Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.
Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.
Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.
METHODS: PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.
RESULTS: During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).
CONCLUSIONS: Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.
CLINICAL TRIALS REGISTRATION: NCT03056391.
METHODS: A retrospective review of medical records was performed among patients with acute or perforated appendicitis who underwent LA between December 2015 and January 2017. With the use of multivariable logistic regression analyses, the predictors of conversion from laparoscopic to OA were investigated.
RESULTS: Out of 120 patients, 33 cases were converted to OA which gives a conversion rate of 27.5%. Among 33 patients who were converted to OA, 27 patients (81.8%) had perforated appendix, while in the LA group, perforated appendix cases consisted of 34.5% (P<0.001). Histopathology of the appendix was the predictor of conversion from LA to OA (adjusted odds ratio, 8.82; 95% confidence interval, 3.13-24.91; P<0.001).
CONCLUSION: The result from our study shows that the overall conversion rate for the study period was high. Patients with perforated appendicitis had a higher risk of conversion to OA. Therefore, preoperative diagnosis of perforated appendicitis may be paramount in predicting conversion to OA.
METHODS: A cross-sectional survey collected self-report data from April to June 2021 on side effects following the first dose of the vaccine. An online validated questionnaire using the Google Docs® platform was circulated via email and social media platforms.
RESULTS: More than 40% of participants experienced at least one side effect after the first dose of vaccination; the most common were mild and resolved within three days after vaccination. More than 91% of respondents received the Covishield (AstraZeneca) vaccine; the most prevalent adverse effects were soreness of the injected arm (78.9%), tiredness (71.1%), and fever (54.9%). Logistic regression showed that women were almost 60% less likely to report side effects.
CONCLUSION: Findings supported the safety of the first dose of the COVID-19 vaccine based on relatively few self-limiting side effects, mainly soreness of the injected arm and tiredness. Further research is needed to determine the long-term safety of COVID-19 vaccines, especially after booster doses.
METHODOLOGY: Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes.
RESULTS: Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference.
CONCLUSION: This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.
OBJECTIVE: The present study aimed to assess grit level and its related factors among undergraduate pharmacy students from 14 countries amid the COVID-19 pandemic.
METHODS: A cross-sectional survey-based study was conducted among pharmacy students from 14 countries in Asia and the Middle East. A 31-item questionnaire was developed, validated, and pilot-tested, including the validated short scale for grit assessment. The data was collected between 1 February and 15 April 2022. Descriptive and inferential statistics were employed as appropriate.
RESULTS: A total of 2665 responses were received, mainly from females (68.7 %), living in urban areas (69.2 %) and studying at private universities (59.1 %). The average grit score on a scale of 5 was 3.15 ± 0.54. The responses revealed higher favourable responses to items on the perseverance of efforts (34.9 % to 54 %) compared to items on the consistency of interests (26.5 % to 31.1 %). Students who did not exercise (AOR: 0.47, 95 %CI: 0.33-0.67) or exercised irregularly (AOR: 0.64, 95 %CI: 0.45-0.90) were less likely to have higher grit scores than those who exercised regularly. Additionally, students who did not receive COVID-19 vaccination (AOR: 0.50, 95 %CI: 0.36-0.71) or received only one dose (AOR: 0.67, 95 %CI: 0.46-0.99) were less likely to have higher grit scores than those who received their booster vaccination. Interestingly, students who chose the pharmacy program as their only available or reasonable choice (AOR: 0.33, 95 %CI: 0.17-0.62) and students from public universities (AOR: 0.82, 95 %CI: 0.68-0.98) were less likely to have higher grit scores. On the other hand, students who did not face educational challenges with online learning (AOR: 1.19, 95 %CI: 1.003-1.416) and students with excellent (AOR: 2.28, 95 %CI: 1.57-3.31) and very good (AOR: 2.16, 95 %CI: 1.53-3.04) academic performance were more likely to have higher grit scores.
CONCLUSION: The findings revealed moderate grit levels. Higher grit levels were thought to be associated with several personal, lifestyle and academic factors. Further interventions to support students' grit attributes are required, particularly concerning the consistency of interests.
METHODS: The 30-day hospitalization related to COVID-19 was determined using 1 to 1 propensity score-matched real-world data in Malaysia from 14 July 2022 to 14 November 2022. To determine the total per-person costs related to COVID-19, we added the cost of drug (nirmatrelvir/ritonavir or control), clinic visits and inpatient care. Incremental cost-effectiveness ratio (ICER) per hospitalization averted was calculated.
RESULTS: Our cohort included 31,487 patients. The rate of hospitalization within 30 days was found to be 0.35% for the group treated with nirmatrelvir/ritonavir, and 0.52% for the control group. The nirmatrelvir/ritonavir group cost an additional MYR 1,625.72 (USD 358.88) per patient. This treatment also resulted in a reduction of 0.17% risk for hospitalization, which corresponded to an ICER of MYR 946,801.26 (USD 209,006.90) per hospitalization averted.
CONCLUSION: In Malaysia, where vaccination rates were high, nirmatrelvir/ritonavir has been shown to be beneficial in the outpatient treatment of adults with COVID-19 who have risk factors; however, it was only marginally cost effective against hospitalization for healthy adults during the Omicron period.