Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

Impact of nationwide essential trace element shortages: A before-after, single-center analysis of hospitalized adults receiving home parenteral nutrition therapy.

BACKGROUND: Recent data on the prevalence of essential trace element (ETE) deficiencies in home parenteral nutrition (HPN) patients are scarce. We investigated whether ETE deficiencies are still an important issue for HPN patients and whether the prevalence of such deficiencies may be influenced by nationwide drug shortages. METHODS: We conducted a single-institution, retrospective analysis from 2006 to 2015 of hospitalized HPN patients who continued PN during and in between hospitalizations. In subgroup analysis, patients were dichotomized as those with HPN duration <1 vs ≥1 year. Zinc (Zn), copper (Cu), and selenium (Se) levels were abstracted for patients over the study period. Prevalence of ETE deficiency was compared using chi-squared test for patients hospitalized during nonshortage vs shortage (2011-2014) periods. RESULTS: Ninety-six patients were included in the analysis. Prevalence of ETE deficiency during nonshortage vs shortage periods was 48% vs 54% (Zn), 15% vs 21% (Cu), and 24% vs 48% (Se; P = .01), respectively. When comparing patients who received HPN <1 year vs ≥1 year, the prevalence of Se deficiency doubled during shortage in both subgroups (24% to 42% vs 26% to 49%); and Cu deficiency tripled during shortage period in the group receiving HPN ≥1 year (5% to 16%). CONCLUSION: ETE deficiency is prevalent in hospitalized HPN patients and was exacerbated during nationwide shortages of parenteral supplements. Statistical significance may be limited by small sample size. Future studies are needed to determine optimal ETE supplementation strategies for minimizing the impacts of nationwide drug shortages on HPN patients.

Effect of Integrating Substance Use Disorder Treatment into Primary Care on Inpatient and Emergency Department Utilization.

BACKGROUND: Components of substance use disorder (SUD) treatment have been shown to reduce inpatient and emergency department (ED) utilization. However, integrated treatment using pharmacotherapy and recovery coaches in primary care has not been studied. OBJECTIVE: To determine whether integrated addiction treatment in primary care reduces inpatient and ED utilization and improves outpatient engagement. DESIGN: A retrospective cohort study comparing patients in practices with and without integrated addiction treatment including pharmacotherapy and recovery coaching during a staggered roll-out period. PARTICIPANTS: A propensity score matched sample of 2706 adult primary care patients (1353 matched pairs from intervention and control practices) with a SUD diagnosis code, excluding cannabis or tobacco only, matched on baseline utilization. INTERVENTION: A multi-modal strategy that included forming interdisciplinary teams of local champions, access to addiction pharmacotherapy, counseling, and recovery coaching. Control practices could refer patients to an addiction treatment clinic offering pharmacotherapy and behavioral interventions. MAIN MEASURES: The number of inpatient admissions, hospital bed days, ED visits, and primary care visits. KEY RESULTS: During the follow-up period, there were fewer inpatient days among the intervention group (997 vs. 1096 days with a mean difference of 7.3 days per 100 patients, p = 0.03). The mean number of ED visits was lower for the intervention group (36.2 visits vs. 42.9 per 100 patients, p = 0.005). There was no difference in the mean number of hospitalizations. The mean number of primary care visits was higher for the intervention group (317 visits vs. 270 visits per 100 patients, p < 0.001). Intervention practices had a greater increase in buprenorphine and naltrexone prescribing. CONCLUSIONS: In a non-randomized retrospective cohort study, integrated addiction pharmacotherapy and recovery coaching in primary care resulted in fewer hospital days and ED visits for patients with SUD compared to similarly matched patients receiving care in practices without these services.

Satisfaction With Health Care Among Patients Navigated for Preventive Cancer Screening.

BACKGROUND: Patient navigation (PN) programs can improve cancer screening in underserved populations. PN may advance quality and equity of care by supporting individuals at increased risk of not receiving recommended care. OBJECTIVE: To evaluate patient satisfaction with medical care and PN for cancer screening. METHODS: We conducted a telephone survey of patients enrolled in a randomized control trial evaluating the impact of PN for cancer screening to assess their satisfaction with overall medical care and the PN program. We measured patient satisfaction with medical care using the Patient Satisfaction Questionnaire-18 and evaluated patient satisfaction with PN in the navigated group using the Patient Satisfaction with Interpersonal Relationships with Navigator questionnaire. KEY RESULTS: Satisfaction surveys were completed by 114 navigated and 108 non-navigated patients (33% response rate). Patients who received PN had higher satisfaction scores with overall medical care (71.0 vs 66.8; P < .001). CONCLUSIONS: Our findings show that patients at high risk of nonadherence with comprehensive cancer screening were satisfied with PN and suggest that PN could positively influence patient satisfaction with overall medical care.

Medical Oncologists' Beliefs, Practices, and Knowledge Regarding Marijuana Used Therapeutically: A Nationally Representative Survey Study.

Background Although almost every state medical marijuana (MM) law identifies cancer as a qualifying condition, little research supports MM's use in oncology. We hypothesized that the discrepancy between these laws and the scientific evidence base poses clinical challenges for oncologists. Oncologists' beliefs, knowledge, and practices regarding MM were examined in this study. Methods In November 2016, we mailed a survey on MM to a nationally-representative, random sample of 400 medical oncologists. Main outcome measures included whether oncologists reported discussing MM with patients, recommended MM clinically in the past year, or felt sufficiently informed to make such recommendations. The survey also queried oncologists' views on MM's comparative effectiveness for several conditions (including its use as an adjunct to standard pain management strategies) and its risks compared with prescription opioids. Bivariate and multivariate analyses were performed using standard statistical techniques. Results The overall response rate was 63%. Whereas only 30% of oncologists felt sufficiently informed to make recommendations regarding MM, 80% conducted discussions about MM with patients, and 46% recommended MM clinically. Sixty-seven percent viewed it as a helpful adjunct to standard pain management strategies, and 65% thought MM is equally or more effective than standard treatments for anorexia and cachexia. Conclusion Our findings identify a concerning discrepancy between oncologists' self-reported knowledge base and their beliefs and practices regarding MM. Although 70% of oncologists do not feel equipped to make clinical recommendations regarding MM, the vast majority conduct discussions with patients about MM and nearly one-half do, in fact, recommend it clinically. A majority believes MM is useful for certain indications. These findings are clinically important and suggest critical gaps in research, medical education, and policy regarding MM.

Patient Navigation for Comprehensive Cancer Screening in High-Risk Patients Using a Population-Based Health Information Technology System: A Randomized Clinical Trial.

IMPORTANCE: Patient navigation (PN) to improve cancer screening in low-income and racial/ethnic minority populations usually focuses on navigating for single cancers in community health center settings. OBJECTIVE: We evaluated PN for breast, cervical, and colorectal cancer screening using a population-based information technology (IT) system within a primary care network. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted from April 2014 to December 2014 in 18 practices in an academic primary care network. All patients eligible and overdue for cancer screening were identified and managed using a population-based IT system. Those at high risk for nonadherence with completing screening were identified using an electronic algorithm (language spoken, number of overdue tests, no-show visit history), and randomized to a PN intervention (n = 792) or usual care (n = 820). Navigators used the IT system to track patients, contact them, and provide intense outreach to help them complete cancer screening. MAIN OUTCOMES AND MEASURES: Mean cancer screening test completion rate over 8-month trial for each eligible patient, with all overdue cancer screening tests combined using linear regression models. Secondary outcomes included the proportion of patients completing any and each overdue cancer screening test. RESULTS: Among 1612 patients (673 men and 975 women; median age, 57 years), baseline patient characteristics were similar among randomized groups. Of 792 intervention patients, patient navigators were unable to reach 151 (19%), deferred 246 (38%) (eg, patient declined, competing comorbidity), and navigated 202 (32%). The mean proportion of patients who were up to date with screening among all overdue screening examinations was higher in the intervention vs the control group for all cancers combined (10.2% vs 6.8%; 95% CI [for the difference], 1.5%-5.2%; P < .001), and for breast (14.7% vs 11.0%; 95% CI, 0.2%-7.3%; P = .04), cervical (11.1% vs 5.7%; 95% CI, 0.8%-5.2%; P = .002), and colon (7.6% vs 4.6%; 95% CI, 0.8%-5.2%; P = .01) cancer compared with control. The proportion of overdue patients who completed any cancer screening during follow-up was higher in the intervention group (25.5% vs 17.0%; 95% CI, 4.7%-12.7%; P < .001). The intervention group had more patients completing screening for breast (23.4% vs 16.6%; 95% CI, 1.8%-12.0%; P = .009), cervical (14.4% vs 8.6%; 95% CI, 1.6%-10.5%; P = .007), and colorectal (13.7% vs 7.0%; 95% CI, 3.2%-10.4%; P < .001) cancer. CONCLUSIONS AND RELEVANCE: Patient navigation as part of a population-based IT system significantly increased screening rates for breast, cervical, and colorectal cancer in patients at high risk for nonadherence with testing. Integrating patient navigation into population health management activities for low-income and racial/ethnic minority patients might improve equity of cancer care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02553538.

Adequate Nutrition May Get You Home: Effect of Caloric/Protein Deficits on the Discharge Destination of Critically Ill Surgical Patients.

BACKGROUND: Macronutrient deficit in the surgical intensive care unit (ICU) is associated with worse in-hospital outcomes. We hypothesized that increased caloric and protein deficit is also associated with a lower likelihood of discharge to home vs transfer to a rehabilitation or skilled nursing facility. MATERIALS AND METHODS: Adult surgical ICU patients receiving >72 hours of enteral nutrition (EN) between March 2012 and May 2014 were included. Patients with absolute contraindications to EN, <72-hour ICU stay, moribund state, EN prior to surgical ICU admission, or previous ICU admission within the same hospital stay were excluded. Subjects were dichotomized by cumulative caloric (<6000 vs ≥ 6000 kcal) and protein deficit (<300 vs ≥ 300 g). Baseline characteristics and outcomes were compared using Wilcoxon rank and χ(2) tests. To test the association of macronutrient deficit with discharge destination (home vs other), we performed a logistic regression analysis, controlling for plausible confounders. RESULTS: In total, 213 individuals were included. Nineteen percent in the low-caloric deficit group were discharged home compared with 6% in the high-caloric deficit group (P = .02). Age, body mass index (BMI), Acute Physiology and Chronic Health Evaluation II (APACHE II), and initiation of EN were not significantly different between groups. On logistic regression, adjusting for BMI and APACHE II score, the high-caloric and protein-deficit groups were less likely to be discharged home (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.08-0.96; P = .04 and OR, 0.29; 95% CI, 0.0-0.89, P = .03, respectively). CONCLUSIONS: In surgical ICU patients, inadequate macronutrient delivery is associated with lower rates of discharge to home. Improved nutrition delivery may lead to better clinical outcomes after critical illness.

Antibiotic Regimen after a Total Abdominal Colectomy with Ileostomy for Fulminant Clostridium difficile Colitis: A Multi-Institutional Study.

BACKGROUND: Fulminant Clostridium difficile colitis (fCDC) is a highly lethal disease with mortality rates ranging between 12% and 80%. Although often these patients require a total abdominal colectomy (TAC) with ileostomy, there is no established management protocol for post-operative antibiotics. In this study we aim to make some recommendations for post-operative antibiotic usage, while describing the practice across different institutions. METHODS: Multi-institutional retrospective case series including fCDC patients who underwent a TAC between January 1, 2007, and June 30, 2012. We first analyzed the complete cohort and consecutively performed a survivor analysis, comparing different antibiotic regimens. Additionally we stratified by time interval (antibiotics for ≤7 d, or ≥8 d). Primary outcome was in-hospital mortality. Additional secondary outcomes included hospital length of stay (HLOS), ICU LOS, number of ventilator-free days, and occurrence of intra-abdominal complications (proctitis, abscess, sepsis, etc.). RESULTS: A total of 100 fCDC patients that underwent a TAC were included across five institutions. Four different antibiotic regimens were compared; A (metronidazole IV+vancomycin PO), B (metronidazole IV), C (metronidazole IV+vanco PO and PR), and D (metronidazole IV+vancomycin PR). The combination of IV metronidazole with or without PO vancomycin showed superior outcomes in terms of a shorter ICU length of stay and more ventilator-free days. However, when comparing metronidazole alone vs. metronidazole and any combination of vancomycin, no significant differences were found. Neither the addition of vancomycin enema, nor the time interval changed outcomes. CONCLUSION: Patients, after a TAC for fCDC, may be placed on either IV metronidazole or PO vancomycin depending upon local antibiograms, and proctitis may be treated with the addition of a vancomycin enema (PR). There was no data to support routine treatment of more than 7 d.

Healthcare system effects of pay-for-performance for smoking status documentation.

OBJECTIVES: To evaluate the impact on smoking status documentation of a payer-sponsored pay-for-performance (P4P) incentive that targeted a minority of an integrated healthcare delivery system's patients. STUDY DESIGN: Three commercial insurers simultaneously adopted P4P incentives to document smoking status of their members with 3 chronic diseases. The healthcare system responded by adding a smoking status reminder to all patients' electronic health records (EHRs). We measured change in smoking status documentation before (2008-2009) and after (2010-2011) P4P implementation by patient P4P eligibility. METHODS: The P4P-eligible patients were compared primarily with a subset of non-P4P-eligible patients who resembled P4P-eligible patients and also with all non-P4P-eligible patients. Multivariate models adjusted for patient and provider characteristics and accounted for provider-level clustering and preimplementation trends. RESULTS: Documentation increased from 48% of 207,471 patients before P4P to 71% of 227,574 patients after P4P. Improvement from 56% to 83% occurred among P4P-eligible patients (adjusted odds ratio [AOR], 3.6; 95% confidence interval [CI], 2.9-4.5) and from 56% to 80% among the comparable subset of non-P4P-eligible patients (AOR, 3.0; 95% CI, 2.3-3.9). The difference in improvement between groups was significant (AOR, 1.3; 95% CI, 1.1-1.4; P = .009). CONCLUSIONS: A P4P incentive targeting a minority of a healthcare system's patients stimulated adoption of a system wide EHR reminder and improved smoking status documentation overall. Combining a P4P incentive with an EHR reminder might help healthcare systems improve treatment delivery for smokers and meet "meaningful use" standards for EHRs.

Thirty-day mortality after ischemic stroke and intracranial hemorrhage in patients with atrial fibrillation on and off anticoagulants.

BACKGROUND AND PURPOSE: Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation. METHODS: We followed 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors. RESULTS: We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45-0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88-2.98). Therapeutic international normalized ratios (2-3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20-0.70), whereas international normalized ratios>3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21-5.86). CONCLUSIONS: Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.

Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery.

INTRODUCTION: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the ß-adrenergic blocker propranolol, to reduce this overconsolidation. AIMS: In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. RESULTS: Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. CONCLUSIONS: The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.

The net clinical benefit of warfarin anticoagulation in atrial fibrillation.

BACKGROUND: Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage. OBJECTIVE: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation. DESIGN: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003. SETTING: An integrated health care delivery system. PATIENTS: 13 559 adults with nonvalvular atrial fibrillation. MEASUREMENTS: Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism. RESULTS: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used. LIMITATIONS: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable. CONCLUSION: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation. PRIMARY FUNDING SOURCE: National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Phosphorus binders and survival on hemodialysis.

Although hyperphosphatemia is a risk factor for mortality, there are limited data on whether therapy with phosphorus binders affects survival. We analyzed a prospective cohort study of 10,044 incident hemodialysis patients using Cox proportional hazards analyses to compare 1-yr all-cause mortality among patients who were or were not treated with phosphorus binders. We performed intention-to-treat analyses to compare patients who began treatment with phosphorus binders during the first 90 d after initiating hemodialysis (n = 3555) with those who remained untreated during that period (n = 5055). We also performed as-treated analyses that modeled phosphorus binder treatment as a time-dependent exposure. We compared survival in a subcohort of treated (n = 3186) and untreated (n = 3186) patients matched by their baseline serum phosphate levels and propensity score of receiving phosphorus binders during the first 90 d. One-year mortality was 191 deaths/1000 patient-years at risk. Treatment with phosphorus binders was independently associated with decreased mortality compared with no treatment in the intention-to-treat, as-treated, and matched analyses. The results were independent of baseline and follow-up serum phosphate levels and persisted in analyses that excluded deaths during the first 90 d of hemodialysis. In summary, treatment with phosphorus binders is independently associated with improved survival among incident hemodialysis patients. Although confirmatory studies are needed in the dialysis setting, future placebo-controlled, randomized trials of phosphorus binders might focus on predialysis patients with chronic kidney disease and normal serum phosphate levels.

A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer.

Therapy-induced stimulation of angiogenic molecules can promote tumor angiogenesis leading to enhanced tumor growth and cancer metastasis. Several standard and emerging therapies, such as radiation and photodynamic therapy (PDT), can induce angiogenic molecules, thus limiting their effectiveness. PDT is approved for the treatment of several cancers; however, its induction of vascular endothelial growth factor (VEGF) creates conditions favorable to enhanced tumor growth and metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative PDT in an orthotopic model of prostate cancer (LNCaP) increases not only VEGF secretion (2.1-fold) but also the fraction of animals with lymph node metastases. PDT followed by administration of an antiangiogenic agent, TNP-470, abolished this increase and reduced local tumor growth. On the other hand, administration of TNP-470 before PDT was less effective at local tumor control. In addition, animals in all groups, except in the PDT + TNP-470 group, had a weight loss of >3 g at the time of sacrifice; the weight of the animals in the PDT + TNP-470 group did not change. The significant reduction (P < 0.05) in tumor weight and volume observed between the PDT + TNP-470 group and the control group suggests that the combination of PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local tumor growth and metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes.

Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study.

OBJECTIVES: To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy. DESIGN: Cohort study. SETTING: Integrated healthcare delivery system. Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation. MEASUREMENTS: Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring >or=2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (<60, 60-69, 70-79, and >or=80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage. RESULTS: A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0-1.4) per older age category in patients taking warfarin and 1.5 (95% CI=1.3-1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio=1.8, 95% CI=1.1-3.1 for those taking warfarin, adjusted rate ratio=4.7, 95% CI=2.4-9.2 for those not taking warfarin) than in those younger than 80. CONCLUSION: Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients.

Increasing operating room efficiency through parallel processing.

OBJECTIVE: Because of rising costs and shrinking reimbursements, hospitals must continually find ways to improve efficiency and productivity. This study attempts to increase caseloads in ambulatory surgery operating rooms while maintaining patient satisfaction and safety. SUMMARY BACKGROUND DATA: In most hospitals, patients move through their operative day in a linear fashion, starting at registration and finishing in the recovery room. Given this pattern, only 1 patient may occupy the efforts of the operating room team at a time. By processing patients in a parallel fashion, operating room efficiency and patient throughput are increased while costs remain stable. METHODS: Patients undergoing hernia repairs under local anesthesia with intravenous sedation were divided into a control group and an experimental group. Patients in the control group received their local anesthesia in the operating room at the start of the surgery. The experimental group patients received their local anesthesia in the induction room by the surgeon while the operating room was being cleaned and set up. RESULTS: While operative time for the control group and the experimental group were nearly identical, the turnover time and the induction time were significantly shorter for the experimental group. The cumulative reduction in time during the operative day was sufficient to allow the addition of new operative cases. CONCLUSIONS: This study demonstrates a system of increasing operating room efficiency by changing patient flow rather than simply working to streamline existing steps. This increase in efficiency is not associated with the expansion of hospital budgets or a decrease in patient safety or satisfaction.

Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo.

BACKGROUND: Epithelial ovarian cancer often develops resistance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the efficacy of a treatment regimen that combines immunotherapy to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the development of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistry-based modality that is effective against chemo- and radioresistant ovarian tumors. METHODS: We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic efficacy was evaluated in acute treatment response and survival studies that used 9-19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided. RESULTS: Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95% confidence interval [CI] = 2.3% to 17.3%, P < .001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6% (95% CI = 58.7% to 74.4%, P < .001) and 38.2% (95% CI = 29.3% to 47.0%, P < .001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P < .001, analysis of variance) and improvements in survival (P = .0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33% [95% CI = 7% to 70%]) than mice in the C225-only (0/12; 0% [95% CI = 0% to 22%]) or PDT-only (1/10; 10% [95% CI = 0.2% to 44%]) groups. CONCLUSION: A mechanistically nonoverlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice.

Rapid absorption of tumescent lidocaine above the clavicles: a prospective clinical study.

BACKGROUND: Tumescent local anesthesia has been adapted for surgery of the face and neck, but there are no data regarding drug absorption when tumescent injection is used in this region. The aim of this study was to characterize the changes in plasma lidocaine concentrations over time when a tumescent solution is injected into the subcutaneous tissue of the neck. The study was carried out in human volunteer subjects, and injection of lidocaine to the thighs provided control data. METHODS: Eight healthy female volunteer subjects were studied twice using a prospective, crossover design. Tumescent lidocaine solution was injected into the subcutaneous tissue of the neck in one session and the thighs in another session. The order of injection was randomized. Blood samples were collected for 14 hours after injection, and the plasma concentration of lidocaine measured. The injected solution consisted of lidocaine 0.1%, NaHCO3 12.5 mEq/L, and epinephrine 1:1,000,000 in normal saline. A standardized dose of lidocaine (7 mg/kg) was used for each injection and no surgical procedure was performed. RESULTS: All subjects completed the study. Subject weight was 66.1 +/- 12.8 kg, body fat was 29.0 +/- 4.7 percent, and body mass index was 23.8 +/- 3.1 kg/m2. The average time to reach peak lidocaine concentration after neck injection was 5.8 hours, whereas peak lidocaine concentration after thigh injection did not occur until 12.0 hours. This difference of 6.2 hours was highly significant (p = 0.009). The average peak concentration after neck injection was 16 percent greater than that after thigh injection (0.94 microg/ml versus 0.81 microg/ml), with the difference approaching significance (p = 0.06). No adverse reactions were noted. CONCLUSIONS: Tumescent injection above the clavicles results in a rapid rise in plasma lidocaine concentration when compared with injection to the lower extremities. Toxic symptoms could occur much earlier than expected for lower extremity tumescent anesthesia. In addition, dangerous plasma levels could occur if tumescent anesthesia in the lower extremities is followed by tumescent injection above the clavicles, because the absorption curves would be superimposed.

Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs.

BACKGROUND: Inhaled nitric oxide (NO) is a potent and selective pulmonary vasodilator, which induces cGMP synthesis by activating soluble guanylate cyclase (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to influence smooth muscle tone via activation of sGC. We examined whether direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO. METHODS AND RESULTS: In awake, instrumented lambs, the thromboxane analogue U-46619 was intravenously administered to increase mean pulmonary arterial pressure to 35 mm Hg. Intravenous infusion of BAY 41-2272 (0.03, 0.1, and 0.3 mg x kg(-1) x h(-1)) reduced mean pulmonary arterial pressure and pulmonary vascular resistance and increased transpulmonary cGMP release in a dose-dependent manner. Larger doses of BAY 41-2272 also produced systemic vasodilation and elevated the cardiac index. N(omega)-nitro-l-arginine methyl ester abolished the systemic but not the pulmonary vasodilator effects of BAY 41-2272. Furthermore, infusing BAY 41-2272 at 0.1 mg x kg(-1) x h(-1) potentiated and prolonged the pulmonary vasodilation induced by inhaled NO (2, 10, and 20 ppm). In contrast, inhaled CO (50, 250, and 500 ppm) had no effect on U-46619-induced pulmonary vasoconstriction before or during administration of BAY 41-2272. CONCLUSIONS: In lambs with acute pulmonary hypertension, BAY 41-2272 is a potent pulmonary vasodilator that augments and prolongs the pulmonary vasodilator response to inhaled NO. Direct pharmacological stimulation of sGC, either alone or in combination with inhaled NO, may provide a novel approach for the treatment of pulmonary hypertension.

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

CONTEXT: Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. OBJECTIVE: To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. DESIGN: Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. SETTING: Large integrated health care system in Northern California. PATIENTS: Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. MAIN OUTCOMES: Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. RESULTS: Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559). CONCLUSIONS: Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.