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1.
Saudi Pharm J ; 31(9): 101710, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37559866

RESUMO

Background: Geriatric cancer patients are susceptible to adverse drug events due to the complexity of their chemotherapy regimens and collateral treatments for their comorbid conditions. Prescribing medications with anticholinergic burden characteristics can complicate their condition, leading to negative impacts on their health outcomes and quality of life, including an increase in adverse drug event frequency, physical and cognitive impairments. Objective: This study aims to examine the prevalence of anticholinergic prescribing and identify the cumulative anticholinergic load risk associated with drugs prescribed to elderly cancer patients. Also, to identify the predictors that might lead to raised anticholinergic burden in these patients. Methodology: This retrospective cross-sectional study included elderly patients (age ≥ 65) diagnosed with cancer and admitted to the adult oncology unit at King Abdullah University Hospital (KAUH) in Jordan during the period between (January 1st, 2019, and January 1st, 2022). The medication charts of 420 patients were evaluated for study outcomes. Results: Of the total subjects, females represented 49.3%, and the average age was 72.95 (SD = 7.33). A total of 354 (84.3%) patients were prescribed at least one drug carrying anticholinergic burden properties. Median for anticholinergic medications was 3 (IQR = 4). Our study found that 194 (46.2%) patients were at a high risk of adverse events associated with anticholinergic load (cumulative score ≥ 3). Metoclopramide, furosemide, and tramadol were the most frequently prescribed drugs with anticholinergic properties. Alimentary tract drugs with anticholinergic action were the most commonly encountered items in our study population. Conclusion: Our study revealed a significantly high prevalence of anticholinergic prescribing among elderly cancer patients. Nearly half of the patients were at high risk of developing serious effects related to anticholinergic activity from the drugs administered. Polypharmacy was strongly associated with increased anticholinergic burden score. Evidence-based recommendations utilizing prescribing strategies for safer alternatives and deprescribing of inappropriate medications could reduce such inappropriate prescribing.

2.
Saudi Pharm J ; 31(8): 101700, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37555012

RESUMO

Background: Artificial intelligence (AI) is the capacity of machines to perform tasks that ordinarily require human intelligence. AI can be utilized in various pharmaceutical applications with less time and cost. Objectives: To evaluate community pharmacists' willingness and attitudes towards the adoption of AI technology at pharmacy settings, and the barriers that hinder AI implementation. Methods: This cross-sectional study was conducted among community pharmacists in Jordan using an online-based questionnaire. In addition to socio-demographics, the survey assessed pharmacists' willingness, attitudes, and barriers to AI adoption in pharmacy. Binary logistic regression was conducted to find the variables that are independently associated with willingness and attitude towards AI implementation. Results: The present study enrolled 401 pharmacist participants. The median age was 30 (29-33) years. Most of the pharmacists were females (66.6%), had bachelor's degree of pharmacy (56.1%), had low-income (54.6%), and had one to five years of experience (35.9%). The pharmacists showed good willingness and attitude towards AI implementation at pharmacy (n = 401). The most common barriers to AI were lack of AI-related software and hardware (79.2%), the need for human supervision (76.4%), and the high running cost of AI (74.6%). Longer weekly working hours (attitude: OR = 1.072, 95% C.I (1.040-1.104), P < 0.001, willingness: OR = 1.069, 95% Cl. 1.039-1.009, P-value = 0.011), and higher knowledge of AI applications (attitude: OR = 1.697, 95%Cl (1.327-2.170), willingness: OR = 1.790, 95%Cl. (1.396-2.297), P-value < 0.001 for both) were significantly associated with better willingness and attitude towards AI, whereas greater years of experience (OR = 20.859, 95% Cl (5.241-83.017), P-value < 0.001) were associated with higher willingness. In contrast, pharmacists with high income (OR = 0.382, 95% Cl. (0.183-0.795), P-value = 0.010), and those with<10 visitors (OR = 0.172, 95% Cl. (0.035-0.838), P-value = 0.029) or 31-50 visitors daily (OR = 0.392, 95% Cl. (0.162-0.944), P-value = 0.037) had less willingness to adopt AI. Conclusions: Despite the pharmacists' positive willingness and attitudes toward AI, several barriers were identified, highlighting the importance of providing educational and training programs to improve pharmacists' knowledge of AI, as well as ensuring adequate funding support to overcome the issue of AI high operating costs.

3.
Saudi Pharm J ; 31(9): 101746, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37649677

RESUMO

Introduction: Drug-related problems (DRPs) are events or circumstances involving drug therapy that actually or potentially interferes with desired health outcomes. Objectives: To assess community pharmacists' knowledge and practice regarding DRP-reduction services, as well as the barriers and factors associated with decreased provision of these services. Methods: This cross-sectional study utilized a validated questionnaire to assess pharmacists' knowledge, practice, and barriers to the provision of DRP-reduction services in the community pharmacy setting. Binary regression model was used to assess the variables associated with the practice of DRP-reduction services. Results: A total of 412 pharmacists participated in the study. The pharmacists demonstrated strong knowledge but inadequate practice of DRP-reduction services. The most reported DRPs were inappropriate combination of drugs, or drugs and herbal medications, or drugs and dietary supplements (52.4%), patients' inability to understand instructions properly (46.1%), inappropriate drug according to guidelines (43.7%), and too high dose (40.3%). The most common barriers to these services were increased workload (60.5%), limited time (53.2%), and lack of good communication skills (49.8%). The presence of a counselling area in the pharmacy increased the practice of DRP-reduction services (OR: 3.532, 95%Cl: 2.010-5.590, P < 0.001), while increased weekly working hours (OR: 0.966, 95%Cl: 0.947-0.986), P < 0.01) and serving < 10 patients daily (OR = 0.208, 95%Cl: 0.072-0.601, P < 0.01) decreased it. Conclusions: Community pharmacists' practice of DRP-reduction services showed a scope for improvement. Future pharmaceutical care initiatives should increase the number of personnel working in the pharmacy and provide them with opportunities for continued education and training in order to improve the provision of DRP services and optimize patients' outcomes.

4.
Saudi Pharm J ; 30(12): 1773-1780, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36601509

RESUMO

Objective: The study aimed to identify the current practice carried out by community pharmacists to dispose of expired medications in their workplace and assess any practical steps utilized to reduce medication waste. Method: A cross-sectional study was conducted among community pharmacists in the United Arab Emirates (UAE). The participants were asked about their routine practice in disposing of different expired medications and the current actions taken to reduce the number of disposed medicines. Results: The study included (n = 418) community pharmacists. More than a third of expired liquid, solid, and semi-solid dosage forms were collected by licensed contractors. In addition, more than a third of the pharmacists disposed of different dosage forms via unauthorized methods (general garbage, sink and toilet). Most expired drugs were skin and hair products, antibiotics and analgesics. The majority of pharmacists (68.4 %, n = 286) agreed that expired pharmaceutical and non-pharmaceutical products, other than those disposed of via contractor, should be done through a specialized centre. This opinion was found to be strongly associated with years of practice as community pharmacists (P < 0.05). Conclusion: Part of the existing disposal practices for expired pharmaceutical products in the UAE is carried out by contractors licensed by health authorities. However, concern remains regarding some pharmaceutical and non-pharmaceutical products that have not been disposed of correctly. Additionally, there is a need for a specialized center for medication disposal (p < 0.05). A stock limitation is the best practice for managing medication quantities in stock (p < 0.05).

5.
J Community Health ; 46(5): 942-950, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33754294

RESUMO

Breast cancer (BC) is one of the most prevalent cancers and the leading cause of cancer related deaths among women worldwide with a steadily increasing global annual incidence. This study aims is to evaluate the knowledge, attitude, and practice of females in the UAE toward BC and Breast Self-Examination practice in the seven Emirates. This was a face-to-face questionnaire-based study using CAM (Breast Cancer Awareness Measure) conducted over 3 months (from March to June 2019) on a random sample of females across the UAE. Of the 400 females who filled the questionnaire, 112 (28%) did the CBE at least once, and 184 (46%) practice BSE. Only 33% of participants were aware of the incidence of the BC in the UAE and those females were more likely to practice BSE (P < 0.05). In contrast, the majority showed a high awareness level in identifying cancer as a curable (91.5%) and non-transmittable (87%) disease that can be diagnosed at its earlier stages (93%). Only 11% of the participants identified weight reduction as a way to prevent BC. Knowledge of breast cancer sign/symptoms were good, as 41-87% of respondents were able to identify at least a single sign/symptom. The lack of awareness of BC among females in the UAE is of concern as it leads to low practices of screening and early detection, which ultimately will result in increased morbidity, mortality, and treatment costs. Further initiatives should be taken to increase practice, knowledge and awareness on early detection and screening for BC in the UAE community.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Autoexame de Mama , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Programas de Rastreamento , Inquéritos e Questionários
6.
Saudi Pharm J ; 28(4): 504-508, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32273811

RESUMO

BACKGROUND: Worldwide, the prescribing pattern of the Nonsteroidal Anti-inflammatory Drugs (NSAIDs) has increased. They are considered highly effective medications in controlling various conditions including inflammatory diseases. They are associated with various adverse effects including gastrointestinal bleeding and ulcer and renal toxicity though. These adverse effects are generally potentiated when NSAIDs are co-prescribed with other drugs that share similar adverse effects and toxicities. Developing severe side effects from NSAIDs is more prone among elderly patients. Hence, it is crucial to evaluate prescribing pattern of these agents to prevent/decrease the number of unwanted side effects caused by NSAIDs. AIM: The aim of this study is to assess the prescribing pattern of NSAIDs among elderly and the co-prescribing of NSAIDs and different interacting drugs, which could lead to more incidences of NSAIDs-induced toxicities among Jordanian elderly patients. SETTINGS AND METHODOLOGY: A multicenter retrospective study was performed during a three months period in Jordan. The study involves a total number of (n = 5916) elderly patient's records obtained from Four governmental hospitals in Jordan. RESULTS: A total number of (n = 20450) drugs were prescribed and dispensed for patient. NSAIDs drugs prescribing percentage was 10.3% of total medications number. Aspirin was the most commonly prescribed NSAIDs among patients (70.4%), followed by Diclofenac sodium in all dosage forms (25.1%) and oral Ibuprofen (3.1%. In addition, Aspirin was the highest NSAIDs co-prescribed with ACEI (e.g., Enalapril), ARBs (e.g. Candesartan and Losartan), Diuretics (Furosemide, Indapamide, Hydrochlorothiazide, Amiloride, and Spironolactone), Warfarin and antiplatelets (Clopidogreal and Ticagrelor) followed by Diclofenac and other NSAIDs. CONCLUSION: NSAIDs prescribing rate among elderly patients was high. Additionally the co-prescribing of NSAIDs especially Aspirin with other agents, which contributes to NSAIDs nephrotoxicity and gastrointestinal toxicity, were high. Strict measurements and action plans should be taken by prescribers to optimize the medical treatment in elderly through maximizing the benefits and decreasing the unwanted side effects.

7.
Saudi Pharm J ; 26(8): 1146-1154, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30532635

RESUMO

BACKGROUND: Torsade de Pointes (TdP) is an abnormal cardiac rhythm associated with a prolongation of QT interval. Although in most cases it spontaneously returns to the normal rhythm, TdP can lead to sudden cardiac death. Medications are the main cause of QT-prolongation and subsequent TdP flare, even though the exact mechanism of why some people evoke TdP but others do not is still unknown. It is evident that elderly patients are more susceptible to experience drug's side effects especially with chronically used medications. OBJECTIVES: To describe the pattern of prescribing drugs with risk of Torsade's de Pointes among elderly patients who were visiting different outpatient clinics in North Jordan Hospitals. METHODS: All patients who were aged ≥65 years old and were visiting outpatient clinics in King Abdullah University Hospital (KAUH) and Princess Basma Hospital (PBH) through December 2016 were included in the study. A total of 5319 patients' dispending records were collected and analyzed for the prevalence of drug-induced TdP using both Microsoft Excel and the SPSS statistical software. RESULTS: A total of 5319 patients were included in the study, more than half (58.5%, n = 3114) of patients were consuming drugs with risk of TdP. Almost half (49.4%, n = 1539) of these patients were women. The majority of patients (62.3%, n = 1939) were using only one drug with TdP risk. However, other patients were found to take five or six different TdP-inducing drugs. Excluding age and gender, 94.3% (n = 2937) of patients who were using TdP-inducing drugs had at least one additional risk factor of inducing TdP. CONCLUSION: High usage of TdP-inducing drugs among geriatric patients in North Jordan demonstrated the urgent need for increasing awareness of TdP's risk induced by commonly prescribed medications.

8.
Saudi Pharm J ; 26(3): 301-305, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29556120

RESUMO

BACKGROUND: Diabetes is increasingly becoming a major health problem in Jordan and glycemic goals are often not achieved. OBJECTIVE: To explore the patients' perspectives regarding type 2 diabetes and its management in order to "fine-tune" future pharmaceutical care intervention programs. METHOD: Focus groups method was used to explore views from individuals with type 2 diabetes attending outpatient diabetes clinic at the Royal Medical Services Hospital. All interviews were recorded, transcribed and analyzed using a thematic analysis approach. RESULTS: A total of 6 focus groups, with 6 participants in each one, were conducted. Participants in the present study demonstrated a great information needs about diabetes and the prescribed treatment. Medication regimen characteristics including rout of administration, number of prescribed medications and dosage frequency in addition to perceived side effects represented the major barriers to medication adherence. In addition to demonstrating negative beliefs about the illness and the prescribed medications, participants showed negative attitudes and low self-efficacy to adhere to necessary self-care activities including diet, physical activity and self-monitoring of blood glucose. CONCLUSION: Future pharmaceutical care interventions designed to improve patients' adherence and health outcomes in patients with type 2 diabetes should consider improving patients' understanding of type 2 diabetes and its management, simplifying dosage regimen, improving patient's beliefs and attitudes toward type 2 diabetes, prescribed medications and different self-care activities in addition to improving patient's self efficacy to perform different treatment recommendations.

9.
Cell Mol Life Sci ; 73(20): 3917-33, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27113546

RESUMO

Vascular permeability regulated by the vascular endothelial growth factor (VEGF) through endothelial-barrier junctions is essential for inflammation. Mechanisms regulating vascular permeability remain elusive. Although 'Akt' and 'Src' have been implicated in the endothelial-barrier regulation, it is puzzling how both agents that protect and disrupt the endothelial-barrier activate these kinases to reciprocally regulate vascular permeability. To delineate the role of Akt1 in endothelial-barrier regulation, we created endothelial-specific, tamoxifen-inducible Akt1 knockout mice and stable ShRNA-mediated Akt1 knockdown in human microvascular endothelial cells. Akt1 loss leads to decreased basal and angiopoietin1-induced endothelial-barrier resistance, and enhanced VEGF-induced endothelial-barrier breakdown. Endothelial Akt1 deficiency resulted in enhanced VEGF-induced vascular leakage in mice ears, which was rescued upon re-expression with Adeno-myrAkt1. Furthermore, co-treatment with angiopoietin1 reversed VEGF-induced vascular leakage in an Akt1-dependent manner. Mechanistically, our study revealed that while VEGF-induced short-term vascular permeability is independent of Akt1, its recovery is reliant on Akt1 and FoxO-mediated claudin expression. Pharmacological inhibition of FoxO transcription factors rescued the defective endothelial barrier due to Akt1 deficiency. Here we provide novel insights on the endothelial-barrier protective role of VEGF in the long term and the importance of Akt1-FoxO signaling on tight-junction stabilization and prevention of vascular leakage through claudin expression.


Assuntos
Células Endoteliais/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Junções Íntimas/metabolismo , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/metabolismo , Angiopoietina-1/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Claudina-5/metabolismo , Células Endoteliais/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Camundongos Transgênicos , Microvasos/citologia , Proteínas Proto-Oncogênicas c-akt/deficiência , Junções Íntimas/efeitos dos fármacos , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/farmacologia
10.
Int J Clin Pharmacol Ther ; 55(5): 425-432, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28139971

RESUMO

BACKGROUND: Irrational drug prescribing is considered one of the major challenges for the healthcare sectors worldwide, leading to negative outcomes in patients including various drug-related problems, such as polypharmacy, adverse drug events, more demands on drug monitoring, and unwanted increase in treatment cost. OBJECTIVE: The main objective of this study was to evaluate the trends and issues related to prescription at outpatient hospital pharmacies in Jordan and to contrast that to the WHO rational medication list and WHO drug use indicators. METHOD: This study was a cross-sectional study, conducted between January 2014 and May 2014. It involved a total number of 24,089 patient encounters from five teaching and referral hospitals in Jordan. The encounters included patients who were prescribed at least one medication during their visit to outpatient clinics in those hospitals. RESULTS: The average number of drugs per prescription was 2.93. The percentage of encounters which had antibiotics or injections in the prescription was 17.7% and 8.1%, respectively. The top three most common prescribed antibiotics were amoxicillin (n = 2,129, 49.9%), ciprofloxacin (n = 609, 14.3%), and clarithromycin (n = 267, 6.3%), while the most common prescribed injections were insulin and insulin analogs (n = 766, 39.2%), cyanocobalamin (Vitamin B12) (n = 612, 31.3%), and erythropoietin (n = 80, 4.1%). The percentage of prescriptions by generic was 57.6%, whereas the prescribing from the essentials drug list (formulary) was close to optimal (99.8%). CONCLUSION: The average number of prescribed drugs per encounter was higher than what was considered ideal according to WHO standards; the other issue found was a lower percentage of generic prescribing compared to WHO ideal value. The rest of prescribing indicators including the injections prescribing, antibiotics prescribing, and prescribing from the essential drug list were within the optimal range of values recommended by the WHO.
.


Assuntos
Hospitais de Ensino/tendências , Prescrição Inadequada/tendências , Ambulatório Hospitalar/tendências , Padrões de Prática Médica/tendências , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Estudos Transversais , Prescrições de Medicamentos , Revisão de Uso de Medicamentos , Medicamentos Essenciais/uso terapêutico , Medicamentos Genéricos/uso terapêutico , Feminino , Fidelidade a Diretrizes/tendências , Humanos , Hipoglicemiantes/uso terapêutico , Prescrição Inadequada/prevenção & controle , Jordânia , Masculino , Pessoa de Meia-Idade , Serviço de Farmácia Hospitalar/tendências , Polimedicação , Guias de Prática Clínica como Assunto , Fatores de Tempo , Adulto Jovem
11.
Biochim Biophys Acta ; 1853(5): 1229-39, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25746720

RESUMO

Transforming growth factor beta (TGFß) is believed to play a dual role in prostate cancer. Molecular mechanism by which TGFß1 suppresses early prostate tumor growth and induces epithelial-to-mesenchymal transition (EMT) in advanced stages is not known. We determined if P21-activated kinase1 (Pak1), which mediates cytoskeletal remodeling is necessary for the TGFß1 induced prostate cancer EMT. Effects of TGFß1 on control prostate cancer PC3 and DU145 cells and those with IPA 3 and siRNA mediated Pak1 inhibition were tested for prostate tumor xenograft in vivo and EMT in vitro. TGFß1 inhibited PC3 tumor xenograft growth via activation of P38-MAPK and caspase-3, 9. Long-term stimulation with TGFß1 induced PC3 and DU145 cell scattering and increased expression of EMT markers such as Snail and N-cadherin through tumor necrosis factor receptor-associated factor-6 (TRAF6)-mediated activation of Rac1/Pak1 pathway. Selective inhibition of Pak1 using IPA 3 or knockdown using siRNA both significantly inhibited TGFß1-induced prostate cancer cell EMT and expression of mesenchymal markers. Our study demonstrated that TGFß1 induces apoptosis and EMT in prostate cancer cells via activation of P38-MAPK and Rac1/Pak1 respectively. Our results reveal the potential therapeutic benefits of targeting TGFß1-Pak1 pathway for advanced-stage prostate cancer.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Fator de Crescimento Transformador beta1/farmacologia , Quinases Ativadas por p21/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Dissulfetos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Naftóis/farmacologia , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição da Família Snail , Fator 6 Associado a Receptor de TNF/metabolismo , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Ativadas por p21/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/metabolismo
12.
Nanomedicine ; 12(5): 1231-1239, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26949163

RESUMO

P21 activated kinases-1 (PAK-1) is implicated in various diseases. It is inhibited by the small molecule 'inhibitor targeting PAK1 activation-3' (IPA-3), which is highly specific but metabolically unstable. To address this limitation we encapsulated IPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of -28.1, neither of which changed over 14days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulation for the treatment of prostate cancer.


Assuntos
Dissulfetos/administração & dosagem , Naftóis/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Humanos , Lipossomos , Masculino , Quinases Ativadas por p21/antagonistas & inibidores , Quinases Ativadas por p21/efeitos dos fármacos
13.
J Biol Chem ; 288(5): 3025-35, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23258534

RESUMO

P21-activated kinases (Paks) are major effectors downstream of the small Rho family of GTPases. Among the six isoforms, Pak1 is the most ubiquitous and the best characterized member. Previous studies have shown that inhibition of Pak6, which is predominantly present in the prostate compared with other tissues, inhibits prostate tumor growth in vivo. Even though Pak1 has been identified in normal prostatic epithelial cells and cancer cells, its specific role in the development of prostate cancer remains unclear. We report here that highly invasive prostate cancer cells express significantly higher levels of Pak1 protein compared with non-invasive prostate cancer cells. Furthermore, prostate tumor tissues and prostate cancer metastasized to lungs showed a higher expression of Pak1 compared with normal tissues. Interestingly, Pak6 protein expression levels did not change with the invasive/metastatic potential of the cancer cells or tumors. Although inhibition of Pak1, and not Pak6, resulted in impaired PC3 cell migration, the effects of Pak1 knockdown on transendothelial migration (microinvasion), tumor growth, and tumor angiogenesis was higher compared with Pak6 knockdown. Finally, gene array data revealed reduced expression of matrix metalloproteinase 9 with the ablation of either Pak1 or Pak6 gene expression in PC3 cells, whereas protein levels of TGFß was elevated significantly with specific modulation of Pak1 activity or ablation of the Pak1 gene. Our observations suggest that although some level of functional redundancy exists between Pak1 and Pak6 in prostate cancer cells, targeting Pak1 is a potential option for the management of prostate tumor growth, microinvasion, and metastasis.


Assuntos
Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Fator de Crescimento Transformador beta/metabolismo , Quinases Ativadas por p21/metabolismo , Androgênios/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica/enzimologia , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Ativadas por p21/antagonistas & inibidores
14.
J Pharmacol Exp Ther ; 350(3): 635-45, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24990940

RESUMO

Angiotensin II receptor type 1 blockers (ARBs), widely used antihypertensive drugs, have also been investigated for their anticancer effects. The effect of ARBs on prostate cancer in experimental models compared with meta-analysis data from clinical trials is conflicting. Whereas this discrepancy might be due to the use of supratherapeutic doses of ARBs in cellular and animal models as compared with the clinical doses used in human trials, further investigation of the effects of clinical doses of ARBs on prostate cancer in experimental models is warranted. In the current study, we sought to determine the effects of candesartan on prostate cancer cellular function in vitro and tumor growth in vivo, and characterize the underlying mechanisms. Our analysis indicated that clinically relevant doses of candesartan significantly inhibited growth of PC3 cell tumor xenografts in mice. Interestingly, the same concentrations of candesartan actually promoted prostate cancer cellular function in vitro, through a modest but significant inhibition in apoptosis. Inhibition of tumor growth by candesartan was associated with a decrease in vascular endothelial growth factor (VEGF) expression in tumors and inhibition of tumor angiogenesis, but normalization of tumor vasculature. Although candesartan did not impair PC3 cell viability, it inhibited endothelial-barrier disruption by tumor-derived factors. Furthermore, candesartan significantly inhibited expression of VEGF in PC3 and DU145 cell lines independent of angiotensin II type 2 receptor, but potentially via angiotensin II type 1 receptor inhibition. Our findings clearly demonstrate the therapeutic potential of candesartan for prostate cancer and establish a link between ARBs, VEGF expression, and prostate tumor angiogenesis.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Benzimidazóis/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Tetrazóis/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Compostos de Bifenilo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Nus , Neovascularização Patológica/patologia , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
PLoS One ; 19(8): e0309618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39208059

RESUMO

BACKGROUND: The prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate. OBJECTIVE: To assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus. METHODS: The study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022. RESULTS: Electronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits. CONCLUSION: Current study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Pacientes Ambulatoriais , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemia/epidemiologia , Idoso , Masculino , Feminino , Prevalência , Pacientes Ambulatoriais/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hospitalização/estatística & dados numéricos
16.
Vasc Health Risk Manag ; 20: 27-37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318252

RESUMO

Background: Acquired prolonged corrected QT (QTc) interval can lead to life-threatening Torsade de Pointes (TdP) arrhythmia. Multiple risk factors including medications, comorbidities, and electrolyte imbalances contribute significantly to acquired manifestations of the QTc prolongation. Critically ill patients are particularly more vulnerable to TdP due to complex medical conditions, aging, and polypharmacy. Objective: This study aimed to assess the prevalence of TdP-associated medication prescribing, identify risk factors for QTc prolongation and TdP, and determine primary predictors of high TdP medication usage in critically ill patients in Jordan. Methods: We conducted a retrospective cross-sectional analysis of electronic medical records for patients from King Abdullah University Hospital who were admitted to Intensive Care Unit (ICU) between (July 2012-July 2022). We collected data on patients' demographics, clinical characteristics, comorbidities, laboratory results, and prescribed medications. Medications were categorized into three TdP risk levels according to CredibleMeds® assessment tool. Data were analyzed using descriptive statistics and a binary logistic regression model. Results: Of the 13,300 patients (58.2% male, median age 62 years). Prescribing prevalence for medications with known TdP risk was 19%, possible risk (24.7%), conditional risk (21.6%), and confirmed conditional risk (8.3%). Common comorbidities included hypertension (40.9%), diabetes (33.3%), and cancer (15.4%). Drugs with known TdP risk included citalopram, amiodarone, clarithromycin, and ciprofloxacin. A binary regression model revealed that as age increased, the odds of TdP associated medication prescribing decreased (OR = 0.989, p < 0.001), while patients on more than five medications had higher odds (OR = 4.281, p < 0.001). Conclusion: The study identified a notable prevalence of prescribing for medications with QTc prolongation/TdP risk in critically ill patients. Healthcare providers in the ICU should exercise caution to minimize the inadvertent prescription of TdP associated medications especially among older patients and those with polypharmacy.


Assuntos
Síndrome do QT Longo , Torsades de Pointes , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Prevalência , Estado Terminal , Estudos Transversais , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico , Torsades de Pointes/epidemiologia , Fatores de Risco , Proteínas de Ligação a DNA , Eletrocardiografia
17.
Int J Telemed Appl ; 2024: 5755493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39188938

RESUMO

Background: Telepharmacy, utilizing telecommunications to dispense pharmaceutical products and deliver patient care, offers numerous benefits for both the public and pharmacists. Previous research on exploring attitudes and willingness to use telepharmacy services has primarily focused on pharmacists rather than the general population. Aim: This study is aimed at assessing the attitudes and willingness of the United Arab Emirates (UAE) population to utilize telepharmacy services and identifying the factors influencing their inclination to use these services. Methods: In this cross-sectional study, a survey was distributed using convenience and snowball sampling to individuals aged 18 or older across the UAE through various social media platforms, including Twitter, Facebook, and WhatsApp. The survey domains included sociodemographics, attitudes, and readiness to utilize a telepharmacy service. A binary logistic regression analysis was conducted to investigate the variables associated with participants' willingness to utilize telepharmacy in the future. Results: In total, 963 individuals participated in the study. Participants showed overall positive attitudes towards telepharmacy, with 70.9% believing that telepharmacy saved time and effort. While only 32% of the participants acknowledged that numerous telepharmacy services were available for use in the UAE, most were interested in using telepharmacy services in the future (79.2%). Participants who had higher attitude scores (AOR = 1.147, 95% confidence interval [CI]: 1.11-1.18) and those who had used these services previously (AOR = 3.270, 95% CI: 1.692-6.320) were more interested in using telepharmacy services in the future. Conclusion: Forthcoming healthcare strategies should focus on expanding the availability of telepharmacy services throughout various regions of the country. This expansion will facilitate the broader utilization of these services and ultimately contribute to improved health outcomes.

18.
Ther Clin Risk Manag ; 19: 913-928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023626

RESUMO

Aims of the Study: This study aimed to investigate the prevalence and predictors of Drug-related problems (DRPs), as well as to evaluate the impact of DRPs on the health-related quality of life in geriatric patients with type 2 diabetes mellitus. Methodology: A cross-sectional study was conducted over a three-month period. Patients aged 60 years and older visited diabetes clinics from October 1, 2022, to December 31, 2022, were included in the study. Data were collected through structured questionnaires, whereas lab results, medication records, comorbidities, and the consequences of DRPs were collected from electronic medical records. DRPs were identified and classified using the PCNE V501 classification system. Health-related quality of life (HRQoL) was evaluated using the validated EuroQol criteria. Results: A total of 491 patients participated in the study, and the mean age of the patients was 67.51 years (SD = 5.84 years). Female patients represented 52.34% of total subjects. A total of 461 (around 94%) experienced at least one drug-related problem (DRP), ranging from one to nine DRPs per patient, with a total number of DRPs equal to 1625 identified. The most common DRP was the drug choice problem, affecting 52.98% of patients. Factors such as high drug frequency, living conditions, the number of diabetes medications, comorbidities, and smoking were significantly associated with higher numbers of DRPs. Higher numbers of DRPs were found to significantly worsen health-related quality of life (HRQoL) among patients. Conclusion: Geriatric individuals with type 2 diabetes mellitus encounter a significant prevalence of DRPs, with drug choice problems being the most common followed by dosing problems. Risk factors contributing to these DRPs include high drug frequency, living conditions, high number of diabetes medications, multimorbidity, and smoking. Also, the study concluded that the increased number of DRPs was associated with negative impact on HRQoL domains in geriatric patients with type 2 diabetes.

19.
Patient Prefer Adherence ; 17: 3107-3118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38050627

RESUMO

Aims of the Study: To evaluate medication adherence level and identify predictors of poor medication adherence in elderly patients with Cardiovascular (CVS) diseases and type 2 diabetes in Jordan. Methods: This cross-sectional study was conducted on elderly patients who attended King Abdullah University Hospital (KAUH) outpatient diabetes and cardiology clinics from March 6, 2023, to July 6, 2023. Data on age, sex, socio-demographics, biological variables, medication characteristics, and chronic comorbidities were obtained from electronic patients' medical records and a validated questionnaire. Medication adherence levels (low, moderate, and high) were assessed using the Arabic version of the 4-item Morisky, Green, and Levine Medication Adherence Scale-Medication Assessment Questionnaire. Results: Data from 506 elderly patients were analyzed. The average age of the participants was 67.93 years (SD = 6.22). 7.9% of patients showed low adherence levels, 33.6% showed moderate adherence level, and 58.5% of patients showed a high level of adherence toward their prescribed medications. Multivariable ordinal logistic regression analysis revealed that single/currently unmarried patients and patients who were living with others were more likely to have a higher adherence level; Odd Ratios (ORs) were 4.75 and 4.10, respectively. Patients who took their medications ≥ 3 and 2 times a day showed higher adherence to their medications than those who only took them once a day.; ORs were 2.15 and 2.36, respectively. Conclusion: This study indicated an inadequate level of adherence among patients with type 2 diabetes and cardiovascular comorbidities. This study revealed the necessity of implementing programs to help in raising the awareness among elderly patients with type 2 diabetes and CVDs of the importance of adherence to prescribed long-term medication regimens.

20.
Clin Interv Aging ; 18: 1653-1661, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810955

RESUMO

Aims of the Study: This study aimed to identify the prevalence and significant predictors of both potentially inappropriate medications (PIMs) and potentially omitted medications (POMs) events among geriatric patients with advanced cancer using the STOPP (Screening Tool of Older Persons' Prescriptions) and START (Screening Tool to Alert to Right Treatment) criteria. Methods: This retrospective cross-sectional study included patients aged ≥65 years who were diagnosed and treated for advanced stage of cancer. Patients' medical charts were evaluated to identify polypharmacy (≥5 medications) prevalence as well as potential PIMs and POMs incidents and their associated predictors. SPSS software was used to perform the analysis. Multivariate logistic regression models were used to identify factors associated with dependent variables including PIMs use and POMs. Results: Electronic medication charts of 510 patients were evaluated. The average age of the patients was 73.25 years, and 264 (51.8%) patients were males. The average number of medications prescribed per patient was 10.3 (range-2-26). Polypharmacy was present in 85.9% of patients, while excessive polypharmacy prevalence was 52.2%. At least one PIM was encountered in 253 patients (49.6%), while at least one POM was encountered in all patients owing to the omission of pneumococcal vaccines. The most common PIMs were opioid analgesics, followed by benzodiazepines, and hypnotics. Additionally, the most omitted medications, excluding vaccinations, were cardiovascular agents and laxatives in patients on regular opioid analgesics. Polypharmacy and diagnosis with solid cancer compared to hematological cancer were associated with increased odds for PIMs occurrence (ORs = 1.293 (p < 0.001) and 3.022 (p = 0.03), respectively), while coexistence of hypertension diagnosis in cancer patients was associated with increased the odds for POMs events (OR = 2.286 (p = 0.007)). Conclusion: Polypharmacy, PIMs, and POMs were highly prevalent among older cancer patients based on the polypharmacy definition and STOPP/START Criteria.


Assuntos
Prescrição Inadequada , Neoplasias , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Prescrição Inadequada/prevenção & controle , Neoplasias/tratamento farmacológico , Polimedicação , Prevalência , Estudos Retrospectivos
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