METHODS: We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum-positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps).
RESULTS: In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008-2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008-2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017.
DISCUSSION: This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.
METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.
ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.
Materials and Methods: Forty carious primary molars indicated for pulpotomy within the age group of 4-9 years were selected and divided into two groups of 20 each using simple randomization, Group 1: Diode laser MTA and Group 2: Diode laser ZOE pulpotomy. The teeth were evaluated clinically for 1 year at 3, 6, and 12 months interval and radiologically for 6 and 12 months.
Results: Clinically and radiographically, 100% teeth treated with diode laser MTA and 94% treated with diode laser ZOE were considered successful after 12-month follow-up interval. No significant difference was seen between two groups.
Conclusion: Despite the success rate, the cost factor of diode laser and MTA could be the limiting factor in its judicious use in pulpotomy procedure.
METHODS: Head and neck cancer patients were recruited from July 2016 till March 2017 at National Cancer Institute, Ministry of Health, Malaysia. All study participants continued their standard oncology surveillance. Treatment group participants additionally received Chinese herbal treatment. The assessments included unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and QoL questionnaire.
RESULTS: Of 42 recruited participants, 28 were in the treatment group and 14 were in the control group. Participants were mainly Chinese (71.4%), stage III cancer (40.5%), and had nasopharynx cancer (76.2%). The commonly used single herbs were Wu Mei, San Qi, and Tian Hua Fen. Sha Shen Mai Dong Tang, Liu Wei Di Huang Wan, and Gan Lu Yin were the frequently prescribed herbal formulas. The baseline characteristics, USFR, SSFR, and QoL between control and treatment groups were comparable (p > 0.05). USFR between control and treatment groups were similar throughout the 6-month study period. SSFR for the treatment group significantly improved from 0.15 ± 0.28 ml/min (baseline) to 0.32 ± 0.22 ml/min (p = 0.04; at the 3rd month) and subsequently achieved 0.46 ± 0.23 ml/min (p = 0.001; at the 6th month). The treatment group had better QoL in terms of speech (p = 0.005), eating (p = 0.02), and head and neck pain (p = 0.04) at the 6th month.
CONCLUSION: Herbal treatment may improve xerostomia and QoL in post-radiotherapy head and cancer patients.
Methods: This retrospective study involved 32 patients with SSD who were prescribed CBD gel at the Subang Jaya Medical Centre, Selangor, Malaysia, between January 2016 and December 2017. The Physician Global Assessment Scale was used to assess disease severity. Itching/discomfort was evaluated using a visual analogue scale.
Results: The mean age was 35.8 ± 6.9 years. Severe disease was seen in 53.1%. Complete clearance was recorded in 15.6%, 40.6% and 59.4% of patients at weeks two, six and 10, respectively. By week 10, 87.5% had achieved marked improvement. Both mean itching and discomfort scores significantly improved at weeks two, six and 10 (P <0.001). Better outcomes were significantly associated with disease duration and itching intensity and discomfort at presentation (P <0.050).
Conclusion: CBD gel should be considered as an option for SSD cases not adequately controlled by prior conventional treatment.
METHODS: A total of 36 subjects (94.5% Fitzpatick Type IV-V) were recruited in this randomized double-blinded, split-face, controlled trial. Each side of the face was randomly assigned for treatment with either JS or SA. Subjects were treated once fortnightly for a total of three sessions. Lesion counting, Michaelsson acne score (MAS), photographs, and postacne hyperpigmentation index (PAHPI) were used to objectively assess the improvement. Complications were assessed during each visit. Statistical analysis was conducted using SPSS v22.0. Significance was set at P = 0.05.
RESULTS: At the end of therapy, significant reduction in inflammatory, noninflammatory lesions, MAS, and PAHPI scores (P
METHODS: CLSI broth microdilution methodology was used to determine antimicrobial activity and EUCAST breakpoints version 9.0 were used to determine rates of susceptibility and resistance. Isolates were also screened for the genes encoding extended-spectrum β-lactamases (ESBLs) or carbapenemases (including metallo-β-lactamases [MBLs]).
RESULTS: Between 2015 and 2017, this study collected a total of 7051 Enterobacterales isolates and 2032 Pseudomonas aeruginosa isolates from hospitalized patients in Australia, Japan, South Korea, Malaysia, the Philippines, Taiwan, and Thailand. In the Asia-Pacific region, Enterobacterales isolates that were ESBL-positive, carbapenemase-negative (17.9%) were more frequently identified than isolates that were carbapenemase-positive, MBL-negative (0.7%) or carbapenemase-positive, MBL-positive (1.7%). Multidrug-resistant (MDR) isolates of P. aeruginosa were more commonly identified (23.4%) than isolates that were ESBL-positive, carbapenemase-negative (0.4%), or carbapenemase-positive, MBL-negative (0.3%), or carbapenemase-positive, MBL-positive (3.7%). More than 90% of all Enterobacterales isolates, including the ESBL-positive, carbapenemase-negative subset and the carbapenemase-positive, MBL-negative subset, were susceptible to amikacin and ceftazidime-avibactam. Among the carbapenemase-positive, MBL-positive subset of Enterobacterales, susceptibility to the majority of agents was reduced, with the exception of colistin (93.4%). Tigecycline was active against all resistant subsets of the Enterobacterales (MIC90, 1-4 mg/L) and among Escherichia coli isolates, > 90% from each resistant subset were susceptible to tigecycline. More than 99% of all P. aeruginosa isolates, including MDR isolates and the carbapenemase-positive, MBL-positive subset, were susceptible to colistin.
CONCLUSIONS: In this study, amikacin, ceftazidime-avibactam, colistin and tigecycline appear to be potential treatment options for infections caused by Gram-negative pathogens in the Asia-Pacific region.
METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.
RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.
CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.
TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.
METHODS: A total of 151 P. falciparum isolates were collected between April 2018 and March 2019 from 12 of the governorates in Jazan region. Genomic DNA was extracted from dried blood spots and amplified using nested PCR. Polymorphisms in the propeller domain of the P. falciparum k13 (pfkelch13) gene and point mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by sequencing.
RESULTS: No mutations in the pfkelch13 propeller domain were found in any of the 151 isolates. However, point mutations in the pfdhfr and pfdhps genes were detected in 90.7% (137/151) of the isolates. The pfdhfr double mutations N51I + S108N (i.e. ACICNI haplotype) and triple mutations N51I + C59R + S108N (i.e. ACIRNI haplotype) were detected in 47% and 37.8% of the isolates, respectively. Moreover, the pfdhps single mutation at codon A437G and double mutations A437G + K540E (i.e. SGEAAI haplotype) were observed in 4.6% and 51.7% of the isolates, respectively. Interestingly, 23.8%, 25.1 and 12.6% of the isolates had quintuple, quadruple and triple mutated combined pfdhfr-pfdhps genotypes, respectively. Furthermore, significant associations were found between the prevalence of mutant haplotypes and the age, gender and nationality of the patients (P drug, thereby threatening the main falciparum malaria treatment policy in Saudi Arabia, i.e. the use of AS + SP. Therefore, the continuous molecular and in-vivo monitoring of ACT efficacy in Jazan region is highly recommended.