bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Pharmaceutical Care Programs on Glycemic Control in Patients with Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials
Authors: Li Xin , Mao Mao , Ping Qineng
Published: September 2013

Background:

Diabetes mellitus is a common disease that has an increasing influence on the health of human beings. While the role of pharmaceutical care (PC) programs in the treatment of patients with diabetes mellitus is well established, there is little research that quantitatively and comprehensively assesses the impact of PC programs on glycemic control in diabetics.

Objective:

To evaluate the effect of PC programs on glycemic control in patients with diabetes mellitus.

Methods:

Publications on PC programs and randomized controlled trials (RCTs) of glycemic control were retrieved by searching MEDLINE, Embase, Cochrane, Elsevier, Chinese Biomedicine Database, and Chinese Journal Full-Text Database databases from January 1996 through February 2010. Data were extracted by 2 reviewers independently, based on their correlation with this project, and then evaluated with meta-analysis. The meta-analysis was conducted using STATA version 10.1. Begg-Mazumdar's funnel plot was generated to determine the potential impact of publication bias.

Results:

Fourteen RCTs, with a total of 1770 patients with diabetes mellitus, were included in this meta-analysis. Pharmacists were involved in all of these PC interventions. The average ± SD study period of included trials was 9.5 ± 4.1 months. Drug counseling, drug therapy management, lifestyles education, self-monitoring, and recommendations of drug therapy changes were the most frequently used interventions. All of the trials reported the reduction of hemoglobin A1c (A1C) as the primary clinical outcome of PC intervention. Compared with the usual-care control groups, the PC intervention groups had significant reduction in A1C levels (weighted mean difference −0.68; 95% CI-1.03 to −0.34; p = 0.000).

Conclusions:

PC programs delivered separately or in combination by pharmacists and other health professionals can lead to an improvement in glycemic control. The incorporation of PC programs into disease management should be strongly considered.
The Role of Statins in the Prevention and Treatment of Alzheimer's Disease
Authors: Desilets Alicia R , Koslowski Danielle A , Dunican Kaelen C
Published: September 2013

Objective:

To review the role of statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) in the prevention and treatment of Alzheimer's disease (AD).

Data Sources:

Literature was retrieved from EMBASE (1980–2010, week 22) and MEDLINE (1950-May 2010, week 4), using the key words statins, HMG-CoA reductase inhibitors, and Alzheimer's disease, as well as a bibliographic review of published articles.

Study Selection and Data Extraction:

All clinical trials that involved humans, were published in the English language, and evaluated statins in the prevention and/or treatment of AD were included in this review.

Data Synthesis:

Recent studies have evaluated the use of statins in the prevention and treatment of AD; results from these studies are conflicting. One randomized, placebo-controlled trial found that statins may improve the ADAS-Cog (Alzheimer's Disease Assessment Scale on Cognition) by 0.1–1.8 points in patients with AD during the first 6 months of treatment. Alternatively, another randomized controlled trial found that atorvastatin did not provide benefit on the ADAS-Cog. Although many of the prevention trials did find potential benefit with statin use, these trials were observational.

Conclusions:

Due to insufficient evidence of benefit in both the prevention and treatment of AD, statins cannot be recommended at this time.
A Targeted Review of Smoking Cessation Aids and Their Pharmacology for the Pharmacy Technician
Authors: Rowe Stacy L , Daugherty Kimberly K
Published: September 2013

Objective:

To review the pharmacologic treatment options available for smoking cessation.

Data Synthesis:

Nicotine replacement therapy (NRT) has a less rapid onset than that of nicotine received from smoking; therefore, it does not cause the same pleasurable response but helps to decrease the cravings. NRT is available over the counter as a gum, lozenge, and patch. NRT is also available by prescription as a nasal spray and inhaler. Information is also provided on the dosing and adverse effect profiles of 2 non-NRT prescription products used for smoking cessation including bupropion SR and varenicline.

Conclusions:

It is important for pharmacy technicians to be aware of the NRT and non-NRT products available both over the counter and by prescription so that they can better work with the pharmacist to aid patients in the smoking cessation process. Current guidelines do not specify any of the medications as first line. Patients should be educated on all of the options available so that they can decide which option they think will help them succeed.
Asenapine: A Novel Atypical Antipsychotic Agent for Schizophrenia and Bipolar I Disorder
Authors: Timpe Erin M , Chopra Ritika A
Published: September 2013

Objective:

To review the literature regarding asenapine, a recently approved atypical antipsychotic, and to evaluate its safety and efficacy profile.

Data Sources:

Primary literature was identified by conducting a MEDLINE search (1950–June 2010). English-language articles were searched using the key words asenapine, Saphris, schizophrenia, and bipolar disorder. All data were reviewed for clinical trials evaluating the safety and efficacy of asenapine. Data were also obtained directly from the manufacturer.

Study Selection and Data Extraction:

English-language articles on studies conducted in humans were reviewed.

Data Synthesis:

Asenapine is a novel atypical antipsychotic agent available as a treatment option for patients with schizophrenia, as monotherapy for the acute treatment of bipolar I manic or mixed episodes, and as adjunctive therapy with either lithium or valproate for the acute treatment of bipolar I manic or mixed episodes. Compared with other atypical antipsychotic agents, asenapine has a favorable adverse effect profile in terms of weight gain and metabolic disorders. Multiple studies have established its efficacy and safety profile. Asenapine has been shown to be superior to placebo in 4 clinical trials in patients with schizophrenia and in 2 clinical trials in patients with bipolar I disorder. Two studies comparing asenapine with olanzapine found asenapine to be similar in efficacy, 1 found olanzapine to be more effective, and 1 trial found asenapine to be associated with more adverse effects than olanzapine. This new agent is formulated as a sublingual tablet and is administered at either 5 or 10 mg twice daily. Common adverse effects reported include extrapyramidal symptoms, somnolence, sedation, and dizziness.

Conclusions:

Asenapine offers a viable treatment option for the acute treatment of patients affected by schizophrenia and bipolar I disorder. Future studies are needed to compare asenapine directly against other atypical antipsychotics to determine its appropriate place in therapy.
Tapentadol: A Novel, Centrally Acting Analgesic for Moderate-to-Severe Acute Pain
Authors: Matthews Michele L , Lufkin Richard
Published: September 2013

Objective:

To review the role of tapentadol in the treatment of moderate-to-severe acute pain.

Data Sources:

Primary literature was retrieved by searching MEDLINE (1950–August Week 3, 2010), EMBASE (1980–Week 34, 2010), International Pharmaceutical Abstracts (1970-August 2010), and Google Scholar, A bibliographic review of published articles was also performed. Search terms included tapentadol, Nucynta, and acute pain.

Study Selection and Data Extraction:

Randomized controlled trials available in the English language that evaluated the efficacy and/or safety of tapentadol were included in this review.

Data Synthesis:

Tapentadol is a centrally acting analgesic that simultaneously activates μ-opioid receptors and inhibits the reuptake of norepinephrine in the central nervous system without affecting serotonin reuptake. We identified 6 randomized controlled trials that evaluated the use of tapentadol in over 3,000 adult patients in various acute pain models. Tapentadol was found to be superior to placebo for the management of moderate-to-severe acute pain and was found to be noninferior to oxycodone in the setting of post-bunionectomy pain and acute pain related to end-stage joint disease. Although the incidence of somnolence and dizziness was similar to that of oxycodone, tapentadol was less likely to cause nausea, vomiting, or constipation.

Conclusions:

Tapentadol is a novel analgesic with dual mechanisms of action that appears to be safe and effective for the management of moderate-to-severe acute pain. Future studies should focus on comparative efficacy as well as the role of tapentadol in chronic pain.
Warfarin and Supplement Interactions: Survey of Published Literature
Authors: Marino Joanna , Motz David , Shields Kelly
Published: September 2013

Objective:

To review published literature related to potential interactions between warfarin and common dietary supplement products.

Data Sources:

Tertiary databases including Micromedex, LexiComp, and Natural Medicines Comprehensive Database were used to assess drug interactions with warfarin. Searches of literature from database inception through July 2010 were conducted in MEDLINE, International Pharmaceutical Abstracts, and Iowa Drug Information Service and were restricted to the English language. The following search terms were used: warfarin, ginkgo biloba, St. John's wort, garlic, coenzyme Q10, ginger, ginseng, red clover, fish oil, dong quai, cranberry, green tea, saw palmetto, bilberry, soy, chamomile, glucosamine, chondroitin, echinacea, interactions, anticoagulation/antiplatelet, bleeding, herbals, and pharmacokinetics/pharmacodynamics.

Study Selection and Data Extraction:

Thirty-two English language publications were identified and analyzed. Reference lists of each of the included articles were reviewed to obtain related articles for further analysis.

Data Synthesis:

Quality of existing data for interactions between warfarin and commonly available dietary supplements varies greatly. The majority of information available is derived from case reports, although for some products pharmacokinetic studies have been performed to assess the effect of supplement use in patients concurrently using warfarin. Some of the data that suggest interactions with warfarin were gleaned from case reports or from an understanding of supplement mechanisms of action that would indicate such an interaction. The strength of evidence for the majority of the herbal products studied seems to be lacking and therefore it is difficult to draw firm conclusions.

Conclusions:

Based on the narrow therapeutic window of warfarin therapy, practitioners should be encouraged to document any potential drug interaction. However, it seems inappropriate to suggest absolute avoidance of all dietary supplements in all patients using warfarin therapy. Instead, diligent monitoring and reporting should be implemented to detect such events.
Methylphenidate for Chronic Migraine and Cluster-Type Headaches: A Case Report
Authors: Detweiler Mark B , Halling Mary H , Detweiler Jonna G
Published: September 2013

Objective:

To report the successful treatment of a case of chronic, treatment-resistant migraine and cluster headaches that started after an accidental exposure to toxic gas in a patient with recurrent major depression, hypersomnia, and chronic fatigue.

Case Summary:

A 50-year-old female presented with a 32-year history of recurrent major depression, hypersomnia, and chronic fatigue in addition to migraine and cluster headaches that started after accidental exposure to toxic gas during an army training exercise. The frequent and severe headaches led to discharge from the army and to the patient's being fired from multiple jobs due to repeated absences. She became depressed, with hypersomnia and chronic fatigue, spending most of the day in bed for about 2 decades. This also interfered with her partner relationship. She had received tricyclic antidepressants (TCAs), anticonvulsants, triptans, migraine agents, nonsteroidal antiinflammatory drugs, and biofeedback for the headaches, all without lasting benefit. Medications for depression had included TCAs, serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors without resolution of chronic depression. Treatment for depression and fatigue began with titration of citalopram to 60 mg daily, followed by titration of bupropion SA to 300 mg in the morning and 150 mg in the afternoon. Her mood improved; however, the hypersomnia and fatigue remained along with the chronic migraine and cluster headaches. Methylphenidate immediate release was added to reduce the hypersomnia and fatigue, and her headaches markedly decreased. The patient apparently stopped taking the prescribed methylphenidate due to medication name confusion with medroxyprogesterone, and the migraine and cluster headaches returned to their prior level of severity. Methylphenidate was retitrated to 15 mg twice/day with resolution of the chronic migraine and cluster headaches, hypersomnia, and fatigue.

Discussion:

The literature on the use of methylphenidate, a methyl α-phenyl-2-piperidineacetate hydrochloride, for headache treatment and prophylaxis consists of 1 other case report. Methylphenidate stimulates the central nervous system, increasing norepinephrine and dopamine levels by impeding uptake and increasing release. By augmenting dopamine and norepinephrine levels in the medial prefrontal cortex and hypothalamus, methylphenidate may modulate depression and somnolence. Methylphenidate may also alter brain stem serotoninergic action, resulting in methylphenidate-mediated analgesia, perhaps modulating headache symptoms.

Conclusions:

Methylphenidate may have an application as a third- or fourth-tier medication for headache treatment and prophylactic action in selected treatment-resistant cases. Response appears to be dose-related.
Ohio Physicians' Intent to Adopt Electronic Prescribing
Authors: Pinto Sharrel L , Weber Nick S
Published: September 2013

Background:

Currently in health care, communication between prescribers and pharmacists routinely entails paper and a telephone. Many professional associations have strongly advocated the adoption of electronic prescribing (e-prescribing) in physicians' clinical practices to decrease medication errors and adverse drug events. However, very few physicians have adopted this technology in the US.

Objective:

To determine the relationship between Ohio physicians' demographics and their intention to adopt e-prescribing; assess the relationships between attitudes, subjective norms, and perceived behavioral control as applied to physicians' intention to adopt e-prescribing; and identify factors that can predict physicians' intention toward the adoption of e-prescribing.

Methods:

In this exploratory cross-sectional study, we used a self-administered survey. The survey was developed based on the constructs of the Theory of Planned Behavior. It was mailed to 1500 physicians currently practicing in Ohio. Demographic information about the respondents was collected. Pearson correlation was used to assess the relationship between demographics and intention to adopt e-prescribing. Multiple regression analysis was used to identify the factors predicting intention.

Results:

The overall survey response rate was 15.33% (N = 230). A significant weak negative correlation was found between physicians' ages (r = −0.180; p = 0.007) and their intent to adopt electronic prescribing. A statistically significant negative correlation was also found between practice type (r = −0.196; p = 0.003) and the intention to adopt electronic prescribing. Attitude was the strongest predictor of intention to adopt e-prescribing (β = 0.539; p = 0.000).

Conclusions:

Physicians with more positive attitudes, positive subjective norms, and positive perceived behavioral control have a stronger intention to adopt e-prescribing.
Pharmacologic Options for the Management and Prevention of Migraines
Authors: Freeland Kathryn N , Vandenberg Amy
Published: September 2013

Objective:

To review available pharmacologic options for the management and prevention of migraine headaches.

Data Sources:

A PubMed literature search (1985–December 2010) was conducted using the following MeSH search terms: migraine, aura, headache, triptans, ergot derivatives, NSAIDs, opioids, analgesics, antiepileptics, antidepressants, β-blockers, calcium channel blockers, and prophylaxis. Tertiary references and prescribing information for included medications were used for dosing recommendations.

Study Selection and Data Extraction:

English-language reviews, tertiary references, guidelines, and clinical trials of newly released medications were reviewed for inclusion. Articles using pharmacotherapy in human models were reviewed.

Data Synthesis:

Migraine headaches are a costly and painful problem that affects 12% of the US population. Current treatment options may be divided into either acute treatments or preventive therapy. Nonpharmacologic therapy, such as the identification of triggers and maintenance of a headache diary, is an important addition to either medication regimen. Patients experiencing mild-to-moderate migraine pain may be able to manage the pain using nonsteroidal antiinflammatory drugs or analgesics. More severe migraine pain may require the use of different medications, such as opioid pain relievers or a triptan. Patients who report frequent migraines or migraines that significantly affect their activities of daily life may become candidates for migraine prophylaxis. Agents for migraine prophylaxis include antiepileptics, β-adrenergic antagonists, antidepressants, and calcium channel blockers.

Conclusions:

There are several options available for both the management and prevention of migraine headaches. Choice of pharmacotherapy depends on the intensity and frequency of a patient's migraines. In addition, patients should be encouraged to avoid triggers and to keep a log of migraine symptoms in order to best manage their migraines.
Developing a Weight Management Program in a Community Setting
Authors: Mistry Amee D , Lee Karen W , Machado Matthew R
Published: September 2013

Background:

Managing body weight is important for a patient's overall well-being. Developing a weight management program for patients is a basis for providing structure and assistance to patients who may not understand what is necessary to achieve a healthy body weight.

Objective:

To describe implementation of a pharmacist-run weight management program in a community pharmacy.

Methods:

From July to December 2007, we created a weight management program which was implemented in January 2008 in a community pharmacy setting by utilizing nutritional information readily available online, purchasing commercially available weight management machines, and offering counseling sessions.

Results:

Preliminary results show that patients have been able to decrease their weight with the assistance of this pharmacist-run program.

Conclusions:

A community pharmacy-based weight management program can assist patients in decreasing their total body weight and give pharmacists an opportunity to be involved in managing obesity.
Antidepressant Pharmacology: Introduction for the Pharmacy Technician
Authors: Cates Marshall E , Wensel Terri M , Waldrop Bruce A , Iranikhah Maryam M
Published: September 2013

Objective:

To review the pharmacology of antidepressants and describe clinical applications of antidepressants in the treatment of depression.

Data Sources:

A MEDLINE/PubMed search (1995–July 2011) was conducted for English-language articles using the terms pharmacology, antidepressant, tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, venlafaxine, desvenlafaxine, duloxetine, bupropion, trazodone, nefazodone, mirtazapine, vilazodone, efficacy, adverse effects, and drug interactions. Book chapters related to the pharmacology of antidepressants were also searched.

Study Selection and Data Extraction:

Articles and book chapters relevant to the pharmacology of antidepressants were reviewed.

Data Synthesis:

Antidepressants exert pharmacologic actions via enzyme inhibition, reuptake inhibition, receptor antagonism, and receptor partial agonism. These actions can cause both therapeutic and adverse effects. Each antidepressant possesses a unique blend of pharmacologic actions, which helps to differentiate antidepressants and aids in the understanding of their particular efficacy profiles, adverse effect profiles, and pharmacodynamic drug interaction profiles.

Conclusions:

There are important clinical applications of the pharmacologic properties of antidepressants. Gaining familiarity with antidepressant pharmacology will enable the pharmacy technician to develop a more thorough understanding of the drug class.
Profound Neurotoxicity and Treatment Response following One Cycle of Bortezomib Therapy in an Elderly Male with Multiple Myeloma
Authors: Eaton Ellen , Wachter Adam , Tesson Alan , Cooper April A
Published: September 2013

Objective:

To report a case of peripheral and autonomic neuropathy following one cycle of bortezomib in a patient with newly diagnosed multiple myeloma.

Case Summary:

A 75-year-old male who was highly functional prior to therapy rapidly became bed-bound from hypotension, syncope, and peripheral neuropathy after initiating bortezomib. Orthostatic hypotension and syncope persisted despite exclusion of infection and endocrine derangements and his receiving adequate intravenous hydration. Five weeks after this single cycle, the patient had a complete treatment response, including undetectable M-spike, improved anemia, and return to baseline renal function. An objective causality assessment revealed that an adverse drug event was probable.

Discussion:

Although neurotoxicity is an adverse effect of bortezomib, a MEDLINE search revealed little evidence on autonomic neuropathy, such as orthostatic hypotension and syncope. Also unique is the patient's complete treatment response following this single cycle. One explanation for the toxicities and dramatic treatment response is increased bortezomib exposure due to decreased drug metabolism. Both drug interactions and genetic polymorphisms can reduce bortezomib metabolism via effects on cytochrome P450 enzymes. Our patient was concomitantly taking 4 CYP inhibitors; amiodarone and omeprazole were longstanding, and ciprofloxacin and fluconazole were recently initiated prior to chemotherapy. Of these, fluconazole inhibits CYP2C9, 2C19, and 3A4; amiodarone inhibits CYP3A4, 1A1, 1A2, 2B6, and 2D6; ciprofloxacin inhibits CYP1A2 and 3A4; and omeprazole inhibits CYP1A2, 2C19, 2C9, 2D6, and 3A4. Similarly, genetic variables affect CYP enzymes. Genetic testing can predict response to bortezomib therapy, but pretherapy testing is not standard practice due to availability and cost, as in our patient's case.

Conclusions:

CYP-inhibiting drugs and many genetic polymorphisms can reduce bortezomib metabolism and increase serum concentrations of the drug, but guidelines on drug-drug interactions, monitoring, and genetic testing prior to bortezomib toxicity are needed.
Metformin-Associated Exacerbation of Chronic Pancreatitis: A Possible Adverse Drug-Disease Interaction
Authors: Wadsworth Thomas G , Kiester Jo , Thompson E Gregory
Published: September 2013

Objective:

To report a case of metformin-associated exacerbation of chronic pancreatitis and examine this possible drug-disease interaction.

Case Summary:

A 59-year-old woman with chronic pancreatitis (CP) experienced a severe exacerbation of her characteristic chronic abdominal pain 3 weeks after initiation and titration of metformin therapy; the exacerbation resolved upon discontinuation of metformin. The patient presented to the emergency department experiencing nausea and severe right upper quadrant abdominal pain with radiation to the right flank. Persistent abdominal pain, which had been a primary feature of CP, was previously mild and easily controlled with oral analgesics. Laboratory studies ruled out acute pancreatitis and were significant only for elevated glucose (168 mg/dL). Subsequently, she was given intravenous pain and nausea medications and discharged to home. The pain and nausea shortly returned and continued for 3 more days, at which point she telephoned her gastroenterologist, who advised that she discontinue metformin because of possible adverse reaction. Within a few days of discontinuing metformin, the nausea resolved and abdominal pain gradually returned to baseline level.

Discussion:

Metformin is not generally known to cause or exacerbate pancreatitis, although cases of acute pancreatitis associated with metformin therapy have been reported in the literature. No cases involving chronic pancreatitis have been reported. Consequently, metformin's prescribing guidelines do not contain precautions or contraindications for patients with chronic pancreatitis. Use of the Naranjo probability scale for assessment of this case revealed that the adverse drug effect was possible, reflecting the symptomatic resolution upon discontinuation while accounting for the lack of causative certainty, previous conclusive case reports, as well as the presence of possible nondrug causes.

Conclusions:

To our knowledge, this is the first case describing metformin-associated exacerbation of chronic pancreatitis. Although this occurrence may be rare, cautionary consideration, education, and monitoring should accompany initiation of metformin therapy in select patients with chronic pancreatitis.
Dofetilide Overdose—A Case of Unintentional Ingestion Due to Misinterpretation of the Dose
Authors: Iyer Praneet S , Neufeld Robert J , Giambra Theresa , Norgard Nicholas B
Published: September 2013

Objective:

To report a case of unintentional overdose of dofetilide due to patient misinterpretation of the prescribed dose.

Case Summary:

A 50-year-old white male unintentionally ingested dofetilide 5000 μg instead of the prescribed dose of 500 μg because of a simple mathematical calculation error. The patient was given activated charcoal in the emergency department and also received 1 dose of magnesium sulfate 2 g and 1 dose of potassium chloride 80 mEq by mouth. He was admitted to the intensive care unit for cardiac monitoring for 1 day and was discharged when his QT/QTc interval was stable.

Discussion:

During recent years, studies have focused on errors that occur while medications are in the control of health care professionals. As health care delivery shifts from inpatient to outpatient settings, the burden of proper medication use also shifts from providers to patients. Low health literacy and lack of understanding of instructions have been cited as important root causes of medication errors in the outpatient setting. Effective communication with patients who have limited health literacy offers the potential to improve their understanding about their medical problems and treatments. Dofetilide, a class III antiarrhythmic agent, is highly regulated due to safety concerns. The drug is efficacious in the maintenance of normal sinus rhythm in patients with atrial fibrillation. Cardiac toxicity is of utmost concern when treating dofetilide overdose. The mainstay of treatment focuses on supportive care and prevention of drug absorption.

Conclusions:

Medication errors will not cease to occur unless patients understand their dosing instructions and health care responsibilities. This case highlights the need for the monitoring of patient understanding, especially when drugs with high safety risk are being used.
Do Sugar Substitutes Have Any Impact on Glycemic Control in Patients with Diabetes?
Authors: Behnen Erin M Timpe , Ferguson McKenzie C , Carlson Amy
Published: September 2013

Objective:

To evaluate the impact of nonnutritive sugar substitutes on glycemic control in patients with diabetes.

Data Sources:

A comprehensive review of the literature was conducted in PubMed (1966-March 2012) and Scopus. A combination of MeSH terms and keywords were used, including acesulfame, aspartame, diabetes, neotame, rebiana, saccharin, stevia, and sucralose.

Study Selection and Data Extraction:

Clinical studies evaluating the impact of nonnutritive sweeteners on measures of diabetic control, including, but not limited to, blood glucose levels, postprandial blood glucose, and hemoglobin A1c were selected for review. Searches were limited to only nonnutritive sweeteners available in the US.

Data Synthesis:

Nine clinical trials that evaluated nonnutritive sweeteners in a total of 490 patients with diabetes were found. Doses of sweeteners in the studies varied from below acceptable daily intake levels for 3 consecutive days to daily dosing for up to 18 weeks and up to 3.5 times the acceptable daily intake levels. No significant differences in overall effects on glycemic control and insulin response were found.

Conclusions:

Nonnutritive sweeteners do not appear to affect glycemic control in patients with diabetes. Patients should be counseled to maintain an appropriate energy balance in their diet, with or without the use of nonnutritive sweeteners.
Role of CYP450 in Antiplatelet Therapy: Considerations for Patients at Risk for Further Cardiovascular or Cerebrovascular Problems
Authors: Linn Chase E , Shah Niren K , Epstein Benjamin J
Published: September 2013

Objective:

To determine how interactions with cytochrome P450 ( CYP450) isoenzyme pathways may influence the selection of antiplatelet therapy in patients with cardiovascular and cerebrovascular disease.

Data Sources:

A MEDLINE search (1966-September 2012) was performed using the following MeSH search terms: clopidogrel, prasugrel, ticagrelor, aspirin, dipyridamole, drug interactions, polymorphism, cytochrome P450, platelets, platelet reactivity testing, and platelet function. In addition, reference citations were reviewed.

Study Selection and Data Extraction:

Selected studies analyzed the effects of CYP450 isoenzymes on the efficacy of antiplatelet therapy and potential drug-drug interactions.

Data Synthesis:

Antiplatelet therapy is pivotal in reducing the risk of acute coronary syndromes. Thienopyridines are commonly prescribed for antiplatelet drug therapy; however, a multitude of factors can influence their efficacy, given that thienopyridines require activation through CYP450 isoenzymes. Genetic polymorphisms in CYP450 isoenzymes and the susceptibility of drug-drug interactions mediated through the CYP450 system have led to variability in antiplatelet response. Two factors in particular have been prime targets in elucidating the role of CYP450 isoenzymes on thienopyridine activity and bioavailability: CYP2C19*2 polymorphisms and drug interactions with proton pump inhibitors. Additionally, many studies have surfaced in an attempt to quantify a patient's response to antiplatelet therapy but, to date, none has determined whether platelet reactivity testing is mandatory prior to initiation of therapy or whether it correlates with clinical efficacy. This review spotlights the pharmacokinetic and pharmacodynamic influences that CYP450 isoenzymes exert on antiplatelet therapies and attempts to categorize the role of platelet reactivity testing in determining the clinical significance of drug interactions.

Conclusions:

Suboptimal responses to antiplatelet therapy may occur because of interactions with CYP450 isoenzyme pathways. Further studies are warranted to clarify the impact of genetic polymorphisms and drug-drug interactions on clinical outcomes in patients with cardiovascular/cerebrovascular disease.
Ipilimumab-Induced Pneumonitis: A Case Report
Authors: Mis Lydia , Clarke Jeffrey M
Published: September 2013

Objective:

To report a case of ipilimumab-induced pneumonitis in a patient with metastatic melanoma.

Case Summary:

A 74-year-old woman with metastatic melanoma presented to the emergency department with progressive shortness of breath and dyspnea of 1 week's duration following her third cycle of ipilimumab. Upon presentation, she was hypoxic, with oxygen saturation of 66% on room air. After stabilization, she was transferred to the inpatient unit where she was placed on broad-spectrum antibiotics (intravenous vancomycin, piperacillin/tazobactam, oral ciprofloxacin, and oral trimethoprim/sulfamethoxazole) and a high-dose corticosteroid (intravenous methylprednisolone 30 mg every 6 hours). Bronchoscopy was negative for infection, and results of blood, urine, and respiratory cultures were negative. Antibiotics were eventually stopped and the patient responded to a high-dose corticosteroid for probable ipilimumab-induced pneumonitis.

Discussion:

Ipilimumab is a recombinant, human monoclonal antibody that was approved for the treatment of metastatic melanoma. A black-box warning exists for immune-mediated adverse reactions, which can involve any organ system and are a result of T-cell activation and proliferation. The most common sites for these reactions are the gastrointestinal tract, skin, liver, and pituitary gland. The Naranjo probability scale indicated a probable relationship between the development of pneumonitis and ipilimumab therapy. Review of the literature through October 2012 did not yield any reports of single-agent, ipilimumab-associated pneumonitis in patients with metastatic melanoma. Infection was ruled out, and no other etiology was identified for the patient's acute symptoms. Furthermore, she responded quickly to a high-dose corticosteroid.

Conclusions:

Ipilimumab is associated with immune-mediated toxicities that can be severe or fatal. Prompt recognition and treatment of these reactions is necessary to prevent morbidity or mortality. This is the first reported case of single-agent, ipilimumab-associated pneumonitis in a patient with metastatic melanoma.
Gingival Hypertrophy Associated with Amlodipine Use in an HIV-Infected Woman
Authors: Jacobs David M , Duggan Joan M , Sahloff Eric G
Published: September 2013

Objective:

To report the case of a 46-year-old woman with HIV infection who developed gingival hypertrophy while taking amlodipine for hypertension and review the literature discussing gingival hypertrophy associated with amlodipine and other calcium channel blockers.

Case Summary:

A 46-year-old HIV-infected female was taking amlodipine 5 mg daily to manage hypertension. After 4 1/2 years of exposure to amlodipine, the patient presented with new-onset gingival hypertrophy. Concurrent medications included atazanavir, ritonavir, tenofovir/emtricitabine, a multivitamin, and ibuprofen and tramadol as needed. Amlodipine was discontinued and lisinopril was initiated to manage hypertension. Resolution of gingival hypertrophy was noted at 3- and 12-month follow-up visits.

Discussion:

Drug-induced gingival hypertrophy has been associated with anticonvulsants, immunosuppressants, and calcium channel blockers. Cases of gingival hypertrophy are uncommon, especially after such extended exposure. The Naranjo probability scale classified the reaction as probable. Discontinuation of amlodipine led to resolution of gingival hypertrophy.

Conclusions:

Patients with new-onset gingival hypertrophy should have a complete medication review to identify potential causative agents. Development of gingival hypertrophy may present acutely or with extended exposure. Resolution of gingival hypertrophy generally occurs with discontinuation of the inciting agent.
Compliance with Renal Dosing Guidelines for Outpatient Antiinfective Prescriptions
Authors: Durand Cheryl R , Carr Robert J , Boudreau Samantha M
Published: September 2013

Background:

More than 80–95% of adverse drug events occurring among renally impaired patients are related to excessive dosing.

Objective:

To assess current prescribing practices with antiinfectives for patients with estimated creatinine clearance (CrCl) less than 51 mL/min who were in a local health care system.

Methods:

Outpatient antiinfective prescriptions written during a 10-day period in July 2012 were reviewed. The following information was collected for each patient: age, sex, serum creatinine, weight, height, drug dose and schedule, and discharge unit/outpatient service. Kidney function was estimated by calculating CrCl using either the Cockcroft-Gault or the Jelliffe equation. Two resources were used to identify appropriate dosing for renal function; if the 2 resources differed, the stricter of the 2 was used for assessment. Institutional review board approval was obtained for this study.

Results:

A total of 91 prescriptions, written for 87 different patients, met inclusion criteria and were reviewed. Average CrCl and age among the study population was 37.82 mL/min, and 75.7 years, respectively. Doses were excessive in 30% of outpatient prescriptions. The most common medications involved in excessive dosing were trimethoprim/sulfamethoxazole (TMP/SMX), cephalexin, fluconazole, and acyclovir. TMP/SMX was dosed excessively in 80% of prescriptions. Both fluconazole and acyclovir were dosed excessively in 75% of prescriptions, while cephalexin was dosed in excess in 36% of prescriptions. A comparison of discharge units/outpatient services revealed that 56% of prescriptions from urgent care centers were dosed in excess, compared with 30% from hospital discharge, 20% from emergency department discharge, and 25% from outpatient services.

Conclusions:

Our study indicates that there is room for improvement when dosing antiinfective medications for outpatients with renal insufficiency. Appropriate renal dosing can help protect patients from dangerous toxicities and other adverse drug events.
Worsening of Myasthenia Gravis following the Addition of Gabapentin for Essential Tremor
Authors: Seymour Nicole , Patel Tejal , Dixon Heather
Published: September 2013

Objective:

To report a case of worsening myasthenia gravis after the initiation of gabapentin for treatment of essential tremor.

Case Summary:

A 69-year-old man experienced minor ptosis of the left eyelid, slight neck weakness, and transient difficulties in chewing food on day 6 of a slow gabapentin dosage titration. As the titration continued, the myasthenia symptoms progressed to bilateral ptosis, and there was dramatic worsening of weakness by day 23. He was taking gabapentin 1500 mg daily at the time; the drug was then tapered to discontinuation. All myasthenia gravis symptoms were reported as resolved 3 days after discontinuation of gabapentin. The initiation and discontinuation of gabapentin also coincided with improvement, then worsening of the patient's tremor.

Discussion:

Three published case reports describe worsening of myasthenia gravis during use of gabapentin for the treatment of various neuropathies. To the best of our knowledge, this is the first case report of a patient experiencing worsening of myasthenia gravis upon initiation of gabapentin for essential tremor. The Naranjo probability scale suggests a probable association between gabapentin and worsening of myasthenia gravis symptoms in our patient. Several myasthenia-like symptoms are listed in the gabapentin mongraph as low-frequency adverse events, increasing the possibility that gabapentin may have been unmasking or worsening myasthenia gravis in clinical trials. However, myasthenia gravis is not identified as a contraindication or caution for gabapentin use.

Conclusions:

Gabapentin should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy.
Metallographic and fracture characteristics of resistance spot welded TWIP steels
Authors: Saha D C , Cho Y , Park Y-D
Published: September 2013

In this study, the microstructural characterisation, mechanical testing and fractography investigation were performed on twinning induced plasticity (TWIP) steels, fabricated with resistance spot welding. Failure mode during the cross-tensile test was found to follow the sequences of strain localisation of both sheets, crack initiation at notch tip, crack following along the fusion boundary and, finally, ductile shear fracture along the sheet thickness direction. On the other hand, failure in the tensile shear test was always directed along the sheet/sheet (s/s) interface; the interfacial failure and shear deformation were observed at the weld centreline. Solidification occurred as a primary austenitic solidification mode, and no martensitic transformations were detected through electron backscatter diffraction analysis. The fusion zone was mainly composed of austenite with directional solidification towards the centreline; the columnar dendritic and equiaxed structures were identified. Interdendritic C and Mn cosegregation were confirmed by electron probe microanalysis.
Phylogeographic evidence of cognate recognition site patterns and transformation efficiency differences in H. pylori: theory of strain dominance
Authors: Maldonado-Contreras Ana , Mane Shrinivasrao P , Zhang Xue-Song , Pericchi Luis , Alarcón Teresa , Contreras Monica , Linz Bodo , Blaser Martin J , Domínguez-Bello María Gloria
Published: September 2013

Background

Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. We hypothesized that genomes from hspAmerind strains that evolved from a small founder population have lost CRS for RMS and active methylases, promoting hpEurope’s DNA invasion. We determined the observed and expected frequencies of CRS for RMS in DNA from 7 H. pylori whole genomes and 110 multilocus sequences. We also measured the number of active methylases by resistance to in vitro digestion by 16 restriction enzymes of genomic DNA from 9 hpEurope and 9 hspAmerind strains, and determined the direction of DNA uptake in co-culture experiments of hspAmerind and hpEurope strains.

Results

Most of the CRS were underrepresented with consistency between whole genomes and multilocus sequences. Although neither the frequency of CRS nor the number of active methylases differ among the bacterial populations (average 8.6 ± 2.6), hspAmerind strains had a restriction profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians strains also exhibited higher transformation rates than European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa.

Conclusions

The geographical variation in the pattern of CRS provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian strains in Latin America via DNA recombination.
Assessment of quality of life of the children and parents affected by inborn errors of metabolism with restricted diet: preliminary results of a cross-sectional study
Authors: Fabre Alexandre , Baumstarck Karine , Cano Aline , Loundou Anderson , Berbis Julie , Chabrol Brigitte , Auquier Pascal
Published: September 2013

Introduction

The development in therapeutic strategies has increased survival of children affected by inborn errors of metabolism with restricted diet (IEMRD). These diseases have mild- and long-term consequences on the health. Little is known about the impact on the quality of life (QoL) of children and their families. The aims of this study were: to compare the QoL of the children and parents affected by IEMRD with the QoL of the general population and one pathology associated with long-term consequences.

Patients and methods

This cross-sectional study was performed at the French Reference Center for inborn metabolic disorders (Marseille, France). Inclusion criteria were: a child with a diagnosis of organic aciduria, urea cycle defect, or maple syrups urine disease (MSUD). Socio-demographics, clinical data, and QoL were recorded.

Results

Twenty-one of 32 eligible families were included during a planned routine visit. Ten (47%, 95% CI 27-69%) children were affected by organic aciduria, six (29%, 95% CI 10-48%) by urea cycle defects, and five (24%, 95% CI 6-42%) by MSUD. Among the younger children, the general well-being was significantly lower in the children with IEMRD than in the leukemia children (58 ± 16 versus 76 ± 15, p = 0.012), and among the older children, the leisure activities were significantly lower in the children with IEMRD than in the leukemia children (29 ± 18 versus 62 ± 22, p < 10-3), while the relationships with teachers were better (76 ± 23 versus 60 ± 23, p = 0.01). The physical QoL score was lower in the parents than in the French norms (66 ± 21 versus 75 ± 1, p = 0.05). Factors modulating QoL were: eating and neurologic disorders, enteral nutrition, and feeding modalities.

Conclusion

The children and the parents of children affected presented altered ‘physical’ and ‘social’ QoL scores compared with the norms and patients with leukemia and their families. Future studies based on larger cohort studies should determine the different weights of potential predictive factors of QoL.
The existence of solutions to a class of boundary value problems with fractional difference equations
Authors: Pan Yuanyuan , Han Zhenlai , Sun Shurong , Hou Chuanxia
Published: September 2013

In this paper, we study the existence and uniqueness of solutions for the boundary value problem of fractional difference equations

{

−

Δ
ν

y
(
t
)
=
f
(
t
+
ν
−
1
,
y
(
t
+
ν
−
1
)
)
,

y
(
ν
−
3
)
=
0
,

Δ
y
(
ν
−
3
)
=
0
,

y
(
ν
+
b
)
=
g
(
y
)

and

{

−

Δ
ν

y
(
t
)
=
λ
f
(
t
+
ν
−
1
,
y
(
t
+
ν
−
1
)
)
,

y
(
ν
−
3
)
=
0
,

Δ
y
(
ν
−
3
)
=
0
,

y
(
ν
+
b
)
=
g
(
y
)
,

respectively, where

t
=
1
,
2
,
…
,
b

,

2
<
ν
≤
3

,

f
:
{
ν
−
1
,
…
,
ν
+
b
}
×
R
→
R

is a continuous function and

g
∈
C
(

[
ν
−
3
,
ν
+
b
]

Z

ν
−
3

,
R
)

is a continuous functional. We prove the existence and uniqueness of a solution to the first problem by the contraction mapping theorem and the Brouwer theorem. Moreover, we present the existence and nonexistence of a solution to the second problem in terms of the parameter λ by the properties of the Green function and the Guo-Krasnosel’skii theorem. Finally, we present some examples to illustrate the main results.

MSC:34A08, 34B18, 39A12.
Altered inflammatory responsiveness in serotonin transporter mutant rats
Authors: Macchi Flavia , Homberg Judith R , Calabrese Francesca , Zecchillo Claudia , Racagni Giorgio , Riva Marco A , Molteni Raffaella
Published: September 2013

Background

Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of depression. Indeed, depressed patients exhibit increased levels of inflammatory markers in both the periphery and the brain, and high comorbidity exists between major depression and diseases associated with inflammatory alterations. In order to characterize the link between depression and inflammation, we aimed to investigate whether an altered inflammatory system is present in a genetic model of vulnerability for depression, namely rats with partial or total deletion of the serotonin transporter (SERT) gene.

Methods

Wild-type, heterozygous and homozygous SERT rats were analyzed under basal condition or following a challenge with an acute injection of lipopolysaccharide (LPS) and killed 24 h or 5 days later.

Results

We found that SERT mutant rats show altered cytokine expression in the dorsal and ventral hippocampus at basal conditions, and they also display an exacerbated cytokine response to the LPS challenge. Moreover, mutant rats exhibit differences in the expression of markers for microglia activation.

Conclusion

Based on these data, we suggest that basal or functional alterations of immune/inflammatory systems might contribute to the phenotype of SERT rats and to their heightened susceptibility to depressive-like behavior.