Kyle John Wilby

A review of the effect of immunization programs on antimicrobial utilization

The objective of this review is to summarize and evaluate the literature pertaining to antimicrobial utilization with respect to implementation of immunization programs or within clinical studies assessing vaccine effectiveness. A literature search was performed using the search terms vaccine; immunization; antimicrobial; antibiotic; influenza; pneumococcal; haemophilus; meningococcal in MEDLINE (1948-May 2012), EMBASE (1980-May 2012), International Pharmaceutical Abstracts (1970-May 2012), Google, and Google Scholar. Identified clinical or epidemiological studies were included if antimicrobial utilization was listed as a reported outcome. Seven articles (three randomized controlled trials and four epidemiological studies) were identified and included in the review. These studies reported outcomes associated with pneumococcal and influenza immunization programs. All studies reported decreased antibiotic use associated with initiation of immunization programs or increased uptake of available vaccines. Large-scale epidemiological studies confirm population-wide decreases observed from short-term randomized controlled trials. Antibiotic reductions ranged from 5 to 10% in randomized controlled trials to relative reductions of 64% in epidemiological studies. These findings suggest that immunization programs may reduce antibiotic utilization. As such, vaccination status queries and updates should become part of routine care for both hospitalized and non-hospitalized patients. Immunization programs should be considered as part of institution-wide antimicrobial stewardship programs.

Use of Proton Pump Inhibitors in the Management of Gastroesophageal Varices A Systematic Review

Objective: To review the efficacy and safety of proton pump inhibitors (PPIs) in gastroesophageal varices (GEVs). Data Sources: MEDLINE (1946 to September 2014), EMBASE (1974 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), Cochrane Central Register of Controlled Trials (1991 to September 2014), Google, and Google Scholar were searched using the following terms: esophageal varices, gastroesophageal varices, variceal hemorrhage, variceal bleeding, banding ligation, endoscopic variceal ligation, sclerotherapy, proton pump inhibitor, PPI, omeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, and esomeprazole. Study Selection and Data Extraction: Published and unpublished studies evaluating the clinical outcomes of PPI use for GEVs were included regardless of study design. Non-English and nonhuman studies were excluded. Data Synthesis: Of 1156 studies, 20 were included after assessment. There was wide methodological heterogeneity and moderately high risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal ulcer size post–elective esophageal ligation; the clinical importance of such findings is not known given the self-limiting nature of esophageal ulcer. Available evidence does not support a role of PPIs for long-term prophylaxis of portal hypertension–related bleeding and high-dose infusion for acute management of GEV hemorrhage. Retrospective data demonstrate a potential increase in the incidence of spontaneous bacterial peritonitis in patients with cirrhosis receiving PPIs. Conclusions: The best available evidence supports the use of short-course (10 days) PPI post–endoscopic variceal ligation to reduce ulcer size if ulcer healing is a concern. Practices such as high-dose infusion and prolonged use should be discouraged until evidence of benefit becomes available.

Therapeutic Drug Monitoring of Voriconazole in the Management of Invasive Fungal Infections: A Critical Review

The broad-spectrum triazole antifungal agent voriconazole is highly efficacious against invasive fungal infections (IFIs) caused by Aspergillus spp. and Candida spp. IFIs are associated with high rates of mortality and morbidity, especially in vulnerable populations such as patients with hematopoietic stem cell transplant as well as other immunocompromised patients. Efficacy of voriconazole in these patients is critical to ensure positive outcomes and reduce mortality. However, a major limitation of voriconazole is the risk of adverse events such as hepatotoxicity and neurotoxicity. As such, therapeutic drug monitoring (TDM) has been suggested as a mechanism to optimize both efficacy and safety. The aim of this review was to summarize and evaluate evidence from the primary literature that assessed TDM outcomes for voriconazole as well as evaluate the association between CYP2C19 polymorphism and the clinical outcomes of voriconazole. Findings showed associations for both efficacy and safety outcomes with measurement of drug concentrations, yet exact targets or thresholds remain unclear. As such, TDM should be reserved for those patients not responding to therapy with voriconazole or those experiencing adverse drug reactions. Future studies should attempt to further define these populations within controlled settings. Studies that evaluated the effect of CYP2C19 genetic polymorphism on clinical outcomes found no significant relationship between CYP2C19 genotype and hepatotoxicity. These negative findings may be due to lack of power, use of phenotypes not well-defined, and the presence of other interacting factors that may impact voriconazole pharmacokinetics. Future well-designed studies are warranted to confirm these findings.

A Review of Pharmacokinetic Drug–Drug Interactions with the Anthelmintic Medications Albendazole and Mebendazole

Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration–time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

Pharmacogenetics of Risperidone: A Systematic Review of the Clinical Effects of CYP2D6 Polymorphisms

OBJECTIVE To summarize and evaluate the pharmacogenetic literature pertaining to the effects of CYP2D6 polymorphism on clinical outcomes of risperidone therapy. DATA SOURCES A systematic literature search was performed using the search terms risperidone, pharmacogenetics, cytochrome P-450 enzyme system, cytochrome P-450 CYP2D6, and polymorphism (genetic) in MEDLINE (1946-October 2012), EMBASE (1980-October 2012), PubMed (1947-October 2012), International Pharmaceutical Abstracts (1970-October 2012), and Google Scholar. STUDY SELECTION AND DATA EXTRACTION Identified articles were included if they measured the association between CYP2D6 genetic polymorphisms and clinical outcomes in at least 2 patients taking risperidone. The data elements extracted from these articles consisted of study design, number of subjects, indication for risperidone therapy, CYP2D6 phenotype status, mean daily dose of risperidone, and effects on clinical outcomes. DATA SYNTHESIS The identified citations consisted of 10 prospective nonrandomized, uncontrolled cohort studies, 1 retrospective cohort study, 1 prospective case-control study, and 1 retrospective case series. Studies were of variable quality and none provided high-quality evidence; they included heterogeneous patient populations with varying clinical diagnoses and drug therapy regimens. Most studies reported nonsignificant trends but were limited by power to detect statistical significance and short trial duration. However, increased risk of adverse effects (including QT interval prolongation) was observed in patients with inactive alleles. CONCLUSIONS While there were trends toward increased adverse effects in poor metabolizers, most outcomes were not significant. As such, routine genotyping should not be used for screening. Future usefulness cannot be ruled out, as many studies had significant limitations that preclude determination of clinical relevance. Adequately powered clinical and epidemiologic studies are warranted to clarify the role of CYP2D6 genotyping in practice.

Attitudes of pharmacy and nutrition students towards team-based care after first exposure to interprofessional education in Qatar

Abstract Little is known regarding attitudes of healthcare professional students towards team-based care in the Middle East. As modernization of health systems is rapidly occurring across the Gulf Cooperation Council countries, it is important for students to engage in interprofessional education (IPE) activities. The objective of this study was to assess pre-clinical students’ attitudes towards interprofessional healthcare teams after completion of their first IPE activity. A previously validated questionnaire was distributed to 25 pharmacy and 17 nutrition students at Qatar University after participation in an IPE event. Questions related to quality of team-based care and physician centricity. Results showed high agreement regarding high quality care provided by teams yet students were unsure of the value of team-based care when considering required time for implementation. Results provide baseline data for future studies to assess student attitudes throughout the professional programs and give valuable insight for future IPE program design in the Middle East.

A review of the pharmacokinetic implications of schistosomiasis.

Schistosomiasis is a common parasitic disease, with over 230 million people requiring treatment annually. The worldwide increase in medication access poses risks for patients living in regions endemic for schistosomiasis because of the potential impact of pharmacokinetic changes on clinical outcomes. Thus, the objective of this review is to summarize and evaluate the published literature reporting pharmacokinetic parameters of medications in patients with schistosomiasis and to assess associated clinical implications. Thirteen articles that described the pharmacokinetics of a total of 9 different medications (cefoperazone, propranolol, praziquantel, theophylline, metronidazole, acetaminophen/paracetamol, antipyrine, oxamniquine, and oral contraceptives) in patients with schistosomiasis were included in the review. The major finding is that pharmacokinetic changes occur in patients infected with schistosomiasis but to varying degrees depending on the extent of disease (e.g., varying stages of fibrosis, with or without signs and/or symptoms of liver disease) and medication being administered. Affected patients may consequently be at risk of adverse clinical outcomes. In general, drugs with high extraction ratios demonstrate increased bioavailability in patients with schistosomiasis compared to controls. For example, propranolol and praziquantel, respectively, show an association with increased clinical and toxic effects in patients with schistosomiasis. Conversely, the pharmacokinetics of low hepatic clearance drugs (such as metronidazole and oxamniquine) are largely unchanged unless patients present with liver disease (as in the case of antipyrine, the prototypical low clearance drug). Limitations of studies included the very small numbers of patients, being primarily single-dose studies, and the high inter-individual variability. Future clinical studies should include pharmacokinetic outcomes to further clarify dosing and administration strategies for target medications, especially those that primarily undergo metabolism and are associated with significant adverse effects. Until the results of these future studies are available, clinicians should be acutely aware of complications from schistosomiasis and carefully screen patients for signs and symptoms of liver disease prior to prescribing, dispensing, or administering potentially harmful medications.

Levetiracetam for seizure prevention in brain tumor patients: a systematic review

Seizures are common complications for patients with brain tumors. No clear evidence exists regarding the use of antiepileptic agents for prophylactic use yet newer agents are being favoured in many clinical settings. The objective of this systematic review was to determine the efficacy of levetiracetam for preventing seizures in patients with brain tumors. A literature search was completed using the databases PubMed (1948 to December 2015), EMBASE (1980 to December 2015), Cochrane Database of Systematic Reviews, and Google Scholar. Studies were included if they reported seizure frequency data pertaining to levetiracetam use in patients with brain tumors as either monotherapy or as an add on agent. The literature search produced 21 articles (3 randomized controlled trials, seven prospective observational studies, and 11 retrospective observational studies). All studies were found to be at high risk of bias. Overall, studies show levetiracetam decreased seizure frequency in brain tumor patients with or without craniotomy. Safety outcomes were also favourable. As such, levetiracetam appears effective for reducing seizures in patients with brain tumors and may be considered a first-line agent. However, there is an urgent need for more high quality prospective data assessing levetiracetam and other antiepileptic drugs in this population.

The Therapeutic Effects of Camel Milk A Systematic Review of Animal and Human Trials

The clinical effectiveness and value of camel milk as a therapeutic agent is currently unclear. MEDLINE (1946 to March 2016), EMBASE (1974 to March 2016), and Google Scholar were searched using the following terms: milk, bodily secretions, camels, camelus, camelini, camelidae, dromedary, bactrian camel, body fluid, and bodily secretions. Articles identified were reviewed if the study was investigating the use of camel milk for the potential treatment of diseases affecting humans. Of 430 studies, 24 were included after assessment. Identified studies highlighted treatment with camel milk of diseases, including diabetes, autism, cancer, various infections, heavy metal toxicity, colitis, and alcohol-induced toxicity. Although most studies using both the human and animal model do show a clinical benefit with an intervention and camel milk, limitations of these studies must be taken into consideration before widespread use. Based on the evidence, camel milk should not replace standard therapies for any indication in humans.

Review of Evidence for Measuring Drug Concentrations of First-Line Antitubercular Agents in Adults

Measurement of drug concentrations and performing therapeutic drug monitoring (TDM) are widely used to optimize efficacy and safety of many commonly used drugs today. Although TDM of first-line antitubercular drugs is used during the treatment of tuberculosis, the extent of any benefit achieved is currently unknown. This review summarizes the available literature describing TDM of first-line treatment agents in patients with tuberculosis and describes clinical associations with achievement of target drug concentrations, including data from special populations. A literature review was conducted for articles describing drug concentration and TDM outcomes for first-line tuberculosis agents in adults. A total of 40 studies were included in the review. Studies were a mixture of controlled trials, observational studies, cross-sectional studies, and case reports. The majority of the studies showed standard dosing does not consistently achieve target concentrations for the first-line antitubercular drugs; however, the clinical implications of this finding are still unclear. Presence of HIV and diabetes mellitus appeared to indicate achievement of lower than target concentrations and this warrants further study in prospective studies. Current published data neither prove nor disprove the utility of TDM for general tuberculosis populations but evidence does not currently support routine measurement of drug concentrations.