Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study.

BACKGROUND & AIMS: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC. METHODS: A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes. RESULTS: Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10-0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02-0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21-2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls. CONCLUSIONS: Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.

Incorporating preauthorization into antimicrobial stewardship pharmacist workflow reduces Clostridioides difficile and gastrointestinal panel testing.

OBJECTIVE: To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea. DESIGN: Single center, quasi-experimental before-and-after study. SETTING: Tertiary-care, academic medical center in Ann Arbor, Michigan. PATIENTS: Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours. INTERVENTION: A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained. RESULTS: An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56-0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37-0.77; P = .001), respectively. CONCLUSIONS: We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.

Cirrhosis, Thrombosis, Finding FaXts about Doses: Dosing of Unfractionated Heparin for Venous Thromboembolism in Cirrhosis.

Background: Despite known disease-specific alterations to anti-factor Xa (AXA) levels, the physiological response of patients with cirrhosis to unfractionated heparin (UFH) infusions is not well established in clinical settings. Objective: The purpose of this study was to characterize the dosing and safety profile of UFH in patients with varying degrees of cirrhosis when treated for venous thromboembolism (VTE). Methods: This retrospective observational study was conducted at a single academic medical center in the United States. Patients with a diagnosis of cirrhosis who received UFH infusions for greater than 48 hours for treatment of VTE were included. Comparisons between heparin infusion rates, AXA levels, and safety outcomes based on severity of cirrhosis were made to define differences between those groups. Results: When compared by compensation status or by Child-Turcotte-Pugh (CTP) class, patients with more severe disease trended toward lower initial AXA levels on heparin initiation and higher heparin requirements to achieve therapeutic levels and were significantly less likely to achieve therapeutic levels than patients with less severe disease (P = 0.001 for compensation, P = 0.017 for CTP). Additionally, bleeding rates were higher in patients with more severe disease, without reaching statistical significance. Conclusion and Relevance: Patients with severe cirrhosis required higher doses of heparin to achieve the same therapeutic AXA levels, but also tended to have higher rates of bleeding compared with less severe cirrhosis. These results represent further evidence of changes in heparin response as cirrhosis severity increases and may suggest that current monitoring methods are suboptimal in this patient population.

Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say.

Historically, coagulopathy related to cirrhosis has been managed primarily as a bleeding disorder. However, several recent studies have shown that patients with cirrhosis have an increased risk of both bleeding and clotting. These coagulopathic changes are a result of the decreased synthetic capabilities of the cirrhotic liver. Vitamin K is often given to correct prolonged prothrombin times (PT) in patients with cirrhosis. However, this practice is not well defined and its effectiveness is questionable. The objective of our literature review is to determine the effectiveness of vitamin K to correct coagulopathy in cirrhosis. This report evaluates data published between 1981 and 2017. Published articles relevant to vitamin K use in cirrhotic patients were reviewed and summarized. The available literature regarding the use of vitamin K in cirrhosis is limited, and the research published so far does not appear to support its use. The routine uses of vitamin K to correct PT/international normalized ratio in hepatic cirrhosis should be avoided unless further studies can demonstrate true clinical benefit.

Evaluation of Vancomycin Dosing in Patients With Cirrhosis: Beginning De-Liver-ations about a New Nomogram.

Background: Reduced hepatic production of creatinine precursors in patients with decompensated cirrhosis leads to falsely low serum creatinine values. Therefore, when performing empiric dosing of vancomycin, an overestimation of creatinine clearance may result in significantly supratherapeutic vancomycin levels and increased risks of nephrotoxicity. Objective: The objective of the study is to evaluate vancomycin dosing requirements in patients with cirrhosis stratified by Child-Pugh Score, with subsequent comparison with doses that are recommended in the previously published and validated Kullar nomogram. Methods: A retrospective evaluation of patients with cirrhosis who received vancomycin for at least 3 full days and had at least 1 serum concentration drawn. Vancomycin daily dose and corresponding serum concentration were collected with patients stratified by Child-Pugh Score for comparison. Each patient had their vancomycin dose compared with the dose suggested by a published nomogram. Results: A total of 201 courses of vancomycin were followed. There were no significant differences between the Child-Pugh cohorts with respect to initial vancomycin dosing. There was also no significant difference in the median initial vancomycin trough concentration between the 3 cohorts (Child-Pugh A: 13.7 µg/mL [interquartile range, IQR: 10.4-22.1]; Child-Pugh B: 20.2 µg/mL [IQR: 15.1-25.9]; Child-Pugh C: 19.3 µg/mL [IQR: 14.9-25.2, P = .08]. The median vancomycin dose using the Kullar nomogram would have been 3.0 g/day (IQR: 2.0-3.75, P < .001), but the median dose actually used in this patient population was significantly less at 2.0 g/day. Nonetheless, the median vancomycin trough concentration in the entire patient population was 19.8 µg/mL (IQR: 15.4-25.9). Conclusion: In patients with cirrhosis, there was a high incidence of supratherapeutic vancomycin serum concentrations despite the fact that dosing was significantly less than that suggested by the published Kullar nomogram.

Efficacy of Induction Therapy With High-Intensity Tofacitinib in 4 Patients With Acute Severe Ulcerative Colitis.

As many as 25% of patients diagnosed with ulcerative colitis are hospitalized with an episode of acute severe ulcerative colitis (ASUC).1 The standard of care for patients hospitalized with ASUC relies on rapid induction with intravenous (IV) corticosteroids. Up to 30% of patients do not respond to corticosteroids alone.2 Rescue therapy with infliximab or cyclosporine has been shown to reduce rates of colectomy to 20% by 90 days.3,4 This still represents a significant rate of treatment failure, which leads to an unplanned and irreversible surgery. In recent years, increasing numbers of patients admitted with ASUC have already failed infliximab therapy, highlighting the need for additional treatment options for these patients. Tofacitinib is a rapidly acting, oral, small-molecule Janus kinase inhibitor that was recently approved by the Food and Drug Administration for treatment of ulcerative colitis.5 We present the first reported use of off-label, high-intensity tofacitinib in 4 patients admitted to our institution with ASUC predicted to fail medical management.

Dosing of Enoxaparin in Renal Impairment.

OBJECTIVE: To review enoxaparin treatment dosing, pharmacokinetics, and clinical outcomes data in patients with renal impairment and to examine the current two-tiered dosing regimen approved by the Food and Drug Administration (FDA). DATA SOURCES: A literature search of PubMed (1990-2016) was performed using the search terms low-molecular-weight heparin, unfractionated heparin, bleeding, enoxaparin, renal impairment, pharmacokinetics, and hemodialysis. STUDY SELECTION AND DATA EXTRACTION: All studies assessing the pharmacokinetic properties of enoxaparin in patients with renal impairment were evaluated. In addition, all retrospective and prospective studies assessing the safety and efficacy of enoxaparin treatment in this population were evaluated. DATA SYNTHESIS: Five pharmacokinetic studies evaluated changes in the pharmacokinetics of enoxaparin in patients with renal impairment. In these studies, enoxaparin clearance was reduced by 17% to 44% in patients with mild and moderate renal impairment. Six retrospective studies evaluated the safety of enoxaparin in patients with renal impairment. In one study, patients with moderate renal impairment were at increased risk of bleeding when using the current FDA-approved two-tiered scheme (odds ratio, 4.7; 95% confidence interval, 1.7-13.0; P = 0.002). Another study demonstrated that individualized enoxaparin dosing, when compared to FDA-approved dosing, resulted in a decreased risk of bleeding. Two retrospective studies evaluated efficacy. One of these studies compared reduced-dose enoxaparin with unfractionated heparin; there was a trend toward lower incidences of thromboembolism and 30-day mortality with reduced-dose enoxaparin. Hospital length of stay also decreased with reduced-dosed enoxaparin. CONCLUSIONS: This paper highlights the differences in the pharmacokinetic properties and safety and efficacy outcomes in multiple degrees of renal impairment when using treatment-dose enoxaparin. Given the literature highlighted in this review, a more multitiered enoxaparin renal dosing strategy-perhaps shifting from the current two-tier approach to at least three or four tiers-should be considered.

Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis.

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, "rounding up" of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Do SSRI Antidepressants Increase The Risk of Extrapyramidal Side Effects In Patients Taking Antipsychotics?

PURPOSE: Among antidepressants, selective serotonin reup-take inhibitors (SSRIs) have enjoyed great popularity among clinicians as well as generally wide acceptance and tolerance among patients. A potentially overlooked side effect of SSRIs is the occasional occurrence of extrapyramidal symptoms (EPS), which could be a concern when SSRIs are used with antipsychotics. This study was designed to explore the possible association between SSRI antidepressant use and the incidence of EPS side effects in patients who take concomitant antipsychotic medications. METHODS: The University of Michigan conducted a study at the four Michigan state mental health hospitals between May 2010 and October 2010. The Michigan Public Health Institute collected data using the InterRAI Mental Health Assessment (InterRAI MH). The present study is a retrospective cohort analysis of the cross-sectional data that were collected. Within these institutions, 693 residents were using antipsychotics. We measured the observed frequency of seven EPS recorded in the InterRAI MH within three groups of patients: 1) those on antipsychotic drugs who were taking an SSRI antidepressant; 2) those on antipsychotic drugs who were not taking an antidepressant; and 3) those on antipsychotic drugs who were taking a non-SSRI antidepressant. Differences in the prevalence of EPS were tested using one-way analysis of variance. RESULTS: There were no significant differences in the observed EPS frequencies among the three groups (F 2,18 = 0.01; P < 0.9901). CONCLUSION: In this study, SSRIs did not appear to potentiate the occurrence of EPS in patients using antipsychotics.

Anticoagulation in Patients With Cirrhosis: Caught Between a Rock-Liver and a Hard Place.

OBJECTIVE: To review current literature for anticoagulation in patients with cirrhosis and provide a summary of the effects of cirrhosis on the coagulation cascade, therapeutic monitoring through interpretation of antifactor Xa (anti-Xa), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) as well as current prophylaxis and treatment recommendations in cirrhotic patients. METHODS: A systematic electronic literature search was conducted in PubMed using the key termsanticoagulation, warfarin, low-molecular-weight heparin(LMWH),unfractionated heparin(UFH),target-specific oral anticoagulants, deep-vein thrombosis(DVT),pulmonary embolism(PE),portal vein thrombosis(PVT),venous thromboembolism, anti-Xa, activated partial thromboplastin time, anticoagulation therapeutic monitoring, coagulopathy, coagulation cascade, chronic liver disease, cirrhosis, anddecompensated liver disease STUDY SELECTION: Studies written in the English language from January 2000 to December 2015 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by authors independently. CONCLUSIONS: Patients with cirrhosis are at higher risk for both bleeding and thrombosis-related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels. LMWH is the treatment of choice for the prevention and treatment of DVT/PE/PVT in patients with cirrhosis, and monitoring with anti-Xa levels for dose adjustment is not recommended. UFH is an alternative in cirrhotic patients for shorter-term use and in cases of severe renal dysfunction and/or hemodynamic instability. Cirrhotic patients on anticoagulation therapy should be monitored closely for signs and symptoms of bleeding and thrombosis.

Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection.

OBJECTIVES: To review the pharmacology, efficacy, and safety of daclatasvir in the treatment of patients with chronic hepatitis C virus (HCV) infection. DATA SOURCES: A literature search through EMBASE and PubMed was conducted (January 1966 to August 2015) using the terms BMS-790052, daclatasvir, and hepatitis C. References from retrieved articles were reviewed for any additional material. Additionally, the new drug application and prescribing information were retrieved. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English. Phase 1, 2, and 3 studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daclatasvir for HCV were identified. DATA SYNTHESIS: Daclatasvir, a nonstructural 5A protein inhibitor, combined with sofosbuvir, is indicated for adult patients with chronic HCV genotype 3 regardless of treatment or cirrhosis status. The phase III ALLY-3 trial (n = 152) demonstrated that daclatasvir taken once daily with sofosbuvir for 12 weeks was effective at achieving sustained virological response (SVR) rates in treatment-naïve (97%) and treatment-experienced (94%) patients without cirrhosis. Patients with cirrhosis had significantly lower SVR rates (58 and 69%, respectively). The most common adverse drug events associated with daclatasvir and sofosbuvir in ALLY-3 were headache (20%), fatigue (19%), and nausea (12%). CONCLUSIONS: Daclatasvir, when combined with sofosbuvir, is an effective agent to treat HCV genotype 3, with SVR rates above 90% for patients without cirrhosis who are treatment naïve or experienced. SVR rates for treatment-naïve or -experienced patients with cirrhosis are not as robust (58%-69%).

Valproic Acid as a potentiator of metabolic syndrome in institutionalized residents on concomitant antipsychotics: fat chance, or slim to none?

BACKGROUND: Valproic acid (VPA) is one of the most commonly used antiepileptic medications worldwide; it is also a popular mood stabilizer for use in bipolar disorder and dementia. This study assessed whether VPA may potentiate metabolic side effects in patients with psychiatric disorders taking concomitant antipsychotics (APs). VPA alone has been associated with weight gain, dyslipidemia, hypertension, and diabetes. Patients with psychiatric disorders, especially those on second-generation (atypical) APs, appear to be at increased risk of these metabolic effects. A secondary purpose was to determine if a linear dose-response relationship exists between the VPA dose and adverse metabolic effects. METHODS: This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m(2)); very high BMI (BMI greater than 40 kg/m(2)); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects. RESULTS: Patients in the VPA plus APs group were 3.2 kg heavier than those in the APs group (P = 0.05) at baseline. Compared with the APs group, the VPA plus APs group had a higher prevalence of high and very high BMI, diabetes, hypertension, and the combination of any three factors of high BMI, hyperlipidemia/dyslipidemia, diabetes, and hypertension. However, these differences were not statistically significant. Conversely, there was a slight but non-significant reduction in the prevalence of weight gain, prescribed statins, and hyperlipidemia/dyslipidemia in the VPA plus APs group than the APs group. Finally, higher doses of VPA were not found to be associated with a higher incidence of these metabolic side effects. CONCLUSION: Although the patients on VPA were slightly more than 3 kg heavier, VPA did not appear to be associated with significant metabolic effects in patients with psychiatric conditions taking typical and atypical APs. These metabolic effects also do not appear to be related to the dose of VPA.

"Triple Phase" Budesonide Capsules for the Treatment of Olmesartan-Induced Enteropathy.

OBJECTIVE: To describe the treatment of a case of olmesartan-induced enteropathy in a patient with inflammatory areas widely distributed along the gastrointestinal tract. CASE SUMMARY: A 75-year-old patient presented with a 5-month history of recurrent severe diarrhea, diagnosed as olmesartan-induced enteropathy. A modified regimen of oral enteric-coated budesonide (EC-BUD), in combination with other antidiarrheal and anti-inflammatory therapies, was prescribed. The patient experienced rapid improvement in symptoms and was able to titrate off all enteropathy medications, including budesonide within 4 months after hospital discharge. DISCUSSION: Olmesartan-induced enteropathy is a recently identified adverse effect of this angiotensin II receptor blocker. Oral budesonide is indicated for use in Crohn's disease to provide topical anti-inflammatory therapy without significant systemic steroid absorption. Budesonide, as enteric-coated oral 3-mg capsules, was chosen as therapy in this patient because of its localized effect and proven efficacy in gastrointestinal inflammatory disorders. The administration technique was modified to target areas of inflammation throughout the gastrointestinal tract. CONCLUSIONS: We postulate that this modified administration of EC-BUD may be an effective therapeutic modality for olmesartan-induced enteropathy. It may likewise be an appropriate adjunct to other conditions involving widespread gastrointestinal inflammation, including eosinophilic gastroenteritis and gastrointestinal graft versus host disease.

Combination therapy for the treatment and prevention of hepatic encephalopathy.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE). DATA SOURCES: A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English. STUDY SELECTION AND DATA EXTRACTION: Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and/or probiotics. DATA SYNTHESIS: Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose/neomycin versus placebo or rifaximin/lactulose, 1 assessed the use of rifaximin/lactulose without a control group, and the fourth found no significant difference between lactulose/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics. CONCLUSIONS: The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.

Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach's "acid mantle" against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H(+)/K(+)-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H(2)RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H(2)RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H(2)RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H(2)RAs should be used as the preferred agents over PPIs.

The ezetimibe controversy: implications for clinical practice.

Low-density lipoprotein cholesterol (LDL-C) remains the primary target of lipid-lowering therapy. Achieving LDL-C goals as outlined by the National Cholesterol Education Program Adult Treatment Panel III can be difficult with statins alone; therefore, adjunctive therapy is often indicated to reduce cardiovascular risk. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-high-density lipoprotein cholesterol and apolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, because of randomized trials that demonstrated mixed results about atherosclerotic plaque regression via carotid intima-media thickness and a concern about cancer risk, ezetimibe's role in lipid therapy has been questioned. Currently, a large randomized controlled trial is in progress to answer if ezetimibe improves clinical outcomes in patients with high-risk acute coronary syndrome. A smaller trial in patients with chronic kidney disease demonstrated reduced clinical events, including myocardial infarction, stroke and revascularization for patients taking the combination of ezetimibe and simvastatin versus those taking statin or placebo alone. In this paper, we review the trials that have led to the ezetimibe controversy and then discuss the possible role of ezetimibe in specific patient populations until the results of ongoing clinical trials are known.

Interventions to curb the overuse of Acid-suppressive medications on an inpatient general medicine service.

PURPOSE: We conducted a study to measure the impact of three sequential levels of intervention on prescribing patterns of acid-suppressive medications (ASMs) on an inpatient internal medicine service at a university hospital. METHODS: THIS RETROSPECTIVE REVIEW COMPARED PRESCRIBING PATTERNS ON FOUR DIFFERENT TIERS: a phase 1 study, conducted one year before the phase 2 intervention study; and three phase 2 interventions. Each group was assessed for the percentage of all patients receiving ASMs and the percentage of patients receiving these drugs with an inappropriate indication. The three phase 2 studies are described in this article. RESULTS: Intervention A (a beginning-of-year lecture to all interns) was not enough to decrease total in-hospital use of these medications, compared with the phase 1 historical controls (62% vs. 66%, respectively); however, it did decrease the rate of inappropriate use from 59% to 37% (P < 0.001). When Intervention B (an early-in-the-month rotation "reminder lecture") was added, the volume of agents used was significantly reduced to 53% (P = 0.025) and the number of inappropriate prescriptions was reduced to 32% (P < 0.001), compared with rates in phase 1. Finally, when Intervention C (a clinical pharmacist making rounds with the health care team on most post-call days) was added to Interventions A and B, the total volume of drug use in the hospital declined to 53% (P = 0.025) and the number of inappropriate prescriptions fell to 19%, compared with rates in phase 1 (P < 0.001). CONCLUSION: Providing educational lectures for interns was helpful in curbing the inappropriate prescribing of ASMs, but the benefit was augmented when a clinical pharmacist was added to the team.

Impact of a pharmacist-facilitated hospital discharge program: a quasi-experimental study.

BACKGROUND: Medication discrepancies are common at hospital discharge and can result in adverse events, hospital readmissions, and emergency department visits. Our objectives were to characterize medication discrepancies at hospital discharge and test the effects of a pharmacist intervention on health care utilization following discharge. METHODS: We used a prospective, alternating month quasi-experimental design to compare outcomes of patients receiving the intervention (n = 358) with controls (n = 366). All patients were discharged to home and were at high risk for medication-related problems following discharge because of the number or types of medications they were prescribed, multiple medication changes during hospitalization, or problems managing medications. The intervention consisted of medication therapy assessment, medication reconciliation, screening for adherence concerns, patient counseling and education, and postdischarge telephone follow-up. The primary outcomes were 14-day and 30-day readmission rates and emergency department visits within 72 hours of discharge. Medication discrepancies occurring at discharge were also characterized. RESULTS: Medication discrepancies at discharge were identified in 33.5% of intervention patients and 59.6% of control patients (P < .001). Although all discrepancies were resolved in the intervention group prior to discharge, readmission rates did not differ significantly between groups at 14 days (12.6% vs 11.5%; P = .65) and 30 days (22.1% vs 18%; P = .17), nor did emergency department visits (2.8% vs 2.2%, respectively; P = .60). CONCLUSION: While our intervention improved the quality of patient discharge by identifying and reconciling medication discrepancies at discharge, there was no effect on postdischarge health care resource utilization.