Antibiotic Susceptibility Surveillance in the Punjab Province of Pakistan: Findings and Implications.

Background and Objectives: The increase in antimicrobial resistance (AMR) across countries has seriously impacted the effective management of infectious diseases, with subsequent impact on morbidity, mortality and costs. This includes Pakistan. Antimicrobial surveillance activities should be mandatory to continually assess the extent of multidrug-resistant bacteria and the implications for future empiric prescribing. The objective of this retrospective observational study was to monitor the susceptibility pattern of microbes in Pakistan. Materials and Methods: Clinical samples from seven laboratories in Punjab, Pakistan were collected between January 2018 and April 2019, with Punjab being the most populous province in Pakistan. The isolates were identified and their antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion assay and micro broth dilution methods. The antibiotics assessed were those typically prescribed in Pakistan. Results: In total, 2523 bacterial cultural reports were studied. The most frequently isolated pathogens were Staphylococcus aureus (866, 34.3%), followed by Escherichia coli (814, 32.2%), Pseudomonas aeruginosa (454, 18.0%) and Klebsiella pneumoniae (269, 10.7%). Most pathogens were isolated from pus (1464, 58.0%), followed by urine (718, 28.5%), blood (164, 6.5%) and sputum (81, 3.2%). Conclusions: The findings suggest that current antimicrobial options are severally restricted in Pakistan due to the emergence of multidrug-resistant pathogens. This calls for urgent actions including initiating antimicrobial stewardship programs to enhance prudent prescribing of antibiotics. This includes agreeing on appropriate empiric therapy as part of agreed guidelines, in line with the WHO EML and AWaRe book, whilst awaiting culture reports. This is alongside other measures to reduce inappropriate antimicrobial prescribing and reverse the threat of rising AMR.

Determinants of anxiety and depression among university teachers during third wave of COVID-19.

BACKGROUND: To estimate the determinants of anxiety and depression among university teachers in Lahore, Pakistan, during COVID-19. METHODS: A cross-sectional study was conducted by enrolling 668 teachers from the universities of Lahore, Pakistan. Data were collected using a questionnaire. Chi-square for significance and logistic regression for the association were used. RESULTS: Majorly, the university teachers, with an average age of 35.29 years, had regular jobs (72.8%), job experience of > 6 years (51.2%) and good self-reported health (55.4%). The majority of the teachers were working as lecturers (59.6%), lecturing in arts (33.5%) or general science (42.5%) departments, having MPhil (37.9%) or master (28.9%) degrees, and teaching via synchronous video (59.3%) mode. Anxiety and depression, severe and extremely severe, were higher among lecturers, MPhil or master degree holders, teachers lecturing arts and general science subjects, and in those on contract employment. Anxiety was significantly associated with academic departments; arts (OR;2.5, p = 0.001) and general science (OR;2.9, p = 0.001), poor health status (OR;4.4, p = 0.018), and contractual employment (OR;1.8, p = 0.003). Depression was associated with academic departments; arts (OR;2.7, p = 0.001) and general science (OR;2.5, p = 0.001), and health status (OR;2.3, p = 0.001). CONCLUSION: Among university teachers, anxiety and depression, severe and extremely severe, were prevalent among lecturers having MPhil or master degrees, belonging to arts and general science departments, and among contract employees. Anxiety and depression were significantly associated with academic disciplines, lower cadre, and poor health status.

Knowledge, Attitudes, Perceptions, and Acceptance of COVID-19 Vaccination among Pharmacy and Non-Pharmacy Students.

University students are a sub-group of the population at high risk of COVID-19 infection, and their judgments on vaccination affect the public attitudes towards vaccination. Thus, the present study aimed to assess the knowledge, attitudes, perceptions, and acceptance of the COVID-19 vaccine among pharmacy and non-pharmacy students. A cross-sectional study was conducted by enrolling pharmacy (375) and non-pharmacy (225) students from the universities in Lahore. Chi-square analysis was used for significant frequency distributions and a 5-point Likert scale was used to score attitude, perception, and acceptance. The majority of the students were aged between 19-24 years, hailing from urban and middle-class families with good self-reported health. The preferred vaccine was Pfizer, followed by Sinopharm and Sinovac. The major source of information was social media, followed by government campaigns and family members. The pharmacy students demonstrated better knowledge and positive attitudes toward COVID-19 vaccination. The non-pharmacy students scored higher for the questions based on scientific leads, myths, and baffling conspiracies. The non-pharmacy students showed higher hesitancy/barrier total scores related to their trust in the health system, COVID-19 vaccine storage, and efficacy. Data suggested that pharmacy students exhibited better knowledge, positive attitudes, and perceptions about COVID-19 vaccination. Overall, vaccine efficacy and safety were mutual concerns. Nonetheless, non-pharmacy students were hesitant due to mistrust in the health system of Pakistan.

Structural and functional insight into thiazolidinone derivatives as novel candidates for anticancer drug design: in vitro biological and in-silico strategies.

The compounds 2a-2h containing a thiazolidinone pharmacophore were synthesized via hetrerocylization of thiosemicarbazones with dimethyl acetylenedicarboxylate. The hybrid molecules were evaluated for anticancer activity against the human cell lines MCF-7, T47D (human breast adenocarcinoma) and HeLa (cervical cancer). Compounds 2c showed effective cytotoxicity on MCF-7 and HeLa (GI50 6.40 ± 0.10 µM/mL and GI5010.30 ± 1.09 µM/mL), and compound 2d also showed effective cytotoxicity against MCF-7 and HeLa cell lines i.e., (GI50 16.60 ± 0.21 µM/mL and GI50 15.02 ± 0.14 µM/mL). These findings were comparable to cisplatin (azane;dichloroplatinum) the standard drug (GI50 13.20 ± µM/mL and 15.10 µM/mL respectively) and consequently nominated for determination of the mode of cell death. The results revealed the cytotoxic effects of 2c and 2d by induction of apoptosis in MCF-7 and HeLa cell lines. Moreover the results were further supported by the Molecular Docking which predicts the binding interactions of the best anticancer ligands with Ribonucleotide reductase (RNR), which is essential enzyme required for de-novo synthesis of DNA precursors. Molecular dynamic simulations were also performed to determine the stability of protein-ligand complex under different simulated conditions. In addition, the computational studies including DFTs, ADMET properties suggested these compounds can act as lead molecules, for the synthesis of novel drug candidates for the treatment of specific cancer and its associated malignancies.

Pilot drug and therapeutic committee programme in Sierra Leone: A descriptive mixed method study.

AIMS: Irrational medicine use is a global crisis, but incidences are proportionately higher in low- and middle-income countries such as Sierra Leone. This study explores the structure, functions and challenges of drug and therapeutics committees (DTCs), an intervention towards irrational medicine use recently piloted in Sierra Leone. METHODS: A 2-phase mixed-method study design was used in this study. Firstly, a cross-sectional survey was conducted on all pharmacists who have worked for at least 1 year in DTC-piloted hospitals, using an online questionnaire to assess DTCs' structure, indicators and challenges. In phase 2, all eligible pharmacists were invited for a semistructured online interview using the WhatsApp messaging application to get deeper insights into the key issues that emerged from the survey; however, only 5 of the 7 consented to participate. MS Excel 2019 and NVivo version 12 were respectively used for data management and analysis. RESULTS: A total of 6 survey responses and 5 interviews were included in the analysis. Participants are pharmacists from the 7 hospitals in Sierra Leone where DTC was piloted. Most DTCs are comprised of a minimum of 10 members consisting of both medical and hospital administrative staff. The main functions of DTCs are ensuring rational medicines use, monitoring and reporting adverse drug reactions. All 7 hospitals with established pilot DTCs have different subcommittees operating at varying functionality levels, ranging from effective to nonfunctional. The main challenges in DTC functions and maintenance are funding (n = 6), DTC decision implementation (n = 4), and unmotivated members (n = 4). Strategies suggested to improve DTCs at public hospitals and nationwide include resource allocation, monitoring and evaluating DTC functions and its members' capacity building. CONCLUSION: DTCs present a compelling opportunity towards achieving rational medicines use at the hospital level in Sierra Leone. Nonetheless, the lack of funding and operational resources are significant limitations that must be noted by policymakers before expanding DTC programmes to other hospitals in Sierra Leone.

In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization.

The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds i.e., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1/AKR1B10 for curing colon cancer and related malignancies.

Views of Pharmacists and Government Representatives Toward the Pilot Chief Pharmacist System in Chinese Hospitals: A Multicenter Exploratory Qualitative Study.

Background: In China, the pharmacy departments of most hospitals have changed their main focus from drug procurement and distribution to providing pharmaceutical care services. Various regions of China have successively implemented the pilot Chief Pharmacist System (CPS) to help improve pharmaceutical care services and rational drug use in hospitals. This study was designed to explore the perspectives of pharmacists and government officials on CPS, including the advantages and barriers to the successful implementation of CPS. Methods: A qualitative study, based on semi-structured interviews, was conducted from October 1, 2018 to March 1, 2019. The interview data were gathered from 18 pharmacy staff and government representatives working in five distinct regions of China using purposive sampling. A thematic analysis approach and NVivo version 12 Plus was utilized to code and analysis of all interviews. Results: Five broad themes were identified: the role of the chief pharmacist; their attitudes toward the CPS; the advantages and results of the CPS; the barriers toward CPS; and their suggestions toward CPS. Most of the participants believed that the chief pharmacist played a vital role in a hospital. Under CPS, the hospital pharmacy department pays more attention to prescription review, medication monitoring, and pharmaceutical consultation. However, an insufficient number of pharmacy personnel, unclear authority, and inadequate salaries were the main barriers to the implementation of the CPS. Conclusion: The attitudes of most of the participants were found to be positive toward CPS in China. The CPS can enhance the prestige of the hospital pharmacy department, improve the quality of hospital pharmaceutical care services, and promote rational drug use. Nevertheless, certain barriers highlighted in this study should be addressed promptly.

Discovery of Phenylcarbamoylazinane-1,2,4-Triazole Amides Derivatives as the Potential Inhibitors of Aldo-Keto Reductases (AKR1B1 & AKRB10): Potential Lead Molecules for Treatment of Colon Cancer.

Both members of the aldo-keto reductases (AKRs) family, AKR1B1 and AKR1B10, are over-expressed in various type of cancer, making them potential targets for inflammation-mediated cancers such as colon, lung, breast, and prostate cancers. This is the first comprehensive study which focused on the identification of phenylcarbamoylazinane-1, 2,4-triazole amides (7a−o) as the inhibitors of aldo-keto reductases (AKR1B1, AKR1B10) via detailed computational analysis. Firstly, the stability and reactivity of compounds were determined by using the Guassian09 programme in which the density functional theory (DFT) calculations were performed by using the B3LYP/SVP level. Among all the derivatives, the 7d, 7e, 7f, 7h, 7j, 7k, and 7m were found chemically reactive. Then the binding interactions of the optimized compounds within the active pocket of the selected targets were carried out by using molecular docking software: AutoDock tools and Molecular operation environment (MOE) software, and during analysis, the Autodock (academic software) results were found to be reproducible, suggesting this software is best over the MOE (commercial software). The results were found in correlation with the DFT results, suggesting 7d as the best inhibitor of AKR1B1 with the energy value of −49.40 kJ/mol and 7f as the best inhibitor of AKR1B10 with the energy value of −52.84 kJ/mol. The other potent compounds also showed comparable binding energies. The best inhibitors of both targets were validated by the molecular dynamics simulation studies where the root mean square value of <2 along with the other physicochemical properties, hydrogen bond interactions, and binding energies were observed. Furthermore, the anticancer potential of the potent compounds was confirmed by cell viability (MTT) assay. The studied compounds fall into the category of drug-like properties and also supported by physicochemical and pharmacological ADMET properties. It can be suggested that the further synthesis of derivatives of 7d and 7f may lead to the potential drug-like molecules for the treatment of colon cancer associated with the aberrant expression of either AKR1B1 or AKR1B10 and other associated malignancies.

4-Chlorophenyl-N-furfuryl-1,2,4-triazole Methylacetamides as Significant 15-Lipoxygenase Inhibitors: an Efficient Approach for Finding Lead Anti-inflammatory Compounds.

Lipoxygenases (LOXs) are a class of enzymes that catalyze the production of pro-inflammatory mediators, such as leukotrienes and lipoxins, via an arachidonic acid cascade as soon as they are released from the membrane phospholipids after tissue injury. In continuation of our efforts in search for new LOX inhibitors, a series of chlorophenyl-furfuryl-based 1,2,4-triazole derivatives were prepared and evaluated for their 15-LOX inhibitory activities. A simple precursor, 4-chlorobenzoic acid (a), was consecutively transformed into benzoate (1), hydrazide (2), semicarbazide (3), and N-furfuryl 5-(4-chlorobenzyl)-4H-1,2,4-triazole (4), which when further merged with electrophiles (6a-o) resulted in end products (7a-o). The structural elucidations of the newly synthesized compounds (7a-o) were carried out by Fourier transform infrared, 1H-, 13C NMR spectroscopy, EI-MS, and HR-EI-MS spectrometry. The inhibitive capability of compounds (7a-o) on soybean 15-LOX was performed in vitro using the chemiluminescence method. The compounds 7k, 7o, 7m, 7b, and 7i demonstrated potent activities (IC50 17.43 ± 0.38, 19.35 ± 0.71, 23.59 ± 0.68, 26.35 ± 0.62, and 27.53 ± 0.82 µM, respectively). These compounds revealed 79.5 to 98.8% cellular viability as measured by the MTT assay at 0.25 mM concentration. The structure-activity relationship (SAR) studies showed that the positions and the nature of substituents bonded to the phenyl ring are important in the determination of 15-LOX inhibitory activities. ADME, in silico, and density functional theory studies supported the evidence as yet another class of triazoles with potential lead properties in search for anti-LOX compounds with a safe gastrointestinal safety profile for various inflammatory diseases. Further work is in progress on the synthesis of more derivatives in search for anti-inflammatory agents.

Structure and surface analyses of a newly synthesized acyl thiourea derivative along with its in silico and in vitro investigations for RNR, DNA binding, urease inhibition and radical scavenging activities.

N-((4-Acetylphenyl)carbamothioyl)-2,4-dichlorobenzamide (4) was synthesized by the treatment of 2,4-dichlorobenzoyl chloride with potassium thiocyanate in a 1 : 1 molar ratio in dry acetone to afford the 2,4-dichlorobenzoyl isothiocyanate in situ which on reaction with acetyl aniline furnished (4) in good yield and high purity. The compound was confirmed by FTIR, 1H-NMR, and 13C-NMR and single crystal X-ray diffraction studies. The planar rings were situated at a dihedral angle of 33.32(6)°. The molecules, forming S(6) ring motifs with the intramolecular N-H⋯O hydrogen bonds, were linked through intermolecular C-H⋯O and N-H⋯S hydrogen bonds, enclosing R2 2(8) ring motifs, into infinite double chains along [101]. C-H⋯π and π⋯π interactions with an inter-centroid distance of 3.694 (1) Å helped to consolidate a three-dimensional architecture. Hirshfeld surface (HS) analysis further indicated that the most important contributions for the crystal packing were from H⋯C/C⋯H (20.9%), H⋯H (20.5%), H⋯Cl/Cl⋯H (19.4%), H⋯O/O⋯H (13.8%) and H⋯S/S⋯H (8.9%) interactions. Thus C-H⋯π (ring), π⋯π, van der Waals interactions and hydrogen bonding played the major roles in the crystal packing. The electronic structure and computed DFT (density functional theory) parameters identified the reactivity profile of compound (4). In silico binding of (4) with RNA indicated the formation of a stable protein-ligand complex via hydrogen bonding, while DNA docking studies inferred (4) as a potent groove binder. The experimentally observed hypochromic change (57.2%) in the UV-visible spectrum of (4) in the presence of varying DNA concentrations together with the evaluated binding parameters (K b; 7.9 × 104 M-1, ΔG; -28.42 kJ mol-1) indicated spontaneous interaction of (4) with DNA via groove binding and hence supported the findings obtained through docking analysis. This compound also showed excellent urease inhibition activity in both in silico and vitro studies with an IC50 value of 0.0389 ± 0.0017 µM. However, the radical scavenging efficiency of (4) was found to be modest in comparison to vitamin C.

Exploring ibuprofen derivatives as α-glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies.

This study reports the synthesis of a series of ibuprofen derivatives, including thiosemicarbazides 4a-f, 1,3,4-oxadiazoles 5a-f, 1,3,4-thiadiazoles 6a-f, 1,2,4-triazoles 7a-f, and their S-alkylated derivatives 8a-d. All of the newly synthesized derivatives were analyzed using 1 H NMR, 13 C NMR spectroscopy, and high-resolution mass spectra (electron ionization) spectrometry. These synthetic molecules were examined for their in vitro baking yeast α-glucosidase and soybean 15-lipoxygenase (15-LOX) inhibition and cell viability studies. The results revealed that the compounds N-(3,4-dichlorophenyl)-5-[1-(4-isobutylphenyl)ethyl]-1,3,4-oxadiazol-2-amine 5f (IC50 3.05 ± 1.23 µM) and N-(3-fluorophenyl)-5-[1-(4-isobutylphenyl)ethyl]-1,3,4-oxadiazol-2-amine 5b (IC50 3.12 ± 1.21 µM) were the most potent with respect to the α-glucosidase enzyme while in case of 15-LOX, the compound 4-(2,4-dichlorophenyl)-1-[2-(4-isobutylphenyl)propanoyl]thiosemicarbazide 4e showed potent inhibition with an IC50 value of 55.41 ± 0.41 µM. All these compounds were found least toxic by displaying a blood mononuclear cell viability value of 69.2%-97.8% by the MTT assay compared to the standards when assayed at 0.25 mM concentration. Molecular docking analyses were conducted to evaluate the inhibition profiles of these derivatives against the said enzymes and the data supported the in vitro profiles.

Access to Insulin Products in Pakistan: A National Scale Cross-Sectional Survey on Prices, Availability, and Affordability.

Background: Diabetes is among the top ten most prevalent diseases in Pakistan, and the availability of medicines to treat the disease is vital for a great percentage of the country's population. Insulin was discovered a century ago; however, its access in several parts of the globe remains an issue. This study aims to evaluate prices, availability, and affordability (access components) of insulin and five comparator medicine access in Pakistan. Methods: A nationwide cross-sectional survey was conducted to evaluate the access to insulin and some comparator medicines in eight cities of Pakistan, using a modified WHO/HAI methodology. The survey included 80 medicine outlets, i.e., 40 private pharmacies and 40 public hospitals. Data for every unique insulin product available in the Pakistani market were obtained, including five comparator medicines. Percentage availability, median unit prices (MUPs), and affordability (the number of days' wages (NDWs) required for a month's course by the lowest-paid unskilled government worker) of all products were calculated, including originator brands (OBs) and biosimilar (BS) products. Results: Of all insulin products surveyed (n = 320), 87.5% were manufactured by foreign multinational companies (MNCs). None of the insulin products had an ideal availability of 80% in any of the surveyed health facilities. In the public sector, none of the insulin products had an availability of more than 50%. In the public sector, the overall availability of human insulin was 70% (including OB and BS). While in the private sector, the overall availability of human insulin was 90% and that of analog insulin was 62.5%. The analog insulin products were 72.8% costlier than the human insulin products. The median prices of BS insulin were 25.4% lower than the OB products, indicating that almost one-fourth of the cost could be saved by switching to BS human insulin from OB human insulin. All oral anti-diabetic medicines were found to be affordable, whereas none of the insulin was affordable. The NDWs for human and analog insulin were 1.38 and 5.06. Conclusion: In Pakistan, the insulin availability falls short of the WHO's benchmark of 80%. Insulin continues to be unaffordable in both private and government sectors. To increase insulin access, the government should optimize insulin procurement at all levels, promote local production, enforce biosimilar prescribing, and provide financial subsidies for these products.

Impact of Nutrition Support Team in Achieving Target Calories in Children Admitted in Pediatric Intensive Care Unit.

OBJECTIVE: To determine the impact of nutrition support team (NST) on achieving an early target caloric goal in mechanically ventilated children admitted in pediatric intensive care unit (PICU). METHODS: An early enteral nutrition protocol (EENP) was implemented by NST to ensure early and adequate nutrition provision to PICU patients. All children (1 month- 18 years) that were admitted in PICU for >2days and received mechanical ventilation, with no contraindications to enteral feed, were included and data was compared with those of pre-intervention. The adequacy of energy intake was defined as 70% achievement of target energy intake on the third day of admission. Chi-square/t-test was used to determine the difference between different variables pre and post intervention. RESULTS: Total 180 patients (99 and 81 in pre- and post-intervention group, respectively) were included. Overall, 115 (63.9%) received adequate calories (70%) on third day of admission. Of which 69 (85.2%) were from post intervention (P  < 0.001; odds ratio [OR] 6.6, 95% confidence interval [CI] 3.195-13.73). Moreover, NST intervention also promoted adequate protein intake in 62 (76.5%) children compared to 37 (37.4%) in pre-intervention group (P < 0.001, OR 5.468, 95% CI 2.838- 10.534). The median (interquartile range) length of PiCU stay in pre-NST group was 6 (4-9) days and in NST supported group was 4 (3-4) days (OR 0.580, CI 0.473-0.712, P < 0.001). Age, severity of illness, multiorgan dysfunction syndrome, sepsis, need of organ support had no effect in achievement of caloric target in both the groups (P > 0.05). CONCLUSION: Introduction of EENP with NST helped in the achievement of better and quicker target caloric intake.

Community pharmacists' perception and exposure to drug promotion in Pakistan: a cross-sectional study.

OBJECTIVE: Drug promotion is a factor that promotes the irrational use of drugs and sometimes negatively influences the prescribing/dispensing pattern. So there was a need to assess the views about accepting gifts and attitudes/influence towards drug promotion among community pharmacists in Punjab, Pakistan. SETTING: Adopting a preused questionnaire, we conducted a cross-sectional multiple-site survey study. We distributed questionnaires to pharmacists in the community pharmacies to investigate the exposure, scepticism and acceptance to drug promotion as well as their perception about the appropriateness of gifts and to check if they had been taught about dealing with medical representatives. Data were analysed in simple percentages, and the χ2 test was used to evaluate association with demographics. All the analysis was done using SPSS V.23.0. RESULTS: A total 86.9% (463/533) pharmacists completed the survey. One out of four pharmacists reported being taught about the ethics of drug promotion (26.8%) and about how to interpret drug promotional material (25.0%) and were significantly associated with higher age (age 31%-35 years, 81.9%; p<0.05). More than two-thirds of the respondents found it appropriate to accept stationery (73.4%) and textbooks (70.6%) as gifts, and only 17.5% felt it was appropriate to accept direct money. Less than half of the pharmacists (47.3%) perceived drug companies were useful for gaining knowledge about new drugs. Majority (76.2%) thought these drug promotions play a role in the irrational prescribing of antibiotics and 18.6% dispensed antibiotics due to these promotions. CONCLUSION: The majority of pharmacists participating in this study felt it was appropriate to receive small value gifts from pharmaceutical companies. Only a small proportion of the respondents was given ethical training and education about drug promotion. Improving the syllabus and updating the pharmacist's knowledge after graduation, as part of continued pharmacy education, will eventually improve the healthcare professionals' capability to act for the patients' welfare.

Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): a narrative review and the implications.

INTRODUCTION: The emergence of antimicrobial resistance (AMR) is a threat to public health. In 2015, the World Health Organization (WHO) introduced a global action plan to tackle AMR in the World Health Assembly. Pakistan's national action plan (NAP) for AMR was released in May 2017 by the Ministry of National Health Services. Based on the NAP, strategies have been initiated on a national and provincial scale in Pakistan. AREAS COVERED: This narrative review of the five components of the Pakistan NAP has been undertaken to discuss some of the challenges in implementation of the NAP for AMR in Pakistan including different opinions and views of key stakeholders, combined with suggestions on potential ways to reduce the burden of the AMR. EXPERT OPINION: Going forward, healthcare authorities should focus on screening and monitoring of all the objectives of the NAP by establishing proper policies as well as promoting antimicrobial stewardship interventions and Infection prevention and control (IPC) practices. Overall, the comprehensive strengthening of the healthcare system is required to adequately implement the NAP, tackle continued inappropriate antimicrobial use and high AMR rates in Pakistan.

HLA repertoire of 115 UAE nationals infected with SARS-CoV-2.

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies.

Artificial Intelligence (AI) in Pharmacy: An Overview of Innovations.

Artificial Intelligence (AI) emerged as an intervention for data and number-related problems. This breakthrough has led to several technological advancements in virtually all fields from engineering to architecture, education, accounting, business, health, and so on. AI has come a long way in healthcare, having played significant roles in data and information storage and management - such as patient medical histories, medicine stocks, sale records, and so on; automated machines; software and computer applications like diagnostic tools such as MRI radiation technology, CT diagnosis and many more have all been created to aid and simplify healthcare measures. Inarguably, AI has revolutionized healthcare to be more effective and efficient and the pharmacy sector is not left out. During the past few years, a considerable amount of increasing interest in the uses of AI technology has been identified for analyzing as well as interpreting some important fields of pharmacy like drug discovery, dosage form designing, polypharmacology, and hospital pharmacy. Given the growing importance of AI, we wanted to create a comprehensive report which helps every practicing pharmacist understand the biggest breakthroughs which are assisted by the deployment of this field.

Drug Shortage: Causes, Impact, and Mitigation Strategies.

Drug shortage is a global issue affecting low, middle, and high-income countries. Many countries have developed various strategies to overcome the problem, while the problem is accelerating, affecting the whole world. All types of drugs, such as essential life-saving drugs, oncology medicines, antimicrobial drugs, analgesics, opioids, cardiovascular drugs, radiopharmaceutical, and parenteral products, are liable to the shortage. Among all pharmaceutical dosage forms, sterile injectable products have a higher risk of shortage than other forms. The causes of shortage are multifactorial, including supply issues, demand issues, and regulatory issues. Supply issues consist of manufacturing problems, unavailability of raw materials, logistic problems, and business problems. In contrast, demand issues include just-in-time inventory, higher demand for a product, seasonal demand, and unpredictable demand. For regulatory issues, one important factor is the lack of a unified definition of drug shortage. Drug shortage affects all stakeholders from economic, clinical, and humanistic aspects. WHO established global mitigation strategies from four levels to overcome drug shortages globally. It includes a workaround to tackle the current shortage, operational improvements to reduce the shortage risk and achieve early warning, changes in governmental policies, and education and training of all health professionals about managing shortages.

WHO key access antibiotics price, availability and affordability in private sector pharmacies in Pakistan.

BACKGROUND: Poor availability and unaffordability of key access antibiotics may increase antimicrobial resistance in the community by promoting inappropriate antibiotic selection and abridged therapy compliance. OBJECTIVE: To check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan. METHODOLOGY: A survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient's affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook. RESULTS: The mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day's wage (median) if using OB and 0.4 day's wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1). CONCLUSION: There is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.

Public knowledge, attitude, and practice regarding antibiotics use in Punjab, Pakistan: a cross-sectional study.

OBJECTIVES: Public awareness about antibiotics use is critical in antimicrobial resistance. We evaluated knowledge, attitudes, and practices among the general population of Punjab, Pakistan in this cross-sectional study. METHODS: We used a 50-item questionnaire to collect information on participant demographics, knowledge, and attitudes about antibiotics use and to evaluate the practices of taking antibiotics without a doctor's prescription. RESULTS: Of the 2106 participants who completed surveys, 35.4% thought antibiotics could cure viral infections; 47.5% believed they are effective against cold and flu. Nearly 60% percent of respondents had self-medicated with antibiotics. Married people (adjusted odds ratio (AOR) = 1.285, 95% confidence interval (CI): 1.004-1.643 p = 0.046), higher antibiotics use knowledge (AOR = 0.818, 95% CI: 0.674-0.993 p = 0.042), ever purchased antibiotics without a physician's prescription (AOR = 2.024 95% CI: 1.674-2.457 p ≤ 0.001) and storing antibiotics at home (AOR = 0.801 95% CI: 0.652-0.985 p = 0.035) were significantly associated with self-medication practices. CONCLUSIONS: A high proportion of inappropriate antibiotics use exists among the general population of Punjab. Interventions are needed to improve health literacy and supervise antibiotics sales in retail pharmacies.