 nonalcoholic morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass with liver biopsy, to identify risk factors for nonalcoholic fatty liver disease. The histologic grade of liver disease was compared with preoperative body mass index, age, and liver function tests. Simple steatosis and steatohepatitis were present in 90% and 42% of patients, respectively. Elevated transaminaselevels were an independent risk for liver disease. Body mass index and liver disease were not correlated with univariate analysis. Regression analysis performed on age, body mass index, and liver disease demonstrated that the risk for liver disease increased with body mass index in the younger (<35 years old) age group and decreased with body mass index in the older (<45 years old) age group. There was a high incidence of steatosis and steatohepatitis in these nonalcoholic bariatric patients, and elevated transaminase level was indicative of disease. Body mass index was a positive risk factor for liver disease in younger patients but a negative risk factor in the older patients.

Clinical predictors of injuries not identified by focused abdominal sonogram for trauma (FAST) examinations.

This studys objective was to identify clinical characteristics of patients with a blunt traumatic injury that increased the risk of peritoneal or pericardial fluid collections and abdominal organ injuries not identified by a bedside focused abdominal sonogram for trauma (FAST) examination. This observational study used a retrospective chart review of a cohort of patients identified through a query of the University of Nebraska Medical Centers trauma registry, a tertiary referral center for portions of Nebraska, Iowa, and Missouri. Adult patients presenting to the Emergency Department (ED) for an evaluation of blunt traumatic injury from September 1996 to December 2002 were eligible if their ED course included admission to the trauma service after completion of a bedside FAST examination (US) and a confirmatory study (Conf) such as an abdominopelvic computed tomography scan or exploratory laparotomy within 12 h of completion of the ED FAST examination. The medical records of those patients with a US+/Conf+ or US-/Conf+ examination were reviewed. Clinical characteristics were recorded on a standard data collection form. Statistically significant predictors of a US-/Conf+ examination were found using a stepwise logistic regression procedure. A query of the trauma registry for the study period revealed 1453 adult individuals with blunt abdominal trauma, with 458 patients meeting the inclusion criteria. The clinical characteristics of the 79 US+/Conf+ examinations were compared to those of the 53 US-/Conf+ examinations. The presence of a radiographically proven pelvic fracture (odds ratio 3.459; 95% confidence interval of 1.308-9.157) and a radiographically or operatively proven renal injury (odds ratio 3.667; 95% confidence interval of 1.013-13.275) were found to be significant predictors. The presence of a pelvic fracture or renal injury in adult victims of blunt abdominal trauma increases the likelihood of a US-/Conf+ examination. Patients with a negative FAST examination and pelvic fracture may benefit from additional radiographic or operative evaluations for occult injuries.

Improvement in Prescribing Habits and Economic Outcomes Associated With the Introduction of a Standardized Approach for Surgical Antimicrobial Prophylaxis

A quasi-experimental before-after study was conducted to determine the impact on prescribing habits and economic outcomes of an intervention that required use of an order form for surgical antimicrobial prophylaxis. Implementation of this intervention improved compliance with guidelines for prevention of surgical site infections, particularly with respect to choice of antibiotic, duration of use, and dosage, and resulted in decreased cost of surgical prophylaxis.

Cytomegalovirus viremia in solid organ transplantation: does the initial viral load correlate with risk factors and outcomes?

Abstract:  Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV‐V (asymptomatic viremia) or CMV‐D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time‐to‐event curves. Twenty‐eight recipients were identified: five CMV‐V, 23 CMV‐D. Patients with CMV‐D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV‐V (2500 copies/mL; p < 0.05). No patients with CMV‐V had an initial QnPCR > 10 000 copies/mL compared with 83% of the CMV‐D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.

Is Linezolid Superior to Vancomycin for Complicated Skin and Soft Tissue Infections Due to Methicillin-Resistant Staphylococcus aureus?

It is with interest that we read the article by J. Weigelt et al. (2). While this study aims to demonstrate that linezolid may be used for complicated skin and soft tissue infections (CSSTIs), we are concerned with the studys conclusions. The study was designed to prove superiority of linezolid over vancomycin with respect to the primary end point of clinical cure, with a power of 0.90 and a significance level of 0.05 for a two-sided test. The primary outcome result was not statistically significant based on the trial design (intent-to-treat [ITT] population clinical cure for linezolid, 92.2%, and for vancomycin, 88.5%; 95% confidence interval, −0.11%, 7.47%). A subgroup analysis based on the microbiological outcomes was performed, and the authors reached the conclusion that linezolid is “… superior to vancomycin in the treatment of CSSTIs due to MRSA” (2). This was based on the methicillin-resistant Staphylococcus aureus (MRSA) subgroup analysis, in which the direct comparison yielded a significantly higher proportion of microbiological outcomes in the linezolid arm than in the vancomycin arm. Baseline characteristics within each MRSA subgroup that could have biased the results in either arm were not provided. In addition, an interaction test to understand if there was a difference in the magnitude of the effect based on the type of microorganism was also not provided. This is not in accordance with the CONSORT guidelines (1) for clinical trial reporting. We performed this analysis with the published data and found no significant treatment by microorganism (MRSA versus non-MRSA organism) interaction for either the MRSA modified intent-to-treat (MITT) (P = 0.24) or MRSA microbiologically evaluable (ME) (P = 0.07) subgroups, indicating that there was not a differential treatment effect based on microorganism type. Also, it was surprising that we could not find the “clinical response” analysis (the primary end point of the study) with respect to this same MRSA subgroup in the published paper. This is of paramount importance. For a microbiological cure to be meaningful, it has to be accompanied by a clinical cure. Due to its obvious importance, the clinical response outcome (cured, improved, failed, or indeterminate) should have been reported within the MRSA subgroup, and results (similar to those of Table 4 [2]) should be presented along with baseline characteristics and interaction tests, as suggested above for the “microbiological outcomes” analysis. In addition, we are concerned with the safety conclusion: “Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial” (2). However, this is not appropriate, since thrombocytopenia (P < 0.001), diarrhea (P = 0.0006), and nausea (P = 0.006) were highly statistically significantly more frequent in the linezolid than in the vancomycin arm. In conclusion, this study failed to prove linezolids superiority over vancomycin in the CSSTI population. The rate of “microbiological cure” (secondary outcome) in the MRSA subgroup was higher with linezolid, but the rate of “clinical cure” (primary outcome) was not presented. Moreover, the absence of significant interaction suggests that the treatment effect was not influenced by the type of microorganism. Another trial needs to be done to confirm the results from the MRSA subgroup analysis. Finally, the papers conclusion should also state that the rates of thrombocytopenia, diarrhea, and nausea were statistically significantly higher with linezolid than with vancomycin.

Diagnosis and treatment of adult attention-deficit/hyperactivity disorder at US ambulatory care visits from 1996 to 2003

ABSTRACT Objective: To determine national-estimates and characteristics of United States (US) ambulatory care visits made by adults, aged 18 years or older, with attention-deficit hyperactivity disorder (ADHD) diagnosis, treatment patterns, and significant factors associated with adult-ADHD treatment. Methods: Retrospective analyses were conducted of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey over a combined 8‐year period (1996–2003). Mental-health disorder (including ADHD) visits were identified using International Classification of Diseases, 9th revision, Clinical Modification (ICD‐9‐CM) diagnostic codes. Significant factors of adult-ADHD treatment were determined in multivariable logistic regression analyses. Results: An estimated total 10.5 million ambulatory-ADHD visits accounted for 3.5% of 301 million adult mental-health disorder visits. The census-adjusted visit rate was 0.3–0.4%. Increasing in numbers from the year 2000, ADHD visits were most often to psychiatrists, by Caucasian men, aged 18 to 40 years. Significantly fewer ADHD visits without, versus with, psychiatric comorbidity (mainly depression) received various treat-ments – behavioral (46% vs. 83%), antidepressant (18% vs. 66%), or combined behavioral and ADHD-specific (stimulant or atomoxetine) pharmacotherapy (36% vs. 57%) respectively. However, more ADHD visits without than with psychiatric comorbidity received ADHD-specific pharmacotherapy alone (76% vs. 68%) or no treatment (14% vs. 6.5%). At ADHD visits, adjusting for gender, age, and US census geographic-region, psychiatric comorbidity (odds ratio [OR], 6.5, 95% confidence interval [Cl], 3.5–12.4, p < 0.05) and self-pay reimbursement-source (OR, 2.7, 95% Cl, 1.3–5.7, p < 0.05) significantly increased the likelihood of behavioral treatment. Insurance reimbursement-sources other than private and self-pay significantly decreased the likelihood of an ADHD-specific pharmacotherapy (OR, 0.4, 95% Cl, 0.2–0.7, p < 0.05) or any ADHD-treatment (OR, 0.2, 95% Cl, 0.1–0.5, p < 0.05). Conclusions: Adult-ADHD visits have increased in recent years, with a census-adjusted visit rate of 0.3–0.4%. Psychiatric comorbidity and reimbursement-source were associated with ADHD-treatment. Limited treatment may be a significant problem in US-ambulatory care. It is important to continue validation studies, educate providers, examine the efficacy of multimodal-treatments, and study insurance-related barriers to adult ADHD-treatment.

Minocycline-induced hyperpigmentation in rheumatoid arthritis.

Background:Minocycline is recognized as an effective, well-tolerated therapy in rheumatoid arthritis (RA), although its use has been associated with the development of cutaneous hyperpigmentation. Objectives:To assess the clinical determinants and frequency of minocycline-induced hyperpigmentation in patients with RA. Methods:A retrospective medical record review of all patients with RA seen in 2 academic rheumatology practices was performed to identify subjects who had received at least 1 month of continuous minocycline therapy. Patient demographics, disease characteristics, medication use, and medication side effects were abstracted from the medical record. Using Cox proportional hazards regression and restricting the analysis to the initial minocycline course, we examined the association of patient factors and concomitant medications with the development of hyperpigmentation. Results:Of 121 patients with at least 1 minocycline course of 30 days or more, 44 (36%) developed documented hyperpigmentation, including 33 during the initial course over a median duration of 9.1 month (range 2.2–77.8 months). Hyperpigmentation was most commonly seen on the upper and lower extremities and the head/neck region. Minocycline-induced hyperpigmentation led to the discontinuation of treatment in 3 patients, with 12 additional patients receiving a dose reduction. Increasing age was the only clinical determinant significantly associated with hyperpigmentation (HR = 1.04; 95% CI 1.00–1.07, P = 0.04). There were no significant associations of sex, weight, concomitant prednisone, or aspirin use with the development of hyperpigmentation. Conclusions:Minocycline-induced hyperpigmentation is a common complication seen with minocycline use in the treatment of RA, and seems to increase with age.

Drug-Induced QTc-Interval Prolongation in the Intensive Care Unit: Incidence and Predictors:

There is a paucity of information regarding QTc prolongation in critically ill patients. A prospective observational study was conducted to assess the incidence and predictors of QTc prolongation associated with medications in intensive care unit (ICU) patients. Consecutive adult patients prescribed prespecified QTc-prolonging medications were assessed for development of the combined incidence of QTc >500 ms at anytime and QTc increase >60 ms above baseline. Over 3 months, 200 consecutive patients (63 ± 18 years; 52% female; 73% Caucasian; baseline QTc 447.3 ± 51.5 ms) were evaluated. The primary end point occurred in 48% of the patients (QTc >500 ms 40%, QTc increase >60 ms 29%). The majority of patients experienced a QTc >470 or 450 ms (60.5%). Mean increase in QTc at 48 hours was 20 ± 35 ms. Upon multivariate analysis, length of stay [odds ratio 1.30, 95% confidence interval (1.15, 1.47)] and baseline QTc [1.01 (1.01, 1.02)] were associated with an increased risk for the primary end point, while beta-blockers [0.41 (0.20, 0.81)] were associated with a risk reduction. In conclusion, increased risk of proarrhythmia, as assessed by QTc prolongation, occurs in the majority of ICU patients when prescribed medications with electrophysiologic properties. Increased vigilance is warranted. The possible protective effect of beta-blockers requires confirmation.