ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock.

BACKGROUND: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. METHODS: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. RESULTS: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2-161.5], p = 0.0028). Similarly, oxygenation index decreased by - 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus - 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI - 8.6 to - 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5-47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. CONCLUSIONS: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

The impact of intensive care unit physician staffing change at a community hospital.

OBJECTIVES: A high-intensity staffing model has been defined as either mandatory intensivist consultation or a closed intensive care unit in which intensivists manage all aspects of patient care. In the current climate of limited healthcare resources, transitioning to a closed intensive care unit model may lead to significant improvements in patient care and resource utilization. METHODS: This is a single-center, retrospective cohort study of all mechanically ventilated intensive care unit admissions in the pre-intensive care unit closure period of 1 October 2014 to 30 September 2015 as compared with the post-intensive care unit closure period of 1 November 2015 to 31 October 2016. Patient demographics as well as outcome data (duration of mechanical ventilation, length of stay, direct costs, complications, and mortality) were abstracted from the electronic health record. All data were analyzed using descriptive and inferential statistics. Regression analyses were used to adjust outcomes for potential confounders. RESULTS: A total of 549 mechanically ventilated patients were included in our analysis: 285 patients in the pre-closure cohort and 264 patients in the post-closure cohort. After adjusting for confounders, there was no significant difference in mortality rates between the pre-closure (40.7%) and post-closure (38.6%) groups (adjusted odds ratio = 0.82; 95% confidence interval = 0.56-1.18; p = 0.283). The post-closure cohort was found to have significant reductions in duration of mechanical ventilation (3.71-1.50 days; p < 0.01), intensive care unit length of stay (5.8-2.7 days; p < 0.01), hospital length of stay (10.9-7.3 days; p < 0.01), and direct hospital costs (US $16,197-US $12,731; p = 0.009). Patient complications were also significantly reduced post-intensive care unit closure. CONCLUSION: Although a closed intensive care unit model in our analysis did not lead to a statistical difference in mortality, it did demonstrate multiple beneficial outcomes including reduced ventilator duration, decreased intensive care unit and hospital length of stay, fewer patient complications, and reduced direct hospital costs.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Implementation and evaluation of a virtual learning advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 restricted student involvement in direct patient care. Virtual learning is an effective education strategy in pharmacy curriculums. This study aimed to evaluate student perceptions of virtual learning advanced pharmacy practice experiences (APPE) utilizing an electronic 12-question survey. EDUCATIONAL ACTIVITY AND SETTING: Virtual learning was developed and implemented, and students were surveyed at the end of the APPE. The survey was comprised of one open-ended and 11 Likert scale questions. It assessed implementation and use of virtual learning in place of a standard on-site APPE. FINDINGS: Responses were attained from 19 students. Questions regarding resources provided and virtual learning enabling autonomous, independent learning had the highest percent of strong agreement. No responses indicated strong disagreement. Three questions solicited >10% response rate of somewhat disagree, 16% associated with virtual learning helping the student become a better member of the healthcare team after graduation. Open-ended responses acknowledged appreciation of the virtual APPE and presented material. One in six students commented on the ability to apply the learned information to direct patient care. Feedback was delivered on consideration for increased utility of patient care-orientated applications to facilitate simulation of real-life patient cases. SUMMARY: Students who completed the virtual APPE were satisfied overall. Virtual teaching modalities may be incorporated into APPEs, particularly when direct patient care access is limited, but should not be used to completely replace the experience gained during direct patient care.

Comparison of Melatonin and Zolpidem for Sleep in an Academic Community Hospital: An Analysis of Patient Perception and Inpatient Outcomes.

Hospitalizations can significantly disrupt patient sleep patterns and contribute to insomnia, which places patients at a higher risk of altered mental status as well as other complications. Despite attempts to control environmental factors, deliriogenic medications are often prescribed for the management of hospital-related insomnia. The primary objective of this study is to compare patient-perceived effectiveness of zolpidem versus melatonin in hospitalized patients. All inpatients who received melatonin or zolpidem the previous night as asleep aid and had no acute psychological issues or history of substance abuse were eligible for participation in this single-center, prospective, observational cohort study. The Verran and Snyder-Halpern sleep scale was utilized to evaluate sleep perception in 3 domains: sleep disturbance, effectiveness, and supplementation. A total of 439 patients were screened and 100 patients met study criteria and consented to the study. In the melatonin and zolpidem groups, the estimated adjusted means for the total sleep effectiveness (206.8 mm, 95% confidence interval [CI], 168.7-253.5vs 187.4 mm, 95% CI, 152.8-229.7; P=.513), sleep disturbance(362.1 mm, 95% CI, 310.1-422.7 vs 339.54 mm, 95% CI, 290.8-396.4; P=.573), and sleep supplementation (111.4 mm, 95% CI, 86.3-143.8 vs 120.9 mm, 95% CI, 94.1-155.2; P=.661) domains were not statistically different. Both melatonin and zolpidem were well tolerated with grogginess and headache as the only reported adverse effects. Melatonin demonstrated no significant difference in patient-perceived sleep effectiveness, disturbance, supplementation, or adverse effects when compared to zolpidem.

Mesenteric venous thrombosis: A lethal complication of hyperglycemic crises.

PURPOSE: Although hyperglycemic crises can lead to a hypercoagulable state, few instances of associated mesenteric venous thrombosis (MVT) have been reported. Worsening abdominal pain in the context of shock requiring vasopressor support should prompt urgent further investigation. SUMMARY: A 44-year-old Hispanic male arrived at an emergency department with chief complaints of lethargy, polydipsia, and polyuria. His past medical history included type 2 diabetes, epilepsy, obesity, tobacco smoking, and noncompliance with his medications. On arrival the patient had a serum glucose concentration of >1,600 mg/dL, and hyperosmolar hyperglycemic syndrome (HHS) was diagnosed. The patient was admitted to the intensive care unit with respiratory failure and subsequently developed shock refractory to fluid resuscitation, necessitating vasopressor support. On hospital day 4, a computerized tomogram obtained for investigation of increasing abdominal tenderness revealed superior MVT and pneumatosis intestinalis. Despite an emergency laparotomy and enterectomy, the patient ultimately succumbed on hospital day 41 due to recurrent pneumonia complicated by acute respiratory distress syndrome and septic shock. CONCLUSION: Shock that is refractory to aggressive fluid resuscitation, necessitating pressor support, in the setting of HHS or diabetic ketoacidosis should prompt investigation for the underlying source of shock. Other etiologies, including hypovolemic, cardiogenic, and obstructive shock, should be considered; however, infection is the leading trigger of hyperglycemic crises. Although rarely reported, MVT should be considered in the diagnostic algorithm in the absence of an identified infectious source. Prompt investigation should include use of diagnostic modalities such as computed tomography to assess for MVT.

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

Appropriateness of thrombophilia testing in patients in the acute care setting and an evaluation of the associated costs.

Thrombophilia testing is rarely recommended in acute care settings due to the high likelihood of false-positive and false-negative results. Inappropriately performing these tests in the acute care setting is associated with inaccurate interpretation and an increased economic burden. In this retrospective analysis, the appropriateness of thrombophilia tests ordered for patients in an acute care setting was evaluated in terms of both clinical utility and economic costs. This analysis included adult inpatients discharged from an academic community medical center from November 1, 2016 to November 1, 2017 who received thrombophilia testing. Patients were stratified into two groups: appropriately tested and inappropriately tested based on data abstracted directly from the electronic health record. The primary outcome, the appropriateness of the tests, was based on published criteria for thrombophilia testing and included concurrent anticoagulation use, patient admitting diagnosis, and/or comorbidities associated with thrombosis risk. The secondary endpoint was the financial burden of inappropriate thrombophilia testing based on assay charges. The analytic sample included 200 patients and 1393 thrombophilia tests. In 179 patients (89.5%), 1168 tests (83.8%) were inappropriately conducted. From 179 patients, tests in 85 were inappropriate due to concurrent anticoagulant use and/or provoked venous thromboembolism (VTE), and tests in 94 were inappropriate due to a lack of 2 or more risk factors for thrombophilia. Only 21 patients (10.5%) had appropriate testing with 225 tests (16.2%). The financial impact of inappropriate testing was estimated as excess charges amounting to $148,151.16/year. Restricting testing to avoid unnecessary risks and costs warrants further analysis.

Evaluation of treatment options for methicillin-resistant Staphylococcus aureus infections in the obese patient.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major cause of infection in both the hospital and community setting. Obesity is a risk factor for infection, and the prevalence of this disease has reached epidemic proportions worldwide. Treatment of infections in this special population is a challenge given the lack of data on the optimal antibiotic choice and dosing strategies, particularly for treatment of MRSA infections. Obesity is associated with various physiological changes that may lead to altered pharmacokinetic parameters. These changes include altered drug biodistribution, elimination, and absorption. This review provides clinicians with a summary of the literature pertaining to the pharmacokinetic and pharmacodynamic considerations when selecting antibiotic therapy for the treatment of MRSA infections in obese patients.

The Burns Registry of Australia and New Zealand: progressing the evidence base for burn care.

OBJECTIVE: Analysis of data from the Burns Registry of Australia and New Zealand (BRANZ) to determine the extent of variation between participating units in treatment and in specific outcomes during the first 4 years of its operation. DESIGN: BRANZ, an initiative of the Australian and New Zealand Burn Association, is a clinical quality registry developed in accordance with the Australian Commission on Safety and Quality in Healthcare national operating principles. SETTING: Patients with burn injury who fulfil pre-defined criteria are transferred to and managed in designated burn units. There are 17 adult and paediatric units in Australia and New Zealand that manage almost all patients with significant burn injury. Twelve of these units treat adult patients. PARTICIPANTS: Data on 7184 adult cases were contributed by ten acute adult burn units to the registry between July 2010 and June 2014.Major outcomes: In-hospital mortality, hospital length of stay, skin grafting rates, and rates of admission to intensive care units. RESULTS: Considerable variations in unit profiles (including numbers of patients treated), in treatment and in outcomes were identified. CONCLUSIONS: Despite the highly centralised delivery of care to patients with severe or complex burn injury, and the relatively small number of specialist burn units, we found significant variation between units in clinical management and in outcomes. BRANZ data from its first 4 years of operation support its feasibility and the value of further development of the registry. Based on these results, the focus of ongoing research is to improve understanding of the reasons for variations in practice and of their effect on outcomes for patients, and to develop evidence-informed clinical guidelines for burn management in Australia and New Zealand.

Assessment of low-dose i.v. ketamine infusions for adjunctive analgesia.

PURPOSE: The results of a study evaluating all patients treated with adjunctive low-dose ketamine for analgesia over a three-year period are presented. METHODS: A retrospective single-center analysis evaluated all adult patients who received adjunctive low-dose i.v. ketamine infusions from September 2010 to September 2013. Patients were excluded if they received concomitant oral ketamine, if ketamine was used to treat seizures, or if the patients received ketamine boluses without infusion. The primary endpoint was to identify the patient populations receiving low-dose intravenous ketamine. Secondary endpoints included an assessment of clinical variables and adverse events. Demographic information, level of care, clinical variables, adverse events, and patient outcomes were recorded. RESULTS: A total of 460 patients were evaluated. Of these, 396 were included in this analysis. Ketamine was administered to 69.9% of the patients in association with a surgical procedure, as opposed to 30.1% who received ketamine for medical management of pain. The percentage of patients receiving intensive care unit level care was 24%. Before initiation of ketamine, patient-reported pain scores averaged 7.1 ± 2.63 S.D.; during the ketamine infusion, patient-reported pain scores averaged 6.42 ± 2.01 S.D.; (p < 0.001). In the safety analysis, hypertension occurred in 21.4% of patients, hypotension occurred in 15.1% of patients, and respiratory depression occurred in 6.3% of patients. CONCLUSION: A retrospective review found that patients receiving continuous ketamine infusions in addition to opioid therapy saw a reduction in pain scores and experienced cardiovascular adverse effects in greater than 20% of cases.

Improving Antibiotic De-Escalation in Suspected Ventilator-Associated Pneumonia: An Observational Study With a Pharmacist-Driven Intervention.

BACKGROUND: Recommendations for treatment of ventilator-associated pneumonia (VAP) emphasize early empiric broad-spectrum antibiotics. However, appropriate antibiotic de-escalation is also critical for optimal patient care. MATERIALS AND METHODS: We examined how often intensivists in our institution appropriately de-escalated antibiotics in cases of suspected VAP, and whether decision support by intensive care unit pharmacists could improve rates of antibiotic targeting and early antibiotic discontinuation in low-risk patients. MAIN RESULTS: A total of 92 (observation phase = 50; intervention phase = 42) patients with suspected VAP were identified. During the observation phase, 39 cases yielded positive sputum cultures, but in only 23 (59%) were antibiotics targeted to culture results. This rate improved during the intervention phase when 29 (91%) of 32 cases with positive cultures were targeted (P value .003). There were 48 cases in which the risk of pneumonia was considered low. Of the 26 low-risk cases in the observation phase, 5 (19%) had antibiotics discontinued early versus 5 (23%) of the 22 cases in the intervention phase. CONCLUSIONS: Decision support by clinical pharmacists significantly improved rates of appropriate antibiotic targeting in cases of culture-positive suspected VAP but did not have a significant effect on early antibiotic discontinuation in patients at low risk of true pneumonia.

Role of dexmedetomidine in adults in the intensive care unit: an update.

PURPOSE: The role of dexmedetomidine for the management of pain, agitation, and delirium in adult patients in the intensive care unit (ICU) is reviewed and updated. SUMMARY: Searches of MEDLINE (July 2006-March 2012) and an extensive manual review of journals were performed. Relevant literature with a focus on data published since our last review in 2007 was evaluated for topic relevance and clinical applicability. Optimal management of pain, agitation, and delirium in ICUs requires a systematic and multimodal approach aimed at providing comfort while maximizing outcomes. Dexmedetomidine is among multiple agents, including opioids, propofol, benzodiazepines, and antipsychotics, used to facilitate and increase patients' tolerability of mechanical ventilation. This article reviews the newest evidence available for dexmedetomidine use for sedation and analgesia in medical-surgical ICUs. Adverse effects associated with dexmedetomidine were similar among the studies examined herein. The most common adverse effects with dexmedetomidine were bradycardia and hypotension, in some cases severe enough to warrant the use of vasoactive support. Due to the adverse events associated with rapid dosage adjustment and bolus therapy, dexmedetomidine may not be the best agent for treating acute agitation. CONCLUSION: In medical-surgical ICUs, dexmedetomidine may be a viable non-benzodiazepine option for patients with a need for light sedation. In cardiac surgery patients, dexmedetomidine appears to offer no advantage over propofol as the initial sedative. The role of dexmedetomidine in unique patient populations such as neurosurgical, trauma, and obstetrics is yet to be established.

Age-related blood pressure patterns and blood pressure variability among hemodialysis patients.

BACKGROUND AND OBJECTIVES: Despite the high prevalence of cardiovascular disease among hemodialysis patients, the relationship between age and blood pressure (BP) is not well understood. It was postulated that the relationship of BP to age differs among hemodialysis patients versus the general population and that there is significant variability in dialysis unit BP measurements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To explore this hypothesis, the patterns of systolic, diastolic, mean arterial, and pulse pressures in the general population using data from National Health and Nutrition Examination Survey participants (n = 9242) were compared with those in a cohort of hemodialysis patients (n = 9849). RESULTS: In contrast to the increase in systolic BP with age in the general population, systolic BP was elevated in young hemodialysis patients and declined slightly among the elderly. The inverted "U"-shape relationship between age and diastolic BP in the general population was absent in hemodialysis patients. Diastolic BP was elevated among hemodialysis patients <50 yr of age and declined with advancing age. Mean arterial and pulse pressures were elevated among young hemodialysis patients and exhibited less age dependency than in the general population. Variability in BP within patients was similar to that between patients. CONCLUSIONS: The relationship of BP to age differed from that in the general population. The variability in dialysis unit BP measurements may limit their use in managing hypertension and predicting outcomes. Nevertheless, dialysis unit BP measurements are necessary to minimize acute complications during the dialysis procedure.

Azacitidine-induced interstitial and alveolar fibrosis in a patient with myelodysplastic syndrome.

A 71-year-old Caucasian man diagnosed with myelodysplastic syndrome developed interstitial and alveolar fibrosis after receiving a 7-day course of azacitidine therapy. The patient's pulmonary function began to deteriorate immediately after the administration of his chemotherapy regimen. Other potential causes of pulmonary toxicity were ruled out such as viral, fungal, and bacterial pathogens, as well as other concomitant drugs. To our knowledge, this is the first case report documenting biopsy-proven interstitial and alveolar fibrosis associated with azacitidine. The frequency of this adverse drug reaction is unknown but may become more evident with increasing exposure of the population to azacitidine.

Watershed fires - The making of mutant floods

While the Stafford Act clearly "encourages hazard mitigation," as noted above, there are many impediments in the process that in fact discourage mitigation. As we find ourselves arguing about eligibility, it is really the level of assistance that is being debated. How much is enough, and who should pay for it? We are thus joined with the debate of "cost containment" versus "cost benefit," and what the federal role should be