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Khezar Hayat
University of Veterinary and Animal Sciences, Pakistan
Fahad Saleem
University of Balochistan, Pakistan
Sreekanth K. Mallineni
Department of Preventive Dental Sciences, Faculty of Dentistry at Al Zulfi, Majmaah University, Saudi Arabia
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Front. Med., 29 April 2022
Sec. Regulatory Science
Volume 9 - 2022 | https://doi.org/10.3389/fmed.2022.816320
Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities
Tauqeer Hussain Mallhi1*, Abdullah Salah Alanazi1,2, Yusra Habib Khan1*, Nasser Hadal Alotaibi1, Muhammad Salman3, Abdulaziz Ibrahim Alzarea1, Salah-Ud-Din Khan4, Nabil K. Alruwaili5, Alaa Salah Alenazi6, Ahmed D. Alatawi1, Zafar Iqbal7, Muhammad Hammad Butt8 and Muhammad Shahid Iqbal9*
1Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
2Health Sciences Research Unit, Jouf University, Sakaka, Saudi Arabia
3Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
4Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
5Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
6Riyadh Second Health Cluster, Ministry of Health, Rayyad, Saudi Arabia
7Department of Pharmaceutical Services, Armed Forces Hospital, King Abdulaziz Airbase, Dhahran, Saudi Arabia
8Department of Clinical Pharmacy, Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan
9Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
Background: Despite a series of "boxed warnings" (BWs) issued by the US Food and Drug Administration (FDA), fluoroquinolones (FQs) are among the most prescribed antibiotics across the world. Moreover, few studies demonstrated that BW of FQs had less or no impact on prescribing patterns among healthcare professionals (HCPs), which might be attributed to the lack of knowledge toward such warnings. Since FQs contribute to a major proportion of antimicrobial prescriptions in the Kingdom of Saudi Arabia (KSA), this study aimed to ascertain the extent of knowledge toward safety profile, use, and BW of FQs among HCPs working in the KSA.
Methods: This cross-sectional study (May–August 2021) was conducted among HCPs working in KSA through a validated questionnaire. The HCPs were requested to identify the indications, adverse effects (AEs), and BW of FQs. The knowledge score (out of 40) was estimated among participants, and its association with demographics was ascertained through the chi-square test, Student's t-test, or Mann-Whitney U-test and one-way ANOVA, or Kruskal-Wallis test, where appropriate.
Results: Of the 573 participants (age: 36.1 ± 10.6 years, men: 59.7%), 262 (45.8%) were prescribers reporting frequent use of ciprofloxacin, levofloxacin, and ofloxacin. One-fourth (25.6%) of the prescribers did not recognize nalidixic acid as an agent from FQs class. About 60% of participants correctly identified the mechanism of action of FQs. The average knowledge score was 14.8 ± 6.4, where only 21.5% of respondents scored ≥50%. The average knowledge score for indications, AEs, and BW domains was 5.29 ± 3.05, 6.17 ± 4.05, and 2.3 ± 1.5, respectively. Only 75 (13.1%) participants recognized half of the BW, and 38.6% of participants identified at least one warning. The HCPs aged >40 years (p = 0.043), having non-Saudi's nationality (p < 0.001), working in Riyadh and Eastern regions (p < 0.001), having pharmacy and medicine disciplines (p < 0.001), practicing in public sectors (p = 0.004), and having more than 10 years of experience (p < 0.001) were significantly associated with high knowledge score.
Conclusion: This study demonstrates the unsatisfactory knowledge toward safety profile, use, and BW of FQs among HCPs which may put patients at increased risks of AEs. The knowledge score differed among various socio-demographic groups. There is a dire need to initiate the antimicrobial-focused educational campaigns among HCPs regardless of their specialties and methods to improve education and disseminate FDA warnings in practice.
Antibiotics contribute to a substantial proportion of prescriptions for both inpatients and outpatients (1). Approximately, half of the patients admitted to the hospital receive antibiotics, particularly for pneumonia and urinary tract infection (UTI) (2). According to an estimate, about 20% of antibiotic encounters are associated with adverse effects (AEs) (3). Moreover, the lack of drug-related knowledge is found to be significantly correlated with medication errors (MEs). Fluoroquinolones (FQs) are widely used against various bacterial infections and are associated with severe AEs and antimicrobial resistance (2). The US Food and Drug Administration (FDA) has announced several "boxed warnings" (BWs) against FQs and limited their use according to the risks vs. benefits ratio. The first BW against FQs was issued in 2008 that included potentially permanent AEs of tendons, muscles, joints, nerves, and central nervous system (CNS). Subsequently, a series of warnings were announced, including worsening of myasthenia gravis (February 2011), irreversible peripheral neuropathy (August 2013), limiting the use of FQs for complicated infections (November 2015), risks of hypoglycemic coma, mental health AEs (July 2018), and aortic aneurysm (December 2018) (4, 5). It is pertinent to mention that AEs from FQs leading to emergency department visits occur at a rate of 9.2 per 10,000 prescriptions, even higher than macrolides and cephalosporins (6). Current antimicrobial guidelines also discourage the use of FQs as the first-line agents unless benefits overweigh the risks (7).
Despite the series of BW and a substantial number of evidence on toxicities, FQs are still prescribed irrationally in various healthcare settings (7). Although the declining trend of FQs prescriptions following the BW has been observed in a few studies from the United States (8, 9), still these warnings did not impact the prescribing pattern in various countries around the world (5, 7, 10–12). Since the violation of BW may pose serious health hazards to the patients, it has been observed that about 7 of 1,000 outpatients received prescriptions violating the BW, and a substantial number of these patients are at risk of developing serious AEs (13). The FQs are frequently used for various infections in the Kingdom of Saudi Arabia (KSA) (14), where ciprofloxacin is frequently prescribed among the outpatients (15–17). In addition, the widespread use of ciprofloxacin in KSA has been observed among all patients regardless of their age (18). The recent estimates from KSA showed that the FQs accounted for 5% of antibiotics prescribed in the emergency department, 22% of prescriptions for UTIs, 19% of antimicrobial prescriptions in ambulatory care, and 19% of antibiotic prescriptions in outpatient departments (1). The excessive or irrational use of FQs might be associated with the lack of awareness and knowledge among healthcare professionals (HCPs) regarding the safety profile, prescribing guidelines, and BW. Ascertaining the level of knowledge toward FQs among HCPs is of paramount importance to design and implement the targeted educational interventions and to preserve the utility of these drugs. In this context, this study was aimed to evaluate the awareness and extent of knowledge among HCPs (e.g., physicians, pharmacists, dentists, and nurses) toward safety profile, BW, and use of FQs. The findings of this study will underscore and strengthen the need for continued education among HCPs along with system-based interventions to reduce the inappropriate prescribing of these drugs.
This study was approved by the Local Committee of Bioethics (LCBE) at Jouf University, KSA (Ref. 05-08-42). Informed consent was obtained from all participants. All the data were anonymized before analysis.
Study Design and Location
This cross-sectional quantitative survey was conducted among HCPs working in the four provinces of KSA. The survey interviews were administered between May 2021 and August 2021. The four provinces included in this study were Riyadh, Eastern, Al-Jouf, and Northern border. The first two provinces are developed regions in the country, while the last two provinces are considered as least developed regions with limited healthcare facilities. Data collection from these four provinces was intended to ascertain the knowledge among HCPs across regions with maximum and limited health facilities.
The HCPs (e.g., physicians, pharmacists, nurses, and dentists) working in KSA were included in this study. The participants who were willing to participate and have active jobs with at least 1 year of working experience were included in this study. Only participants with an active license of practice from the health commission were included. Healthcare students, professionals having <1 year of experience, and those who refused to participate were excluded from the study. The study flow diagram for this study is presented in Figure 1.
Figure 1. Study flow diagram.
Validation and Reliability of Study Instrument
A 62-item questionnaire comprised of five sections was constructed under the opinions of experts from four health specialties (i.e., physicians, hospital/community pharmacists, dentists, and nurses). Following the face and content validity, the study instrument was administered in a small targeted sample of HCPs (n = 60) having equal distribution of all four specialties (15 participants from each specialty). The internal consistency of the study tool was assessed by alpha value which was found at 0.821, indicating the adequacy and reliability of the tool to evaluate the study objectives.
Components of Study Instrument
All five sections in the study instrument had closed-ended questions. "Introduction" section had 9 items on demographics, including age, gender, qualification, working sector, experience, and nationality. "Methodology" section comprised names of 13 drugs from FQs class and only prescribers (e.g., physicians and dentists) were asked to respond their prescribing frequency of these drugs on a four-item scale (i.e., no use, frequent use, less frequent use, and new drug). Moreover, this section had one multiple-choice knowledge question on the mechanism of action of FQs, where the correct answer (DNA gyrase/topoisomerase IV inhibitor) was scored "1;" otherwise, scored "0." "Results" section had a list of twelve indications of FQs. All the HCPs were asked to respond to these questions on a scale of "Yes," "No," and "Not Sure." Since FQs are prescribed for all listed indications, the option "Yes" was scored "1"; otherwise, scored "zero." Similarly, "Discussion" section had a list of eighteen AEs of FQs, and the HCPs were asked to respond each on a scale of "Yes," "No," and "Not Sure." As these AEs are associated with the use of FQs, the participants who selected "Yes" were scored "1;" otherwise, scored "zero." "Conclusion" section had nine items evaluating the participant's awareness and knowledge toward the BW of FQs. The respondents were requested to answer whether they know that the most recent BW against FQs was issued in 2018 by the FDA. The option "Yes" was scored "1;" otherwise, scored "zero." In addition, "Conclusion" section had a list of eight BWs of FQs, and HCPs were asked to recognize each on a scale of "Yes," "No," and "Not Sure." Since all these BWs are announced by the FDA from 2008 to 2018, the option "Yes" was scored "1;" otherwise, scored "zero." Taken together, this study instrument had 40 items assessing the knowledge of HCPs toward the mechanism of action, indications, AEs, and BW of FQs, yielding a cumulative knowledge score of 40. The average knowledge score was also estimated for each item. Considering the fact that knowledge items in the study tool were in detail and had a high difficulty level, a 50% score was stratified as an "appropriate knowledge."
Using a convenient sampling technique, all the authors were asked to contact the HCPs from public or private health facilities, including hospitals and pharmacies, in four provinces of KSA. Informed consent was obtained from each participant before administering the survey. A brief overview was given to HCPs on the safety profile of FQs after collecting the questionnaire. All the questionnaires were checked for completeness and transferred to the Microsoft spreadsheet for cleaning purposes.
All the data were subjected to Statistical Package for the Social Sciences (SPSS version 22.0). The continuous variables were presented as mean with standard deviation or median with interquartile range (25–75%). The categorical data were described in frequencies (N) along with proportion (%). The mean knowledge score across various healthcare specialties (e.g., physicians, pharmacists, dentists, and nurses) was compared by one-way ANOVA or Kruskal-Wallis test, where appropriate. Moreover, the post-hoc analysis was also performed to ascertain the specific differences of knowledge score between these specialties. The Student's t-test or Mann-Whitney U-test was used to compare the knowledge score among demographics having two categories (bivariate), i.e., age, gender, working sector, and Saudi vs. Non-Saudi. In contrast, the knowledge score among demographics having more than two categories was compared through one-way ANOVA or Kruskal-Wallis test, where appropriate. In addition, we performed binary logistic regression to determine the factors or predictors (e.g., independent variables: age, gender, nationality, field of education, working location and sector, level of education, and working experience) associated with participants having knowledge scores ≥50% (dependent variable). The significant variables from the univariate analysis were considered for multivariate regression. These data were presented as odds ratio (OR) with 95% confidence interval (CI). A significance level of 0.05 was considered throughout the statistical analysis.
Characteristics of the Study Participants
Out of the 615 HCPs who were approached, 573 HCPs were included in the final analysis, yielding a response rate of 93.1% (Figure 1). The mean age of the participants was 36.1 ± 10.6 years [median (interquartile range): 34 (17)] with male preponderance (59.7%). Majority of the respondents were Saudis (64.9%) followed by Egyptians (17.3%). The study population was physicians (40.1%), pharmacists (38.2%), dentists (5.6%), and nurses (16.1%). About 80% of respondents were working in the public sectors, including primary, secondary, and tertiary care hospitals, while 19.9% were from private hospitals and community pharmacies. The demographic features of the study participants are described in Table 1.
Table 1. Demographics of study participants (n = 573).
Prescribing Pattern of FQs
The prescribing pattern of FQs was only evaluated among prescribers (n = 262/573, 45.8%). Ciprofloxacin (64.5%), levofloxacin (39.3%), ofloxacin (27.5%), and moxifloxacin (24.8%) were most prescribed FQs by the physicians and dentists. More than half of the prescribers reported that they do not prescribe gemifloxacin, delafloxacin, norfloxacin, gatifloxacin, nalidixic acid, and cinoxacin. Alarmingly, a large number of prescribers reported that trovafloxacin (42.7%), sparfloxacin (37%), cinoxacin (33.6%), lomefloxacin (30.5%), gatifloxacin (26%), nalidixic acid (25.6%), and delafloxacin (23.7%) are new drugs, and they were not aware of them before administering this survey (Table 2).
Table 2. Prescribing pattern of fluoroquinolones among prescribers (physicians and dentists), N = 262.
Participant's Knowledge Regarding Indications and AEs of FQs
The average knowledge score for indications was 5.29 ± 3.05 (Table 3). The highest score was achieved by the physicians followed by pharmacists. Inter-professional comparisons showed that physicians and pharmacists scored significantly higher than nurses (p < 0.001 and p = 0.006, respectively), but inferences were insignificant when their scores were compared with dentists (Table 4). The most commonly reported indications were UTIs (77%) followed by bacterial eye infection (63.4%), typhoid fever (54.1%), respiratory tract infections (RTIs) (50.3%), gonorrhea (49%), otitis externa (44.3%), and skin and soft tissue infections (SSTIs) (42.2%). About one-fourth of the participants reported that FQs are not indicated for surgical prophylaxis, meningococcal meningitis, and SSTIs. More than half of the study population were not sure that FQs are indicated for anthrax and fistulating Crohn's disease (Table 3). Although FQs are prescribed for all listed twelve indications, none of the respondents selected all from the list.
Table 3. Participants' knowledge toward indications and adverse effects of fluoroquinolones.
Table 4. Comparison of knowledge score toward indications and adverse effects across different specialties of healthcare professionals.
The average knowledge score for AEs was 6.17 ± 4.05 (Table 3). The highest score was achieved by the pharmacists followed by physicians. Inter-professional comparisons showed that pharmacists scored significantly higher than dentists (p = 0.031) and nurses (p = 0.030), but inferences were insignificant when their scores were compared with physicians. The most commonly reported AEs were nausea or vomiting (80.3%), diarrhea (71.9%), photosensitivity or skin reactions (47.8%), headache (46.6%), dizziness (44.3%), musculoskeletal pain (43.6), arthropathy (37.3%), renal impairment (37.2%), and cardiovascular problems (30.9%) (Table 3). More than half of the respondents were not sure that hepatic impairment, asthenia, trouble sleeping, loss of appetite, sensation abnormalities, altered smell sensation, seizures, dyspnea, Clostridium difficile infections, and cardiovascular problems are the AEs of FQs. Although the use of FQs is associated with all of these AEs, none of the respondents selected them all from the list. Alarmingly, 217 (37.9%) respondents did not identify the correct mechanism of action of FQs (average score: 0.62 ± 0.49), where most of the respondents were dentists (81.2%) and nurses (89.1%).
Participants' Awareness and Knowledge Toward BWs of FQs
The majority of the participants (n: 356, 62.1%) were not aware that the most recent BW on FQs was issued in 2018. The participants were asked to identify the BW from the list of eight warnings issued by the FDA. The aortic aneurysm was recognized by most of the respondents (45.9%) followed by tendinitis or tendon rupture (38.7%) and hypoglycemia (36.5%) (Table 5). Alarmingly, only 5 participants (0.9%) identified all eight BW, while 4 (0.7%) and 2 (0.3%) participants recognized 7 and 6 warnings, respectively. Only 75 (13.1%) respondents recognized half of the BW from the list. The proportion of respondents who identified at least one warning was 38.6% (Figure 2). The average knowledge score for BW was 2.3 ± 1.5. The knowledge score for BW among physicians significantly differed (p = 0.028) from pharmacists and nurses, but not from dentists (p = 0.896). These findings showed that prescribers had a higher knowledge score for BW than non-prescribers.
Table 5. Participant's knowledge toward boxed warnings on fluoroquinolones.
Figure 2. The frequency distribution on the selection of boxed warnings (BWs) against FQs among study participants.
Association of Demographics With Knowledge Score
The total knowledge score among HCPs was 14.8 ± 6.4, where only 21.5% had appropriate knowledge (score ≥ 50%). Of these, most of the respondents were working in public sectors (n = 110, p = 0.003) and had working experience of >10 years (n = 63, <0.001). The score was significantly higher among HCPs with age >40 years (p = 0.039), Indian nationals (p = 0.001), expatriates (p < 0.001), HCPs working in Riyadh and Eastern regions, physicians and pharmacists (p < 0.001), and those who were practicing in public sectors (p = 0.003). In addition, the HCPs having working experience of <5 years had significantly (p < 0.001) lower knowledge scores than those with working experience of >5 years. However, knowledge scores did not differ significantly among the gender and education levels of the participants. Table 6 indicates the average knowledge score of demographic parameters along with Tukey's honestly significant difference (HSD) post-hoc analysis. The adjusted logistic regression analysis found that the HCPs working in Riyadh (OR: 7.7) and Eastern region (OR: 5.8), and those with working experience of 5–10 years (OR: 2.7) and >10 years (OR: 2.4) were associated with the propensity of achieving 50% or above knowledge score (Table 7).
Table 6. Predictors of achieving ≥50% knowledge score.
Table 7. Association of participant's demographics with knowledge score.
To the best of our search, this is the first large-scale study to explore the awareness and extent of knowledge about safety profile, usage, and FDA BWs of FQs among HCPs in the KSA. The "BWs." formerly known as "black box warnings," are the most serious safety-related warnings instituted by the FDA in 1979. These warnings are intended to inform the HCPs regarding cautious decision-making during the treatment. Alarmingly, more than 600 medications have BW and about 40% of patients receive at least one such drug. The continuous increase in the number of BW warrants HCPs to remain up to date on the safety profile of drugs. However, recent data indicate that a series of BW against FQs did not impact the prescribing pattern of these drugs among HCPs across the world (2, 5, 7, 10–12). The non-adherence to BW among prescribers might be attributed to the lack of knowledge of such warnings. Smollin et al. reported that physicians in emergency and pediatric departments had limited knowledge of medications with BW or the content of such warnings. The authors reported that only 36.3% of physicians had correctly identified the drugs with BW from the list of 15 medications (19). The violation of BW has also been observed in another study where 7 of 1,000 patients received a prescription having drugs with BW (13).
The FQs belong to the list of the world's most commonly prescribed antibiotics. In 2014, FQs were marked as the fourth most commonly prescribed class of antibiotics in the United States (20). In KSA, the use of FQs accounted for up to 19% of antimicrobial prescriptions in ambulatory care and outpatient departments (1). The safety of FQs is under investigation for the last two decades amid several reports on their association with disabilities among users (20). In this context, it was imperative to ascertain the knowledge of HCPs regarding the safety profile of these drugs in KSA, specifically when FQs prescription rates are very high in the country.
Alarmingly, HCPs indicated unsatisfactory knowledge in this study, where only one-fifth of participants have achieved ≥50% knowledge score. The results are consistent with the findings of another study where only one-third of physicians were able to identify the drugs with BW (19). These findings necessitate the need for urgent measures from health authorities in terms of educational campaigns and antibiotic stewardship programs (ASP).
About 46% of the participants in this study were prescribers, and ciprofloxacin was reported as the most prescribed drug followed by levofloxacin. Alarmingly, a large proportion of the prescribers were not aware of certain drugs from FQs class, such as trovafloxacin, sparfloxacin, cinoxacin, lomefloxacin, gatifloxacin, nalidixic acid, and delafloxacin. Our analysis showed that prescribers were only familiar with ciprofloxacin, levofloxacin, and ofloxacin. Nalidixic acid, discovered in 1962 and gained its clinical importance in 1967, was the first agent from FQs class (21). However, 25% of prescribers did not recognize this drug as a member of FQs class, indicating the lack of basic concepts which should be considered as a serious concern for the healthcare authorities. These results urge the need for continuous education programs emphasizing the introduction and core concepts of antimicrobials.
Our findings indicate that the knowledge of the HCPs for indications and AEs of FQs was unsatisfactory. The interprofessional comparisons showed that physicians and pharmacists had better knowledge of indications and AEs of FQs as compared to dentists and nurses. The UTIs were reported by most of the participants as indications of FQs, followed by bacterial eye infection and typhoid fever. It is pertinent to mention that a large proportion of the participants reported that surgical prophylaxis, meningitis, and SSTIs are not indications for FQs. A single dose of ciprofloxacin (500 mg) before the procedure is an effective prophylactic regime (22). In addition, the clinical practice guidelines for antimicrobial prophylaxis in surgery also suggest the use of FQs within 120 min of the procedure (23). Similarly, the efficacy of ciprofloxacin has been well-established for the treatment or prophylaxis of meningococcal meningitis (24). However, the ciprofloxacin-resistant strain of Neisseria meningitidis has been evolved in recent years (25). Moreover, the FQs have proved as a promising addition to the current armamentarium against SSTIs with an additional benefit of dosage convenience (26). The HCPs were also asked to select the AEs of FQs from the list of eighteen. The most commonly reported AEs were nausea, vomiting, diarrhea, headache, dizziness, skin reactions, and musculoskeletal pain. However, a large proportion of HCPs were not able to identify other AEs. The use of FQs is broadly linked with AEs of all major organ systems, including cardiovascular (18.6%), central nervous (11.9%), peripheral nervous (6.8%), gastrointestinal (15.3%), musculoskeletal (6.8%), and dermatological (20.3%) systems (27, 28). A recent umbrella review investigated the relationship of FQs with emerging AEs through pooling the data from various meta-analyses. The authors ascertained that the use of FQs is markedly associated with neuropsychiatric toxicities and cardiovascular events, including aortic dissection, tendon rupture, and retinal detachment (29). In our study, about 80% of participants were either disagreed or not sure that asthenia, trouble sleeping, altered smell sensation, loss of appetite, hepatic impairment, sensation abnormalities, seizures, and dyspnea are the AEs of the FQs. It is pertinent to mention that all the listed AEs in the study tool are present in product literature or British National Formulary and categorized as common or uncommon side effects (30). Taken together, this study underscored that the HCPs lack sufficient information on the use and safety of the FQs. These findings trigger the need for regular training in hospitals and community pharmacies. In addition, these training campaigns could be considered a prerequisite for licensure renewal to ensure that the HCPs have up-to-date information regarding optimal disease management.
Our results underscored poor participants' knowledge toward the BW, reflected by the finding that 62% of HCPs were not aware that the most recent BW against FQs was issued in 2018. The aortic aneurysm was selected by most of the HCPs (45.9%) as a BW of FQs. Of the list of eight, half of the BWs were selected by only 13% HCPs, while one-third of participants identified at least one warning. Unfortunately, we did not come across any study evaluating the knowledge of BW of FQs among HCPs for direct comparison with our findings. However, few studies have evaluated the extent of awareness and recognition of BW among HCPs, regardless of the drugs. These studies have shown insufficient knowledge of physicians and pharmacists toward the BW (19, 31). Other studies investigating the knowledge of BW among pharmacy and medical students reported a low level of knowledge which was directly proportionate to their study years (32, 33). Since lack of information regarding BW may put patients at increased risks, the FDA along with other health authorities should adopt an appropriate mechanism of communication for such warnings and should also develop systematic feedback to ensure that all BW are communicated to HCPs across the world. Although we did not find any study with similar objectives assessed in this study, other recent investigations have reported unsatisfactory knowledge among HCPs toward the reporting of adverse events and basics of pharmacovigilance (34–37).
The exact mechanisms underlying the serious AEs precipitated by the FQs are under debate. However, FQs-induced mitochondrial toxicities due to oxidative stress across a range of mammalian cells are considered the most plausible pathogenesis for serious AEs (20).
Though this study reported a considerably low level of knowledge among all categories of HCPs, the knowledge score was comparatively higher among physicians and pharmacists than dentists and nurses. Similarly, the HCPs working in public sectors (hospitals) had higher knowledge scores than those working in private sectors (e.g., private hospitals and community pharmacies). In addition, the working experience was positively associated with the knowledge among study participants. Interestingly, the HCPs working in Riyadh and Eastern regions demonstrated better knowledge as compared to those from Al-Jouf and Northern Border regions. The regional disparities in knowledge score might be attributed to the preference of competent professionals to pursue their jobs in Riyadh and Eastern regions, as these two regions are more developed and have the state-of-the-art health facilities. However, the Northern border and Al-Jouf regions are least developed with limited health facilities, and the HCPs from these regions may have fewer opportunities for continuous learning (38). Where this study urges the need for educational campaigns for HCPs, at the same time, our results underscored the targeted groups of HCPs requiring dire attention of the health authorities. These factors must be considered if health authorities decide to initiate targeted or selected educational programs.
Our analysis carries a few limitations which should be considered while interpreting the results. We used a self-report as the main method of inquiry, which may have introduced recall bias. The findings of this study are, however, limited to HCPs from the four provinces of KSA and may not be generalized in a broader context. However, the results can be implicated to other provinces as study participants were included from developed, developing, and underdeveloped provinces of the KSA. The proportion of responses from dentists and nurses was comparatively less which may bias the findings toward clinicians and pharmacists. This shortcoming (selection bias) underscores the consideration of equal response proportion in future investigations. The knowledge evaluation in this study was based on difficult and detailed items, and there is a high propensity that questions or items of a medium-level difficulty may yield better scores among participants. The choice of indications and AEs included in the survey could be less familiar to some of the participants as HCPs may only know the indications or AEs which are specific to certain agents of FQs approved in their health facilities. However, these indications and AEs are explicitly included in the product's leaflets and popular tertiary information sources. Moreover, the HCPs may feel reluctant to answer the questions honestly amid the threats of professional self-esteem, reputation, and perceiving them as incompetent. We aim to mitigate such bias by administering the survey in an anonymous fashion. In addition, we requested the participants to avoid any information source to get the answer in order to ensure the assessment of their inherent knowledge. Nevertheless, this study is strengthened by the first large-scale analysis including diverse categories of the HCPs from various disciplines. The findings of this study will serve to design and implement medication-related knowledge initiatives for HCPs by the ministry of health and Saudi FDA (SFDA).
This study underscored that HCPs working in KSA have inadequate knowledge toward safety profile, use, and BW of FQs which may put patients at increased risks of adverse events. Interprofessional comparisons showed that physicians and pharmacists have higher knowledge scores than dentists and nurses. In addition, subgroup analysis indicated a significant association of age, nationality, working location or sector, country of graduation, field of education, and working experience with the knowledge score. There is a dire need to initiate antimicrobial-focused educational campaigns for HCPs. Moreover, methods to improve education and disseminate FDA warnings in practice are needed. Our findings also necessitate the need for more comprehensive and elaborative surveys to ascertain the familiarity of HCPs with the safety profiles of the high-risk drugs.
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
The studies involving human participants were reviewed and approved by Local Committee of Bioethics, Jouf University. The patients/participants provided their written informed consent to participate in this study.
THM, ASAla, YHK, and NHA: conception or design of the work. MS, AIA, S-U-DK, ADA, NKA, and ASAle: analysis or interpretation of data for the work. MS, AIA, ADA, NKA, ASAle, and MSI: data collection. YHK, MS, ZI, S-U-DK, and MHB: drafting the work. THM, ASAle, NHA, ASAla, and MSI: revising the manuscript critically for important intellectual content. All authors provided approval for publication of the content and are accountable for all aspects of the work and contributed to the article and approved the submitted version.
The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research Grant No. DSR2020-04-2565.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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Keywords: anti-infective agents, antibiotics, fluoroquinolones, boxed warnings, United States Food and Drug Administration (FDA), safety, adverse effects, antibiotic stewardship
Citation: Mallhi TH, Alanazi AS, Khan YH, Alotaibi NH, Salman M, Alzarea AI, Khan S-U-D, Alruwaili NK, Alenazi AS, Alatawi AD, Iqbal Z, Butt MH and Iqbal MS (2022) Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities. Front. Med. 9:816320. doi: 10.3389/fmed.2022.816320
Received: 16 November 2021; Accepted: 07 March 2022;
Published: 29 April 2022.
Khezar Hayat, University of Veterinary and Animal Sciences, Pakistan
Fahad Saleem, University of Balochistan, Pakistan
Sreekanth Kumar Mallineni, Majmaah University, Saudi Arabia
Copyright © 2022 Mallhi, Alanazi, Khan, Alotaibi, Salman, Alzarea, Khan, Alruwaili, Alenazi, Alatawi, Iqbal, Butt and Iqbal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Tauqeer Hussain Mallhi, tauqeer.hussain.mallhi@hotmail.com; thhussain@ju.edu.sa; Yusra Habib Khan, yusrahabib@ymail.com; yhkhan@ju.edu.sa; Muhammad Shahid Iqbal, m.javed@psau.edu.sa
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Medication Errors in the 21st Century: Extent, Causes, and Interventions
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text:
How the Great Reset Was First Thought Up by the Original Proselytizer of Totalitarianism and the Father of Neo-Conservatism
Cynthia Chung
© Photo: Flickr/Levan Ramishvili
Burnham describes how it is necessary that the masses believe the revolution to be beneficial to them, when in reality it is just to transition from one ruling class to the other.
"[James Burnham is] the real intellectual founder of the neoconservative movement and the original proselytizer, in America, of the theory of 'totalitarianism.'"
– Christopher Hitchens, "For the Sake of Argument: Essay and Minority Reports"
In the first part of this two part series, I went over how the roots for the World Economic Forum's Great Reset can very clearly be traced back to 80 years ago, when an American, former high-level Trotskyist who later went on to become the intellectual founding father of neo-conservatism, James Burnham, wrote a book on his vision for "The Managerial Revolution." And that it was in fact, these ideologies of Burnham that triggered Orwell to write his "1984".
From Trotsky's Permanent Revolution to Global Fascism: Burnham's Recruitment into Allen Dulles' OPC
"Burnham was a consultant to OPC on virtually every subject of interest to our organization. … He had extensive contacts in Europe and, by virtue of his Trotskyite background, was something of an authority on domestic and foreign Communist parties and front organizations."
– E. Howard Hunt's Memoirs (Watergate 'plumber' and famous CIA dirty trickster)
It is understandably the source of some confusion as to how a former high level Trotskyist became the founder of the neo-conservative movement; with the Trotskyists calling him a traitor to his kind, and the neo-conservatives describing it as an almost road to Damascus conversion in ideology.
However, the truth of the matter is that it is neither.
That is, James Burnham never changed his beliefs and convictions at any point during his journey through Trotskyism, OSS/CIA intelligence to neo-conservatism, although he may have back-stabbed many along the way, and this two-part series will go through why this is the case.
As I discussed in part one, Burnham had by May 21, 1940 officially resigned from the "'philosophy of Marxism,' dialectical materialism," and by 1941 achieved fame and fortune with his book "The Managerial Revolution."
Burnham, made clear in this book, that he was not only very ready to accept the outcome of a victorious Nazi Germany (this was his conclusion at the time), but that this was both a natural and an inevitable course that the entire world would have no choice but to follow. Burnham made no qualms that Nazi Germany was considered by himself as the most superior form of his concept of a "managerial society."
He would go on to state in his "The Managerial Revolution" that the Russian Revolution, WWI and its aftermath, the Versailles Treaty gave final proof that capitalist world politics could no longer work and had come to an end. He described WWI as the last war of the capitalists and WWII as the first, but not last war, of the managerial society. And, that many more wars would have to be fought after WWII before a managerial society could finally fully take hold.
This ongoing war would lead to the destruction of sovereign nation states, such that only a small number of great nations would survive, culminating into the nuclei of three "super-states", which Burnham predicted would be centered around the United States, Germany and Japan. He goes on to predict that these super-states will never be able to conquer the other and will be engaged in permanent war until some unforeseeable time.
He predicted that Russia would be broken in two, with the west being incorporated into the German sphere and the east into the Japanese sphere. (Note that this book was published in 1941, such that Burnham was clearly of the view that Nazi Germany and fascist Japan would be the victors of WWII.) Burnham states that "sovereignty will be restricted to the few super-states."
This future of "forever wars" amongst a few super-states has obvious remnant influences from Trotsky's "Permanent Revolution" militant ideology.
This was also just the kind of thing Allen Dulles was talent searching for.
During the 1920s and 1930s both Dulles brothers acted as significant players in the "Rearming of Germany by Night," largely organised through their law firm Sullivan & Cromwell, which operated as the center of an intricate international network of banks, investment firms, and industrial conglomerates that helped rebuild Germany after WWI.
The German representative of the Dulles brothers' law firm was Dr. Gerhardt Alois Westrick, who acted simultaneously as a financial agent for Hitler and an Abwehr spymaster in the United States. In January 1940 Westrick was given the title of Wehrwirtschaftsführer for his contributions to the war effort. He was then assigned by von Ribbentrop to undertake a mission to the United States to meet American business leaders and gain their support for Germany. (1)
Allen Dulles was also a director of the J. Henry Schroder bank, whose German chairman, SS General Baron Kurt von Schroder, was one of the main assistants to Schacht in organizing the fund that financed Hitler's 1933 rise to power. Allen Dulles remained on the board of the Schroder Bank until 1944, well after he had taken his post as chief of the OSS in Switzerland.
Allen Dulles also worked very closely with Thomas McKittrick, an old Wall Street friend who was president of the Bank for International Settlements (BIS). Five of its directors would later be charged with war crimes, including Hermann Schmitz, one of the many Dulles' law clients involved with BIS. Schmitz was the CEO of IG Farben the chemical conglomerate that became notorious for its production of Zyklon B, the gas used in Hitler's death camps, and for its extensive use of slave labour during the war. (2)
David Talbot writes in his "The Devil's Chessboard":
"The secretive BIS became a crucial financial partner for the Nazis. Emil Puhl – vice president of Hitler's Reichsbank and a close associate of McKittrick – once called BIS the Reichsbank's only 'foreign branch.' BIS laundered hundreds of millions of dollars in Nazi gold looted from the treasuries of occupied countries."
Allen Dulles was first recruited into the OSS (Office of Strategic Services) in October 1941, a forerunner of sorts of the CIA. During most of his work with the OSS he was stationed in Bern, Switzerland, where he was later found to be implicated in a number of incredibly suspect activities that would raise concern that his allegiance and loyalty was really with Nazi Germany.
Such activities included sabotaging the success of operations by American intelligence and engaging in secret negotiations on behalf of individuals directly or indirectly affiliated with the Nazi Party, one of the most well-known incidents of this is Dulles' curious conduct during Operation Sunrise, aka the Bern incident, in favour of SS Gen. Kurt Wolff.
[In a previous three-part series paper I go through further details of the fascist roots of the CIA, and how Allen Dulles, and his brother Foster Dulles, play instrumental roles in all of this.]
The Office of Policy Coordination (OPC) was created as a department of the CIA in 1948, but operated as a rogue operation until Oct. 1950. Many of the agency's recruits were "ex" Nazis. (3)
OPC was preceded by the Special Procedures Group (SPG), whose creation in March 1948 had been authorized in December 1947 with President Harry Truman's approval of the top-secret policy paper NSC 4-A.
NSC 4-A was a new directive to cover "clandestine paramilitary operations, as well as political and economic warfare," this provided the authorization for the intervention of the CIA in the Italian elections of April 1948 (in favour of Italy's Christian Democrats, which hid thousands of fascists in its ranks, over what would have been the election of the Communist Party of Italy, who were admired for leading the fight against Mussolini). This success in tampering with the Italian elections demonstrated that psychological/political warfare could be the key to "winning" the Cold War.
When OPC was created, it inherited all of SPG's resources.
On June 18, 1948, NSC 4-A was replaced by NSC 10/2, creating the Office of Policy Coordination (OPC). NSC 10/2 was the first presidential document which specified a mechanism to approve and manage covert operations, and also the first in which the term "covert operations" was defined.
George F. Kennan, the director of the State Department's Policy Planning Staff, was the key figure behind the OPC's creation. (4) Frank Wisner, who worked as a Wall Street lawyer for the law firm Carter, Ledyard & Milburn, was former OSS and very close to Allen Dulles. He would be called in from the State Department as OPC's first director.
From 1948-1950 the OPC, though technically a department within the CIA was not under the CIA's control, it was a renegade operation run by Allen Dulles and Frank Wisner. OPC was brought under CIA control in October 1950, when Walter Bedell Smith became Director of Central Intelligence, and it was renamed the Directorate of Plans (for more on this refer to my paper).
During the period of 1948-1950, Dulles and Wisner were essentially operating their own private spy agency, likely with the special blessing of George F. Kennan, as the OPC was actually more beholden to the State Department then the CIA during this period. (5)
During WWII, Burnham would leave his teaching post at NYU to work for the OSS and carried on to work for the CIA when the OSS was disbanded in Sept. 1945. He would later be recommended by George F. Kennan to lead the semi-autonomous "Psychological Strategy Board" (PSB) division of the Office of Policy Coordination (OPC). (6)
This is hardly a coincidence, as Jewish-American author Naomi Wiener Cohen states in her book "Jacob H. Schiff: A Study in American Jewish Leadership" concerning the disastrous effects to Russia of the British-inspired Russo-Japanese war (Feb 1904-Sept 1905), which provoked the 1905 Russian 'revolution' that lasted until 1907. That revolution paved the way for the overthrow of the Tsar and the coming to power of the Bolsheviks in the October revolution of 1917:
"The Russo-Japanese war allied Schiff with George Kennan in a venture to spread revolutionary propaganda among Russian prisoners of war held by Japan (Kennan had access to these). The operation was a carefully guarded secret and not until the revolution of March 1917 was it publicly disclosed by Kennan. He then told how he had secured Japanese permission to visit the camps and how the prisoners had asked him for something to read. Arranging for the 'Friends of Russian Freedom' to ship over a ton of revolutionary material, he secured Schiff's financial backing. As Kennan told it, fifty thousand officers and men returned to Russia [as] ardent revolutionists. There they became fifty thousand "seeds of liberty" in one hundred regiments that contributed to the overthrow of the Tsar."
Thus one can make a good case that George Kennan brought Burnham in, specifically due to his history as an experienced high-level Trotskyist with "the right stuff," for his, as Orwell puts it, readiness to worship the power of the moment and his agreement that ultimate power could only be achieved through a "permanent revolution."
George Kennan was also not an ideological socialist, best known as the author of the Cold War strategy of "containment," he adamantly opposed FDR's recognition of the Soviet Union, refused to support the United States working with the Soviets in defeating Hitler, accusing Stalin of being just as bad…or perhaps he preferred Hitler's succession to power?
Kennan writes in his Memoirs:
"We should have no relationship at all with them [the Soviets]…Never- neither then nor at any later date- did I consider the Soviet Union a fit ally or associate, actual or potential, for this country."
Kennan made it clear he was no fan of Stalin's Soviet Union, but he certainly thought differently about the uses of "former" militant Trotskyists, possibly it was this branch of the Bolsheviks he truly wished to see succeed? Perhaps they were to play a similar role for subversion from within in the United States as they did in Russia?
[In a future installment I will discuss how "former" Trotskyists infiltrated the RAND Corporation, the Pentagon, and the CIA (as part of the second purge of American intelligence). For part of the story you can refer here.]
As Paul Fitzgerald and Elizabeth Gould put it in their excellent article "How the CIA Created a Fake Western Reality for Unconventional Warfare":
"Burnham functioned as a critical connection between Wisner's office and the intelligentsia moving from the extreme left to the extreme right with ease. Burnham found the congress to be a place to inveigh not just against Communism but against the non-communist left as well and left many wondering whether his views weren't as dangerous to liberal democracy as Communism.
According to Frances Stoner Saunders [author of the acclaimed book 'The Cultural Cold War'], members of the British delegation found the rhetoric coming out of the congress to be a deeply troubling sign of things to come… 'I felt, well, these are the same people who seven years ago were probably baying in the same way to similar German denunciations of Communism coming from Dr. Goebbels in the Sports Palast. And I felt, well, what sort of people are we identifying with? That was the greatest shock to me. There was a moment during the Congress when I felt that we were being invited to summon up Beelzebub in order to defeat Stalin.'
The Congress for Cultural Freedom didn't need Beelzebub. It already had him in the form of Burnham, [Sidney] Hook and Wisner, and by 1952, the party was just getting started… In 1953 Burnham was called upon again by Wisner to reach beyond Communism to help overthrow the democratically elected Mohammed Mossadegh in Tehran, Iran…His book, "The Machiavellians: Defenders of Freedom," would become the CIA's manual for displacing Western culture with an alternative doctrine for endless conflict in a world of oligarchs." [emphasis added]
The Machiavellians: Burnham's "Managerial" Defenders of Freedom
"The modern state … is an engine of propaganda, alternately manufacturing crises and claiming to be the only instrument that can effectively deal with them. This propaganda, in order to be successful, demands the cooperation of writers, teachers, and artists not as paid propagandists or state-censored time-servers but as 'free' intellectuals capable of policing their own jurisdictions and of enforcing acceptable standards of responsibility within the various intellectual professions."
– Christopher Lasch "The Agony of the American Left", author of "Britain's Secret Propaganda War"
In Burnham's "The Managerial Revolution," he writes:
"Most of these intellectuals are not in the least aware that the net social effect of the ideologies which they elaborate contributes to the power and privilege of the managers and to the building of a new structure of class rule in society. As in the past, the intellectuals believe that they are speaking in the name of truth and for the interests of all humanity…Indeed, the intellectual, without usually being aware of it, elaborate the new ideologies from the point of view of the position of the managers."
What this means is that the intellectuals themselves do not understand who in fact will benefit in the end by the philosophies and theories they support and defend, they are mere instruments for the propagation of a new ruling class and hold no true power. Aldous Huxley's, who also promoted a managerial ruling class in his "Brave New World," speech to naïve Berkeley students, titled "The Ultimate Revolution" comes to mind…
As Huxley put it:
"There will be, in the next generation or so, a pharmacological method of making people love their servitude, and producing dictatorship without tears, so to speak, producing a kind of painless concentration camp for entire societies, so that people will in fact have their liberties taken away from them, but will rather enjoy it."
As already stated, Burnham had been recommended by George F. Kennan to lead the semi-autonomous "Psychological Strategy Board" (PSB) division of the Office of Policy Coordination (OPC). The PSB D-33/2, created on May 5, 1953, laid out the strategy for how "free intellectuals" could be manipulated against their own interests to facilitate a CIA dictated transformation of Western culture. In fact, as Frances Stoner Saunder's makes the point in "The Cultural Cold War," it is likely Burnham himself was the one to draft PSB D-33/2.
Paul Fitzgerald and Elizabeth Gould write in "The Final Stage of the Machiavellian Elite's Takeover of America":
"PSB D-33/2 foretells of a 'long-term intellectual movement, to: break down world-wide doctrinaire thought patterns' while 'creating confusion, doubt and loss of confidence' in order to 'weaken objectively the intellectual appeal of neutralism and to predispose its adherents towards the spirit of the West.' The goal was to 'predispose local elites to the philosophy held by the planners,' while employing local elites 'would help to disguise the American origin of the effort so that it appears to be a native development.'
While declaring itself as an antidote to Communist totalitarianism, one internal critic of the program, PSB officer Charles Burton Marshall, viewed PSB D-33/2 itself as frighteningly totalitarian, interposing 'a wide doctrinal system' that 'accepts uniformity as a substitute for diversity,' embracing 'all fields of human thought — all fields of intellectual interests, from anthropology and artistic creations to sociology and scientific methodology.' He concluded: 'That is just about as totalitarian as one can get.'
With 'The Machiavellians' Burnham had composed the manual that forged the old Trotskyist left together with a right-wing Anglo/American elite. The political offspring of that volatile union would be called neoconservatism, whose overt mission would be to roll back Russian/Soviet influence everywhere. Its covert mission would be to reassert a British cultural dominance over the emerging Anglo/American Empire and maintain it through propaganda." [emphasis added]
As already discussed in part one, Burnham describes how it is necessary that the masses believe the revolution to be beneficial to them, when in reality it is just to transition from one ruling class to the other. The promise of some form of socialism free from the oppression of capitalism is offered, but the masses are told that true socialism will need time and can only be achieved further in the future, in the meantime, a managerial class is put in place.
Burnham writes:
"The ideology must ostensibly speak in the name of 'humanity,' 'the people,' 'the race,' 'the future,' 'God,' 'destiny,' and so on. Furthermore, in spite of the opinion of many present-day cynics, not just any ideology is capable of appealing to the sentiments of the masses. It is more than a problem of skilful propaganda technique. A successful ideology has got to seem to the masses, in however confused a way, actually to express some of their own interests.
…At the present time, the ideologies that can have a powerful impact, that can make a real headway, are, naturally, the managerial ideologies, since it is these that alone correspond with the actual direction of events…In place of the 'individual,' the stress turns to the 'state,' the people, the folk, the race…In place of private enterprise, 'socialism' [only by name] or 'collectivism.' In place of 'freedom' and 'free initiative,' planning. Less talk about 'rights' and 'natural rights'; more about 'duties' and 'order' and 'discipline.' Less about 'opportunity' and more about 'jobs'."
He goes on to discuss the need to change the meaning of words such "destiny," "the future," "sacrifice," "power," from the old ideologies of capitalism to suit the new ideologies of managerialism.
George Orwell would address this in his "1984," where Burnham's "The Managerial Revolution" appears pseudonymously as "The Theory and Practice of Oligarchical Collectivism."
Burnham continues:
"There will be no the managerial ideology any more than there was a the capitalist ideology. The several managerial ideologies will, however, revolve around a common axis, as the capitalist ideologies revolved around a common and different axis…In this country, Technocracy and the much more important New Dealism are embryonic and less-developed types of primitive, native-American managerial ideologies."
Burnham's reference to New Dealism as a managerial policy may be troubling to some, however, Burnham only looks at the mechanics of a social situation and its potential uses in a managerial society, it does not mean that the thing he is talking about as it is currently functioning is a form of oppression on the people. As Burnham states in his book, Roosevelt's New Dealism is not what was intended on paper so to speak.
"The firmest representatives of the New Deal are not Roosevelt or the other conspicuous 'New Deal politicians,' but the younger group of administrators, experts, technicians, bureaucrats who have been finding places throughout the state apparatus…in short, managers."
Keynes' vision for New Dealism opposed that of Roosevelt. Burnham expresses frustration that a man that had nothing to do with the creation of an idea was now pulling the strings, for more on this refer here. One example of the sort of New Dealism Burnham is referencing, fit for his vision of a managerial society, can be found in the Green New Deal, or the anti-BRI Build Back Better for the World (aka: B3W).
These are the sorts of ideologies we are told will be universally beneficial, when in reality they are meant to benefit a select ruling class, in this case a managerial class, with the intention to maximize global control to the detriment of the majority.
As Orwell put it in his essay "Second Thoughts on Burnham":
"It will be seen that Burnham's theory is not, strictly speaking, a new one. Many earlier writers have foreseen the emergence of a new kind of society, neither capitalist nor Socialist, and probably based upon slavery…"
The Great Reset: Oligarchical Collectivism
"What you radicals, and we who hold opposing views differ about, is not so much the end as the means, not so much what should be brought about, as how it should, and can, be brought about."
– Otto H. Kahn (speaking to the League of Industrial Democracy in New York Dec 30th 1924), partner of Jacob Schiff and Felix Warburg's Kuhn, Loeb & Co. and director of American International Corp.
Burnham concludes in his "The Managerial Revolution":
"The new world political system based on a small number of super-states will still leave problems-more, perhaps, than a unified single world-state; but it will be enough of a 'solution' for society to keep going. Nor is there any sufficient reason to believe that these problems of the managerial world system, including the managerial wars, will 'destroy civilization.' It is almost inconceivable even what it could mean for civilization – to be literally destroyed. Once again: what is being destroyed is our civilization, not civilization."
For the destruction of our civilization, this is precisely the intent of the World Economic Forum and its Club of Rome/Henry Kissinger affiliations, and it is their intention that the very people who will be enslaved by such a ruling class, will ironically be the ones who passionately fight to see it through. The masses themselves will be the ones willing to sacrifice and defend at all costs a growing power structure that intends to bring about their very own destruction.
There are perhaps even those who know this and believe in such a cause nonetheless, after all, if they agree that "the real enemy is humanity itself" as concluded by the Club of Rome on solving the problems of mankind, then the destruction of our civilization is not only justified, it is also our duty to bring it about.
But if such an ideology proves to be a sham, a fairy-tale meant to benefit a select ruling class, its believers will be complicit in bringing about the most atrocious crimes ever committed upon humanity in our entire history of existence.
We are now standing on that precipice…
Orwell concludes in his "Second Thoughts on Burnham":
"It is curious that in all his talk about the struggle for power, Burnham never stops to ask why people want power. He seems to assume that power hunger, although only dominant in comparatively few people, is a natural instinct that does not have to be explained, like the desire for food. He also assumes that the division of society into classes serves the same purpose in all ages. This is practically to ignore the history of hundreds of years…The question that he ought to ask, and never does ask, is: Why does the lust for naked power become a major human motive exactly now, when the dominion of man over man is ceasing to be necessary? As for the claim that 'human nature', or 'inexorable laws' of this and that, make Socialism impossible, is simply a projection of the past into the future. In effect, Burnham argues that because a society of free and equal human beings has never existed, it never can exist. By the same argument one could have demonstrated the impossibility of aeroplanes in 1900, or of motor cars in 1850.
…so long as they [the Nazis] were winning, Burnham seems to have seen nothing wrong with the methods of the Nazis…This implies that literally anything can become right or wrong if the dominant class of the moment so wills it…That a man of Burnham's gifts should have been able for a while to think of Nazism as something rather admirable, something that could and probably would build up a workable and durable social order shows, what damage is done to the sense of reality by the cultivation of what is now called 'realism'."
The author can be reached at https://cynthiachung.substack.com/
(1) Bloomenkranz, Sol (2012-07-06). Charles Bedaux – Deciphering an Enigma. iUniverse. ISBN 978-1-4759-2637-8.
(2) David Talbot "The Devil's Chessboard: Allen Dulles, the CIA, and the Rise of America's Secret Government"
(3) Ibid., pg 128
(4) Corke, Sarah-Jane (1 May 2006). "George Kennan and the Inauguration of Political Warfare". Journal of Conflict Studies. 26 (1). ISSN 1715-5673
(5) Miscamble, Wilson D. (1992). George F. Kennan and the Making of American Foreign Policy, 1947-1950. Princeton University Press. p. 199. ISBN 0691024839.
(6) Kimball, Roger (September 2002). "The power of James Burnham". The New Criterion. Archived from the original on 2019-10-14. Retrieved 2020-06-03
CIA Establishment Freedom Globalism Great Reset James Burnham United States
The Double Helix of Entwined Pandemic and Economic Strategy
Did Klaus Schwab Create an Army of Davos 'Yes Men' to Facilitate His Great Reset?
The Glory of the American Experiment
Why Putin Criticized the Bolshevik Counter Revolution: Trotsky, Parvus and the War on Civilization
The War on Science and the 20th Century Descent of Man
Klaus Schwab's Marx: A Sorcerer With the Powers of the Netherworld
Debunking Anti-Chinese Psy Ops: Jesuits, Tavistock and the Battle for the Soul of China
Cultural Warfare in the 20th Century: How Western Civilization Came Undone
Challenge for World Peace… the United States and NATO Are Incapable of Disarming Cold War Mentality
If Austria and Switzerland Are Exempt From NATO Then Why Not Ukraine?
Competing Conspiracies. With Patrick Armstrong. The Strategy Session, Episode 43
Competing Conspiracies. The Strategy Session, Episode 43 with Patrick Armstrong
This Is How the U.S. Does 'Dialogue'
VIDEO: Mueller Report Witch Hunt
VIDEO: Why Russia Is Ready to Check-Mate the U.S. and its Western Empire
Why Russia Is Ready to Check-Mate the U.S. and Its Western Empire
Why Would Americans Work for the Russians? The Curious Case of the Strategic Culture Foundation
The Strategy Session, Episode 39
Arrest of Surveillance Officers Shows Denmark Is US's Lead Eye Into Spying on Other European Allies
Americans Need a Conspiracy Theory They Can All Agree on
Now or Never: The Great 'Transition' Must Be Imposed
'Ideological Fanaticism': The Folly of Seeing Human Systems as Hardware
Australia Refuses to Reveal Additional Proof of Its Role in Chile's CIA-Backed Coup
CIA Chief Comes to Moscow… Russia Gets the U.S. Deep State to Pay Attention
Panopticon: How Mainstream Academia Normalized Mass Imprisonment
Julian Assange Exposes Western Corruption More Than Ever, Even While in Solitary Confinement
Who Will Be Brave in Huxley's New World?
Debunking Anti-Chinese Psy Ops: Social Credit as Distasteful Necessity in an Age of Asymmetric Warfare
Deplorable Until Proven Compliant: Kafka, Social Credit, & Critical Theory
Silencing Julian Assange: Why Bother With a Trial When You Can Just Kill Him?
Guterres and the Great Reset: How Capitalism Became a Time Bomb
Pandemic Politics… Democrats and GOP Are the Disease Party
No Joke: Late-Night Talk Shows Are a Powerful Propaganda Arm of the Democratic Party
Breaking From Cycles of Destruction by Leaping to a Multipolar Future
Robert E. Lee Has Been Taken Down. Is the Rest of America Next?
Smart Cities & the End of the Era of Man
Cynthia Chung is a lecturer, writer and co-founder and editor of the Rising Tide Foundation (Montreal, Canada).
Huxley's Ultimate Revolution: The Battle for Your Mind and the Relativity of Madness
The Origins of the Counterculture Movement: A Gathering of Anarchists, Occultists and Psychoanalysts for a New Age

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Can an invidual sell ArcGIS Pro add-ins at ArcGIS Marketplace? I have an add-in that I would like to sell to ArcGIS pro users. I checked the ESRI website and they have only mentioned ESRI Network partners as eligible providers. Can an indvidual not list products at ArcGIS Marketplace?

Who are ArcGIS Marketplace program providers?
Providers are Esri Partner Network partners, including Startup and NGO partners and Distributors, in good standing. Contact ArcGIS Marketplace Resource Center for information and to apply to become a provider. https://doc.arcgis.com/en/marketplace/provider/faq.htm#anchor2

redpajama_set_name: RedPajamaStackExchange


Farmhouse Lily is situated near the centre of the village with open views of a fertile valley and the fortification of Chambray. The nearest swimming area is Ix-Xatt l-Ahmar. The original part of this house is over two hundred years old and is built in rubble stone. The recently done renovation extended the property to accommodate comfortably four persons.
The hall way is unique, splendidly displaying the craftsmanship of the local builders in the old days. The open plan kitchen / dining / sitting area enjoy lovely unobstructed country views. The house is split in three levels with two bedrooms both in antique furniture, 3 bath/shower rooms, small garden, terrace and roof that has open sea views reaching the island of Comino and the main land Malta.
Air Conditioning consumption is by Coin Operated Metre that accepts one and two Euro coins.


text:
Injury cases are not uncommon in and around the Peoria area, but a catastrophic injury can lead to major setbacks that last a lifetime. Unfortunately, injury victims regularly struggle to recover compensation in these situations. At Gerber Injury Law, our team is standing by to help if you need a Peoria catastrophic injury attorney. We know how complicated these claims can become, and you need someone by your side to help you recover maximum compensation so you can move forward with your life.
Choose Gerber Injury Law for a Peoria Catastrophic Injury Claim
At Gerber Injury Law, our team has extensive experience handling complex injury claims throughout Arizona, and we have recovered more than $100 million in settlements and verdicts over the last two decades.
We focus exclusively on personal injury law, which allows us to conduct thorough investigations into catastrophic injury claims.
We take Peoria catastrophic injury cases on a contingency fee basis. This means that clients do not have to pay any upfront or out-of-pocket while their case is ongoing.
How Will an Attorney Help a Peoria Catastrophic Injury Case?
An attorney will play a multi-faceted role for a catastrophic injury victim. First, an attorney will conduct a complete investigation into the incident in order to determine liability. This will include gathering any evidence to show what happened, such as photo or video surveillance, eyewitness statements, and police reports.
Due to the severity of these injuries, an attorney may even work with an accident reconstruction expert who can use science and math along with the evidence already gathered to put together a 3D rendering or computer model to show an injury jury what happened.
Understanding Catastrophic Injuries and How They Occur
A catastrophic injury is defined as a physical injury or illness regarded as so extreme or serious that it has a considerable impact on a person's ability to live a normal life. Even though catastrophic injuries may not always be permanent, they can take years to heal. Often, the full extent of a catastrophic injury is not fully known for some time after an incident occurs.
Some of the prominent examples of catastrophic injuries include extensive burn injuries, the loss of a limb, spinal cord injuries, traumatic brain injuries, paralysis, and more. These injuries can affect major bodily systems, including the central nervous system, the respiratory system, reproductive organs, gastrointestinal organs, the urinary tract, hearing and vision, etc.
Individuals who sustain catastrophic injuries need to file these claims as quickly as possible. The personal injury statute of limitations in Arizona is two years from the date an injury occurs. Failing to file a claim within this timeframe will likely result in an injury victim becoming unable to recover compensation for their losses.
Call a Peoria Catastrophic Injury Attorney
If you or somebody you love has sustained a severe injury caused by the negligent actions of someone else in the Peoria, Arizona area, reach out to the team at Gerber Injury Law as soon as possible. We have attorneys ready to step in and handle every aspect of your claim, including investigating the incident in order to determine liability. Our goal is to recover maximum compensation for losses so you can make as full of a recovery as possible.
When you need a Peoria catastrophic injury attorney, you can contact us for a free consultation of your case by clicking here or calling us at (602) 900-9286.


WATERLOO, Ont. – BlackBerry, a global leader in mobile communications, announced that CarePartners has chosen CellTrak's VisitManager solution, running on BlackBerry 10 smartphones and managed by BES12, a multi-OS EMM solution by BlackBerry, to mobilize their home care providers.
CarePartners, based in Kitchener, Ont., is a home care nursing agency that provides personal support services, rehabilitation services, and nursing care to over 70,000 patients each year.
CarePartners issued BlackBerry 10 smartphones provisioned with CellTrak's VisitManager mobile healthcare management application to over 4,000 employees in their mobile workforce.
VisitManager enables CarePartners' home care providers to securely access patient information directly on their BlackBerry 10 smartphones. It allows them to update client records in real-time, and helps them manage their appointments and schedule changes throughout the day. The solution allows for secure real-time communications between care providers and back-office employees.
"With thousands of home care staff visiting clients each and every day, CarePartners recognized very quickly that they required a solution that gives their care providers convenient and secure access to the information they need and delivers a more integrated approach to logging and managing their hours of service," said Barry Billings (pictured), Vice President, CellTrak Canada.
"Partnering with BlackBerry enables us to offer CarePartners a real-time connection to their patient data that is secure from end-to-end, in transit and at rest and a way to increase the productivity of their workforce," he added.
CarePartners is also migrating to BES12 for enterprise mobility management (EMM) to securely manage their deployment of BlackBerry 10 smartphones. BES12 can manage any mobile deployment model such as BYOD, COPE and COBO, and seamlessly supports iOS, Android, Windows Phone, BlackBerry 10 and BlackBerry OS devices.
"With the CellTrak solution on BlackBerry, we have realized greater scheduling efficiency and a drastic reduction in missed visits for our patients," said Kelly Baechler, Manager Organizational Change, CarePartners.
"With BES12, BlackBerry delivers a multi-OS and deeply integrated communications engine that provides the highest levels of trust and security required when exchanging patient health information," said John Sims, President, Global Sales, BlackBerry.


text:
Q: How to change position of nodes vertically in Sankey Diagram How can I change position of the nodes in my Sankey Diagram vertically (y axis) to get them in the middle / central to the previous node and not at the bottom?
My dataset:
> dput(final_df_2)
structure(list(individual_id = c(21L, 21L, 22L, 23L, 24L, 24L,
24L, 25L, 26L, 26L, 26L, 26L, 26L, 26L, 26L, 27L, 27L, 27L, 27L
), number = c(1L, 2L, 1L, 1L, 1L, 2L, 3L, 1L, 1L, 2L, 3L, 4L,
5L, 6L, 7L, 1L, 2L, 3L, 4L), treatment = structure(c(5L, 3L,
2L, 4L, 1L, 5L, 3L, 2L, 3L, 5L, 2L, 5L, 4L, 5L, 1L, 2L, 5L, 5L,
3L), .Label = c("Adalimumab", "Etanercept", "Infliximab", "Rituximab",
"(Missing)"), class = "factor")), row.names = c(1L, 2L, 8L, 14L,
20L, 26L, 27L, 33L, 39L, 45L, 46L, 52L, 53L, 59L, 60L, 66L, 72L,
73L, 74L), class = "data.frame")

My code:
ggplot(final_df_2 , aes(x = number, stratum = treatment, alluvium = individual_id, fill = treatment, label = treatment)) +
  scale_fill_brewer(type = "qual", palette = "Set3") +
  geom_flow(width = 1/10) +
  geom_stratum(width = 1/10, colour = NA) +
  scale_x_continuous(breaks = 1:7, labels = c("1st Therapy", "2nd Therapy", "3rd Therapy", "4th Therapy", "5th Therapy", "6th Therapy", "7th Therapy"))+
  ggtitle("Treatment across observation period")+
  theme_minimal()+
  theme( panel.grid.major = element_blank(),
         panel.grid.minor = element_blank(), axis.text.y = element_blank())

My original Sankey diagram:

What I would like to do represented by the red nodes:

I appreciate any help on this. Thanks in advance.

A: Did you try
  var options = {
  width: 900,
  sankey: { node: { nodePadding: 80 } },
};


text:
Why Can't the World be like NYC?
As much as I am, or was, kinda 'humbug' about it: there's something about New York City. First off: more people live in NYC than in 40 of our 50 states.
But there's also something just ... different ... about NYC, especially at night. Sure there's probably all sorts of sordid stuff going on in the darkest corners that makes for good episodes of cop shows and movies, and there is the darker side of mankind that you read about in the morning papers, but if a bad guy tries to do his thing in front of a bunch of New Yorkers, like in this scene from the first Spiderman, somehow I don't think he'll get too far with it.
New Yorkers have 'a bond' and don't seem to put up with too much crap.
"You mess with one of us, you mess with *all* of us!"
My wife Manuela has always had an affinity for the place. She wasn't born there. She just likes it.
It could be the movies she grew up watching in Italy. It could have been some of the U.S. television shows through which she learned English which may have been shot there. It could be one of her favorite shows "Friends" or "Sex in The City." Hell, it could be Spiderman, (I doubt it, but who knows). She's just always loved it. So when some friends of ours, Angelo and Julia, came to visit us and visit the States for the first time, you can bet NYC was the place. And we'd spend a few days there ...
We were thinking of being married there on a specific date at a specific place some time ago before it became logistically more feasible to run the legal gauntlet in Naples, Italy some years ago but, nevertheless, she's always been in love with 'The Big Apple' since I've known her.
At about midnite on the first night, I got a text:
"Guess where I am!"
Then I was blipped (before my cellphone locked up) with the pic at the top of this post. Her sightseeing partner had fallen asleep (as had I) and she was there by herself.
"I'm on my way," I replied.
But it was the next morning, while I was standing in front of our hotel, across the street from Madison Square Garden, when I remarked to her:
"You know, look at all these people. They're from all over the place. They speak all different languages, they're from everywhere. And they all have their own little purpose and reason for being here, and they're all getting along. Nobody has a problem with anybody else. I mean ... talk about a 'melting pot!'" She patted me on the shoulder and said "It's good to see you're finally getting it."
She does that a lot. I think she thinks I'm mentally challenged. But the thing that really struck me ... and maybe it shouldn't have (?) was: nobody was fighting. Everybody was really getting along, doing their own thing(s) ... with each other. Well, except for the two taxi guys fighting over the right to park in front of the hotel -- but that's a different story.
These people were from all walks of life; tourists, people who lived there, people who worked here, people who were passing by obviously on their way to someplace else, the immigrant I talked to who'd been there for only 2 years and was thrilled to have made a living there ... who knows where they lived before or at that moment, but I'm almost certain that the majority of people I was observing 'came from somewhere else.'
But it seemed at that moment that every kind of person from every kind of place in the world and every station in life was doing their own thing and going in one direction or another, doing this and doing that as I stood there watching. Nobody was bothering me and nobody was bothering anybody else.
It may sound a bit naive, but I couldn't help thinking:
Why can't the planet be like New York City?
Muslims weren't bothering Jews and vice versa. Hardcore Nazi-lookin' folks were putting change into the cups of vagrants of one minority or another (with smiles on their faces as they did so) and the vagrants would answer 'God bless you brother.'
I'll be honest ... there was one colorful young lady who walked by -- tattooed from head to toe (literally) -- and had body piercings and holes in parts of her body where I didn't think you could do that ... and she walked by arm in arm with a seemingly well-dressed man in a nice suit, the 4 taxi drivers and doormen and I who were watching just kinda smirked and snorted our coffee outta our noses and laughed out loud ... one of them said "They have landed, and they are among us!"
But even taking into account the 'alien girl and her elderly escort,' it seemed that every 'political or lifestyle affiliation' you could think of that is currently portrayed in the media as warring with each other was just 'doing their thing' in conjunction with everyone else ... and nobody was having a problem with anybody else.
Why can't the world be like New York City?
One of Manuela's first observations was "Well, could it be that there's 2 or more cop cars everywhere you look?"
Could that have been it? Do we need the show of force? Was that it? If it was, I'm not so sure I have a problem with that, then. Is it the visible presence of 'law and order everywhere?' But doesn't that sound a little too much like 'a police state?' I'm sure that might bother some. People don't like to be 'watched' and made to be felt like they're being babysat. But maybe that was it. Maybe they felt safe?
Whatever it was. it seemed to work. Manuela and I walked up to a pair of cops leaning on their cruiser at about 2am and asked "S'cuse me guys, is there anywhere where can we buy some wine at this time of night?"
Their answer, "Nah. You might try <"blah blah blah over at blah blah, or maybe in Penn Station at blah blah's," but I don't think you'll have that much luck." With a little more chit chat we parted with a "Have a good night!" and a "Good luck!"
Less than 2 minutes later, we had found all we needed at a store about 20 yards away ... got our wine from a guy who'd been in the U.S. less then a few years He was from Bali. "Bali?!" I asked, "Why'd you leave *there?* Isn't it wonderful there?" He became suddenly serious and said "Oh no. It's worse there than you can imagine."
Hmmm ... so maybe the question shouldn't be "Why can't the rest of the world be like New York City?" Maybe it should be "Why can't the rest of the world LEARN TO BE LIKE New York City?"
Everybody pretty much helps you out if you ask for directions or for help. If they don't know, they give it their best shot and, if they don't know the answers to your questions, they send you somewhere to someone who might know.
Everybody was just ... nice.
Even the alien girl and the older gentleman.
Jules and Manuela
I guess "nice" just doesn't make the news and it's that 'news' that shapes what we think about the world? And maybe that's why people target it and try to take it down.
Have you forgotten?
Excused Absence ...


Southold Town Supervisor Scott Russell said he's received an overwhelming response from hotel, motel and bed-and-breakfast owners who oppose the proposed Peconic Tourism Marketing District meant to generate tourism promotion funds in the five East End towns.
"I cannot speak for the rest of the board but, to me, this latest proposal is DOA," he said in an email last Friday.
Brian Deluca, who heads the East End Tourism Alliance and is general manager of Atlantis Holdings, which owns the Long Island Aquarium and Hyatt Hotel in Riverhead, said the Peconic Tourism Marketing District's main focus would be transportation — finding and funding ways to bring visitors from place to place. It would work by collecting a percentage or fixed amount — suggested at $1 — for each overnight stay at a hotel, motel, B&B or other lodging business.
The formation of the marketing district would first require authorization from the state Legislature. Each participating town would then have to approve a home rule message.
Mr. Russell said the Town Board asked the North Fork Promotion Council to reach out to the industry as a whole to gauge support for the idea, which he says they did not. At a work session last month, the Town Board members said they would not comment on legislation without hearing from lodging owners first.
"We asked the NFPC several times in the past to reach out to the whole industry to get a measure of support," Mr. Russell said.
Proponents of the marketing district have been in touch with Assemblyman Fred Thiele (I-Sag Harbor) and state Sen. Ken LaValle (R-Port Jefferson) about drafting legislation at the state level. Mr. Thiele said Monday he would be reluctant to proceed with without all five towns participating.
Mr. LaValle agrees, according spokesperson Greg Blower, who said the senator believes that local control in decision-making is essential.
Mr. Deluca said marketing district backers first wanted input from the towns on what they would and wouldn't want to see in the state legislation. They planned to reach out to industry members on a larger scale once it was clear at the state level that formation of a tourism marketing district was authorized.
One Southold B&B owner who asked not to be named said she doesn't think a marketing district alone could solve traffic problems. She said she thinks it is unfair for the burden to fall entirely on lodging and feels there is a lack of clarity on how the funds would be collected.
The North Fork is too small to support "mass" tourism, the B&B owner said.
She and another lodging owner pointed out that the North Fork has different needs and capacity from Riverhead Town, which has larger hotels.
In the letter, the writer said it is "ridiculous" that the proposed fee would only apply to lodging and not restaurants, wineries and other businesses that cater to North Fork visitors.
Tourists bringing car traffic stay at chain hotels in Riverhead, the writer said.
Referring to the idea of charging $1 more per overnight stay, the writer also said that money could add up and be used for room improvements instead.
When told about the proposal, Sue Halladay, manager at Jamesport Bay Suites in South Jamesport, said she would be up for the idea if it creates more needed transportation options on the North Fork.
"People who stay at the hotels would be loving transportation and not drinking and driving on the weekends," she said.
Supervisors in the four other East End towns that could participate — Riverhead, Southampton, East Hampton and Shelter Island — have shown interest in the marketing district and provided input, Mr. Deluca said.
Riverhead Supervisor Laura Jens-Smith said Monday that she supports the idea, although there were some questions about the by-laws involved with the proposal.