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Fulltext A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine

Albitar O, Harun SN, Ahmad SNA, Sheikh Ghadzi SM

Pharmaceutics, 2021 Jul 22;13(8).
PMID: 34452082 DOI: 10.3390/pharmaceutics13081121

Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients' medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan-Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93-0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97-7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01-1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.
Relations between clinical characteristics and cognitive deficits among adult patients diagnosed with major depressive disorder

Subhas N, Ang JK, Tan KA, Ahmad SNA

Int J Psychiatry Clin Pract, 2023 Sep;27(3):219-231.
PMID: 36448673 DOI: 10.1080/13651501.2022.2149415

OBJECTIVE: The present study examined the relations between clinical characteristics and cognitive deficits in adult patients with major depressive disorder (MDD) from a local outpatient psychiatric clinic in Malaysia.
METHODS: The present sample included 110 participants aged 20-60 years old. Participants were invited to provide their information on sociodemographic variables (age, gender, and educational level) and clinical characteristics (age at onset of depression and duration of illness) and to complete a series of cognitive performance measures including the Trail Making Tests A (psychomotor speed) and B (executive function), the Digit Symbol Substitution Test (attention), and the Auditory Verbal Learning Test (immediate free recall, acquisition phase, and delayed recall). The Mini International Neuropsychiatric Interview Version 6.0 was used to confirm the diagnosis of MDD and the Montgomery-Åsberg Depression Rating Scale was used to assess illness severity.
RESULTS: At the bivariate level, relations of age and educational level to all cognitive deficit domains were significant. At the multivariate level, only educational level and illness severity consistently and significantly predicted all cognitive deficits domains.
CONCLUSIONS: Therapeutic modalities should be individualised whilst considering the impacts of cognitive deficits in an attempt to prevent further deterioration in psychosocial functioning of MDD patients.KEY POINTSCognitive deficits are an elemental component of Major Depressive Disorder (MDD) persisting during a current major depressive episode or during remission, altering individuals' ability to process information and changes the way they perceive and interact with the environment.Cognitive deficits in MDD are evident among the upper-middle income groups in South-Eastern Asian countries warranting more local research as such deficits could lead to functional decline and work performance such as absenteeism and presenteeism.Therapeutic modalities should be individualised by taking the impacts of cognitive deficits into consideration to promote psychosocial functioning of MDD patients.
Fulltext Patients' willingness to pay for their drugs in primary care clinics in an urbanized setting in Malaysia: a guide on drug charges implementation

Wan Puteh SE, Ahmad SNA, Aizuddin AN, Zainal R, Ismail R

Asia Pac Fam Med, 2017;16:5.
PMID: 28392749 DOI: 10.1186/s12930-017-0035-5

BACKGROUND: Malaysia is an upper middle income country that provides subsidized healthcare to ensure universal coverage to its citizens. The challenge of escalating health care cost occurs in most countries, including Malaysia due to increase in disease prevalence, which induced an escalation in drug expenditure. In 2009, the Ministry of Health has allocated up to Malaysian Ringgit (MYR) 1.402 billion (approximately USD 390 million) on subsidised drugs. This study was conducted to measure patients' willingness to pay (WTP) for treatment of chronic condition or acute illnesses, in an urbanized population.
METHODS: A cross-sectional study, through face-to-face interview was conducted in an urban state in 2012-2013. Systematic random sampling of 324 patients was selected from a list of patients attending ten public primary cares with Family Medicine Specialist service. Patients were asked using a bidding technique of maximum amount (in MYR) if they are WTP for chronic or acute illnesses.
RESULTS: Patients are mostly young, female, of lower education and lower income. A total of 234 respondents (72.2%) were not willing to pay for drug charges. WTP for drugs either for chronic or acute illness were at low at median of MYR10 per visit (USD 3.8). Bivariate analysis showed that lower numbers of dependent children (≤3), higher personal and household income are associated with WTP. Multivariate analysis showed only number of dependent children (≤3) as significant (p = 0.009; 95% CI 1.27-5.44) predictor to drugs' WTP.
CONCLUSION: The result indicates that primary care patients have low WTP for drugs, either for chronic condition or acute illness. Citizens are comfortable in the comfort zone whereby health services are highly subsidized through universal coverage. Hence, there is a resistance to pay for drugs.
Pharmacometric modeling of drug adverse effects: an application of mixture models in schizophrenia spectrum disorder patients treated with clozapine

Albitar O, Ghadzi SMS, Harun SN, Ahmad SNA, Kjellsson MC

J Pharmacokinet Pharmacodyn, 2023 Feb;50(1):21-31.
PMID: 36380133 DOI: 10.1007/s10928-022-09833-9

Clozapine has superior efficacy to other antipsychotics yet is underutilized due to its adverse effects, such as neutropenia, weight gain, and tachycardia. The current investigation aimed to introduce a pharmacometric approach to simultaneously model drug adverse effects, with examples from schizophrenia spectrum patients receiving clozapine. The adverse drug effects were represented as a function of time by incorporating a mixture model to describe individual susceptibility to the adverse effects. Applications of the proposed method were presented by analyzing retrospective data from patients' medical records in Psychiatric Clinic, Penang General Hospital. Tachycardia, weight gain, and absolute neutrophils count (ANC) decrease were best described by an offset, a piecewise linear, and a transient surge function, respectively. 42.9% of the patients had all the adverse effects, including weight gain (0.01 kg/m2 increase every week over a baseline of 24.7 kg/m2 until stabilizing at 279 weeks), ANC decrease (20% decrease from 4540 cells/µL week 12-20.8), and tachycardia (14% constant increase over a baseline of 87.9 bpm for a clozapine maintenance dose of 450 mg daily). 32.5% of the patients had only tachycardia, while the remaining 24.6% had none of the adverse effects. A new pharmacometric approach was proposed to describe adverse drug effects with examples of clozapine-induced weight gain, ANC drop, and tachycardia. The current approach described the longitudinal time changes of continuous data while assessing patient susceptibility. Furthermore, the model revealed the possible co-existence of ANC drop and weight gain; thus, neutrophil monitoring might predict future changes in body weight.
Fulltext Density Functional Theory Study of 12mer Single-Strand Guanine Oligomer and Associated Muon Hyperfine Interaction

Zaharim WN, Ahmad SNA, Sulaiman S, Rozak H, Hasan Baseri DF, Mohamad Rosli NA, et al.

ACS Omega, 2021 Nov 09;6(44):29641-29650.
PMID: 34778635 DOI: 10.1021/acsomega.1c03956

Density functional theory method at the B3LYP/6-31G level was used to determine the structure of 12mer single-strand guanine oligomers. The length and width of the optimized structure are 38.7 and 18.2 Å, respectively, and the observed high-resolution transmission electron microscopy image of the 12mer single-strand guanine sample shows similar oligomer dimensions with the calculated ones. Both HOMO and LUMO are significantly delocalized, and the calculated HOMO-LUMO gap is 3.31 eV. A total of 96 muonium trapping sites at C2, C4, C5, C6, C8, N3, N7, and O6 were investigated. All 12 C8 sites have lower energy than the other 84 sites and are clustered in the energy-muon hyperfine coupling constant scatter plot. The calculated muon hyperfine coupling constant at C8 sites range from 384.6 to 481.1 MHz, and the corresponding estimated ALC-μSR resonance for |ΔM| = 1 range from 1.419 to 1.775 T.