Antihypertensive treatment and blood pressure control in patients with hypertension in daily clinical practice: a cross-sectional,multicenter, observational study in Egypt

Objective: Management of hypertension in Egypt is difficult because of various reasons. This real-life study was conducted to determine BP control rate, treatment modalities, factors influencing the choice of antihypertensive drugs, physicians’ satisfaction with the treatment, and demographics of patients with uncontrolled BP who were treated for hypertension in daily clinical practice in Egypt.

Methods: This was a cross-sectional, multicenter, observational study conducted in patients treated for hypertension in out-patient private clinics in Egypt, during October 2011 to June 2012.

Results: Of 4139 patients with hypertension, 1509 (36.5%) had controlled BP and 2630 (63.5%) had uncontrolled BP. In BP controlled vs. uncontrolled groups, respectively, beta-blockers (41.7% vs. 41.0%) were the most frequently used antihypertensive agents, followed by diuretics (40% vs. 37.8%), angiotensin-converting enzyme inhibitors (35.3% vs. 34.9%), angiotensin receptor blockers (31.1% vs.19.4%), and calcium channel blockers (21.3% vs. 19.4%); the factors influencing the choice of antihypertensive therapy were “add-on therapy” (1.5% vs. 32.4%) and “change the current medication” (9.3% vs. 50.8%); physicians’ satisfaction with treatment was rated as “excellent” (31.6% vs. 3.2%) and “poor” (1.6% vs. 58%).

Conclusion: The majority of patients from Egypt had uncontrolled hypertension even after receiving treatment. This might increase awareness among physicians and enable them to prescribe appropriate treatment to patients with uncontrolled BP.

Key limitations: The questionnaire used in the study for the evaluation of patient/physician satisfaction level was not standardized and was based on the choice and practice of the physicians     

Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions,biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research.

Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.

Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.

Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.

Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses.     

Overcoming platinum resistance in ovarian cancer treatment: from clinical practice to emerging chemical therapies

Introduction: The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of platinum resistant (PR) recurrent ovarian cancer (ROC) with particular attention to Phase III and ongoing trials.

Areas covered: Since platinum free interval (PFI) represents the most important predictive factor for response to platinum re-treatment in ROC, non-platinum regimens are conventionally considered the most appropriate approaches.

Impressive progress has been made in recent decades, resulting in the identification of most effective cytotoxic agents and in the development of new target strategies.

However, the efficacy of most of these drugs for the treatment of PR disease is still limited.

Expert opinion: The most favorable benefit for the treatment of PR disease, has been described by the AURELIA trial that showed a 3.3 months increase in progression free survival (PFS) when bevacizumab was combined with non-platinum single agent chemotherapy in bevacizumab-naïve patients.

Nevertheless, the use of novel agents is associated to important costs for just little gains in survival.

Thus, in our opinion the economic evaluation, such as the incorporation of quality of life into the clinical studies is crucial for the development of future trials for PR-ROC.     

Blood pressure and lipid target adherence in Korean patients receiving angiotensin II receptor blockers/statin regimens

Objectives: Hypertension and dyslipidemia are important cardiovascular risk factors. Simultaneously controlling blood pressure (BP) and lipid levels is effective in preventing cardiovascular events and premature death. This study investigated the association between adherence to angiotensin II receptor blocker (ARB)/statin regimens and BP or low density lipoprotein-cholesterol (LDL-C) target attainment in Korean patients with concomitant hypertension and dyslipidemia.

Methods: In this retrospective, multicenter study, we collected case report forms (CRFs) of hypertensive patients with concomitant dyslipidemia who were prescribed an ARB/statin regimen between 1 April 2014 and 31 March 2015 from 51 outpatient clinics. A total of 672 and 609 patients were eventually included for statistical analyses of BP and LDL-C, respectively. Adherence was measured by medication possession ratio (MPR) for 6 months following the index date.

Results: The overall rates of attaining BP and LDL-C targets were 75.6% and 81.1%, respectively. The mean value of MPR for patients attaining target BP or LDL-C was significantly higher than that for those not attaining target BP or LDL-C. After adjustment for all covariates, increases in the quartiles of MPR were significantly associated with an increased probability of attaining target BP or LDL-C in all models (all p-trend <0.05). Attaining of BP control was significantly higher in quartiles 3 and 4 of MPR (MPR >0.95) than the lowest MPR (quartile 1), whereas attaining LDL-C target was associated with quartile 4 of MPR (MPR >0.97).

Conclusion: We identified a strong correlation between medication adherence and BP or LDL-C target achievement in Korean patients with concomitant hypertension and dyslipidemia. The adherence for reaching targets could be different between BP and LDL-C levels.     

Taurine reduces blue light-induced retinal neuronal cell apoptosis in vitro

Background: The massive uptake of organic compatible osmolytes is a self-protective response to multiple stressors.

Objective: This study aimed to determine the protective effects of the osmolyte taurine against blue light-induced apoptosis in retinal neuronal cells in vitro.

Methods: Real-time PCR was used to measure osmolyte transport. Radioimmunoassays were performed to measure osmolyte uptake. Cell Counting Kit-8 assays were conducted to measure cellular viability. Flow cytometry analysis was used to measure apoptosis.

Results: Compared with normotonic stress, hypertonic stress-induced uptake of osmolytes, including betaine, myoinositol, and taurine, into the retinal neuronal cells. Blue light increased osmolyte transporter mRNA expression together with osmolyte uptake. Furthermore, taurine significantly suppressed blue light-induced retinal neuronal cell apoptosis.

Conclusion: The compatible osmolyte taurine may have an important role in cell resistance to blue light and cell survival.     

Taurine prevents ultraviolet B induced apoptosis in retinal ganglion cells

Background: Compatible osmolytes accumulation is an active resistance response in retina under ultraviolet (UV) radiation and hypertonicity conditions.

Objective: The purpose of this research is to investigate the protective role of taurine on retina under UVB radiation.

Methods: Osmolytes transporters were measured by quantitative realtime PCR. Osmolytes uptake was estimated by radioimmunoassay. Cell viability was calculated by MTT assay. Cell apoptosis was measured by flow cytometry analysis.

Results: Hypertonicity accelerated osmolytes uptake into retinal ganglion cells (RGCs) including taurine, betadine, and myoinositol. UVB radiation increased osmolytes transporter expression and osmolytes uptake. In addition, osmolyte taurine remarkably prevented UVB radiation induced cell apoptosis in RGCs.

Conclusions: The effect of compatible osmolyte taurine on cell survival rate may play an important role in cell resistance and adaption to UVB exposure.     

Inflammation in Heart Failure: known knowns and unknown unknowns

Introduction: The review deals with inflammation in heart failure (HF). Many data show that systemic inflammation is frequent in HF and implicate that inflammation contributes to damage and dysfunction of the cardiovascular system.

Areas Covered: Experimental data have been mainly obtained in acute laboratory animal models. It is questionable whether animals’ data can be translated into clinical settings with patients with chronic HF who have concomitant pathologies.

The idea of a common inflammatory pathway that characterizes all different forms of clinical HF is unrealistic. It seems realistic that inflammation differs in non-cardiac and cardiac diseases.

Research therapeutic options address the use of inhibitors of cytokines, of agents antagonizing oxidative stress, of MMP and of PI3K signaling pathways.

Expert Opinion: Considering the many unknowns in our knowledge it is not surprising that early trials aimed to antagonize inflammation in HF have been disappointing. We are far away from having solid therapeutic schedules to use immunomodulation in all subtypes of HF. However, modern trials on HF due to virus infections have proven that immunomodulation is therapeutically effective.

We should wisely use the known facts and accept that we have many unknowns. By appropriate selection of the subtypes of HF we may be able to find the appropriate therapy against inflammation in HF.     

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2012

Background:

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2012. This is an extension of the previously reported study of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, which found that over three-quarters of all these trials were disclosed within 12 months and almost 90% were disclosed by the end of the study.

Methods:

The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2012, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2014.

Outcome measures and results:

The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2014 (end of survey). Of the completed trials associated with 23 new medicines licensed to 17 different companies in 2012, results of 90% (307/340) had been disclosed within 12 months, and results of 92% (312/340) had been disclosed by 31 July 2014.

Conclusions:

The disclosure rate within 12 months of 90% suggests the industry is now achieving disclosure in a timely manner more consistently than before. The overall disclosure rate at study end of 92% indicates that the improvement in transparency amongst company-sponsored trials has been maintained in the trials associated with new medicines approved in 2012.     

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review

Context: Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis.

Objectives: To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically.

Methods: Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded.

Results: Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies.

Conclusion: This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.     

Dapagliflozin for the treatment of type 1 diabetes mellitus

Introduction: In 2017, the management of type 1 diabetes mellitus (T1DM) remains intriguing for the clinician, who has to balance between adequate glycemic control and untoward events related to insulin up-titration. Thus, agents that will complement insulin actions and reduce adverse effects are highly welcome.

Areas covered: In this review, the authors summarize results from studies on the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin in T1DM.

Expert opinion: In T1DM, dapagliflozin is associated with significant antihyperglycemic and metabolic properties, which are achieved with reduction or stabilization of insulin dose and with a very low trend for hypoglycemia. However, there is a lot to learn with respect to diabetic ketoacidosis (DKA), bone fractures and lower limb ischemia.     

Treatment options and considerations for hypertensive patients to prevent dementia

Introduction: Dementia is a worldwide health concern, which leads to loss of autonomy. To date no curative treatment is available so focus on modifiable risk factors is of particular interest. Hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia including vascular dementia (VAD) and Alzheimer disease (AD). In this context, antihypertensive treatments might have a preventive effect.

The objective of this review was to examine the relationship between antihypertensive therapy and cognitive decline or dementia.

Areas covered: A literature search was conducted using PUBMED and the COCHRANE LIBRARY for publications from 1990 onwards mentioning cognitive decline, AD, Vad, mixed dementia, vascular cognitive impairment, hypertension and antihypertensive therapy. Thirty-nine relevant publications including 20 longitudinal studies, 10 randomized-controlled trials and 9 meta-analyses were taken into account.

Expert opinion: Most observational studies have suggested a potential preventive effect of antihypertensive therapies on cognitive decline and dementia, particularly calcium channel blockers and renin-angiotensin system blockers. Randomized clinical trials and meta-analyses provided more conflicting results potentially due to methodological issues.

In conclusion, antihypertensive therapies may reduce cognitive decline and incidence of dementia. Further randomized clinical trials conducted in populations at higher risk of cognitive decline, with longer periods of follow-up and cognition as the primary outcome are still needed.     

Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies

Background: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients.

Objective: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice.

Methods: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered.

Results: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02–12.25), median OS 21.9 months (95% CI: 17.2–26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8–50.7). Median time to PR was 3.8 months (95% CI: 3.86–5.99) and to CR 8.2 months (95% CI: 4.75–9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05)

Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment.     

Considerations and treatment options for patients with comorbid atrial fibrillation and diabetes mellitus

Introduction: Atrial fibrillation (AF) and diabetes mellitus (DM) are common worldwide and their incidence is increasing, representing a significant public health and economic burden as well as an increase in individual increased morbidity and mortality risk profiles. Both conditions are closely related, as patients with DM are at increased risk of incident AF, and AF patients with DM are at higher risk of cardiovascular events compared to non-AF patients.

Areas covered: This review article aims to provide an overview of the current evidence linking DM and AF, as well as the impact of obesity, weight loss and stroke on these coexisting conditions. Second, the effects of new oral anti hyperglycaemic medications on cardiovascular risk will be considered.

Expert opinion: In conclusion, coexisting AF and DM represent a high risk population of patients requiring aggressive risk factor identification and treatment optimisation. The multifactorial interplay between these conditions requires individual assessment of patient risk profiles with the aim of minimising the impact of each modifiable risk factor.     

Dosing strategies to optimize currently available anti-MRSA treatment options (Part 2: PO options)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen in both outpatient and inpatient settings. Research to optimize the dosing of these agents is needed to slow the development of antimicrobial resistance and to decrease the likelihood of clinical failure.

Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 – Present) search was performed to identify relevant literature for this review.

Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones.

Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections.     

Combination therapies for hypertension – why we need to look beyond RAS blockers

Introduction: Hypertension is the leading cause of mortality and disability worldwide. Despite the proven benefits of blood pressure (BP) reduction, lack of BP pressure control continues to be the most important clinical problem in hypertension management.

Areas covered: Factors involved in the lack of BP control and strategies to improve such control have been reviewed, with special focus on the usefulness of combination therapies, those types of combination which include a renin-angiotensin system (RAS) blocker, with diuretics, calcium channel blockers, or both.

Expert commentary: Combination therapy is required for BP control in most hypertensive patients. RAS blockers should be included in such combinations, except contraindicated. Diuretics, and especially calcium channel blockers are the drugs of choice for double or triple combinations. Diuretics stimulate RAS and enhance the effect of RAS blockers, while minimizing the undesirable metabolic effects of diuretics. RAS blockers and calcium channel blockers have synergistic protective effects on the vascular wall and have demonstrated to be superior to other types of combinations, thus becoming the preferred initial treatment for most hypertensive patients. The use of single-pill combinations is associated with better treatment adherence, thus facilitating the achievement of adequate BP control.     

Cardiovascular event incidence and cost in type 2 diabetes mellitus: a Medicare claims-based actuarial analysis

Objective: To assess the economic burden of cardiovascular events in Medicare beneficiaries with type 2 diabetes mellitus (T2DM).

Methods: This claims-based actuarial analysis queried 2013 and 2014 Medicare 5% samples, defining a denominator of fee-for-service beneficiaries. Average per patient per month allowed cost ($PPPM) was calculated for T2DM, demographically adjusted non-T2DM, and denominator. Per member per month allowed cost ($PMPM) was calculated by dividing total population cost by member months in the denominator. Costs of five pre-specified cardiovascular events were calculated as a contribution to denominator $PMPM, as contribution to $PPPM in T2DM, and as incremental cost.

Results: During the study period, 22.1% of Medicare fee-for-service beneficiaries had T2DM; of these, 9.68% experienced a cardiovascular event or cardiovascular-related death. T2DM cost represented 37.9% of total allowed $PMPM for the denominator. Average total allowed $PPPM for a T2DM beneficiary was $1,834, compared with $850 for a non-T2DM beneficiary (2.2-times higher). Annual rates of myocardial infarction, stroke, unstable angina admission, heart failure admission, and coronary revascularization in T2DM were 3.3-, 2.4-, 3.2-, 4.0-, and 2.8-times higher than in non-T2DM, and utilization of health services was also greater in T2DM. Cardiovascular events in T2DM accounted for 50% of denominator cardiovascular event cost; 3.6% of denominator population $PMPM was attributable to cardiovascular events in T2DM. Risk-adjusted incremental cardiovascular event cost represented 18.1% of $PPPM in T2DM or 6.9% of $PMPM in the denominator population.

Conclusions: Cardiovascular events in Medicare fee-for-service beneficiaries with T2DM contribute substantially to Medicare cardiovascular events, resource utilization, and cost.     

A review on phytochemical and pharmacological properties of Litsea coreana

Context: Litsea coreana H. Lév. (Lauraceae) is used as an ethnic herb or beverage in China. Substantial studies indicate that it contains a variety of compounds and shows diverse bioactivities with no toxicity.

Objective: This review analyzes and summarizes the ethnopharmacological applications, phytochemistry, and pharmacological activities and molecular mechanisms of L. coreana.

Methods: Related literature (from 1998 to 2016) was obtained and compiled via searching databases including Scopus, Web of Science, Google Scholar, CNKI and PubMed. Keywords (Litsea coreana, hawk tea, eagle tea and laoying cha) were used to select the articles.

Results: Studies indicate that L. coreana contains characteristic polysaccharides, polyphenols, essential oils, and numerious flavonoids, which exhibit remarkable bioactivities, such as hepatoprotection, hyperglycaemia, anti-inflammation, antioxidation and antibacterial, through multiple molecular mechanisms.

Conclusion: This paper provides a systematic review on the phytochemicals and pharmacological activities of L. coreana which should be useful for further study and application of this medicinal herb.     

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus

Context: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion.

Objective: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase.

Materials and methods: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays.

Results: A new (2RS,3SR)-3,4′,5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity.

Discussion: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents.

Conclusion: The isolated compounds may contribute to the antidiabetic property of C. rotundus.     

Cognitive defusion versus experiential avoidance in the reduction of smoking behaviour: an experimental and preliminary investigation

Background: Brief procedures that reduce smoking behaviour may be useful in reaching the many people that do not seek help for smoking addiction.

Objectives: The current study aimed to determine if one component of Acceptance and Commitment Therapy (ACT), cognitive defusion, could be useful in reducing smoking behaviour in a sample of students.

Methods: The study employed a between-subjects three-arm design. For one week, participants were asked to reduce their cigarette consumption. To aid them in their reduction, participants were randomly allocated to one of three conditions: the first received a defusion procedure, the second received an experiential avoidance procedure and a control condition received no procedure. For a second week, the instruction to reduce cigarette consumption was lifted. During both weeks participants were required to monitor their smoking behaviour via a tally diary system.

Results: The defusion condition smoked significantly less than the control condition during week one and significantly less than the control and experiential avoidance conditions during week two.

Conclusion: Results are discussed in terms of the potential utility of defusion in this domain, and the limitations of this preliminary research that would need to be addressed in future investigations.     

Treatment patterns of rheumatoid arthritis in Japanese hospitals and predictors of the initiation of biologic agents

Objective: To describe the usage of different biologic agents for rheumatoid arthritis (RA) in Japan over time and to identify factors that affects the decision to initiate treatment with biologic agents. Determinants of a switch to another biologic agent for patients who are already on biologic treatment were also analyzed.

Research design and methods: We utilized a hospital claims database containing 36,504 Japanese patients with a confirmed RA diagnosis. To analyze the determinants of treatment choices, we applied logistic regression analysis taking into account socio-demographic and medical factors.

Results: Analyses determined that 11.8% of diagnoses and 25.4% of treated patients in Japan receive a biologic agent. Significant factors associated with biologic treatment initiation include younger age, female sex, and a higher comorbidity index. The route of administration plays a major role when it comes to a switch between different biologic agents.

Conclusions: The lower likelihood of elderly patients to be initiated on biologic treatment might be explained by the risk aversion of Japanese physicians’ and patients who are afraid of the potential side effects of biologics. This finding is also consistent with the notion of an age bias that impedes elderly patients from optimal access to biologic treatment. Because claims data does not contain clinical parameters such as disease activity the results should be validated in a clinical context.