Vancomycin prescribing and therapeutic drug monitoring: Challenges of real clinical practice.

BACKGROUND: Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers. AIMS: Identifying barriers to compliance with vancomycin dosing and therapeutic drug monitoring guidelines (TDM) and possible ways to enhance compliance based on the healthcare providers' (HCPs) perspective. METHODS: A qualitative study based on semi-structured interviews with HCP (physicians, pharmacists, and nurses) was conducted at two Jordanian Teaching Hospitals. Interviews were audio-recorded and analyzed through thematic analysis. The COREQ criteria for qualitative research were utilized to report the study findings. RESULTS: A total of 34 HCPs were interviewed. HCP perceived several factors as barriers to guideline recommendation compliance. Such factors included negative perception towards prescription guidelines, lack of knowledge regarding TDM guidelines, the hierarchy of medication management, work pressure, and ineffective communication among healthcare providers. Potential strategies to optimize guidelines adaptation included providing HCPs with more training and decision support tools in addition to activating the role of clinical pharmacists. CONCLUSIONS: The main barriers to guideline recommendations uptake were identified. Interventions should address those barriers related to the clinical environment, including enhancing interprofessional communication related to vancomycin prescription and TDM, reducing workload and providing support systems, promoting educational and training programs, in addition to adopting guidelines suitable for the local environment.

Vancomycin audit in the paediatric population: Patterns of use and appropriateness of therapeutic drug monitoring.

AIMS: This study aims to investigate prescribing and therapeutic drug monitoring (TDM) practices for vancomycin in paediatrics at the Jordan University Hospital and to determine the impact of inaccuracies in TDM data on dosing decisions. METHODS: Patterns of vancomycin prescriptions, appropriateness of vancomycin dosing, duration, TDM, and the accuracy of the recorded dosing/sampling times were determined prospectively based on prespecified criteria. Finally, Monte Carlo simulations were undertaken using the mrgsolve-package in R to assess the effect of inaccuracies in recording dosing/sampling times on subsequent dose adjustments. RESULTS: Four hundred forty-two vancomycin courses were analysed. Vancomycin prescriptions were mainly empirical (77.4%). Initial vancomycin doses were appropriate in 73.1% of vancomycin courses. Prolonged use (>5 days) was found in 45.7% of admissions with negative cultures; this was related to the diagnosis of suspected sepsis unadjusted-OR: 1.8 (1.1-2.9). TDM was appropriately ordered in 90.7% of concentrations. Discrepancies between the recorded and actual times were noted in 83.9% and 82.7% of audited times of dose administration and sample collection, respectively. Based on simulations, these discrepancies were predicted to result in inappropriate dose adjustment in 37.9% of patients. CONCLUSIONS: Inappropriate empirical and prolonged vancomycin use and inaccuracies in recording dosing/sampling times are important areas of improvement in the current clinical practice.

Correlation of skin cancer and actinic keratosis-related knowledge and sun protection behaviors and sunscreen use among a sample of Jordanian population.

BACKGROUND: The incidence of skin cancer and actinic keratosis has increased worldwide. Measuring the public awareness, attitude, and knowledge about these diseases and the skin protection behaviors are highly important to undertake preventive measures. METHODS: To investigate skin cancer and actinic keratosis-related knowledge, sun protection behaviors, and sunscreen usage among Jordanians, a questionnaire was developed. The questionnaire was provided as a google form to individuals via social media and the data were analyzed using SPSS® 23. RESULTS: A total of 1277 individuals, aged 18-65 years filled the questionnaire. The median melanoma and actinic keratosis knowledge score were 7 (4-9) and 4 (0-9), respectively. The melanoma knowledge was higher among females, those with a medical background, a high level of education, and in the central region, whereas the AK knowledge was higher among those with a medical background. Overall, 75.9% of the participants used sunscreen at least often to prevent sunburn, uneven skin tone, or tanning, 72% were using sunscreen with an SPF of 30 at least. However, 45.3% and 49.2% of sunscreen users did not comply with application, and reapplication times, respectively. Moreover, 58.4% of participants applied less than the recommended amount of sunscreen. CONCLUSION: Our study revealed that public awareness of actinic keratosis is low among Jordanians. Although it was found that a high proportion of Jordanians use sunscreens there are deficits in sunscreen practice indicating an urgent need to design effective interventions to increase awareness of actinic keratosis and correct use of sunscreen via health campaigns or healthcare professions.

Perceived Public Stress Among Jordanians During the COVID-19 Outbreak.

OBJECTIVES: Outbreaks and containment measures implemented to control them can increase stress in affected populations. The impact of the coronavirus disease 2019 (COVID-19) outbreak on perceived stress levels in the Jordanian population is unknown. The aim of the study was to determine the perceived stress level and factors associated with it in the Jordanian population during the COVID-19 outbreak. METHODS: Required data, such as those from the Perceived Stress Scale (PSS-10) and possible predictors of perceived stress, were collected through a Web-based survey. Statistical analysis was conducted through SPSS. RESULTS: The mean (SD) of perceived stress score was 19.8 (6.7). Regression analysis revealed that stress was increased in females, young adults, usually being stressed more than others by a health problem, increased perceived severity of the disease, increased overall worry score, and student's worry regarding their studies/graduation. Perceived stress was decreased if participants' self-rated health status score increased. CONCLUSIONS: In the context of increasing public health preparedness, the results of this study can be used in designing interventions to alleviate stress in susceptible segments of the Jordanian community.

Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review.

BACKGROUND: Digoxin is a cardiac glycoside that was introduced to cardiovascular medicine more than 200 years ago. Its use is associated with large variability, which complicates achieving the desired therapeutic outcomes. OBJECTIVES: To present a synthesis of the available literature on the population pharmacokinetics of digoxin in adults and to identify the sources of variability in its pharmacokinetics. METHODS: This is a PROSPERO registered systematic review (CRD42018105300). A literature search was conducted using the ISI Web of Science, Science Direct, PubMed, and SCOPUS databases to identify digoxin population pharmacokinetic studies of adults that utilized the nonlinear mixed-effect modeling approach. RESULTS: Sixteen articles were included in the present analysis. Only two studies were conducted in elderly subjects as a separate population. Both the pharmacokinetics and pharmacodynamics of digoxin were investigated in one study. Furthermore, the reviewed studies were mostly conducted in East Asian populations (68.8%). Digoxin's pharmacokinetics were usually described by a one-compartment model because of the nature of the collected data. Weight, age, kidney function, presence of heart failure, and co-administered medications such as calcium channel blockers were the most commonly identified predictors of digoxin clearance. The value of apparent clearance in a typical study individual ranged from 0.005 to 0.2 l/h/kg, while the value of the apparent volume of distribution ranged from 3.14 to 15.2 l/kg. The quality of model evaluation was deemed excellent only in 31.3% of the studies. CONCLUSION: This review provides information about variables that need to be considered when prescribing digoxin. The results highlight the need for prospective studies that allow two-compartment pharmacokinetic/pharmacodynamic models to be established, with a special focus on the elderly subpopulation.

Knowledge and awareness about human papillomavirus infection and its vaccination among women in Arab communities.

Cervical cancer (CC) is one of the most common types of cancer that affect females worldwide with hundreds of thousands of women dying annually due to this disease, mainly in developing countries. Infection with human papillomavirus (HPV) is the main risk factor for this cancer. There are no public awareness and national immunization programs in most Arab countries. This study aimed to investigate the knowledge and awareness about the HPV vaccine among females in four Arab countries and their acceptance to receive the vaccine. A cross-sectional study was conducted in several Arab countries: Jordan, Qatar, the United Arab Emirates (UAE), and Iraq. Respondents that fulfilled the desired criteria and were willing to participate in the study were asked to fill out the survey. Knowledge and awareness were assessed using 13 questions. Ethical approvals were given from the four countries. A total of 3658 individuals participated in the study; however, 2804 responses were included in the analysis and more than one third of participants (n = 1007) were aged between 18 and 25 years old. This study revealed poor awareness and knowledge of the participants about HPV and its vaccine among all four countries' participants with relatively better knowledge among participants from the UAE. Participants who are younger (18-25 years old), have a postgraduate education, have an education or career related to the medical field, or had a Pap smear in the last three years tend to have higher knowledge about the HPV vaccine compared to others. Poor knowledge and awareness findings in this study were expected, considering the lack of public education campaigns regarding the HPV virus coupled with the absence of the HPV vaccination from the national immunization schedule in three participating countries (Jordan, Qatar, and Iraq). It is recommended that there is a need to provide national educational campaigns about the HPV vaccine to the public in all Arab populations.

Prevalence of potentially inappropriate prescribing in older adults in Jordan: Application of the STOPP criteria.

OBJECTIVES: To measure the prevalence of cases of potentially inappropriate prescribing (PIP) for older patients and to identify the risk factors for identified cases of PIP. METHODS: STOPP criteria version 2 were used for identifying cases of PIP for older patients (>65 years) who were admitted to a tertiary hospital in Jordan over a period of 18 months. Data were collected by prospectively reviewing the clinical and prescription records of included patients. Descriptive analysis, univariate analysis and multiple linear regression were used to analyse the results. RESULTS: Upon admission, during hospitalisation and on discharge, 144, 182 and 156 cases of PIP were identified, respectively. There was a statistically significant association between the number of prescribed medications and cases of PIP during the hospital journey (P < .05). CONCLUSION: Inappropriate prescribing of medications is highly prevalent among older patients. Application of validated (STOPP) criteria can help to detect and direct development of interventions to prevent PIP occurrence among older patients.

Role of Pharmacists in COVID-19 Disease: A Jordanian Perspective.

OBJECTIVES: The novel 2019 coronavirus outbreak that first appeared in Wuhan has quickly gained global attention, due to its high transmissibility and devastating clinical and economic outcomes. The aim of this study was to assess the possible roles of Jordanian pharmacists in minimizing the stage of community transmission. METHODS: A cross-sectional survey using Google forms targeting Jordanian pharmacists was conducted during March 2020 and distributed electronically by means of social media. Using the survey tool, we measured the pharmacists' knowledge, the educative activities they perform, and their perceptions regarding undertaking traditional and untraditional roles during the COVID-19 outbreak, as specified by the International Pharmaceutical Federation (FIP). Collected data were analyzed using SPSS version-19. RESULTS: Jordanian pharmacists (n = 449) reported performing various educative activities, and in general, they were knowledgeable about various aspects of the COVID-19 disease (median knowledge score: 20 [range, 13-25]), but certain gaps in knowledge were detected that must be addressed. Pharmacists had positive perceptions about both their traditional and untraditional roles specified by the FIP, the median perceptions score was 4 (range, 1-5). CONCLUSIONS: Jordanian pharmacists can be used to reduce community transmission of the outbreak. However, more actions are required to keep pharmacists knowledgeable with recent disease updates to enable them to perform their tasks effectively during times of crisis.

Effect of an educational intervention on public knowledge, attitudes, and intended practices towards diabetes mellitus: A quasi-experimental study.

AIM: To assess the impact of educational workshops on the knowledge, attitudes, and intended practices (KAP) of the general public towards diabetes in Jordan in terms of symptoms, risk factors, complications, and prevention. METHODS: A pharmacist led educational intervention and Propensity score matching was carried out for a convenience sample to assess Jordanians pre- and post-knowledge, attitudes, and practices towards diabetes mellitus (DM) using a validated questionnaire. RESULTS: Among the 357 invited participants, 335 attended the educational workshops (response rate 93.8%). Prior to intervention, participants showed an overall knowledge score of 16.03 ± 4.88. About half of the participants knew that a sedentary lifestyle is a risk factor for getting DM (n = 172, 51.3%). Following educational intervention, knowledge scores significantly improved to be 21.36 ± 2.11 (P value < .001). A similar finding was obtained for attitude scores, where mean attitude scores significantly improved from 2.74 ± 1.94 before intervention to 4.40 ± 1.87 following the workshop (P value < .001). As for the intended practices, the educational intervention improved the participants' intent to exercise, eat healthy foods, and do annual screening. CONCLUSIONS: Participants' knowledge, attitudes, and intended practices improved following a trained pharmacy led educational intervention. These encouraging results highlight the need for continuous national educational interventions about diabetes provided by trained health care professionals such as pharmacists. Future studies are needed to evaluate the impact of improved knowledge and perceptions on actual long-term practice.

A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population.

This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion-exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1-compartment model with only 1 study describing its pharmacokinetics as 2-compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2-compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.

Public knowledge, attitudes and practices toward diabetes mellitus: A cross-sectional study from Jordan.

AIMS: To assess the knowledge and practices toward diabetes in the Jordanian community. METHODS: This study was conducted as a public based cross-sectional study in different cities in Jordan. A previously published validated questionnaire about knowledge, attitudes, and practices (KAP) toward diabetes mellitus (DM) was translated from the Arabic version and used in this study with very minor modification to be suitable for this study of the Jordanian population. RESULTS: A total of 1,702 participants were recruited in the present study. About half of the participants (53.3%) had good knowledge scores. The respondents' knowledge scores were significantly correlated with attitudes (p < 0.001). The education level (university or higher) and education related to a field were predictors for good knowledge and positive attitudes. About 46.3% of participants had positive attitudes toward the disease. As for practices, 37.7% of participants did not engage in regular exercise while more than half of the study subjects had never checked their blood glucose level on an annual basis. The factors influencing the practice of checking blood glucose level have been investigated. CONCLUSION: This study has highlighted the need for more educational interventions to address negative attitudes and promote healthy lifestyle practices and regular health checks especially in certain subgroups of patients, such as those not having a degree related to the medical field and not having a first-degree relative with DM.

Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute Lymphoblastic Leukemia in Jordan

Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and to compare it with other ethnic groups. Methods: We included 52 ALL childhood cases from King Hussein Cancer Research Center in Jordan. Genotyping of the rs1800460, rs1800462, and rs1142345 SNPs was performed by polymerase chain reaction (PCR) followed by sequencing. Comparisons were made with historical data for controls and for both volunteers and cases from other middle-eastern countries. Results: Mutant TPMT alleles were present in 3.8% (2/52) of patients. Allelic frequencies were 1.0% for both TPMT*B and TPMT*C. None of the patients were heterozygous or homozygous for TPMT*3A or TPMT *2. We did not find statistically significant differences in the distribution of mutant alleles between Jordan and other middle-eastern countries for both healthy volunteers or ALL patients. Conclusions: The overall frequency of TPMT mutant alleles was low and did not exhibit differences compared to other middle-eastern countries, including Jordanian studies assessing TPMT mutant alleles in healthy volunteers. The current results question the value of TPMT genotyping in the Jordanian population.

Noncompliance with surgical antimicrobial prophylaxis guidelines: A Jordanian experience in cesarean deliveries.

BACKGROUND: Surgical site infections are common, especially in developing countries. Nevertheless, up to 60% of surgical site infections can be prevented with appropriate perioperative care, which includes among other measures using suitable surgical antimicrobial prophylaxis (SAP). METHODS: After a short interview with patients and retrospective review of medical charts, compliance with 6 SAP parameters was assessed for appropriateness; those parameters are indication, choice, dose, time of administration, intraoperative redosing interval, and duration of prophylaxis in 1,173 operations. RESULTS: Overall compliance was poor; nevertheless, certain components showed high compliance rates, such as indication and choice of antibiotics. The most frequent error noted was extended administration of prophylactic antibiotics, which was observed in 88.2% of the study population. Emergency operations were associated with a lower risk of noncompliance in administering the correct dose at the correct time (odds ratio, 0.63; 95% confidence interval, 0.47-0.83 and odds ratio, 0.21; 95% confidence interval, 0.14-0.3, respectively). On the other hand, women who underwent an emergency operation were associated with a 6-fold higher risk of receiving prophylactic therapy following surgery. CONCLUSIONS: The present study demonstrated the existence of a surprisingly low level of overall compliance with the hospital-adapted SAP guidelines. Factors implicated in noncompliance were investigated, and the present results create a starting point to improve the current practice.

Surgical site infections following caesarean operations at a Jordanian teaching hospital: Frequency and implicated factors.

Surgical site infections (SSIs) following caesarean surgeries are common. The present study aimed to evaluate the frequency of SSIs following caesareans at Jordan University Hospital during the 30 postoperative days and to identify factors associated with increased SSIs risk. Data regarding the occurrence of SSIs were collected both prospectively via follow-up phone calls and retrospectively via reviewing wound culture results and clinical notes. SSI cases were subsequently determined utilizing predefined criteria. Data relating to possible risk factors of SSIs were collected from patient interviews and hospital records. Risk factors for SSIs were identified via logistic regression. A high rate of SSIs (14.4%) was detected; implicated factors included body mass index ≥36 kg/m2 prior to pregnancy odds ratio (OR) 3.8, 95% confidence interval (95% CI) 1.6-9.4, hospital stay longer than 3.5 days OR 2.3, 95% CI 1.4-3.6, having the operation at a gestational age greater than 40 weeks OR 2.2, 95% CI 1.3-3.9. Receiving a higher weight-adjusted dose of the prophylactic antibiotic cefazolin was associated with lower SSIs risk OR 0.967, 95% CI 0.94-0.99.In conclusion, a high rate of SSIs following caesareans was detected, and modifiable risk factors of SSIs should be incorporated into targeted policies aiming to reduce the rate of SSIs.

Reliability and validity of Arabic translation of Medication Adherence Report Scale (MARS) and Beliefs about Medication Questionnaire (BMQ)-specific for use in children and their parents.

OBJECTIVES: to evaluate the reliability and discriminant validity of Arabic translation of the Medication Adherence Report Scale (MARS) and the Beliefs about Medication Questionnaire-specific (BMQ-specific). METHODS: Having developed Arabic translations of the study instruments, a cross-sectional study was carried out between March and October 2015 in two multidisciplinary governmental hospitals in Jordan. An expert panel monitored the forward and backward translation of the MARS and BMQ. Standard Arabic was used (with no specific dialect inclusion) to allow greater generalisability across Arabic speaking countries. Once the Arabic translations of the questionnaires were developed they were tested for consistency, validity and reliability on a group of children with chronic diseases and their parents. RESULTS: A total of 258 parents and 208 children were included in the study. The median age of participated children and parents was 15 years and 42 years respectively. Principle component analysis of all questionnaires indicated that all had good construct validity as they clearly measured one construct. The questionnaires were deemed reliable based on the results of Cronbach alpha coefficient. Furthermore, reliability of the questionnaires was demonstrated by test-retest intraclass correlation coefficients (ICC) which ranged from good to excellent for all scales (ICC>0.706). The Pearson correlation coefficient ranged from 0.546-0.805 for the entire sample which indicated a significant moderate to strong positive correlation between MARS and BMQ items at time 1 and 2. Reported adherence was greater than 59% using MARS-children and MARS-parents scales, and was correlated with beliefs in necessity and independent of the concerns regarding medications. CONCLUSION: The Arabic translations of both BMQ and MARS for use in children and their parents have good internal consistency and proved to be valid and reliable tools that can be used by researchers in clinical practice to measure adherence and beliefs about medications in Arabic speaking patient populations.

Potential interaction between zinc ions and a cyclodextrin-based diclofenac formulation.

Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPßCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPßCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPßCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPßCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPßCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPßCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPßCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPßCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPßCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPßCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.

Potential interaction between zinc ions and a cyclodextrin-based diclofenac formulation.

Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPßCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPßCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPßCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPßCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPßCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPßCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPßCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPßCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPßCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPßCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.