Prescribing trend in cardiovascular patients at Ethiopian university hospital: The number of medications and implication on the clinical improvement.

Investigating the prescribing trend is important to improve rational prescribing. This study aimed at assessing the cardiovascular drug use, pattern, and its impact on clinical outcome. A cross-sectional study was employed in the outpatient department of chronic illness clinic of Gondar University specialized hospital, Ethiopia from 15 January 2017 to 15 March 2017. The independent variables were sociodemographic, medication, and other clinical information while cardiovascular disease improvement is the outcome variable. Binary logistic regression was used to test the association between the independent variables and the outcome variable. Kaplan Meier curve was used to analyze the clinical improvement while the Log-rank test was employed to compare the clinical outcome with the number of medications. Eight hundred thirty-three cardiovascular patient medical records were included in the final analysis. The majority (62.5%) of patients were females and more than 61% were above 50 years of age. Diuretics monotherapy accounted for a third (33.6%) of cardiovascular drug use, followed by combination therapy of angiotensin convertase enzyme inhibitors with Diuretics (21.8%) and calcium channel blockers with diuretics (8.3%). Cardiovascular patients followed for 72 months found to have a good level of clinical improvement on combination medication (Log Rank of 28.9, P = 0.000). In this study, diuretics monotherapy or in combination with angiotensin convertase enzyme inhibitors were found to be the frequently prescribed drugs in cardiovascular patients. Combination therapy has an implication for good cardiovascular improvement on long term follow-up. It seems clinicians were restricted to certain cardiovascular medications while plenty of choices are available from the diverse classes of cardiovascular drugs.

Challenges and opportunities of clinical pharmacy services in Ethiopia: A qualitative study from healthcare practitioners' perspective.

BACKGROUND: Currently, clinical pharmacists have in-depth therapeutic knowledge and scientific skills to act as drug therapy experts in healthcare settings. OBJECTIVE: The aim of this study was to assess the opportunities and challenges of clinical pharmacy services from the health practitioners' perspective in University of Gondar (UOG) hospital Ethiopia. METHODS: A qualitative study was performed using face-to-face in-depth interviews with health practitioners who were directly involved in clinical pharmacy services (clinical pharmacists, physicians, and nurses) in UOG hospital. RESULTS: A total of 15 health professionals from various specialties were interviewed to express their views towards clinical pharmacists' competencies and identified challenges and opportunities regarding their clinical services. Based on interviewees report, the opportunities for clinical pharmacists includes acceptance of their clinical services among health specialties, new government policy and high patient load in hospital. However, inadequacy of service promotions, lack of continuity of clinical pharmacy services in wards, poor drug information services, lack of commitment, lack of confidence among clinical pharmacists, conflict of interest due to unclear scope of practice, and absence of cooperation with health workers were some of the challenges identified by the interviewees. CONCLUSION: We identified health professionals working in UOG hospital are receptive towards clinical pharmacy services, but identified some of the potential challenges that needed to be focused to strengthen and promote clinical pharmacy services. Further, the opportunities at hand also need to be utilized astutely to boost the services.

The impact of pharmacist-led medication therapy management on medication adherence in patients with type 2 diabetes mellitus: a randomized controlled study.

BACKGROUND: Poor adherence to antidiabetic medications leads to a higher rate of hospital admissions and adverse health outcomes in type 2 diabetes mellitus patients. OBJECTIVE: This study aims to evaluate whether a pharmacist-led medication therapy management, compared to the usual care, could enhance medication adherence and reduce hospital admission in patients with type 2 diabetes mellitus. METHODS: A prospective randomized controlled study was conducted in patients with type 2 diabetes mellitus from February 1 to July 30, 2016. Patients in the control group (n=65) received the usual care while patients in the intervention group (n=62) received a personalized pharmacotherapeutic care plan and diabetes education. The two groups were compared by repeated measure ANOVA at 3 and 6-months with medication adherence (using Morisky medication adherence scale) and number of hospital admissions as the main outcome variables. RESULTS: A total of 127 patients were included in the study. A marked and statistically significant increase in medication adherence from baseline to 3 and 6 months were noted in the intervention group (increased from 9.2% at baseline to 61% at 6 month) compared with the control group (increased from 13.2% at baseline (to 30.2% at 6 month; p-value<0.01). Furthermore, at the 6-month follow-up, only 23 patients in MTM group with poorly controlled blood glucose levels resulted in hospital admissions compared to 48 patients in non-MTM group, resulting in a 52.1% fewer hospital admissions (p< 0.001). CONCLUSIONS: The findings of this study implied that pharmacist-led medication therapy management might improve medication adherence and reduce number of hospitalizations in patients with type 2 diabetes mellitus. Hence, policies and guidelines should be in place in order for clinical pharmacists to fully engage in patient care and improve the medication therapy outcomes.

Off-label drug use in hospitalized children: a prospective observational study at Gondar University Referral Hospital, Northwestern Ethiopia.

Most of the medications which are currently used for the treatment of childhood diseases are either not licensed or being prescribed outside the terms of the product license (off-label prescribing). This study aimed at determining the extent of unlicensed and off-label drug uses and associated factors in children hospitalized in Gondar University Referral Hospital, Northwest Ethiopia. An institution-based prospective cross-sectional study was employed from April 15 to July 15, 2016. A total of 243 pediatric patients admitted to Gondar university referral hospital were included in the study using simple random sampling method. Data were collected using structured questionnaire, and the data collected were entered and analyzed using Statistical Packages for Social Sciences (SPSS) version 20. From the total of 800 drugs prescribed, 607 (75.8%) were off-label. Off-label medicine use was frequently observed in antimicrobials (60.6%) followed by central nervous system drugs (14.3%). The extent off-label prescribing was highest in age group of 6-13 years (30%). Inappropriate dosing and frequency (42.3%) were the most common reason for off-label medicine use. Having other variables controlled, age group and undergoing surgical procedure remained to be significant predictors of off-label prescribing in the multivariate regression analysis. Implementing evidence-based approach in prescribing by generating more quality literatures on the safety profile and effectiveness of off-label would improve the injudicious use of drugs in pediatric population.

Differential role of p38 and c-Jun N-terminal kinase 1 mitogen-activated protein kinases in NK cell cytotoxicity.

The serine-threonine mitogen-activated protein kinase (MAPK) family includes extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases. In NK cells, spontaneous or Ab-mediated recognition of target cells leads to activation of an ERK-2 MAPK-dependent biochemical pathway(s) involved in the regulation of NK cell effector functions. Here we assessed the roles of p38 and JNK MAPK in NK cell-mediated cytotoxicity. Our data indicate that p38 is activated in primary human NK cells upon stimulation with immune complexes and interaction with NK-sensitive target cells. FcgammaRIIIA-induced granule exocytosis and both spontaneous and Ab-dependent cytotoxicity were reduced in a dose-dependent manner in cells pretreated with either of two specific inhibitors of this kinase. Target cell-induced IFN-gamma and FcgammaRIIIA-induced TNF-alpha mRNA accumulation was similarly affected under the same conditions. Lack of inhibition of NK cell cytotoxicity in cells overexpressing an inactive form of JNK1 indicates that this kinase, activated only upon FcgammaRIIIA ligation, does not play a significant role in cytotoxicity. These data underscore the involvement of p38, but not JNK1, in the molecular mechanisms regulating NK cell cytotoxicity.

A metaregression analysis of the dose-response effect of aspirin on stroke.

BACKGROUND: We evaluated whether the risk of stroke depends on aspirin dose in patients with a previous transient ischemic attack or stroke. METHODS: We conducted a metaregression analysis of stroke by using published randomized, placebo-controlled trials. We analyzed studies of patients who had recently had a transient ischemic attack or stroke (ie, secondary prevention). We abstracted data on the treatment regimen and stroke. To evaluate the dose-response relationship, we conducted a metaregression analysis of study-specific risk ratios by means of weighted linear regression. RESULTS: Eleven randomized, placebo-controlled trials contributed a total of 5228 patients randomized to aspirin only and 4401 patients randomized to placebo only. The slope of the dose-response curve was virtually flat across a wide range of aspirin doses from 50 to 1500 mg/d (P = .49 for test of slope not =0). Summarizing across studies, aspirin decreases the risk of stroke by about 15% (risk ratio, 0.85;95% confidence interval, 0.77-0.94). CONCLUSIONS: Aspirin reduces the risk of stroke by approximately 15%, and this effect is uniform across aspirin doses from 50 to 1500 mg/d. The lowest effective aspirin dose has not yet been identified, but it could be lower than 50 mg/d.

Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases.

Extracellular signal-regulated kinases (ERK, also known as mitogen-activated protein kinases) are serine-threonine kinases transducing signals elicited upon ligand binding to several tyrosine kinase-associated receptors. We have reported that ERK2 phosphorylation and activation follows engagement of the low affinity receptor for the Fc portion of IgG (CD16) on NK cells, and is necessary for CD16-induced TNF-alpha mRNA expression. Here, we analyzed the involvement of ERK in NK cell-mediated cytotoxicity and IFN-gamma expression induced upon stimulation with targets cells, coated or not with Abs. Our data indicate that, as with immune complexes, ERK2 phosphorylation occurs in human primary NK cells upon interaction with target cells sensitive to granule exocytosis-mediated spontaneous cytotoxicity, and that this regulates both target cell- and immune complex-induced cytotoxicity and IFN-gamma mRNA expression. A specific inhibitor of mitogen-activated protein kinase kinase reduced both spontaneous and Ab-dependent cytotoxicity in a dose-dependent manner involving, at least in part, inhibition of granule exocytosis without affecting effector/target cell interaction and rearrangement of the cytoskeleton proteins actin and tubulin. Involvement of ERK in the regulation of Ca2+-dependent cell-mediated cytotoxicity was confirmed, using a genetic approach, in primary NK cells infected with a recombinant vaccinia virus encoding an ERK inactive mutant. These data indicate that the biochemical pathways elicited in NK cells upon engagement of receptors responsible for either spontaneous or Ab-dependent recognition of target cells, although distinct, utilize ERK as one of their downstream molecules to regulate effector functions.

Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells.

Cytokine-mediated enhancement of spontaneous cytotoxicity depends, at least in part, on modulation of the expression of surface molecules responsible for recognition of target cell structures and triggering or inhibition of the cytotoxic machinery. We previously demonstrated that expression of transcription factors (e.g., Egr-1, JunB, and c-Fos) is differentially regulated by IL-2 and IL-12. Here we show that expression of CD161/NKR-P1A, a molecule involved in triggering cytotoxicity, is specifically upregulated by IL-12. CD161 transcription, mRNA accumulation, and surface expression are increased by IL-12. Other cytokines sharing the IL-2R beta- and/or common gamma-chains (i.e., IL-15, IL-4, and IL-7) do not mediate these effects. In an effort to analyze the mechanisms by which IL-2, IL-12, and IL-15 differentially regulate gene transcription, we have isolated a novel gene, 197/15a, the expression of which in NK and T cells is down-regulated by IL-2 and IL-15, up-regulated by IL-12, and not affected by IL-4 and IL-7. IL-2 and IL-15 act, at least in part, repressing 197/15a transcription; their effect on 197/15a mRNA accumulation is partially independent of novel protein synthesis, likely not mediated by JunB, Bcl-2, or Bax, and requires the activity of rapamycin-sensitive molecule(s). The observation that IL-2 and IL-12 differentially modulate CD161 expression suggests the existence of cytokine-specific mechanisms of modulation of spontaneous cytotoxicity based on the regulation of expression of surface molecules involved in target cell recognition and/or triggering of the cytolytic machinery.