Prevalence of chronic diseases in older Palestinian adults and common pharmacological interventions: a cross-sectional study.

BACKGROUND: Older people (aged 60 years and older) are more susceptible than younger people to multiple medical disorders and are therefore more frequently exposed to polypharmacy. We investigated prevalence of chronic diseases and medical conditions, medications used, and associated sociodemographic factors among older adults of the Palestinian population. METHODS: A cross-sectional study was done between June, 2013, and January, 2014. The study population was Palestinians aged 60 years and older living in the West Bank and East Jerusalem. Study participants were selected in a stratified random manner. The sample was selected from all governorates (strata) according to the size of the population of each governate on the basis of census data from the Palestinian Central Bureau of Statistics. The research team visited and interviewed older residents in their houses. Questionnaire items were explained in informal language to participants by the interviewer, to ensure complete understanding, and answers were recorded by the interviewer. Informed written consent was obtained from each participant. The study design and protocols were revised and approved by the Research Ethics Committee at Al-Quds University. FINDINGS: 1574 older Palestinian adults were invited to participate, of whom 1192 (76%) enlisted. The mean age was 70·3 years (SD 8·58, range 60-110 years). 55% (659 of 1192) were female and 45% (533) were male. The majority (84%; 996) were non-workers or retired; monthly income for 78% of participants (930) was less than 2500 NIS, which falls in the low-income group. More participants (78%; 934) had governmental health insurance than had private insurance (8%; 89) or no insurance (14%; 169). 40 chronic diseases and conditions were reported. The mean number of diseases reported per participant was 2·33 (SD 1·68, range 0-11). Cardiovascular, endocrine, and musculoskeletal conditions were the most frequently reported. 66% of participants (787 of 1192) reported at least one cardiovascular condition, 40% (480) at least one endocrine condition, and 32% (385) at least one musculoskeletal condition. The most prevalent cardiovascular condition was hypertension, which affected 54% of participants (647); the most prevalent endocrine condition was diabetes (38·2%, 455); and the most prevalent musculoskeletal condition was arthritis (13·7%, 163). The total number of different types of medication (both prescribed and over-the-counter drugs) was 175. The mean number of medications per participant was 4·54 (SD 2·83), and the highest number of different medications being taken by one participant was 17. Commonly prescribed therapeutic agents were aspirin (prescribed to 48% of participants, 575 of 1192), angiotensin-converting-enzyme inhibitors (34%, 403), diuretics (34%, 409), metformin (27%, 323), paracetamol (23%, 270), and protein pump inhibitors (23%, 275). INTERPRETATION: The findings provide insights into the most prevalent chronic diseases and conditions, as well as the most commonly used medications among older Palestinians. Cardiovascular, endocrine, and musculoskeletal conditions were the most prevalent diseases. Older Palestinians adults are subjected to polypharmacy, which should be assessed whenever they are evaluated for health problems, and drug interactions should be carefully checked. Physicians, pharmacists, health professionals, and health policymakers in Palestine should consider increasing citizens' health awareness and encourage healthy lifestyles to decrease the incidence of these diseases. In addition, intersectoral cooperation between the governmental and non-governmental organisations will be key in the fight against chronic diseases in older Palestinian adults. FUNDING: None.

Knowledge and attitude of Palestinian women to contraceptives: a cross-sectional study.

BACKGROUND: Contraceptives have documented efficiency, but outcomes are highly dependent on women's understanding of how they should be used. We assessed the knowledge and attitudes of married Palestinian women about contraceptives and understanding of use of the available methods and side-effects. METHODS: This cross-sectional study involved married Palestinian women of childbearing age (18-50 years), and was done between Jan 20, 2017, and Jan, 1, 2018. A stratified random sample of 900 women was selected from each Palestinian governorate in the West Bank and East Jerusalem, with the number selected based on population size. An interviewer-assisted questionnaire was completed by each participant. FINDINGS: 833 women were selected to participate and 771 (93%) completed the questionnaire. 123 (16%) of women reported not using any method of contraception. Among those who used contraception, intrauterine devices were most commonly used (312 [41%] of 771), followed by oral contraceptives (162 [21%]). Progestagen-only pills were the most frequently used type of oral contraceptive (45 [28%] of 162). Female sterilisation was used as a birth control method by 19 (3%) of 771 women. Investigation of the reasons behind contraception use showed that organisation of pregnancies was most common (511 [79%] of 648), followed by having too many children (131 [20%]) and economic reasons (73 [11%]). Regarding attitudes and beliefs towards contraceptive use, of the 771 participants, 49 (6%) believed that religion forbids their use and 112 (14·5%) considered them socially unacceptable. The study revealed poor scores for knowledge about use and possible side effects of contraceptives (mean 8·2 [SD 2·9] correct answers to 14 questions). INTERPRETATION: Most Palestinian women have used contraceptives, but poor knowledge of how to use them and side-effects is apparent. The attitudes of Palestinian women and their partners towards contraceptives indicates general acceptance of their use. A strength of our study is that it included representative sample of Palestinian women and our results and conclusions reflect the knowledge and attitudes towards contraceptives in Palestinian society. FUNDING: None.

Newly Developed Prodrugs and Prodrugs in Development; an Insight of the Recent Years.

BACKGROUND: The design and development of prodrugs is the most common and effective strategy to overcome pharmacokinetic and pharmacodynamic drawbacks of active drugs. A respected number of prodrugs have been reached the drugs market throughout history and the recent years have witnessed a significant increase in the use of prodrugs as a replacement of their parent drugs for an efficient treatment of various ailment. METHODS: A Scan conducted to find recent approved prodrugs and prodrugs in development. RESULTS: Selected prodrugs were reported and categorized in accordance to their target systems. CONCLUSIONS: the prodrug approach has shown many successes and still remains a viable and effective approach to deliver new active agents. This conclusion is supported by the recent approved prodrugs and the scan of clinical trials conducted between 2013-2018.

Successes, failures, and future prospects of prodrugs and their clinical impact.

INTRODUCTION: Ample efforts have been carried out to improve the efficacy of a variety of drugs. The prodrugs approach was found to be a safe haven for providing medications with improved pharmacokinetic and pharmacodynamic properties. Areas covered: Herein, several selected successful prodrugs are reported and categorized. These include prodrugs for the treatment of the cardiovascular system, the central nervous system, the gastrointestinal tract, ophthalmology, the immune system, and oncology. In addition, some successful antiviral, antibacterial, antifungal, antiprotozoal, and several other miscellaneous prodrugs are documented. Further, a number of failed prodrugs are reported followed by those potentially promising prodrugs of the future. Expert opinion: The molecular revolution and accumulation of knowledge on the chemistry of enzymes and transporters has opened the door widely to novel successful prodrugs. For example, newer platelet aggregation inhibitors could signal the end of the warfarin era with their demanding treatment follow-up. The discovery of prodrugs can significantly improve the quality of patient care. Future attention should be focused towards directed enzyme prodrug therapy (DEPT). This strategy employs the design of artificial enzymes to activate prodrugs at specific sites. Agents designed for use in DEPT medicine can be directed at antibodies, genes, viruses, and clostridia.

Strategies for Enhancing the Permeation of CNS-Active Drugs through the Blood-Brain Barrier: A Review.

Background: The blood brain barrier (BBB) is a dynamic and functional structure which poses a vast challenge in the development of drugs acting on the central nervous system (CNS). While most substances are denied BBB crossing, selective penetration of substances mainly occurs through diffusion, carrier mediated transport, or receptor mediated transcytosis. Methods: Strategies in enhancing BBB penetration have been reviewed and summarized in accordance with their type of formulation. Highlights in monoclonal antibodies, peptide-vectors, nanoparticles, and simple prodrugs were included. Conclusion: Nanoparticles and simple prodrugs, for example, can be used for efficient BBB penetration through inhibition of efflux mechanisms, however, monoclonal antibodies are the most promising strategy in BBB penetration. Close follow-up of future development in this area should confirm our expectation.

Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.

Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs), the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A) has dawned.

Recent Approaches to Platinum(IV) Prodrugs: A Variety of Strategies for Enhanced Delivery and Efficacy.

BACKGROUND: Intensive efforts have been implemented to improve the efficacy of platinum complexes especially with emerging cisplatin resistance and elevated cancer deaths. Platinum(IV) agents show better pharmacokinetics and decreased side effects compared to Platinum(II) agents. METHODS: This review aims to summarize and categorize the strategies being employed to improve the efficacy of Platinum-based anticancer agents in recent years. RESULTS: Nanoparticles and nanoplatforms offer a vast variety of strategies in targeting specific tumor types and delivering one or two lethal drugs simultaneously. Theranostic agents are being developed to achieve enhanced imaging and provide further insight into the activity of platinum containing chemotherapy. Moreover, photoactivation of Pt(IV) prodrugs specifically at the tumor site is gaining attention due to a controlled activity. A platinum agent formulated as large multi-activity complex is the most common strategy being employed. CONCLUSION: Platinum(IV) agents offer great potential in targeting, increasing efficacy, and decreasing toxicity of Platinum-based anticancer agents. The strategies being employed are aiming to increase specificity and targeting as well as provide more potent agents.

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease.

Background: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals. Results: A promising ester prodrug for intranasal delivery has been developed. LD methyl ester is currently in Phase III clinical trials. A series of amide prodrugs were synthesized with better stability than ester prodrugs. Both amide and dimeric amide prodrugs offer enhanced blood brain barrier (BBB) penetration and better pharmacokinetics. Attaching LD to sugars has been used to exploit glucose transport mechanisms into the brain. Conclusions: Till now, no DA prodrug has reached the pharmaceutical market, nevertheless, the future of utilizing prodrugs for the treatment of PD seems to be bright. For instance, LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain. Most of the amide, cyclic, peptidyl or chemical delivery systems of DA prodrugs demonstrated enhanced pharmacokinetic properties.

Knowledge and Adherence to Medications among Palestinian Geriatrics Living with Chronic Diseases in the West Bank and East Jerusalem.

BACKGROUND: Adequate patient knowledge about medications is essential for appropriate drug taking behavior and patient adherence. This study aims to assess and quantify the level of knowledge and adherence to medications among Palestinian geriatrics living with chronic diseases and to investigate possible associated socio-demographic characteristics. METHODS AND FINDINGS: We conducted a cross-sectional study during June 2013 and January 2014 among Palestinian geriatrics ≥ 60 years old living with chronic disease in the West Bank and East Jerusalem. A stratified random sample was selected and a questionnaire-assisted interview was applied for data collection. T-test was applied for bivariate analyzing and one-way ANOVA test was applied for multivariate analyses. RESULTS: A total of 1192 Palestinian geriatrics were studied. The average age was 70.3 (SD = 8.58) years and ranged from 60-110 years. The sample comprised 659 (55.3%) females and 533 (44.7%) males. The global knowledge and global adherence scores were (67.57%) and (89.29%), respectively. Adequate levels of knowledge were 71.4%, and of adherence 75%, which were recorded for 705 (59.1%) and 1088 (91.3%) participants, respectively. Significant higher levels of global knowledge and global adherence were recorded for males, and for participants who hold a Bachelor's degree, those who live on their own, and did physical activity for more than 40 hours/week (p-value < 0.05). Furthermore, workers, participants with a higher monthly income, and non-smokers have a higher knowledge level with (p-value < 0.05). We found positive correlation between participants' global adherence and global knowledge (r = 0.487 and p-value < 0.001). Negative correlation was found between participants' global knowledge and adherence with age (r = -0.236, p-value < 0.001 and r = -0.211 and p-value < 0.001, respectively. Negative correlation between global knowledge and the number of drugs taken (r = -0.130, p-value < 0.001) was predicted. CONCLUSION: We concluded that patients with a higher level of knowledge are more adherent to their medications and that better understanding of socio-demographic factors has a clear influence on the level of knowledge and adherence to medications and thus contributes to the development of guidelines for treatment and may consequently lead to favourable clinical outcomes and savings of health care costs.

Prediction of primary breast cancer size and T-stage using micro-computed tomography in lumpectomy specimens.

BACKGROUND: Histopathology is the only accepted method to measure and stage the breast tumor size. However, there is a need to find another method to measure and stage the tumor size when the pathological assessment is not available. Micro-computed tomography. (micro-CT) has the ability to measure tumor in three dimensions in an intact lumpectomy specimen. In this study, we aimed to determine the accuracy of micro-CT to measure and stage the primary tumor size in breast lumpectomy specimens, as compared to the histopathology. MATERIALS AND METHODS: Seventy-two women who underwent lumpectomy surgery at the Massachusetts General Hospital Department of Surgery from June 2011 to September 2011, and from August 2013 to December 2013 participated in this study. The lumpectomy specimens were scanned using micro-CT followed by routine pathological processing. The maximum dimension of the invasive breast tumor was obtained from the micro-CT image and was compared to the corresponding pathology report for each subject. RESULTS: The invasive tumor size measurement by micro-CT was underestimated in 24 cases. (33%), overestimated in 37 cases. (51%), and matched it exactly in 11 cases. (15%) compared to the histopathology measurement for all the cases. However, micro-CT T-stage classification differed from histopathology in only 11. (15.2%) with 6 cases. (8.3%) classified as a higher stage by micro-CT, and 5 cases. (6.9%) classified as lower compared to histopathology. In addition, micro-CT demonstrated a statically significant strong agreement (κ =0.6, P < 0.05) with pathological tumor size and staging for invasive ductal carcinoma. (IDC) group. In contrast, there was no agreement. (κ = -2, P = 0.67) between micro-CT and pathology in estimating and staging tumor size for invasive lobular carcinoma. (ILC) group. This could be explained by a small sample size. (7) for ILC group. CONCLUSIONS: Micro-CT is a promising modality for measuring and staging the IDC.

Comparison of adult and child radiation equivalent doses from 2 dental cone-beam computed tomography units.

INTRODUCTION: With the advent of cone-beam computed tomography (CBCT) scans, there has been a transition toward these scans' replacing traditional radiographs for orthodontic diagnosis and treatment planning. Children represent a significant proportion of orthodontic patients. Similar CBCT exposure settings are predicted to result in higher equivalent doses to the head and neck organs in children than in adults. The purpose of this study was to measure the difference in equivalent organ doses from different scanners under similar settings in children compared with adults. METHODS: Two phantom heads were used, representing a 33-year-old woman and a 5-year-old boy. Optically stimulated dosimeters were placed at 8 key head and neck organs, and equivalent doses to these organs were calculated after scanning. The manufacturers' predefined exposure settings were used. RESULTS: One scanner had a pediatric preset option; the other did not. Scanning the child's phantom head with the adult settings resulted in significantly higher equivalent radiation doses to children compared with adults, ranging from a 117% average ratio of equivalent dose to 341%. Readings at the cervical spine level were decreased significantly, down to 30% of the adult equivalent dose. When the pediatric preset was used for the scans, there was a decrease in the ratio of equivalent dose to the child mandible and thyroid. CONCLUSIONS: CBCT scans with adult settings on both phantom heads resulted in higher radiation doses to the head and neck organs in the child compared with the adult. In practice, this might result in excessive radiation to children scanned with default adult settings. Collimation should be used when possible to reduce the radiation dose to the patient. While CBCT scans offer a valuable tool, use of CBCT scans should be justified on a specific case-by-case basis.

Adenoviral gene transfer of bioactive TGFbeta1 to the rodent eye as a novel model for anterior subcapsular cataract.

PURPOSE: To produce a gene-transfer model of rodent anterior subcapsular cataracts (ASC) using a replication-deficient, adenoviral vector containing active TGFbeta1. Establishment of this model will be important for further investigations of TGFbeta-induced signaling cascades in ASC. METHODS: Adenovirus containing the transgene for active TGFbeta1 (AdTGFbeta1), beta-galactosidase (AdLacZ), green fluorescent protein (AdGFP) or no transgene (AdDL) was injected into the anterior chamber of C57Bl/6, Smad3 WT and Smad3 KO mice. Four and 21 days after injection, animals were enucleated and eyes were processed and examined by routine histology. Immunolocalization of markers indicative of epithelial to mesenchymal transition (EMT), fibrosis, proliferation and apoptosis was also carried out. RESULTS: By day 4, treatment with AdLacZ demonstrated transgene expression in multiple structures of the anterior chamber including the lens epithelium. In contrast to AdDL, treatment with AdTGFbeta1 produced alphaSMA-positive subcapsular plaques in all three groups of mice, which shared features reminiscent of human ASC. At day 21, plaques remained alphaSMA-positive and extensive extracellular matrix deposition was observed. The AdTGFbeta1 model was further employed in Smad3 deficient mice and this resulted in the development of small ASC. CONCLUSIONS: Gene transfer of active TGFbeta1 using an adenoviral vector produced cataractous plaques four days postinjection, which were found to develop independent of functional Smad3.