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  1. Khan RA, Aziz Z
    Int J Clin Pharm, 2017 Aug;39(4):906-912.
    PMID: 28643112 DOI: 10.1007/s11096-017-0499-2
    Background Antibiotic de-escalation is an important strategy to conserve the effectiveness of broad-spectrum antibiotics. However, the outcome of this strategy for the treatment of ventilator-associated pneumonia (VAP) has not been widely studied in developing countries. Objectives To evaluate the outcome on intensive care unit (ICU) mortality, 28 days mortality, and length of ICU stay among VAP patients who receive de-escalation therapy. Setting This study was conducted in an ICU of a Malaysian public hospital. Method The electronic medical records of patients who developed VAP in the ICU were retrieved and relevant data was collected. Records of antibiotic prescriptions were also reviewed to collect the details of changes to antibiotic therapy (de-escalation). Main outcome measure Impact of antibiotic de-escalation on mortality. Results The mean age of the 108 patients was 46.2 ± 18.2 years; the majority being males (80%). The antibiotic de-escalation rate was about 30%. Out of this, 84% involved a change from broad to narrow-spectrum antibiotics and the remaining, withdrawal of one or more antibiotics. ICU mortality was 23% while 28 days mortality was 37%. There was no statistically significant difference in mortality rate, survival probability and the mean length of ICU stay between the de-escalation and the non-de-escalation group. However, patients with Simplified Acute Physiology Score II of ≥50 were significantly associated with ICU mortality and 28 days mortality. Conclusions In VAP patients, antibiotic de-escalation provides an opportunity to promote the judicious use of antibiotics without affecting the clinical outcomes.
  2. Khan RA, Bakry MM, Islahudin F
    Indian J Pharm Sci, 2015 7 17;77(3):299-305.
    PMID: 26180275
    Inappropriate initial antibiotics for pneumonia infection are usually linked to extended intensive care unit stay and are associated with an increased risk of mortality. This study evaluates the impact of inappropriate initial antibiotics on the length of intensive care unit stay, risk of mortality and the co-predictors that influences these outcomes. This retrospective study was conducted in an intensive care unit of a teaching hospital. The types of pneumonia investigated were hospital-acquired pneumonia and ventilator-associated pneumonia. Three different time points were defined as the initiation of appropriate antibiotics at 24 h, between 24 to 48 h and at more than 48 h after obtaining a culture. Patients had either hospital-acquired pneumonia (59.1%) or ventilator-associated pneumonia (40.9%). The length of intensive care unit stay ranged from 1 to 52 days (mean; 9.78±10.02 days). Patients who received appropriate antibiotic agent at 24 h had a significantly shorter length of intensive care unit stay (5.62 d, P<0.001). The co-predictors that contributed to an extended intensive care unit stay were the time of availability of susceptibility results and concomitant diseases, namely cancer and sepsis. The only predictor of intensive care unit death was cancer. The results support the need for early appropriate initial antibiotic therapy in hospital-acquired pneumonia and ventilator-associated pneumonia infections.
  3. Algarni S, Khan RA, Khan NA, Mubarak NM
    Environ Sci Pollut Res Int, 2021 Dec;28(46):65822-65831.
    PMID: 34322813 DOI: 10.1007/s11356-021-15534-6
    Building and its environment are in focus owing to health impact attributed to indoor air quality. This study was carried out to assess indoor air quality in terms of particulate matter (PM) and carbon dioxide in a residential building, during COVD-19 pandemic lockdown from March 25 to April 23, 2020, Abha, Saudi Arabia. The PM concentration range for kitchen, bedroom, and hall were 40,000-81000 μg/m3 (PM0.3), 15,000-26000 μg/m3 (PM0.5), 4000-6000 μg/m3 (PM1), 1100-1500 μg/m3 (PM2.5), 160-247 μg/m3 (PM5), and 60-95 μg/m3 (PM10). The results of this study suggest that bedroom needs to be ventilated as CO2 concentration was reaching 700 ppm during sleep hours. PM concentration was exceeding 300 μg/m3 (unhealthy) for all particle sizes of PM0.3, PM0.5, PM1, and PM2.5 except for PM10 which was also above safe limits (0-50 μg/m3). Also, with influential habit (aromatic smoke), these concentrations increased 2-28 times for PM. The hazard quotient value greater than 1 revealed potential health risk to the inhabitants. Hence, future studies are needed for developing indoor air quality guidelines for residential buildings in Saudi Arabia and better planning and management of energy consumption.
  4. Teh HL, Abdullah S, Ghazali AK, Khan RA, Ramadas A, Leong CL
    Antibiotics (Basel), 2021 Dec 27;11(1).
    PMID: 35052899 DOI: 10.3390/antibiotics11010022
    BACKGROUND: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. This study aims to compare the survival curve of patient de-escalated (early or late) against those not de-escalated on antibiotics, to determine the association of patient related, clinical related, and pressure sore/device related characteristics on all-cause 30-day mortality and determine the impact of early and late antibiotic de-escalation on 30-day all-cause mortality.

    METHODS: This is a retrospective cohort study on patients in medical ward Hospital Kuala Lumpur, admitted between January 2016 and June 2019. A Kaplan-Meier survival curve and Fleming-Harrington test were used to compare the overall survival rates between early, late, and those not de-escalated on antibiotics while multivariable Cox proportional hazards regression was used to determine prognostic factors associated with mortality and the impact of de-escalation on 30-day all-cause mortality.

    RESULTS: Overall mortality rates were not significantly different when patients were not de-escalated on extended or restricted antibiotics, compared to those de-escalated early or later (p = 0.760). Variables associated with 30-day all-cause mortality were a Sequential Organ Function Assessment (SOFA) score on the day of antimicrobial stewardship (AMS) intervention and Charlson's comorbidity score (CCS). After controlling for confounders, early and late antibiotics were not associated with an increased risk of mortality.

    CONCLUSION: The results of this study reinforce that restricted or extended antibiotic de-escalation in patients does not significantly affect 30-day all-cause mortality compared to continuation with extended and restricted antibiotics.

  5. Azemi NFN, Islahudin F, Khan RA, Saffian SM, Loon LC
    J Pharm Policy Pract, 2024;17(1):2337125.
    PMID: 38638422 DOI: 10.1080/20523211.2024.2337125
    INTRODUCTION: Trials have demonstrated the benefits of methylprednisolone in the treatment of coronavirus disease 2019 (COVID-19). However, data on optimal dose, duration and timing of administration are limited. This study investigates the outcome of various methylprednisolone treatment regimens among hospitalised COVID-19 patients.

    METHODS: A retrospective cohort study was conducted on hospitalised adult COVID-19 patients admitted between June and August 2021 in general COVID-19 wards, treated with methylprednisolone. Clinical outcomes evaluated include in-hospital mortality, thirty-day mortality, clinical efficacy (C-reactive protein (CRP), total white blood cells (TWBC) and oxygen requirement) as well as the safety of methylprednisolone.

    RESULTS: Of 278 patients, 1(0.4%) received weight-based dosing of 1 mg/kg/day, 101(36.3%) received weight-based dosing of 2 mg/kg/day, 130(46.8%) received fixed dosing methylprednisolone 250 mg/day and 46(16.5%) received fixed dosing methylprednisolone 500 mg/day. There was a significant difference in in-hospital mortality rates following different methylprednisolone doses whereby in-hospital mortality occurred in 22.5% (n = 23) of patients with 1 or 2 mg/kg/day methylprednisolone, 32.3% (n = 42) with 250 mg/day and 39.1% (n = 18) with 500 mg/day (p = 0.023). On the other hand, no significant difference in thirty-day mortality, clinical efficacy and safety was observed between different dosing regimens (p > 0.05).

    CONCLUSION: The use of methylprednisolone weight-based dosing in hospitalised COVID-19 patients should be considered due to the positive outcome associated with lower in-hospital mortality.

  6. Tan SY, Khan RA, Khalid KE, Chong CW, Bakhtiar A
    Sci Rep, 2022 Feb 24;12(1):3106.
    PMID: 35210515 DOI: 10.1038/s41598-022-07142-2
    Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). A surveillance study was performed in the largest tertiary care hospital in Kuala Lumpur, Malaysia, from 2018 to 2020 to observe the trends of broad-spectrum antibiotics (beta-lactam/beta-lactamases inhibitors (BL/BLI), extended-spectrum cephalosporins (ESC), and fluoroquinolones (FQ)) and antibiotics against MRO (carbapenems, polymyxins, and glycopeptides) usage and the correlation between antibiotic consumption and MROs. The correlation between 3-year trends of antibiotic consumption (defined daily dose (DDD)/100 admissions) with MRO infection cases (per 100 admissions) was determined using a Jonckheere-Terpstra test and a Pearson's Correlation coefficient. The antimicrobial resistance trend demonstrated a positive correlation between ESC and FQ towards the development of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp, ESBL-producing Escherichia coli (E. coli), and MRO Acinetobacter baumannii (A. baumannii). Increasing carbapenem consumption was positively correlated with the occurrence of ESBL-producing Klebsiella spp and E. coli. Polymyxin use was positively correlated with ESBL-producing Klebsiella spp, MRO A. baumannii, and carbapenem-resistant Enterobacteriaceae. The findings reinforced concerns regarding the association between MRO development, especially with a surge in ESC and FQ consumption. Stricter use of antimicrobials is thus crucial to minimise the risk of emerging resistant organisms.
  7. Ali G, Nisar J, Iqbal M, Shah A, Abbas M, Shah MR, et al.
    Waste Manag Res, 2019 Aug 13.
    PMID: 31405341 DOI: 10.1177/0734242X19865339
    Due to a huge increase in polymer production, a tremendous increase in municipal solid waste is observed. Every year the existing landfills for disposal of waste polymers decrease and the effective recycling techniques for waste polymers are getting more and more important. In this work pyrolysis of waste polystyrene was performed in the presence of a laboratory synthesized copper oxide. The samples were pyrolyzed at different heating rates that is, 5°Cmin-1, 10°Cmin-1, 15°Cmin-1 and 20°Cmin-1 in a thermogravimetric analyzer in inert atmosphere using nitrogen. Thermogravimetric data were interpreted using various model fitting (Coats-Redfern) and model free methods (Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose and Friedman). Thermodynamic parameters for the reaction were also determined. The activation energy calculated applying Coats-Redfern, Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose and Friedman models were found in the ranges 105-148.48 kJmol-1, 99.41-140.52 kJmol-1, 103.67-149.15 kJmol-1 and 99.93-141.25 kJmol-1, respectively. The lowest activation energy for polystyrene degradation in the presence of copper oxide indicates the suitability of catalyst for the decomposition reaction to take place at lower temperature. Moreover, the obtained kinetics and thermodynamic parameters would be very helpful in determining the reaction mechanism of the solid waste in a real system.
  8. Khan RA, Khan NA, El Morabet R, Alsubih M, Khan AR, Khan S, et al.
    Environ Res, 2023 Jan 01;216(Pt 1):114437.
    PMID: 36181898 DOI: 10.1016/j.envres.2022.114437
    Pharmaceutical compounds being able to alter, retard, and enhance metabolism has gained attention in recent time as emerging pollutant. However, hospitals which are part of every urban landscape have yet to gain attention in terms of its hospital wastewater treatment to inhibit pharmaceutical compounds from reaching environment. Hence this study evaluated performance of constructed wetland in combination with tubesettler and aeration based on removal efficiency and ecological risk assessment (HQ). The removal efficiency of constructed wetland with plantation was higher by 31% (paracetamol), 102% (ibuprofen), 46%, (carbamazepine), 57% (lorazepam), 54% (erythromycin), 31% (ciprofloxacin) and 20% (simvastatin) against constructed wetland without plantation. Constructed wetland with aeration efficiency increased for paracetamol, ibuprofen, carbamazepine, lorazepam, erythromycin, ciprofloxacin, and simvastatin removal efficiency were higher by 58%, 130%, 52%, 79%, 107%, 57%, and 29% respectively. In constructed wetland with plantation, removal efficiency was higher by 20% (paracetamol), 13% (ibuprofen), 4% (carbamazepine), 14% (lorazepam), 34% (erythromycin), 19% (ciprofloxacin) and 7% (simvastatin). High ecological risk was observed for algae, invertebrate and fish with hazard quotient values in range of 2.5-484, 10-631 and 1-78 respectively. This study concludes that if space is the limitation at hospitals aeration with constructed wetland can be adopted. If space is available, constructed wetland with tubesettler is suitable, economic and environmentally friendly option. Future research works can focus on evaluating other processes combination with constructed wetland.
  9. Alsubih M, El Morabet R, Khan RA, Khan NA, Ul Haq Khan M, Ahmed S, et al.
    Environ Sci Pollut Res Int, 2021 Nov;28(44):63017-63031.
    PMID: 34218378 DOI: 10.1007/s11356-021-15062-3
    Groundwater is a primary natural water source in the absence of surface water bodies. Groundwater in urban environments experiences unprecedented stress from urban growth, population increase, and industrial activities. This study assessed groundwater quality in terms of arsenic and heavy metal contamination in three industrial areas (Shahdara, Jhilmil, and Patparganj), Delhi, India. The water quality was assessed over a 3-year time interval (i.e., 2015 and 2018). The groundwater constituents investigated were As, Fe, Cr, Cd, Ni, Zn, Mn, Cu, and Pb. Metal index and heavy metal pollution indexes were estimated to assess groundwater pollution. The health risk was evaluated in terms of non-carcinogenic and carcinogenic risk assessment. Patparganj industrial area saw increment in concentration for Cu 0.23 mg/L (2015)-0.85 mg/L (2018), Zn 0.51 mg/L (2015)-7.2 mg/L (2018), Fe 0.32 mg/L (2015)-0.9 mg/L (2018), Cr 0.21 mg/L (2015)-0.26 mg/L (2018), Mn 0.14 mg/L (2015)-0.25 mg/L (2018), Ni 0.04 mg/L (2015)-0.34 mg/L (2018), and As 0.01 mg/L (2015)-0.18 mg/L (2018). Cd and Pb concentrations were observed to decrease by 40-90 % and 85-99% for all the three industrial areas. Metal index and heavy metal index values were found to be >1 for all locations. The risk quotient value > 1 was observed for all locations in the year 2015 but was found to increase further to a range of RQ 10-62 in the year 2018, inferring increased non-carcinogenic risk to consumers. The carcinogenic risk was significant with respect to Fe (0.2-0.7), Zn (0.001-0.007), and As (0.002-0.003) for all locations in the year 2015. This study concludes that groundwater in the three industrial areas is highly polluted and is not fit for human consumption. Further studies are required to explore possible control measures and develop methods to mitigate groundwater pollution, sustainable management, and optimized use to conserve it for future generations.
  10. Chang CE, Khan RA, Tay CY, Thangaiyah B, Ong VST, Pakeer Oothuman S, et al.
    PLoS One, 2023;18(3):e0282342.
    PMID: 36867615 DOI: 10.1371/journal.pone.0282342
    BACKGROUND: Clinical pharmacy plays an integral role in optimizing inpatient care. Nevertheless, prioritising patient care remains a critical challenge for pharmacists in a hectic medical ward. In Malaysia, clinical pharmacy practice has a paucity of standardized tools to prioritise patient care.

    AIM: Our aim is to develop and validate a pharmaceutical assessment screening tool (PAST) to guide medical ward pharmacists in our local hospitals to effectively prioritise patient care.

    METHOD: This study involved 2 major phases; (1) development of PAST through literature review and group discussion, (2) validation of PAST using a three-round Delphi survey. Twenty-four experts were invited by email to participate in the Delphi survey. In each round, experts were required to rate the relevance and completeness of PAST criteria and were given chance for open feedback. The 75% consensus benchmark was set and criteria with achieved consensus were retained in PAST. Experts' suggestions were considered and added into PAST for rating. After each round, experts were provided with anonymised feedback and results from the previous round.

    RESULTS: Three Delphi rounds resulted in the final tool (rearranged as mnemonic 'STORIMAP'). STORIMAP consists of 8 main criteria with 29 subcomponents. Marks are allocated for each criteria in STORIMAP which can be combined to a total of 15 marks. Patient acuity level is determined based on the final score and clerking priority is assigned accordingly.

    CONCLUSION: STORIMAP potentially serves as a useful tool to guide medical ward pharmacists to prioritise patients effectively, hence establishing acuity-based pharmaceutical care.

  11. Mohammed HA, Sulaiman GM, Anwar SS, Tawfeeq AT, Khan RA, Mohammed SAA, et al.
    Nanomedicine (Lond), 2021 09;16(22):1937-1961.
    PMID: 34431317 DOI: 10.2217/nnm-2021-0070
    Aims: To evaluate the anti breast-cancer activity, biocompatibility and toxicity of poly(d,l)-lactic-co-glycolic acid (PLGA)-encapsulated quercetin nanoparticles (Q-PLGA-NPs). Materials & methods: Quercetin was nano-encapsulated by an emulsion-diffusion process, and the nanoparticles were fully characterized through Fourier transform infrared spectroscopy, x-ray diffractions, FESEM and zeta-sizer analysis. Activity against CAL51 and MCF7 cell lines were assessed by DNA fragmentation assays, fluorescence microscopy, and acridine-orange, and propidium-iodide double-stainings. Biocompatibility towards red blood cells and toxicity towards mice were also explored. Results: The Q-PLGA-NPs exhibited apoptotic activity against the cell lines. The murine in vivo studies showed no significant alterations in the liver and kidney's functional biomarkers, and no apparent abnormalities, or tissue damages were observed in the histological images of the liver, spleen, lungs, heart and kidneys. Conclusion: The study established the preliminary in vitro efficacy and in vivo safety of Q-PLGA-NPs as a potential anti-breast cancer formulation.
  12. Khan NA, Bokhari A, Mubashir M, Klemeš JJ, El Morabet R, Khan RA, et al.
    Chemosphere, 2022 Jan;286(Pt 3):131838.
    PMID: 34399260 DOI: 10.1016/j.chemosphere.2021.131838
    In this study, Hospital wastewater was treated using a submerged aerobic fixed film (SAFF) reactor coupled with tubesettler in series. SAFF consisted of a column with an up-flow biofilter. The biological oxygen demand (BOD)5, chemical oxygen demand (COD), nitrate and phosphate were the chosen pollutants for evaluation. The pollutants removal efficiency was determined at varying organic loading rates and hydraulic retention time. The organic loading rate was varied between 0.25 and 1.25 kg COD m-3 d-1. The removal efficiency of SAFF and tubesettler combined was 75 % COD, 67 % BOD and 67 % phosphate, respectively. However, nitrate saw an increase in concentration by 25 %. SAFF contribution in the removal of COD, BOD5 and Phosphate was 48 %, 46 % and 29 %, respectively. While for accumulation of nitrate, it was responsible for 56%, respectively. Tubesettler performed better than SAFF with 52 %, 54 % and 69 % reduction of COD, BOD5 and phosphate, respectively. But in terms of nitrate, tubesettler was responsible for 44 % accumulation. The nutrient reduction decreased with an increase in the organic loading rate. Nitrification was observed in the SAFF and tubesettler, which indicated a well-aerated system. An anaerobic unit is required for completing the denitrification process and removing nitrogen from the effluent. The better performance of tubesettler over SAFF calls for necessitates extended retention time over design criteria. Further studies are beneficial to investigate the impact of pharmaceutical compounds on the efficiency of SAFF.
  13. Lee JSF, Cohen RM, Khan RA, Burry J, Casas EC, Chung HY, et al.
    Lancet Glob Health, 2024 Sep;12(9):e1552-e1559.
    PMID: 39151989 DOI: 10.1016/S2214-109X(24)00225-0
    Amphotericin B has long been crucial for treating many serious infectious diseases, such as invasive fungal infections and visceral leishmaniasis, particularly for patients who are immunocompromised, including those with advanced HIV infection. The conventional amphotericin B deoxycholate formulation has largely been replaced in high-income countries with liposomal amphotericin B (LAmB), which has many advantages, including lower rates of adverse events, such as nephrotoxicity and anaemia. Despite an evident need for LAmB in low-income and middle-income countries, where mortality from invasive fungal infections is still substantial, many low-income and middle-income countries still often use the amphotericin B deoxycholate formulation because of a small number of generic formulations and the high price of the originator LAmB. The pricing of LAmB is also highly variable between countries. Overcoming supply barriers through the availability of additional quality-assured, generic formulations of LAmB at accessible prices would substantially facilitate equitable access and have a substantial effect on mortality attributable to deadly fungal infections.
  14. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Jun 28;132(26):261902.
    PMID: 38996325 DOI: 10.1103/PhysRevLett.132.261902
    A combination of fifteen top quark mass measurements performed by the ATLAS and CMS experiments at the LHC is presented. The datasets used correspond to an integrated luminosity of up to 5 and 20  fb^{-1} of proton-proton collisions at center-of-mass energies of 7 and 8 TeV, respectively. The combination includes measurements in top quark pair events that exploit both the semileptonic and hadronic decays of the top quark, and a measurement using events enriched in single top quark production via the electroweak t channel. The combination accounts for the correlations between measurements and achieves an improvement in the total uncertainty of 31% relative to the most precise input measurement. The result is m_{t}=172.52±0.14(stat)±0.30(syst)  GeV, with a total uncertainty of 0.33 GeV.
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