Knowledge, Attitude, Awareness, and Perceptions among Physicians toward Antibiotic Resistance in Hospitals in South Palestine.

Background Antibiotic resistance is a global problem, and the World Health Organization has made this problem one of its priorities for solving. Therefore, a survey was carried out to investigate the knowledge, attitude, awareness, and perceptions of antibiotic resistance among physicians and to assess the correlation between the knowledge of antibiotic resistance and their years of experience in some Palestinian hospitals. Methods This was a cross-sectional study that targeted physicians who are working in different healthcare facilities in Hebron and Bethlehem governorates. We used a questionnaire for data collection. The questionnaire consists of 42 questions to measure the knowledge, attitudes, awareness, and perceptions of antibiotic use and resistance. Results The response rate was 91.33% (137 of 150 physicians completed the questionnaire). The participants' ages ranged from 25 to 56 years, and the majority were males ( n = 116, 84.7%) working in governmental hospitals ( n = 83, 60.6%). Of physicians, 69.3% ( n = 95) perceived antibiotic resistance as a very important worldwide problem, while 54.7% ( n = 75) perceived a very important problem in the country, 54.0% ( n = 74) a very important problem in their hospital, and 59.1% ( n = 81) a very important problem in their departments. Methicillin-resistant Staphylococcus aureus was the most known antibiotic-resistant bacteria followed by extended-spectrum beta-lactamases. Only 47 physicians (34.3%) think that antibiotics are not used appropriately in their department. Respondents' physicians showed that the development of antibiotic resistance was due to various factors that include self-medication n= (92, 67.2%), overuse of antibiotics ( n = 83, 60.6%), and uncompleted treatment (n= 87, 63.5). Senior specialists/consultants were found to be more knowledgeable about antibiotic resistance. Conclusion In our survey, physicians showed variable knowledge and perceptions of antibiotic resistance. Introducing educational programs is necessary to improve their understanding and perceptions of antibiotic resistance, as well as their attitude toward antibiotic use.

Palestinian strategies, guidelines, and challenges in the treatment and management of coronavirus disease-2019 (COVID-19).

BACKGROUND: Coronavirus disease-2019 (COVID-19) outbreak is a global concern and the World Health Organization (WHO) has declared it as a Public Health Emergency of International Concern. The Palestinian Authority (PA) has quickly and effectively responded to the outbreak of COVID-19, using an internationally and nationally coordinated, to contain the spread of the virus within the borders. The PA approaches are containment and suppression, which is designed to protect the citizens from infection while also mitigating the stress on the health care system. The PA immediately declared a State of Emergency when the first cases in Palestine were diagnosed on 5 March 2020 and launched robust national containment measures to encourage the citizens to protect themselves and follow the guidance. OBJECTIVES: There is currently no vaccine or effective treatment for COVID-19, the treatment is either supportive and/ or the treatment of symptoms. Several strategies in the treatment of the disease were applied including medications. This review aims to summarize the different strategies, guidelines, challenges, and treatments used against COVID-19 worldwide and in Palestine. MATERIALS AND METHODS: Different literature and guidelines among different databases were searched. Literature reviewing was conducted using the following search engines, Google Scholar, Medline, Pub Med, EMBASE, Web of Science, and Science Direct. Data also obtained from WHO and PA reports, and the published peer-reviewed articles of 2019-nCoV. The review focuses on the strategies, guidelines, therapeutics, challenges, and different approaches used in the treatment and management of the disease in Palestine and globally. CONCLUSION: The Palestinian Ministry of Health (MoH) strategies to end the COVID-19 pandemic were; slow and stop transmission; provide optimized care for patients; and minimize the impact of the epidemic on health systems, social services, and economic activity. Thus, proper management, right actions, and effective treatment of the disease should be considered to achieve these strategies. The biggest problem for PA to control and stop the outbreak of the disease is the different challenges which include; the Israeli military and economic control, uncontrol the borders, shortage of medical and financial resources, crowded cities and refugee camps, poverty, food insecurity, and the financial crisis. To date, there are no specific vaccines or medicines for COVID-19; and treatments are under investigation through clinical trials. However, an array of drugs approved for other indications, as well as multiple investigational agents, are being studied for the treatment of COVID-19; in several hundred clinical trials around the World. Treatment is essentially supportive and symptomatic.

Patterns of NSAIDs use in Palestinian mid-territories: a prospective study of ambulatory patients in outpatient pharmacies.

The out-patient pharmacies in Ramallah and Bethlehem, central Palestine, were evaluated for NSAIDs utilization and pattern of prescribing and dispensing of these commonly used medications across the whole country. In our study for this area that accounts for almost 25% of the inhabitants of all Palestine (459, 761 inhabitants according to 2011 census), we analyzed the use of NSAIDs whether were prescribed for the patient or were obtained without a prescription in the period of Sept 1(st) to Nov. 30, 2011. The number of defined daily doses, DDD/1000 inh/day, and the percentage utilization from total were determined and analyzed using the simple ATC/DDD model which was developed by WHO for assessment of quality prescribing of medications. From these data we calculated DU 90% for the drugs described in this study. Using a scale for GI toxicity and risk determination from a meta- analysis of controlled epidemiological studies, we determined the GI risk of the drugs in the study. Ketoprofen and piroxicam were found to be associated with the highest risk, on the other hand ibuprofen and diclofenac were associated with low risk of GI toxicity. The average Price/DDD was also determined for the purpose of comparison with the prices in other European countries. Our findings were both exciting and interesting with the total consumption of NSAIDs over the period of study was 31.26 DDD/1000 inh/day comparing to 51.02 DDD/1000 inh/day in the European countries included in the study. Only 5 drugs fell within DU 90% which are respectively along with their percentage NSAIDs consumption: (ibuprofen; 26.48%, diclofenac; 23.38%, etoricoxib; 21.24%, meloxiocam; 12.19%, and celecoxib; 7.16%). The drugs were obtained mostly by prescription except for the first 2 agents (ibuprofen and diclofenac) which were almost exclusively bought without a prescription as OTC with the pharmacist greatly influence their use and dispensing. The price of purchasing for the top DU 90% agents was almost twice the price in Europe for the same drugs taking into consideration the limitations of our study in determining the equipotency or the equivalency of the DDD doses in Palestine and Europe.

Computer-assisted design for paracetamol masking bitter taste prodrugs.

It is believed that the bitter taste of paracetamol, a pain killer drug, is due to its hydroxyl group. Hence, it is expected that blocking the hydroxy group with a suitable linker could inhibit the interaction of paracetamol with its bitter taste receptor/s and hence masking its bitterness. Using DFT theoretical calculations we calculated proton transfers in ten different Kirby's enzyme models, 1-10. The calculation results revealed that the reaction rate is linearly correlated with the distance between the two reactive centers (r(GM)) and the angle of the hydrogen bonding (α) formed along the reaction pathway. Based on these results three novel tasteless paracetamol prodrugs were designed and the thermodynamic and kinetic parameters for their proton transfers were calculated. Based on the experimental t(1/2) (the time needed for the conversion of 50% of the reactants to products) and EM (effective molarity) values for processes 1-10 we have calculated the t(1/2) values for the conversion of the three prodrugs to the parental drug, paracetamol. The calculated t(1/2) values for ProD 1-3 were found to be 21.3 hours, 4.7 hours and 8 minutes, respectively. Thus, the rate by which the paracetamol prodrug undergoes cleavage to release paracetamol can be determined according to the nature of the linker of the prodrug (Kirby's enzyme model 1-10). Further, blocking the phenolic hydroxyl group by a linker moiety is believed to hinder the paracetamol bitterness.

A-ring-substituted estrogen-3-O-sulfamates: potent multitargeted anticancer agents.

Efficient and flexible syntheses of 2-substituted estrone, estradiol and their 3-O-sulfamate (EMATE) derivatives have been developed using directed ortho-lithiation methodology. 2-Substituted EMATEs display a similar antiproliferative activity profile to the corresponding estradiols against a range of human cancer cell lines. 2-Methoxy (3, 4), 2-methylsulfanyl (20, 21) and 2-ethyl EMATEs (32, 33) proved the most active compounds with 2-ethylestradiol-3-O-sulfamate (33), displaying a mean activity over the NCI 55 cell line panel 80-fold greater than the established anticancer agent 2-methoxyestradiol (2). 2-Ethylestradiol-3-O-sulfamate (33) was also an effective inhibitor of angiogenesis using three in vitro markers, and various 2-substituted EMATEs also proved to be inhibitors of steroid sulfatase (STS), a therapeutic target for the treatment of hormone-dependent breast cancer. The potential of this novel class of multimechanism anticancer agents was confirmed in vivo with good activity observed in the NCI hollow fiber assay and in a MDA-MB-435 xenograft mouse model.

Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase.

Steroid sulfatase (STS) is an important new therapeutic target in oncology. Attempts to design nonsteroidal STS inhibitors, because of the oestrogenicity of the original lead oestrone 3-O-sulfamate in rodents, have led to the discovery of benzophenone-4,4'-O,O-bis-sulfamate (BENZOMATE, 3). The nonfused bicyclic BENZOMATE is a highly potent STS inhibitor in vitro, inhibiting STS activity in intact MCF-7 breast cancer cells by > 70% at 0.1 microM and in placental microsomes by > 98% at 10 microM. When MCF-7 cells were pre-treated with 3 at 1 microM and then washed to remove unbound inhibitor, the initial 94% inhibition was reduced to 89% suggesting that 3, like other sulfamate-based STS inhibitors, inhibits the enzyme irreversibly. This agent also inhibits rat liver STS activity by 84% and 93% respectively 24 h after a single dose of 1 or 10 mg/kg, demonstrating that BENZOMATE possesses similar in vivo potency to the established potent nonsteroidal inhibitor 667COUMATE. Several modifications were made to BENZOMATE structurally and effects on in vitro activity were examined. These structure-activity relationship studies show that its carbonyl and bis-sulfamate groups are pivotal for activity, although conformational flexibility is not required. Two rigid anthraquinone-based sulfamate derivatives however showed inhibitory activity significantly better than BENZOMATE in the MCF-7 cell assay. BENZOMATE and related analogues therefore represent an important class of non-steroidal STS inhibitor and lead compounds for future drug design.