Potential Roles of 5-HT3 Receptor Antagonists in Reducing Chemotherapy-induced Peripheral Neuropathy (CIPN).

5-HT3 receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT3 receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5- HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT3 receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.

The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer.

BACKGROUND: An uninterrupted dose of oxaliplatin-based cytotoxic therapy is an essential component in the standard treatment regimen of metastatic colon cancer (mCC). Data on the impacts of dose intensity reduction on the palliative treatment for patients with mCC remain scarce. Hence, this study aimed to investigate the impact of palliative chemotherapy dose modifications (DM) on the survival of patients with mCC. METHODS: Patients with stage IV colon cancer who received first-line palliative FOLFOX regimen chemotherapy between 2014 until 2018 in the Oncology Department of the National Cancer Institute were conveniently sampled retrospectively to analyse the treatment efficacy. The cumulative dose and duration of chemotherapy received by the patients were summarised as relative dose intensity (RDI) and stratified as High RDI (RDI ≥ 70%) or Low RDI (RDI < 70%). Progression-free survival (PFS) and 2-year overall survival (OS) between the two groups were analysed using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Out of the 414 patients identified, 95 patients with mCC were eligible and included in the final analysis. About half of the patients (n = 47) completed the 12-cycle chemotherapy regimen and one patient received the complete (100%) RDI. The overall median RDI was 68.7%. The Low RDI group (n = 49) had a 1.5 times higher mortality risk than the High RDI group [OS, Hazard Ratio (HR) = 1.5, 95% Cl: 1.19-1.82] with a significant median OS difference (9.1 vs. 16.0 months, p <  0.01). Furthermore, patients with lower dose intensity showed double the risk of disease progression (PFS, HR = 2.0, 95% CI: 1.23-3.13) with a significant difference of 4.5 months of median PFS (p <  0.01). Gender and RDI were the independent prognostic factors of both OS and PFS. CONCLUSION: Reduction in the dose intensity of palliative chemotherapy may adversely affect both disease progression and overall survival among mCC patients.

Predictive Factors, Treatment, and Outcomes of Coagulase-Negative Staphylococcal Peritonitis in Malaysian Peritoneal Dialysis Patients: A Single-Center Study.

Aims: Coagulase-negative Staphylococci (CoNS) are frequently isolated in peritoneal dialysis (PD)-related peritonitis with a high rate of relapse and repeat peritonitis after initial response to antimicrobials. The optimal treatment regimen for CoNS peritonitis remains debatable. Hence, this study aimed to describe the clinical and microbiologic characteristics of CoNS peritonitis in a PD center and determine predictive factors influencing the outcomes. Methods: All cases of CoNS peritonitis in Selayang Hospital between 2011 and 2019 were reviewed retrospectively. Results: A total of 906 episodes of peritonitis were recorded; 140 episodes (15%) in 98 patients were caused by CoNS. The oxacillin and gentamicin resistance rates were 47% and 46%, respectively. The overall primary response rate was 90%, and the complete cure rate was 79%. Patients with concomitant exit-site infection (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.01 to 0.40, P < 0.01) and history of recent systemic antibiotic use (OR 0.04, 95% CI 0.01 to 0.82, P=0.04) were less likely to achieve primary response. CoNS episodes that were treated with beta-lactam-based or vancomycin-based therapy had a similar primary response rate and complete cure rate. The rates of relapse and repeat were 12% and 16%, respectively. Relapsed episodes (OR 0.35, 95% CI 0.13 to 0.97, P=0.04) had a significantly lower complete cure rate than the first episodes. Conclusion: Relapsed CoNS peritonitis was common and was associated with worse outcomes than the first episode of CoNS peritonitis. Oxacillin resistance was common, but the treatment outcome remained favourable when a beta-lactam-based regimen was used as empirical therapy.

Preference, Perception, and Acceptability of Fluid Gels as a Potential Age-Appropriate Dosage Form for Elderly Patients with Dysphagia.

The development of pharmaceutical dosage forms that are tailored to specific populations according to their preferences and acceptability could improve medication adherence, which could lead to effective pharmacotherapy. This study evaluated the preference for and perceptions of fluid gels as a potential age-appropriate dosage form for older adults with dysphagia. The palatability and swallowability of the developed fluid gels were also assessed to determine the consumer acceptability of this formulation. A cross-sectional survey was conducted through the electronic distribution of a self-administered questionnaire among adults in Malaysia between April and December 2021. A randomized and double-blinded clinical study was conducted to evaluate the palatability and swallowability of the fluid gels in 30 healthy participants. A cross-sectional study involving 673 respondents revealed that the fluid gels were perceived positively by consumers (64.4%), were easily swallowed (50.8%), were safe to be consumed (45.3%), and were suitable as a new pharmaceutical formulation (43.8%). The clinical study shows that moderately thickened fluid gels masked the bitterness of the medication and were easily swallowed. The newly developed fluid gels were also positively perceived by the participants. Taken together, fluid gels have shown great potential as an innovative oral formulation that is suitable for consumption by elderly patients with dysphagia.

Formulation and Cost-Effectiveness of Fluid Gels as an Age-Appropriate Dosage Form for Older Adults with Dysphagia.

Dysphagia is associated with increased dependency and treatment costs, whereby patients resort to extemporaneous compounding that may further increase the number of adverse events and medical errors. In the management of dysphagia, increasing the bolus viscosity of medication such as fluid gels can be practiced. This study aimed to prepare and characterize the fluid gels as well as to estimate the cost of using fluid gels and compare it to the conventional practice of extemporaneous preparation of thickened liquid. Fluid gels were formulated using gellan gum and determined for physicochemical characteristics and in vitro drug release profile. The cost-based price of the fluid gel was estimated and compared to the cost of administering standard medication as well as administering thickened liquid using thickening powder. Fluid gels exhibited good physicochemical properties with the viscosity within nectar and honey consistency. A similar dissolution profile to the reference was observed for the 0.5% w/v gellan gum fluid gel and exhibiting the Higuchi release model. The price for 100 mL unit of 50 mg/mL paracetamol/acetaminophen and 20 mg/mL ibuprofen fluid gel was estimated to be about USD2.30 and USD2.37, respectively. A dose of 1000 mg paracetamol and 400 mg ibuprofen fluid gel was estimated to be about USD0.46 and USD0.47, respectively, which is lower than the cost of administering the same dose using extemporaneous thickened liquid. Fluid gels could be a cost-effective formulation for delivering medication in patients with dysphagia and can be developed on a profitable scale.

The influence of P-glycoprotein expression in the standard treatment of Helicobacter pylori infection in Sprague Dawley rats.

BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic. OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen. METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively. RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p < 0.05) in P-gp expression level and a more severe ulcer formation compared to the healthy rats. The ulcer developed at different levels in the rats with inhibited, induced, or normal P-gp expression. After receiving the standard therapy for H. pylori, it was observed that the healing rate for ulcer was increased to 91% (rats with inhibited P-gp expression), 82% (rats with induced P-gp expression) and 75% in rats with normal P-gp. The use of rifampicin to induce P-gp level was also shown to be effective in eradicating the H. pylori infection. CONCLUSION: The synergism in the standard therapy by using two antibiotics (clarithromycin and amoxicillin) and proton pump inhibitor (omeprazole) have shown to effectively eradicate the H. pylori infection. Thus, P-gp expression influenced the effectiveness of the treatment.

Practical Problems of Medication Use in the Elderly Malaysians and Their Beliefs and Attitudes Toward Deprescribing of Medications.

OBJECTIVE: This study aimed to investigate the prevalence of practical problems with medications use experienced by elderly patients and the management strategy employed to overcome the problems. This study also aimed to evaluate the belief and attitude of elderly patients toward deprescribing. METHODS: A cross-sectional study was conducted among elderly patients that seeking treatment in a primary care clinic in Malaysia from September to November 2018 using a set of researcher-assisted and validated questionnaire on their consent. FINDINGS: A total of 182 elderly patients were included in this study. A majority of participants (n = 87, 47.8%) admitted experiencing practical problems with their medication use. There are varieties of choice of management strategy employed by elderly patients to overcome the problems. For the willingness to deprescribing, there were positive correlation for patients' age (rs (182) =0.183, P < 0.05) and number of medications (rs (182) =0.271, P < 0.01) with the burden factor. There were also a negative correlation of age (rs (182) = -0.174, P < 0.05) and number of medication (rs (182) = -0.176, P < 0.04) with appropriateness of medications. CONCLUSION: A majority of Malaysian elderly experience practical problems with their medication use. Elderly patients' belief and attitudes toward deprescribing were influenced by age and number of medications.

Predictive factors for contrast-induced acute kidney injury in high-risk patients given N-acetylcysteine prophylaxis.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is rec.ognized as a common complication of radiographic contrast-enhanced procedures. N-acetylcysteine (NAC) is commonly prescribed, but CI-AKI can still develop despite NAC administration as prophylaxis. OBJECTIVE: Identify the predictive factors for development of CI-AKI in patients prescribed NAC. DESIGN: Prospective, cross-sectional. SETTING: A tertiary hospital in Malaysia. PATIENTS AND METHODS: All adult patients who were prescribed NAC for prevention of CI-AKI were identified through an NAC drug us.age monitoring card maintained by the inpatient pharmacy. The study was conducted from March to July 2017. MAIN OUTCOME MEASURES: Statistically significant predictive fac.tors for development of CI-AKI despite NAC administration. SAMPLE SIZE: 152 RESULTS: The most commonly recognized risk factors for CI-AKI present in the study population were renal impairment (n=131, 86.2%), anemia (n=107, 70.4%), and diabetes mellitus (n=90, 59.2%). Hydration therapy was initiated in 128 patients (84.2%) prior to the contrast-enhanced procedure. Sixty-one (40.1%) were treated with nephrotoxic medications concomitantly with NAC. Fifteen (9.9%) patients developed AKI. Hypotension (OR: 6.02; 95% CI 1.25-28.97) and use of high contrast volume (OR: 6.56; 95% CI: 1.41-30.64) significantly increased the odds for AKI. Prior hydration therapy (OR: 0.13; 95% CI 0.03-0.59) showed protective effects. CONCLUSION: The risk predictors identified for CI-AKI were hypotension, high contrast volume and prior hydration therapy. LIMITATION: May not have identified other confounding factors for development of CI-AKI. CONFLICT OF INTEREST: None.

A qualitative study exploring issues related to medication management in residential aged care facilities.

BACKGROUND: Globally, the population of older people is on the rise. As families are burdened with the high cost of care for aging members, demand is increasing for medical care and nursing homes. Thus, medication management is crucial to ensure that residents in a care center benefit and assist the management of the care center in reducing the burden of health care. This study is aimed to qualitatively explore issues related to medication management in residential aged care facilities (RACFs). PARTICIPANTS AND METHODS: A total of 11 stakeholders comprising health care providers, administrators, caretakers and residents were recruited from a list of registered government, nongovernmental organization and private RACFs in Malaysia from September 2016 to April 2017. An exploratory qualitative study adhering to Consolidated Criteria for Reporting Qualitative Studies was conducted. In-depth interview was conducted with consent of all participants, and the interviews were audio recorded for later verbatim transcription. Observational analysis was also conducted in a noninterfering manner. RESULTS AND DISCUSSION: Three themes, namely medication use process, personnel handling medications and culture, emerged in this study. Medication use process highlighted an unclaimed liability for residents' medication by the RACFs, whereas personnel handling medications were found to lack sufficient training in medication management. Culture of the organization did affect the medication safety and quality improvement. The empowerment of the residents in their medication management was limited. There were unclear roles and responsibility of who manages the medication in the nongovernment-funded RACFs, although they were well structured in the private nursing homes. CONCLUSION: There are important issues related to medication management in RACFs which require a need to establish policy and guidelines.

Influences of proton pump inhibitor on Helicobacter pylori adherence to the gastrointestinal cell lines.

BACKGROUND/AIMS: Helicobacter pylori is a carcinogenic bacterium that could induce P-glycoprotein expression in the human gastrointestinal tract. Bacterial adherence to the gastrointestinal cell lines could be influenced by the level of P-glycoprotein. This study aimed to determine the influence of proton pump inhibitors that exhibit an inhibitory effect on P-glycoprotein in gastrointestinal carcinoma cell lines, namely Caco-2 and LS174T, in relation to H. pylori adherence. MATERIALS AND METHODS: Caco-2 and LS174T cells lines treated with omeprazole and esomeprazole were used in this study to assess the bacterial attachment of H. pylori within certain incubation periods. RESULTS: The presence of proton pump inhibitors increased the H. pylori adherence in a time-dependent manner in both Caco-2 and LS174T cell lines. The double inhibition of P-glycoprotein using proton pump inhibitor and P-glycoprotein inhibitor caused low P-glycoprotein expression in the cell lines, resulting in higher H. pylori adherence compared to the control cell lines. CONCLUSION: Proton pump inhibitors may alter P-glycoprotein expression in the gastrointestinal tract, and subsequently H. pylori adherence on the cell lines, and may contribute to resistance to drug therapy.

Factors associated with lipid goal attainment among acute coronary syndrome patients.

BACKGROUND: The incidence of acute coronary syndrome (ACS), one of the most common cardiovascular diseases, is high. Lipid goal attainment is one of the important factors to reduce the risk of recurrent heart attack. Identification of factors influencing lipid goal attainment such as age, female, race, underlying comorbidities, intensity of lipid-lowering therapy, patients' knowledge, and patients' belief about medicine would be beneficial in achieving the lipid goal. This study is aimed to determine lipid profile attainment and prescribing pattern of lipid-lowering therapy as well as to identify factors influencing lipid profile attainment among ACS patients. PATIENTS AND METHODS: This researcher-assisted cross-sectional survey was carried out at a cardiology clinic in a tertiary hospital from March to May 2015. RESULTS: A total of 101 ACS patients were involved in this study. The mean values for low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol levels were 2.75 (0.82) mmol/L and 1.14 (0.27) mmol/L, respectively, while the median value for triglyceride level was 2.75 (0.82) mmol/L. Only 15.8% of our participants achieved the targeted LDL-C. Simvastatin 20 mg was the most common regimen prescribed. Predictors for better LDL-C attainment were younger age (ß=-0.228; P=0.032) and higher knowledge score (ß=-0.255; P=0.049), while predictors for high-density lipoprotein cholesterol attainment were male (ß=0.268; P=0.006), smoking (ß=-0.192; P=0.045), and higher knowledge score (ß=-0.195; P=0.039). Smoking (ß=-0.361; P<0.0001) was the only predictor for higher triglyceride level. CONCLUSION: Younger age, female, lower knowledge score, and smoking status are good predictors for lipid attainment among ACS patients.

Long term use of lithium and factors associated with treatment response among patients with bipolar disorder.

BACKGROUND: Lithium has been the gold standard in treating bipolar disorder. In recent years, the use of lithium seems to be diminished although it is well tolerated among the bipolar disorder patients. SUBJECTS AND METHODS: This study aimed to evaluate the efficacy and tolerability of lithium as well as to determine factors associated with lithium response among patient with bipolar disorder. A retrospective study was done in a tertiary care hospital in Malaysia which included 47 bipolar disorder patients that were prescribed with lithium maintenance therapy in the time frame of January 2009 until December 2013. RESULTS: Of all the baseline characteristics tested, only psychotic feature differentiated lithium monotherapy group and combination therapy group significantly (χ(2)=4.732, p=0.03). When compared to period before lithium maintenance, all outcome measures (i.e. annual relapse rate, proportion time spent ill and duration of mood episode) showed significant improvement after lithium maintenance in both treatment groups. Lithium discontinuation only occurred in five cases of adverse effects. Predominant depressive mood episode before lithium maintenance (OR=0.159, p=0.033) and first euthymic interval after lithium maintenance (OR=1.109, p=0.047) significantly predicted lithium response. DISCUSSION: Lithium significantly reduced the frequency and time spent in relapse in patients with bipolar disorder. Predominant depressive mood polarity before lithium maintenance and longer first euthymic interval after lithium maintenance had been identified to predict lithium response significantly.