Pramodini B. Kale-Pradhan

Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis

This study was presented at the American College of Chest Physicians meeting in Pittsburgh (PA, USA) in October 2011. The study objective was to evaluate the association of proton pump inhibitors (PPIs) and community-acquired pneumonia (CAP). The design was a meta-analysis of nine case–controlled and cohort studies. 120,863 pneumonia cases from 1987 to 2006 were included in the meta-analysis. PubMed and Ovid Medline were searched from inception through May 2011 by two investigators independently using keywords: PPI, pneumonia, CAP, anti-ulcer, antacid, omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. This meta-analysis only included case–controlled and cohort studies that were published in full in English and evaluated PPI use and CAP incidence. Studies were excluded if they included the following patients: pediatric, Helicobacter pylori treatment and critically ill. Bibliographies of recent review articles and systematic reviews were hand-searched. Quality of studies was assessed using the Newcastle–Ottawa Quality Assessment Scale. Two investigators independently extracted data into standardized data collection forms that were confirmed by a third investigator. Data were analyzed based on current use of PPIs, duration of PPI use (<30 days or >180 days) and PPI dose (high vs low). Overall association of PPI and CAP was analyzed using the random effects model (Comprehensive Meta analysis® Version 2.0). Nine studies met all criteria for the primary outcome. Newcastle–Ottawa Quality Assessment Scale scores ranged from 4 to 8 out of 9. Current use of PPIs (odds ratio [OR]: 1.39; 95% CI: 1.09–1.76), PPI use <30 days (OR: 1.65; 95% CI: 1.25–2.19), PPI high dose (OR: 1.50; 95% CI: 1.33–1.68) and PPI low dose (OR: 1.17; 95% CI: 1.11–1.24) were significantly associated with CAP. There was no association between CAP and PPI use >180 days (OR: 1.10; 95% CI: 1.00–1.21). In conclusion, patients currently receiving PPIs, particularly <30 days or high dose, showed an association with CAP. Practitioners need to be vigilant about adverse effects of PPIs and consider alternative therapies.

Role of Lactobacillus in the Prevention of Antibiotic-Associated Diarrhea: A Meta-analysis

Study Objective. To evaluate the efficacy of a Lactobacillus probiotic singleagent regimen in preventing antibiotic‐associated diarrhea (AAD).

Prokinetic agents for the treatment of postoperative ileus in adults : A review of the literature

Metoclopramide, cisapride, and erythromycin are commonly administered to reduce the duration of postoperative ileus (POI). As these agents are not without potential adverse effects, their efficacy in shortening the duration of POI should be evaluated. The etiology of POI is not well understood and therefore the precise treatment is unclear. Nasogastric suction is the mainstay of therapy, and management of fluid and electrolyte imbalances is crucial. The role of prokinetic agents is less understood. Available literature evaluating these drugs specifically for POI were reviewed, but results are confounded by issues such as sample size, variability in types of operations performed, and insensitive end points (flatus, bowel sounds). No literature supports reducing the duration of POI with metoclopramide, and limited data show benefit with cisapride. Data evaluating erythromycin are sparse, and the drug is believed to be ineffective. Domperidone, a prokinetic agent not available in the United States, has not been evaluated in POI. Due to these limitations, treatment remains largely supportive with a limited role for prokinetic agents.

Perils and pitfalls of long-term effects of proton pump inhibitors

This review summarizes the literature regarding long-term adverse effects of proton pump inhibitors (PPIs). A PubMed search (1966 to February 2013) for English language studies was conducted using key terms PPI: omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, pneumonia, Clostridium difficile, osteoporosis, risk of fractures, thrombocytopenia, rhabdomyolysis, anemia, iron deficiency, hypomagnesemia, vitamin B12 and nephritis. The risk of pneumonia was increased 27–39% in short-term use of PPIs in three meta-analyses. C. difficile infections were also associated with the use of PPIs (odds ratio: 2.15; 95% CI: 1.81–2.55; p < 0.00001). This effect appears to be dose related. The US FDA has recently issued a warning regarding fractures and the impaired magnesium absorption associated with the use of PPI. Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported with the use of PPIs. There is mounting evidence that PPIs are associated with serious adverse effects. Practitioners should be vigilant and counsel patients accordingly.

Treating Bugs with Bugs: The Role of Probiotics as Adjunctive Therapy for Helicobacter pylori

Objective: To review the literature on the role of probiotics as adjunctive therapy in the treatment of Helicobacter pylori infections. Data Sources: Literature was accessed through MEDLINE (1966-March 2011) using the terms H. pylori, probiotic, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus clausii, and Propionibacterium. Article references were hand-searched for additional relevant articles and abstracts. Study Selection and Data Extraction: All English-language articles published in full were evaluated. Randomized, double-blind, placebo-controlled trials assessing the use of probiotics combined with standard eradication therapy of H. pylori infection in adults were included in the review. Data Synthesis: Various probiotics, including Lactobacillus spp., Saccharomyces spp., Bifidobacterium spp., and B. clausii, reduce adverse effects such as nausea, taste disturbance, diarrhea, and epigastric pain, and increase tolerability of H. pylori eradication therapy. Based on the studies reviewed, probiotics do not affect H. pylori eradication rates. Conclusions: Probiotics may be beneficial in reducing adverse effects and increasing tolerability of H. pylori eradication regimens. They may especially be helpful in patients with recurrent H. pylori infection and a history of gastrointestinal adverse effects with antibiotics. Pharmacists can play an important role in educating patients regarding probiotic use during H. pylori eradication therapy.

A review of infliximab use in ulcerative colitis

BACKGROUND Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-alpha found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohns disease (CD), with documented success. Infliximabs efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC. OBJECTIVE The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment. METHODS A search of MEDLINE was conducted (1950-November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized. RESULTS Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey. CONCLUSIONS Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximabs impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.

Esomeprazole for Acid Peptic Disorders

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of esomeprazole, a new proton-pump inhibitor (PPI). DATA SOURCES: A MEDLINE search (1966–March 2001) was conducted for relevant literature using the terms esomeprazole, Nexium, and H199/18. Abstracts from the XXXII Nordic Meeting of Gastroenterology and journal articles provided by AstraZeneca were reviewed. STUDY SELECTION AND DATA EXTRACTION: All available studies on the pharmacology, pharmacokinetics, clinical efficacy, and safety of esomeprazole were reviewed. DATA SYNTHESIS: Esomeprazole is a new PPI and is the S—isomer of racemic omeprazole. Esomeprazole has demonstrated acid control comparable to that of the other PPIs currently available. Esomeprazole undergoes less hepatic metabolism compared with omeprazole, and thus may result in less interpatient variability among slow and fast metabolizers of CYP2C19. The oral bioavailability of esomeprazole is approximately 89% with a dose of 40 mg, and the half-life is approximately 1.5 hours. Esomeprazole is effective in the healing of erosive esophagitis, with a rate of healing at week 8 of 93.7% (p < 0.001). In maintenance therapy of healed erosive esophagitis, esomeprazole maintained healing rates <90% (6-mo trial). Esomeprazole is comparable with omeprazole (both in combination with appropriate antibiotics) in the eradication of Helicobacter pylori, with eradication rates of 89.7% and 87.8%, respectively. The drug is well tolerated. The few adverse effects associated with esomeprazole are diarrhea, headache, nausea, abdominal pain, respiratory infection, and sinusitis. CONCLUSIONS: Esomeprazole is a safe and effective PPI. It is effective in the treatment of peptic ulcer disease and gastroesophageal reflux disease.

Prevention of Postoperative Nausea and Vomiting

Objective: To review the literature on the prevention of postoperative nausea and vomiting (PONV) in adults. Data Sources: Literature retrieval was accessed through MEDLINE (1966–December 2006) using the terms postoperative nausea and vomiting, prevention and treatment. Article references were hand-searched for additional relevant articles and abstracts. Study Selection And Data Extraction: All studies published in English were evaluated. Those dealing with prevention and treatment of PONV in adults were included in the review. Data Synthesis: Evidence suggests that providing prophylactic antiemetic medications in high-risk surgical patients is warranted. 5-HT3 receptor antagonists are widely used, with no one agent being clearly superior. However, studies have shown other types of agents to ho more cost-effective. Conclusions: The first step in the prevention of PONV is assessment and reduction of risk factors. Although nonpharmacologic therapies may play a role in the treatment of PONV, the mainstay of therapy for PONV is pharmacologic modalities. Patients at moderate to high risk for PONV need prophylactic antiemetic therapy. High-risk patients may require combination therapy with 2 or 3 agents from different antiemetic classes. Rescue antiemetic therapy is needed by patients who actually develop PONV. The agents of choice in such cases should be from antiemetic classes different from those used for prophylaxis of PONV.

Effect of Bariatric Surgery on Hypertension: A Meta-analysis

Purpose: Obesity is a growing epidemic leading to worldwide public health concerns. Bariatric surgery is an option for patients with a body mass index (BMI) >40 kg/m2 or BMI of >35 kg/m2 with serious comorbid conditions. This meta-analysis examines the effect of bariatric surgery on the improvement or resolution of hypertension. Methods: Two independent investigators conducted a literature search of PubMed (1990-2013) and Cochrane databases using the terms bariatric surgery and hypertension to identify appropriate human adult studies published in English. Studies were included if they reported the number of patients with hypertension prior to undergoing any bariatric surgery procedure and whether the hypertension improved or resolved postsurgery. The number of patients with hypertension and their response rates were extracted and analyzed using RevMan 5.2.5. Results: In all, 31 prospective and 26 retrospective studies met all criteria. The types of bariatric surgery performed included Roux-en-Y, gastric banding, laparoscopic adjustable gastric banding, vertical gastric banding, sleeve gastrectomy, duodenal switch, and biliopancreatic diversion. The time to first follow-up after surgery varied from 1 week to 7 years. Of the 57 studies, 32 reported improvement of hypertension in 32 628 of 51 241 patients (odds ratio [OR] = 13.24; 95% CI = 7.73, 22.68; P < 0.00001); 46 studies reported the resolution of hypertension in 24 902 of 49 844 patients (OR = 1.70; 95% CI = 1.13, 2.58; P = 0.01). A random-effects model was used because the heterogeneity between the studies was high (I2 = 97%). Conclusion: The results of this meta-analysis indicate that patients who undergo bariatric surgery experience improvement and resolution of their hypertension.

Estimating Creatinine Clearance: A Meta-analysis

Study Objectives. To determine which body weight descriptor most accurately predicts measured creatinine clearance (Clcr) and whether rounding serum creatinine concentration (Scr) to 1 mg/dl when it is less than 1 mg/dl accurately predicts measured Clcr.