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Faris Abushamma,1– 3 Zain Khayyat,1 Aya Soroghle,1 Sa’ed H Zyoud,4,5 Ahmad Jaradat,1,2 Maha Akkawi,1,6 Hanood Aburass,1,6 Iyad KK Qaddumi,7 Razan Odeh,8 Husam Salameh,8 Salah Albuheissi3 1Department of Medicine, College of Medicine and Health Sciences, An-Najah National University, Nablus, 44839, Palestine; 2Department of Urology, An-Najah National University Hospital, Nablus, 44839, Palestine; 3Bristol Urological Institute, North Bristol NHS Trust, Bristol, UK; 4Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, an-Najah National University, Nablus, 44839, Palestine; 5Clinical Research Center, an-Najah National University Hospital, Nablus, 44839, Palestine; 6Department of Pathology, An-Najah National University Hospital, Nablus, 44839, Palestine; 7Department of Urology, Rafedia General Hospital, Nablus, 44839, Palestine; 8Department of Oncology, An-Najah National University Hospital, Nablus, 44839, PalestineCorrespondence: Faris AbushammaDepartment of Medicine, College of Medicine and Health Sciences, an-Najah National University, Nablus, 44839, PalestineEmail farisabushamma@hotmail.comPurpose: Non-muscle invasive bladder cancer (NMIBC) is a potentially curable or controllable disease if strict adherence to a surveillance protocol is followed. Management and surveillance of NMIBC begins at the time of diagnosis up to a few years thereafter. There is scanty data in the literature evaluating the impact of non-compliance with the surveillance protocols on progression, recurrence, and mortality rate.Patients and Methods: An observational, retrospective cohort study recruited data between 2012 and 2017 at two tertiary hospitals. Data were collected consecutively. NMIBC patients who had at least 3 years of follow-up data were included. Patients were divided into different groups based on their compliance with the cystoscopy follow-up protocol as recommended by the European guidelines. We compared the cystoscopy compliant group with the non-compliant group in view of recurrence, progression, and mortality. In addition, missing variable items during surveillance were calculated using a new scoring model to predict adverse outcomes.Results: Eighty-eight NMIBC patients met our criteria. Recurrence rate (RR), progression rate (PR), metastasis rate (MsR), and mortality rate (MR) are significantly higher in non-compliant group, RR: (92.6%) (P< 0.001), PR: (54.1%) (P< 0.001), MsR: (37.7%) (P< 0.001), MR: (23.5%) (P= 0.002) respectively. In the subgroup analysis, intermediate and high-risk groups have a PR rate of zero in the compliant group, while it is 100% (P< 0.001) and 56.4% (P=0.001) in the non-compliant group, respectively. Use of a Kaplan Meier (KM) graph shows that compliant patients had a better survival in comparison to non-compliant patients. Scoring there or more is statistically and clinically significantly associated with higher recurrence, progression, and mortality. RR: (94%) (P=0.016), PR: 49% (P< 0.001) and MR (26%) (P=0.012).Conclusion: Non-compliance to a standardized surveillance protocol in NMIBC is associated statistically and clinically with adverse outcomes in comparison to a compliant group. This mandates strict adherence to surveillance guidelines particularly in patients with high-risk disease.Keywords: NMIBC, COVID-19, urological malignancies, haematuria

Background: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity., Methods: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted., Results: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities., Conclusions: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.