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Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia
No full textBackground Type 2 diabetes mellitus (T2DM) and its treatment impact patients’ physical health as well as emotional and social wellbeing. This study aimed to assess health-related quality of life (HRQoL) and associated factors among patients with T2DM at a tertiary care hospital in Ethiopia. Methods A face-to-face cross-sectional survey was conducted among patients with T2DM at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. We collected data using a validated Amharic version of the 5-level EuroQoL-5 dimensions (EQ-5D-5L) questionnaire. Descriptive statistics were used to present patient characteristics. Kruskal-Wallis and Mann-Whitney U tests were performed to explore differences in the median scores of EQ-5D-5L utility and visual analog scale (EQ-VAS). Multivariable Tobit regression models were used to identify predictors of HRQoL. Utility scores were calculated using disutility weights of the Ethiopian general population. Statistical significance was determined at p \u3c 0.05. Results A total of 360 patients with T2DM participated. Mean (SD) age was 64.43(10.61) years. Reported health problems were mostly in the pain/discomfort (67.3%) dimension followed by mobility (60.5%), whereas the usual activities domain (34.1%) was the least health problem being reported. The median (IQR) EQ-5D-5L utility and EQ-VAS scores were 0.95 (0.88–0.96) and 80 (75.0–85.0), respectively. In multivariable Tobit regression models older age, having poor glycemic control, longer duration of diabetes, insulin usage, obesity, and having diabetes-related complications were significant negative predictors of HRQoL. Conclusions Overall, patients with T2DM had lower HRQoL than the general population, which was attributed to being older age, longer duration of diabetes, insulin use, obesity, inadequate glycemic control, and diabetes-related complications. The utility index we generated can be used in future economic evaluations to inform decisions about alternative interventions and resource allocation
Synthesis and structure activity relationship of the first class of LXR inverse agonists
No full textLiver X Receptors (LXRs) are members of the nuclear receptor family, and they play significant role in lipid and cholesterol metabolism. Moreover, they are key regulators of several inflammatory pathways. Pharmacological modulation of LXRs holds great potential in treatment of metabolic diseases, neurodegenerative diseases, and cancer. We were the first group to identify LXR inverse agonists SR9238 (6) and SR9243 (7) and demonstrate their potential utility in treating liver diseases and cancer. Here, we present the results of structure–activity relationship (SAR) studies, based around SR9238 (6) and SR9243 (7). This study led to identification of 16, 17, 19, and 38, which were more potent inverse agonists than SR9238 (6) and SR9243 (7) and inhibited expression of the fatty acid synthase gene in DU145 cells. We previously demonstrated that inhibition of FASN is correlated to the anticancer activity of SR9243 (7) and this suggests that new inverse agonists have great potential as anticancer agents. We identified compounds with distinct selectivity toward both LXR isoforms, which can be excellent tools to study the pharmacology of both isoforms. We employed molecular dynamic (MD) simulations to better understand the molecular mechanism underlying inverse agonist activity and to guide our future design
Master\u27s Graduate Programs in the Pharmaceutical Sciences: An International Survey
No full textInformation on master\u27s programs in the pharmaceutical sciences is lacking; this manuscript addresses this gap in the literature, by reporting on the results of an international survey performed in 2021 of master\u27s programs in the pharmaceutical sciences offered at Schools/Colleges of Pharmacy. Ninety-six responses were received from universities from 23 countries, with the greatest number of responses obtained from India, followed by the United States and Japan. Master\u27s programs in the pharmaceutical sciences are generally full time and 2 years in duration. Only 3% of programs were reported to be examination-based, while the remaining 97% had a research component with 70% of programs having a thesis defense with external and/or internal examiners. Master\u27s programs tended to be larger in Asia and Europe than in North America; as well, programs in North America tended to have more international students. Didactic coursework was included in 96% of master\u27s programs in North America, but only in 38% of Asian and 58% of European programs. The predominant placement of graduates from master\u27s programs in Asia was in the pharmaceutical industry (70%); this contrasted with programs in Europe, Africa and North America where 28–36% enter careers in the pharmaceutical industry and higher percentages enter Ph.D. programs. The major challenge identified by programs was funding of faculty and of graduate students, although decreasing career opportunities was identified as a challenge in Asia and Africa
The threat of multidrug-resistant/extensively drug-resistant Gram-negative respiratory infections: another pandemic
No full textAntibiotic resistance is recognised as a global threat to human health by national healthcare agencies, governments and medical societies, as well as the World Health Organization. Increasing resistance to available antimicrobial agents is of concern for bacterial, fungal, viral and parasitic pathogens. One of the greatest concerns is the continuing escalation of antimicrobial resistance among Gram-negative bacteria resulting in the endemic presence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) pathogens. This concern is heightened by the identification of such MDR/XDR Gram-negative bacteria in water and food sources, as colonisers of the intestine and other locations in both hospitalised patients and individuals in the community, and as agents of all types of infections. Pneumonia and other types of respiratory infections are among the most common infections caused by MDR/XDR Gram-negative bacteria and are associated with high rates of mortality. Future concerns are already heightened due to emergence of resistance to all existing antimicrobial agents developed in the past decade to treat MDR/ XDR Gram-negative bacteria and a scarcity of novel agents in the developmental pipeline. This clinical scenario increases the likelihood of a future pandemic caused by MDR/XDR Gram-negative bacteria
Concordance between reported medication taking behavior and prescription instructions for patients with chronic obstructive pulmonary disease visiting community pharmacies
No full textBackground: Understanding types and frequency of medication taking discrepancies could help design pharmacist interventions to improve adherence, outcomes, and prescribing. Objective: This study aimed to assess concordance between participants\u27 descriptions of chronic obstructive pulmonary disease (COPD) medication taking behaviors and prescription instructions. Methods: Continued analysis of previously collected data. Dispensing data from 35 community pharmacies identified participants at the age of ≥ 40 years, with ≥ 1 COPD maintenance medication in the past year and self-reported COPD. Participants completed a survey of demographics, corticosteroid/antibiotic drug use, and symptom scores. Participants listed each medication and described medication taking behavior. COPD severity was classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) ABCD categories from exacerbation history and symptoms. Aggregate proportion days covered (PDC) for any 1 maintenance medicine was calculated using 12-month dispensing data. Discrepancies between medication taking and instructions were classified: (1) overuse, (2) underuse, or (3) discontinued by participant (without prescriber knowledge). Descriptive statistics summarized survey results. Chi-square compared discrepancies among long-acting bronchodilators (LABDs), inhaled corticosteroids (ICS), and short-acting bronchodilators (SABDs). Results: Most participants (N = 709; 27.6% urban, 70.5% rural) were highly symptomatic (GOLD groups B/D = 89.9%) and high risk (groups C/D = 59.2%). Median medication number was 4. Concordance of ICS and LABD taking behavior with prescriber instructions was 80.6% and 81.8%, respectively (P \u3e 0.05). PDC averaged 0.46 ± 0.37; only 28.7% were adherent (i.e., PDC ≥ 0.80). ICS underuse (11.8%) exceeded LABD (5.5%). LABD discontinuation (7.4%) exceeded ICS (2.7%) or SABD (0.6%). SABD overuse (9.3%) exceeded ICS (3.4%) or LABD (4.3%) (P \u3c 0.5 all comparisons). Conclusion: Although most were highly symptomatic, high risk, and frequently described correct medication taking behavior, overall adherence was very low. Discrepancies included overuse, underuse, and self-discontinuation. Nonadherence and medication taking discrepancies may increase symptoms, exacerbations, and additional medication prescribing. Potential pharmacist strategies include regularly assessing adherence and differentiating intentional versus nonintentional nonadherence to identify and implement patient-specific interventions to encourage medication taking as prescribed
Efforts towards the inhibitor design for New Delhi metallo-beta-lactamase (NDM-1)
No full textAntimicrobial stewardship is imperative when treating bacterial infections because the misuse and overuse of antibiotics have caused pathogens to develop life-threatening resistance mechanisms. The New Delhi metallo-beta-lactamase (NDM-1) is one of many enzymes that enable bacterial resistance. NDM-1 is a more recently discovered beta-lactamase with the ability to inactivate a wide range of beta-lactam antibiotics. Multiple NDM-1 inhibitors have been designed and tested; however, due to the complexity of the NDM-1 active site, there is currently no inhibitor on the market. Consequently, an infection caused by bacteria possessing the gene for the NDM-1 enzyme is a serious and potentially fatal complication. An abundance of research has been invested over the past decade in search of an NDM-1 inhibitor. This review aims to summarize various NDM-1 inhibitor designs that have been developed in recent years
Potent antiplasmodial alkaloids from the rhizobacterium Pantoea agglomerans as hemozoin modulators
No full textGlobal health concern regarding malaria has increased since the first report of artemisinin-resistant Plasmodium falciparum (Pf) two decades ago. The current therapies suffer various drawbacks such as low efficacy and significant side effects, alarming for an urgent need of more effective and less toxic drugs with higher patient compliance. Chemical entities with natural origins become progressively attractive as new drug leads due to their structural diversity and bio-compatibility. This study initially aimed at the targeted isolation of hydroxyquinoline derivatives following our published genomics and metabolomics study of Pantoea agglomerans (Pa). Fermentation of Pa on a pre-selected medium followed by chromatographic isolation, NMR and HRMS analyses led to the characterisation of one new hydroxyquinoline alkaloid together with another six known congeners and two known hydroxyquinolone derivatives. When screened for their antimalarial activity by high throughput screening against asexual blood-stage parasites, almost all compounds showed potent and selective sub-micromolar activities. Computational investigation was performed to identify the antiplasmodial potential targets. Ligand-based similarity search predicted the tested compounds to act as hemozoin inhibitors. Computational target identification results were further validated by competitive hemozoin inhibitory properties of hydroxyquinoline and hydroxyquinolone derivatives in vitro. The overall results suggest this natural scaffold is of potential to be developed as antimalarial drug lead
Momordicine-I, a bitter melon bioactive metabolite, displays anti-tumor activity in head and neck cancer involving c-met and downstream signaling
No full textHead and neck cancer (HNC) is one of the most aggressive cancers, and treatments are quite challenging due to the difficulty in early diagnosis, lack of effective chemotherapeutic drugs, adverse side effects and therapy resistance. We identified momordicine-I (M-I), a bioactive secondary metabolite in bitter melon (Momordica charantia), by performing liquid chromatographyhigh resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. M-I inhibited human HNC cell (JHU022, JHU029, Cal27) viability in a dose-dependent manner without an apparent toxic effect on normal oral keratinocytes. Mechanistic studies showed that M-I inhibited c-Met and its downstream signaling molecules c-Myc, survivin, and cyclin D1 through the inactivation of STAT3 in HNC cells. We further observed that M-I was non-toxic and stable in mouse (male C57Bl/6) blood, and a favorable pharmacokinetics profile was observed after IP administration. M-I treatment reduced HNC xenograft tumor growth in nude mice and inhibited c-Met and downstream signaling. Thus, M-I has potential therapeutic implications against HNC
Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention
No full textCancer remains to be the second highest cause of mortality in our society, falling just short of heart disease. Despite major advancement in cancer therapy over the past decade, momentum has been gaining for an alternative approach of using naturally-occurring and dietary agents for cancer prevention and management. Research on pomegranate (Punica granatum L.), a fruit of the Punicaceae family, has shown enormous potential for cancer prevention and intervention. In addition to a rich source of polyphenols, including flavonoids and ellagitannins, in its juice, pomegranate also houses hundreds of other phytochemicals in its pericarp, seed, flower, bark, flowers and leaves. These phytochemicals provide powerful antiproliferative, anti-inflammatory, antioxidant, anti-invasive, antimigratory, anti-angiogenic and anti-metastatic effects without significant toxicity. This makes the use of its various extracts a very attractive strategy to our current battle against cancer. This review article presents a systematic, comprehensive and critical review of research on pomegranate-derived products in both cancer prevention and intervention. It discusses the chemical constituents of pomegranate, the results of both preclinical (in vitro, ex vivo and in vivo) and clinical studies on the anticancer effect of pomegranate phytochemicals and molecular targets in numerous types of cancers, such as breast, gastrointestinal tract (oral, colon, liver and pancreas), gynecological (uterine and ovarian), hematological (lymphoma, leukemia and myeloma), lung, neurological (glioma), urogenital (bladder and prostate), bioavailability, pharmacokinetics and safety of pomegranate constituents. In order to guide the direction of future research, we have also included current limitations and challenges in the field and our post analysis recommendation
Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Renal Function in Type 1 Cardiorenal Syndrome
No full textIntroduction: Angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) discontinuation during acute heart failure (AHF) is associated with increased mortality following hospitalization. Although the etiology of acute kidney injury (AKI) in type 1 cardiorenal syndrome (CRS) has been linked to renal venous congestion, ACE-I/ARB withdrawal (AW) theoretically promotes renal function recovery. ACE-I/ARBs are dose-reduced or withheld in approximately half of patients with CRS, but the subsequent impact on renal function remains largely uninvestigated. This study compared AW to ACE-I/ARB continuation (AC) during CRS. Methods: This was a retrospective, single-center chart review. Patients aged 18-89 years admitted from April 2018 to August 2019 with AHF and AKI were identified using discharge ICD-10 codes. All patients were treated with an ACE-I/ARB before admission. Key exclusion criteria included shock, pregnancy, and end-stage renal disease. The primary endpoint was change in serum creatinine (SCr) from admission through 72 hours. Data were analyzed utilizing chi-square and Mann-Whitney U tests with SPSS software. Results: A total of 111 admissions were included. AW occurred in 68 patients upon admission. AW patients presented with a higher blood urea nitrogen (P = 0.034), higher SCr (P = 0.021), and lower ejection fraction (P = 0.04). Median SCr change from admission to 72 hours did not differ between groups (AW −0.1 mg/dL vs AC 0.0 mg/dL, P = 0.05). There was no difference in SCr reduction ≥0.3 mg/dL at 72 hours, 30-day readmissions, or ACE-I/ARB prescription at discharge. Conclusions: In patients with type 1 CRS, AW was not associated with improved renal function at 72 hours. A larger sample size is necessary to confirm these results