Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta-analysis.

Studies have shown that angiotensin converting enzyme inhibitors (ACEIs) are superior in primary and secondary prevention for cardiac mortality and morbidity to angiotensin receptor blocker (ARBs). One of the common side effects from ACEI is dry cough. The aims of this systematic review, and network meta-analysis are to rank the risk of cough induced by different ACEIs and between ACEI and placebo, ARB or calcium channel blockers (CCB). We performed a systematic review, and network meta-analysis of randomized controlled trials to rank the risk of cough induced by each ACEI and between ACEI and placebo, ARB or CCB. A total of 135 RCTs with 45,420 patients treated with eleven ACEIs were included in the analyses. The pooled estimated relative risk (RR) between ACEI and placebo was 2.21 (95% CI: 2.05-2.39). ACEI had more incidences of cough than ARB (RR 3.2; 95% CI: 2.91, 3.51), and pooled estimated of RR between ACEI and CCB was 5.30 (95% CI: 4.32-6.50) Moexipril ranked as number one for inducing cough (SUCRA 80.4%) and spirapril ranked the least (SUCRA 12.3%). The order for the rest of the ACEIs are as follows: ramipril (SUCRA 76.4%), fosinopril (SUCRA 72.5%), lisinopril (SUCRA 64.7%), benazepril (SUCRA 58.6%), quinapril (SUCRA 56.5%), perindopril (SUCRA 54.1%), enalapril (SUCRA 49.7%), trandolapril (SUCRA 44.6%) and, captopril (SUCRA 13.7%). All ACEI has the similar risk of developing a cough. ACEI should be avoided in patients who have risk of developing cough, and an ARB or CCB is an alternative based on the patient's comorbidity.

Short Acting Beta Agonist Use Associated with Increased Mortality and Morbidity in Asthma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Short acting b2 agonists are recommended to be used ≤ 2 canisters per year. It is suggested that overuse of b2 agonists will lead to increased morbidity and mortality.  This study aimed to determine if overuse of b2 agonists result in increased morbidity and mortality. METHODS: We performed a systematic review and meta-analysis of the literature to determine if overuse of b2 agonists cause increase mortality, ICU admissions, hospitalization, and exacerbation. RESULTS: A total of 11,888 publications were identified and 4260 duplications were removed, resulting in 7268 abstracts that were screened and 7254 irrelevant studies that were excluded. Ultimately, 14 studies were included. The overall pooled estimated odds ratio (OR) for mortality was 0.83 (95% CI: 0.66, 1.05), 0.99 for ICU admission (95% CI: 0.80, 1.21), 1.22 for hospitalization (95% CI: 0.96, 1.31), and 0.99 for exacerbation (95% CI: 0.85, 1.15). CONCLUSION: There is no statistical difference in mortality, ICU admission rate, hospitalization, or exacerbation with using b2 agonists.

Effects of Vitamin D Serum Level on Morbidity and Mortality in Patients with COVID-19: A Systematic Review and Meta-Analysis.

PURPOSE: It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. Vitamin D is readily available, inexpensive, and easy to administer to subjects infected with COVID-19. If effective in reducing the severity of COVID-19, it could be an important and feasible therapeutic intervention. METHODS: We performed a systematic review and meta-analysis of the literature to determine the effects of Vitamin D serum concentration on mortality and morbidity in COVID-19 patients. The primary objectives were to determine if Vitamin D serum concentration decrease mortality, ICU admissions, ventilator support, and length of hospital stay in COVID-19 patients. RESULTS: A total of 3572 publications were identified. Ultimately, 20 studies are included. A total of 12,806 patients aged between 42 to 81 years old were analyzed. The pooled estimated RR for mortality, ICU admission, ventilator support and length of hospital stay were 1.49 (95% CI: 1.34, 1.65), 0.87 (95% CI: 0.67, 1.14), 1.29 (95% CI: 0.79, 1.84), and 0.84 (95% CI -0.45, 2.13). CONCLUSION: There is no statistical difference in mortality, ICU admission rate, ventilator support requirement, and length of hospital stay in COVID-19 patients with low and high Vitamin D serum concentration.

Comparative peripheral edema for dihydropyridines calcium channel blockers treatment: A systematic review and network meta-analysis.

Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.

Team approach to polypharmacy evaluation and reduction: study protocol for a randomized controlled trial.

BACKGROUND: Polypharmacy in older adults can be associated with negative outcomes including falls, impaired cognition, reduced quality of life, and general and functional decline. It is not clear to what extent these are reversible if the number of medications is reduced. Primary care does not have a systematic approach for reducing inappropriate polypharmacy, and there are few, if any, approaches that account for the patient's priorities and preferences. The primary objective of this study is to test the effect of TAPER (Team Approach to Polypharmacy Evaluation and Reduction), a structured operationalized clinical pathway focused on reducing inappropriate polypharmacy. TAPER integrates evidence tools for identifying potentially inappropriate medications, tapering, and monitoring guidance and explicit elicitation of patient priorities and preferences. We aim to determine the effect of TAPER on the number of medications (primary outcome) and health-related outcomes associated with polypharmacy in older adults. METHODS: We designed a multi-center randomized controlled trial, with the lead implementation site in Hamilton, Ontario. Older adults aged 70 years or older who are on five or more medications will be eligible to participate. A total of 360 participants will be recruited. Participants will be assigned to either the control or intervention arm. The intervention involves a comprehensive multidisciplinary medication review by pharmacists and physicians in partnership with patients. This review will be focused on reducing medication burden, with the assumption that this will reduce the risks and harms of polypharmacy. The control group is a wait list, and control patients will be given appointments for the TAPER intervention at a date after the final outcome assessment. All patients will be followed up and outcomes measured in both groups at baseline and 6 months. DISCUSSION: Our trial is unique in its design in that it aims to introduce an operationalized structured clinical pathway aimed to reduce polypharmacy in a primary care setting while at the same time recording patient's goals and priorities for treatment. TRIAL REGISTRATION: Clinical Trials.gov NCT02942927. First registered on October 24, 2016.

Angiotensin-Converting Enzyme Inhibitor Induced Cough in Chinese Patients: a Systematic Review and Meta-analysis.

PURPOSE: To determine the risk of angiotensin converting enzyme inhibitor (ACEI)-induced cough compared to non-ACEI cough among Chinese patients. METHODS: A comprehensive search was conducted including randomized controlled trials, case-control studies and observational studies that compared ACEI treatment with control treatment in MEDLINE, EMBASE, CINAHL, Scopus, Google Scholar and ProQuest Dissertations & Theses Global. The studies which contained: Chinese population, ACEI, non-ACEI, and indications for the treatment of ACEI were included. The pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare the relative risk of cough between ACEIs and non-ACEI drugs based on the events of reported cough in each study. RESULTS: Eleven randomized controlled trials were included with a total of 1815 patients. The total number of cough events in ACEI treatment was 101 in 930 patients (11%) and 20 in 885 patients (2%) in the Non-ACEI treatment. The pooled RR was 5.16 (95% CI: 3.39-7.85) under fixed model. The discontinuation number of single ACEI treatment due to coughing side effect was 21 and the withdrawal rate was 4.13%. Only two patients discontinued non-ACEIs treatment due to the intolerable cough and the withdrawal rate was 0.34%. The overall RR of withdrawal related to cough was 7.06 (95% CI: 2.49-20.04). CONCLUSIONS: The pooled risk of the incidence of ACEI-induced cough was about five times higher than that of non-ACEI-induced cough in Chinese population. The risk of withdrawal events related to cough in the single ACEI treatment was seven times of that in the non-ACEI treatment.

A De Novo Pharmacist-Family Physician Collaboration Model in a Family Medicine Clinic in Alberta, Canada.

Collaborative practice in health-care has proven to be an effective and efficient method for the management of chronic diseases. This study describes a de novo collaborative practice between a pharmacist and a family physician. The primary objective of the study is to describe the collaboration model between a pharmacist and family physician. The secondary objective is to describe the pharmacist workload. A list of patients who had at least one interaction with the pharmacist was generated and printed from the electronic medical record. There were 389 patients on the patient panel. The pharmacist had at least one encounter with 159 patients. There were 83 females. The most common medical condition seen by the pharmacist was hypertension. A total of 583 patient consultations were made by the pharmacist and 219 of those were independent visits. The pharmacist wrote 1361 prescriptions. The expanded scope of practice for pharmacists in Alberta includes additional prescribing authority. The pharmacists' education and clinical experience gained trust from the family physician. These, coupled with the family physician's previous positive experience working with pharmacists made the collaboration achievable.

Population pharmacokinetics and exposure-response analysis of tigecycline in patients with hospital-acquired pneumonia.

BACKGROUND: Tigecycline has been widely used to treat hospital-acquired pneumonia (HAP) off-label since it is effective against a wide range of multidrug-resistant bacteria. However, no recommended dosage for this indication has been evaluated, resulting in possible inadequate treatment. AIMS: The aims of this study are to establish the population pharmacokinetic (PPK) model of tigecycline in Chinese patients with HAP, as well as to evaluate the exposure-response relationship for the treatment of HAP with multidrug-resistant gram-negative bacteria. METHODS: A PPK analysis of tigecycline was conducted on pooled data from 328 blood samples obtained from 89 patients with HAP. Tigecycline plasma concentrations were measured by a two-dimensional liquid chromatographic system and the data were analysed using Phoenix NLMETM software. Exposure-response analyses for efficacy were performed based on the data from 79 HAP patients with multidrug-resistant gram-negative infections. Classification and regression tree and logistic regression analyses were employed to identify which pharmacokinetic-pharmacodynamic (PK-PD) indices and magnitudes were the significant predictors of tigecycline efficacy. RESULTS: A two-compartment model with zero-order absorption and first-order elimination adequately described the data. A larger body weight was associated with increased central volume of distribution and clearance (P < .005), and increased age, baseline creatinine concentration and aspertate aminotransferase were associated with decreased clearance (P < .005). The AUC0-12h  × V/MIC ratio, APACHEII score and combined Pseudomonas aeruginosa infection are the strong predictors for tigecycline clinical response. Classification and regression tree analyses indicated that the combination of APACHEII score < 24 and AUC0-12h  × V/MIC ratio ≥ 100 was associated with clinical success. CONCLUSIONS: The proposed PPK model may serve as the basis for estimating tigecycline exposure for PK-PD analyses, and the PK-PD index and magnitude found in this study could be used for designing proper dosage regimens of tigecycline.

Determination of efficacy and toxicity of diclofenac microemulsion formulation for musculoskeletal pain: an observational study.

OBJECTIVE: Musculoskeletal pain is often caused by injury to the bones, muscles, tendons, ligaments or nerves. Symptoms can be localized or generalized. Mild-moderate symptoms are treated with topical/oral over the counter drugs. Microemulsion delivery formulations are thermodynamically stable, have superior bioavailability and better penetration of lipophilic and hydrophilic drug into the dermis. A prospective observational study in patients: 18 years or older, with mild-moderate musculoskeletal pain; with severe pain without adequate pain control; with severe pain and could not tolerate oral agents; with renal impairment were invited to try diclofenac 2% in microemulsion foam. They were followed up at 2 and 4 weeks. A 50% reduction on a visual analog pain scale was considered success. Adverse events were defined as irritation, gastrointestinal upset/bleed, rectal bleed, and hematemesis. The objective was to determine the efficacy and toxicity of diclofenac 2% in microemulsion foam. RESULTS: Thirteen consecutive patients with musculoskeletal pain consented to participate. Two patients were lost to follow up. Two of the 11 patients reported minimal improvement, while nine patients reported minimum 50% reduction. No adverse effects were reported. Diclofenac 2% in microemulsion foam is effective in the treatment of mild to moderate musculoskeletal pain and well tolerated.

The Impact of a Training Program on Clinical Pharmacists on Pharmacy Clinical Services in a Tertiary Hospital in Hunan China.

BACKGROUND: Prior to 2015, clinical consultation was the only clinical service provided by clinical pharmacists in Changsha Second Hospital. Between 2015 and 2017, a train-the-trainer program was implemented to train clinical pharmacists to provide pharmaceutical care and to conduct clinical research. The objective of the study is to examine the impact on the clinical services provided by pharmacists after the implementation of the train-the-trainer program. PATIENTS AND METHODS: Between 2004 and 2014, all completed clinical consultation activities were tallied and summarized. The results from the tallied consultation activities were used as a baseline for clinical activities provided by pharmacists prior to the training. A structured training program was implemented between 2015 and 2017 to train clinical pharmacists to provide pharmaceutical care. After the implementation of the training program was completed, all clinical activities provided by pharmacists between January 2017 and December 2017 were documented in the clinical workload form. The clinical activities completed by each pharmacist were tallied and summarized. RESULTS: Between 2004 and 2014, a total of 6569 (average 657 per year) pharmacy consultations were requested and completed from a total of 44 departments. In 2017, a total of 15,078 hrs of clinical activities were logged. The pharmacists completed 3481 consultations in 2017 (an increase of 430%), averaging 316 consultations for each pharmacist and 271.8 hr per pharmacist. Over 2000 hrs (of the 15,078 hrs) were spent on direct patient care by the pharmacists. CONCLUSION: This study shows that there was a 430% increase in clinical pharmacy consultation services provided by the clinical pharmacists after the implementation of the training program. This is directly related to the number of well-trained pharmacists available. After the implementation of the train-the-trainer program, the range of services as well as the number of clinical services and clinical hours spent on providing pharmaceutical care have significantly increased.

The association between hyperuricemia and coronary artery calcification development: A systematic review and meta-analysis.

Hyperuricemia coincides with coronary artery calcification (CAC) development, but the role of serum uric acid (SUA) as a risk factor for CAC remains unclear. The objective of this study was to gain an insight into the association between SUA and CAC in adults by performing a meta-analysis. MEDLINE, EMBASE, the Cochrane Library, and EBSCO (CINAHL) were searched for relevant observational studies published until 2 June 2019. Studies were included only if they reported data on CAC presence (Agatston score > 0) or progression related to hyperuricemia in subclinical adult patients. The pooled estimates of crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) were calculated to evaluate the association between CAC presence or progression and hyperuricemia. A total of 11 studies were identified involving 11 108 adults. The pooled OR based on the frequency of CAC presence showed that patients in the high SUA group had 1.806-fold risk for developing CAC (95% CI: 1.491-2.186) under the minimal threshold of hyperuricemia (more than 6 mg/dL or 357 µmoL/L). When SUA levels were analyzed as categorical variables, the pooled estimate of adjusted ORs was 1.48 (95% CI: 1.23-1.79) for CAC presence. Additionally, for each increase of 1 mg/dL of SUA level, the risk of CAC progression was increased by 31% (95% CI: 1.15-1.49) with an average follow-up duration ranged from 4.6 to 6.1 years. Hyperuricemia is closely associated with increased risk of CAC development and CAC progression in asymptomatic patients.

Clinical experience with tigecycline in the treatment of hospital-acquired pneumonia caused by multidrug resistant Acinetobacter baumannii.

BACKGROUND: Tigecycline, with broad in vitro antibacterial activity, has been widely used off-label for nosocomial pneumonia caused by multi-drug resistant Acinetobacter baumannii (MDRAB). However, many concerns have been raised about the efficacy of tigecycline treatment as the inconsistent results from previous clinical studies. METHODS: This retrospective study evaluated the outcome of adult patients with monomicrobial MDRAB nosocomial pneumonia treated with tigecycline between 2015 and 2017. RESULTS: A total of 77 patients was eligible for this study, and the overall clinical success and 30-day survival rates were 70.03 and 70.13%, respectively, however, the microbiological eradication rate was relatively low (48%). Multivariate analysis indicated that shorter duration of tigecycline use associated with increased clinical failure, whereas higher CURB65 scores, mechanical ventilation and tigecycline resistant to MDRAB have significant association with 30-day mortality. CONCLUSIONS: Our results suggest that tigecycline is one of the potential choices for the treatment of hospital-acquired pneumonia caused by MDRAB, especially with a MIC≤2 mg/L. In addition, a longer duration of tigecycline treatment may be required to insure better clinical outcomes.

Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia.

AIM: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib. METHODS: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model. RESULTS: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: Ka (1/h) = 0.329; CL/F (l/h) = 9.25 × (actual bodyweight/70)0.228; V/F(l) = 222. CONCLUSION: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.

The impact of proton pump inhibitors on the pharmacokinetics of voriconazole in vitro and in vivo.

Voriconazole (VRC) and proton pump inhibitors (PPIs) have similar metabolic pathways. The objectives of the study are to evaluate the impact of PPIs on the pharmacokinetics of VRC. Human liver microsomes model was applied to assess the inhibitory effects of PPIs on the metabolism of VRC in vitro. A retrospective study was also carried out to explore the relationship between the plasma VRC trough concentrations and PPIs uses. Patients were divided into six groups: control (n = 166), lansoprazole (LAN, n = 38), esomeprazole (ESO, n = 19), omeprazole (OME, n = 45), pantoprazole (PAN, n = 43), and ilaprazole (ILA, n = 38) groups. All five PPIs showed concentration-dependent inhibitory effects on the VRC metabolism in human liver microsomes, among which LAN, OME and ESO were three of the most potent inhibitors. Consistently, co-administered with LAN, OME and ESO significantly increased the plasma VRC trough levels (p < 0.05), whereas there was no significant association between VRC concentrations and PAN or ILA use. Interestingly, patients in the PPIs groups were more likely to reach the therapeutic VRC range of 1-5.5 µg/mL in steady state when compared with control patients (75-81% VS 69%). In conclusion, although all PPIs showed inhibitory effects on the VRC metabolism in vitro, only LAN, OME and ESO significantly increased VRC plasma concentrations. This study should be helpful for choice of the type of PPIs for patients administered with VRC.

Diclofenac--Acetaminophen Combination Induced Acute Kidney Injury In Postoperative Pain Relief.

PURPOSE: The objective of this study was to determine: 1) the incidence and the risk factors of diclofenac/acetaminophen combination as a single agent induced Acute Kidney Injury (AKI) in postoperative pain relief 2) the average cost and length of hospital stay for patients in AKI group and non-AKI group. METHODS: All patients with no prior history of chronic kidney disease (CKD) and normal serum creatinine [44~130 µmol /l] who received diclofenac and acetaminophen combination as a single agent intramuscularly (IM) between January and December 2015 in The Second Xiangya Hospital, Changsha, Hunan, China were included in this retrospective own-control study. Baseline serum creatinine (SCr) and SCr during NSAID use were collected. AKI is defined as an increased of Scr over 1.5 times the baseline. Multivariate analyses were performed with a logistic regression model to assess the significant risk factors of AKI. RESULTS: A total of 821 patients were included in the study with 63 [7.7%] patients had diclofenac/acetaminophen combination single agent induced AKI. Multivariate analysis confirmed that using diclofenac/acetaminophen combination after surgeries within 24 h were significantly associated with AKI [odds ratio, OR, 2.173; 95% CI, 1.113-4.243; P=0.023]. The average cost and length of hospitalization in AKI group was 1.87 times [p=0.000] and 1.2 times [p=0.043] comparison than non-AKI group, respectively. CONCLUSIONS: The incidence of diclofenac/acetaminophen combination single agent induced AKI in postoperative pain relief was 7.7%. Patients with hypertension or liver cirrhosis was more likely to develop AKI and using diclofenac/acetaminophen combination after surgeries within 24 h was significant risk factors for AKI. AKI prolonged the cost and length of hospitalization. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Association Between Vancomycin Blood Brain Barrier Penetration and Clinical Response in Postsurgical Meningitis.

PURPOSE: This study investigated the association between vancomycin blood brain barrier penetration and clinical response in patients with postsurgical meningitis. METHODS: Adult patients with postsurgical meningitis were recruited. Eligible patients received vancomycin 500 mg every 6 h for at least 5 days. On day 3 or 4, cerebrospinal fluid (CSF) and simultaneous serum samples were obtained to determine CSF minimum concentrations (Cmin), serum Cmin and CSF to serum Cmin ratio. RESULTS: Twenty-two patients (14 men and 8 women; mean age of 52.6± 12.1 years) were recruited. The vancomycin Cmin was 3.63 ± 1.64 mg/L in CSF and 13.38 ± 5.36 mg/L in serum, with the CSF to serum Cmin ratio of 0.291 ± 0.118. The Cmin in serum and in CSF showed a significant correlation (p=0.005, r =0.575). The vancomycin CSF Cmin had a significant correlation with the decline of white blood cell counts (WBCs) in CSF (p=0.003, r =0.609). CSF Cmin, serum Cmin and CSF to serum Cmin ratio all showed no significant correlation with clinical response (p=0.335, 0.100, 0.679, respectively). CONCLUSIONS: There was a positive correlation between serum Cmin and CSF Cmin. However, only CSF Cmin is positively correlated with WBCs improvement in CSF. All other parameters such as serum Cmin, CSF Cmin and CSF to serum Cmin ratio had no correlation with clinical response. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus.

Background and Objective: Apolipoprotein E (APOE) plays important roles in lipoprotein metabolism and cardiovascular disease. Evidence suggests the APOE gene epsilon2/epsilon3/epsilon4 (ε2/ε3/ε4) polymorphisms might be associated with the susceptibility of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, no clear consensus has yet been established. Therefore, the aim of this meta-analysis is to provide a precise conclusion on the potential association between APOE ε2/ε3/ε4 polymorphisms and the risk of CAD in patients with T2DM based on case-control studies. Methods: Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for all relevant studies prior to August 2017 in English and Chinese language. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the relationships. The between-study heterogeneity was evaluated by Cochran's Q-test and the I2 index to adopt fixed- or random- effect models. Results: A total of 13 studies were eligible for inclusion. There was evidence for significant associations between APOE ε4 mutation and the risk of CAD in patients with T2DM (for ε3/ε4 vs. ε3/ε3: OR = 1.69, 95% CI = 1.38-2.08, P < 0.001; for ε4/ε4 vs. ε3/ε3: OR = 2.72, 95% CI = 1.61-4.60, P < 0.001; for ε4/ε4+ε3/ε4 vs. ε3/ε3: OR = 1.83, 95% CI = 1.52-2.22, P < 0.001; for ε4 allele vs. ε3 allele: OR = 1.64, 95% CI = 1.40-1.94, P < 0.001). In contrast, no significant associations were found in genetic model of APOE ε2 mutation (for ε2/ε2 vs. ε3/ε3: OR = 1.67, 95% CI = 0.90-3.09, P = 0.104; for ε2/ε3 vs. ε3/ε3: OR = 1.18, 95% CI = 0.93-1.51, P = 0.175; for ε2/ε2+ε2/ε3 vs. ε3/ε3: OR = 1.26, 95% CI = 0.88-1.82, P = 0.212; for ε2 allele vs. ε3 allele: OR = 1.34, 95% CI = 0.98-1.84, P = 0.07). Conclusions: The APOE gene ε4 mutation is associated with an increased risk of CAD in patients with T2DM, while the ε2 variation has null association with this disease.

Should We be Worried About QTc Prolongation Using Citalopram? A Review.

PURPOSE: Summarize available information regarding clinical impact of citalopram on the QTc interval. METHODS: A literature search was conducted in Pubmed, EMBASE, and Cochrane databases using the MeSH term "long QT syndrome" and key word "citalopram" on July 11, 2014. RESULTS: Thirty-one studies were evaluated with 4 included in this review. Studies were excluded if they reported acute overdoses of citalopram or did not report on patient-specific risk factors for long QT syndrome (eg, hypokalemia, bradycardia, and increased age). The majority of the available data is derived from case reports. A number of confounders complicate the determination of a causal link between QTc prolongation and citalopram. Of the 4 studies included for review, none identified significant QTc prolongation in patients taking citalopram 20 to 60 mg daily without the patients having one or more patient-specific risk factors for prolonged QTc. CONCLUSION: There is insufficient evidence to establish a causal link between citalopram 20 to 60 mg orally daily and increased risk of TdP. Further research is required to determine the clinical impact and association between citalopram 20 to 60 mg daily and QTc prolongation.

Administration Technique and Acceptance of Inhaler Devices in Patients With Asthma or COPD.

BACKGROUND: Correct technique and patient acceptance of inhalation devices for lung disease influence successful long-term management. Patient ability to use the proper technique may differ depending on the device as well as patient factors. OBJECTIVES: The objectives of our study are to measure self-reported level of acceptability of inhaler devices in community settings and compare correct use of inhaler devices using a novel scale for measuring appropriate inhaler technique. METHODS: This prospective observational study enrolled patients from 3 different practice sites with asthma and/or chronic obstructive pulmonary disease (COPD) who were using an inhaler device. In addition to describing the samples' overall acceptability and correct use scores for the different inhalers, acceptability and correct use scores were compared based on patient characteristics. RESULTS: A total of 161 patients completed the study. The results show that acceptability was lowest for the pressurized metered dose inhaler (pMDI) with a spacer (S); effective use was best demonstrated with pMDI and poorest with pMDI-S. Older patients were found to be more accepting of the HandiHaler device than younger patients. Patients reporting taking more inhaled drugs were found to be more accepting of the pMDI-S than those taking fewer drugs. Finally, patients reporting taking more inhaled drugs demonstrated less-effective use of the HandiHaler device than patients taking fewer drugs. CONCLUSION: Pulmonary disease duration does not ensure improved use for all inhalers; patients taking more drugs demonstrate less-effective use for some devices. Assessment of patient acceptance and factors that predict the ability to use a device should be considered to individualize therapy.