BackgroundPharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An understanding of healthcare providers’ knowledge, perceptions, confidence towards pharmacogenetics, and their active enrollment with pharmacogenetic testing is essential for test acceptance and utilization. This study was designed to assess physicians’ and pharmacists’ knowledge, perceptions, and confidence towards pharmacogenetics, determine the preferred learning format for their future education in pharmacogenetics, and identify the barriers to its application in their practice settings.MethodsA cross-sectional survey was conducted using a pretested self-administered questionnaire on a sample of 629 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis.ResultsThe response rate was 98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics education or training (8.9%), applied pharmacogenetics testing in their practice (9.4%), or provided patient counselling on the results of the pharmacogenetic testing (9.1%), and over 90% of them were physicians. The overall respondents’ mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no significant difference between the physicians and pharmacists scores (p>0.05). Only 16.0% of participants indicated that they felt confident in applying pharmacogenetics in their practice settings. Despite these low levels of knowledge and self-confidence, 70.2% of participants expressed overall positive perceptions towards pharmacogenetics and its clinical implications. These positive overall perceptions were found to be significantly more common among pharmacists compared to physicians (p<0.05). The top two perceived barriers facing the implementation of pharmacogenetics in Kuwait were lack of education or training and clinical guidelines.ConclusionsThese findings highlight important concerns and will aid in the assessment of current pharmacogenetics practice. Also, they will provide further insight in designing future targeted multifaceted interventions to promote the adoption and utilization of pharmacogenetics testing in Kuwait.

Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9 OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

ObjectivesThis study was designed to identify the services provided by community pharmacists in Kuwait and their views regarding self-care in pregnancy and lactation. In addition, it determined the pharmacists’ recommendations for treatment of pregnancy-related and breast feeding-related ailments.DesignCross-sectional questionnaire-based survey.SettingCommunity pharmacies in Kuwait.Participants207 pharmacies were randomly selected from the Ministry of Health database. One registered pharmacist was approached from each pharmacy. One hundred and ninety-two (92.8%) pharmacists agreed to participate and completed a self-administered questionnaire.OutcomesThe proportions of pharmacists offering particular advice for health conditions in pregnancy and lactation, pharmacists’ recommendations for common and specific ailments during pregnancy and breast feeding, and pharmacists’ views about self-care in pregnancy and breast feeding.ResultsThe top services provided to pregnant and lactating women were recommending vitamins and food supplements (89.8%) and contraception advice (83.4%), respectively. More than half of participants indicated that they would recommend medications for headache, constipation, cough, runny nose, sore throat, nausea/vomiting, indigestion, sore or cracked nipple and insufficient milk. Diarrhoea, haemorrhoids, insomnia, varicose vein, swelling of the feet and legs, vaginal itching, back pain, fever, mastitis and engorgement were frequently referred to the physician. Recommendations on medication use were occasionally inappropriate in terms of unneeded drug therapy, off-label use and safety. In relation to offering advice and solving medication and health problems of pregnant and lactating women, more than half of pharmacists indicated that they have sufficient knowledge (61.5%; 50.5%) and confidence (58.3%; 53.1%), respectively. Most of the respondents (88.5%) agreed that a continuing education programme on this topic would be of value for their practice.ConclusionThe present findings show that respondents had different recommendations for treatment of pregnancy-related and lactation-related ailments; and also highlight the need for interventions, including continuing professional development and revision of the undergraduate pharmacy curriculum.

By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFPþ cells of healthy Csf1r-eGFP-KI mice, Csf1rþ/CD11bþ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1rþ/RANKþ cells in vitro. Therefore, Csf1r-eGFPþ/CD11bþ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1rþ/CD11bþ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4þ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4þ OCPs, as well as bone resorption, in the PMMA-injected calvaria, while increasing locally produced SDF-1. Collectively, these data suggest that locally produced MIF in the inflammatory bone lytic site is engaged in the chemoattraction of circulating CXCR4þ OCPs.

Purpose Given their negative influence on community health, vaccine hesitancy and resistance are emerging challenges that require healthcare intervention. Therefore, this study aimed to assess the impact of physician-pharmacist collaborative health coaching on rates of hesitancy and resistance for a COVID-19 vaccine. Methods After an initial assessment of rates of hesitancy and resistance for a COVID-19 vaccine was conducted, hesitant and resistant participants were approached, recruited, and randomized into an active and control group. Pharmacists-physicians collaborative coaching intervention was delivered to active group subjects over two months through Facebook live sessions. The outcome measures were assessed in both groups before coaching, directly after coaching, and a month after coaching. Results The proportions of hesitancy and resistance for a COVID-19 vaccine among subjects in the active group were significantly reduced from 64.3% and 35.7% before coaching to 20.1% and 7.8% directly after coaching, respectively. These proportions were further reduced to 11.1% and 3.3% a month after coaching, respectively. Furthermore, the mean scores for knowledge on, and attitude towards COVID-19 vaccine were significantly increased from 4.6±1.8 and 4.1±1.7 before coaching to 7.5±3.1 and 8.9±3.8 directly after coaching, respectively. However, the change in mean score of beliefs about COVID-19 vaccines among active group subjects was not significant. Conclusion High rates of hesitancy and resistance for a COVID-19 vaccine were found in Jordan. These rates can be significantly reduced through online pharmacists-physicians collaborative coaching, which can also improve knowledge of and attitude towards COVID-19 vaccines.

Locally produced osteoclastogenic factor RANKL plays a critical role in the development of bone resorption in periradicular periodontitis. However, because RANKL is also required for healthy bone remodeling, it is plausible that a costimulatory molecule that upregulates RANKL production in inflammatory periradicular periodontitis may be involved in the pathogenic bone loss processes. We hypothesized that macrophage migration inhibitory factor (MIF) would play a role in upregulating the RANKL-mediated osteoclastogenesis in the periradicular lesion. In response to pulp exposure, the bone loss and level of MIF mRNA increased in the periradicular periodontitis, which peaked at 14 d, in conjunction with the upregulated expressions of mRNAs for RANKL, proinflammatory cytokines (TNF-a, IL-6, and IL-1b), chemokines (MCP-1 and SDF-1), and MIF's cognate receptors CXCR4 and CD74. Furthermore, expressions of those mRNAs were found significantly higher in wild-type mice compared with that of MIF 2/2 mice. In contrast, bacterial LPS elicited the production of MIF from ligament fibroblasts in vitro, which, in turn, enhanced their productions of RANKL and TNF-a. rMIF significantly upregulated the number of TRAP + osteoclasts in vitro. Finally, periapical bone loss induced in wild-type mice were significantly diminished in MIF 2/2 mice. Altogether, the current study demonstrated that MIF appeared to function as a key costimulatory molecule to upregulate RANKL-mediated osteoclastogenesis, leading to the pathogenically augmented bone resorption in periradicular lesions. These data also suggest that the approach to neutralize MIF activity may lead to the development of a therapeutic regimen for the prevention of pathogenic bone loss in periradicular periodontitis.

Collaborative practice between physicians and pharmacists has a positive effect on healthcare outcomes. Understanding the local data related to this collaboration is vital in establishing efficient collaboration. Therefore, this study was designed to assess the collaborative relationships between physicians and pharmacists working in the primary healthcare centres regarding their attitudes and experiences, preferred methods of communication, perceptions related to the role of pharmacists, areas of potential further collaboration, and perceived barriers. A cross-sectional study was conducted using two parallel pretested self-administered questionnaires on a sample of 518 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis. The overall response rate was 86.3%. Although over 98% of respondents agreed that physician-pharmacist collaboration improves patient outcomes, more than half of the physicians (52.1%) and pharmacists (55.7%) had never practised collaboratively. Both groups preferred to communicate face-to-face (76.7%) or via telephone (76.5%). Both professions showed good agreement on pharmacists' roles related to managing side effects, improving adherence, assisting in dosage adjustment, providing advice regarding drug interactions, and providing drug information to physicians. They indicated disagreements on the importance of dispensing of prescriptions and providing advice to physicians regarding modification of drug therapy. Both groups expressed overall positive perceptions of the potential for further collaboration in areas related to the clinical roles of pharmacists, which were significantly higher among those with practice experience of < 10 years and those aged < 40 years (p<0.05). The top four perceived barriers to collaborative practice were lack of time (84.1%), lack of financial compensation (76.3%), lack of face-to-face communication (68.9%), and the possible fragmentation of patient care by the involvement of multiple healthcare professionals (68.9%). The present findings provide valuable input that could be a catalyst to enhance or establish physician-pharmacist collaboration in primary healthcare settings in Kuwait.

The evaluation of medicines burden from the patients' perspectives is a crucial endeavor to identify any barriers that may hinder achieving optimal health outcomes. Therefore, this study was designed, firstly to identify the prevalence of medication-related burden among geriatrics and factors influencing this burden. Secondly, to determine the prevalence of medication adherence and the correlation between the burden and adherence. A crosssectional study was performed using Living with Medicines Questionnaire version-3 (LMQ-3) and Adherence to Refills and Medications Scale (ARMS) questionnaire. Four hundred and fifty patients attending primary healthcare centers were invited to participate, and 424 (94.2%) agreed. Data were collected via face-to-face structured interviews. The vast majority of respondents (97.4%; 95% CI: 95.3-98.6) perceived to suffer from minimum (35.4%) to moderate (62.0%) degrees of medicine burden. The median (IQR) LMQ overall score was 112 (21) indicating a moderate burden. LMQ-3 overall scores revealed a significant trend toward higher perceived burden among respondents aged ≥ 75 years, males, non-Kuwaitis, residents in Al-Farwaniyah and Al-Jahra governorates, using oral and nonoral formulations, paying prescription charges, and needing support with using medicines (p <0.05). Almost 55% (95% CI: 49.8-59.5) of respondents were nonadherent to their medications. The median (IQR) ARMS overall score was 20 (7.0) indicating low adherence to medications. There was a significant positive correlation between LMQ-3 and ARMS scores (p<0.001) showing that the higher the medications burden the lower the level of medication adherence. The key findings of this study underscore the need for multifaceted interventions that could be targeted at the identified problems to reduce medication burden and improve medication adherence.