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Fulltext Modifiable factors associated with bone health in Malaysian adolescents utilising calcaneus quantitative ultrasound

Zulfarina MS, Sharif R, Syarifah-Noratiqah SB, Sharkawi AM, Aqilah-Sm ZS, Mokhtar SA, et al.

PLoS One, 2018;13(8):e0202321.
PMID: 30106982 DOI: 10.1371/journal.pone.0202321

Maximizing bone mineral accrual to attain an optimal peak bone mass (PBM), particularly during adolescence, appears to be an effective protective strategy in the prevention of osteoporosis. This study aimed to evaluate the influence of physical activity (PA), fat mass (FM), lean mass (LM), body mass index (BMI), calcium, or combination of vitamin D supplement intake, smoking and alcohol drinking status on bone health assessed by calcaneus quantitative ultrasound (QUS) in a healthy adolescent population. The participants comprised of 920 male and female secondary school adolescents aged 15-17 years old. Quantitative ultrasound measurements of the left heel were performed using Lunar Achilles EX II, which included results of broadband ultrasound attenuation (BUA), speed of sound (SOS), and a calculated stiffness index (SI). Multivariable linear regression analyses revealed that-PA was positively associated with all three QUS indices in both genders; BMI was positively associated with SI and SOS in females; LM was positively associated with BUA in both genders; and FM was negatively associated with SI in females. These variables accounted for 32.1%, 21.2% and 29.4% of females' SOS, BUA and SI variances (p<0.001), respectively and 23.6%, 15.4% and 17.2% of males' SOS, BUA and SI variances (p<0.001), respectively. Promoting health benefits from physical activity could influence bone status and consequently improve PBM, which is a potent protective determinant against osteoporosis in adulthood.
Fulltext Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

Ibrahim N', Mohd Noor H', Shuid AN, Mohamad S, Abdul Malik MM, Jayusman PA, et al.

Front Pharmacol, 2021;12:706747.
PMID: 34867320 DOI: 10.3389/fphar.2021.706747

Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol-nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague-Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol-PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young's modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol-PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.
Fulltext Comparing the appropriateness of antimicrobial prescribing among medical patients in two tertiary hospitals in Malaysia

Loong LS, Siew Mei Lai P, Jamaluddin NAH, Naina-Mohamed I, Periyasamy P, Lau CL, et al.

J Infect Dev Ctries, 2022 Dec 31;16(12):1877-1886.
PMID: 36753656 DOI: 10.3855/jidc.15925

INTRODUCTION: Malaysia is an upper-middle-income country with national antimicrobial stewardship programs in place. However, hospitals in this country are faced with a high incidence of multidrug-resistant organisms and high usage of broad-spectrum antibiotics. Therefore, this study aimed to use a standardized audit tool to assess clinical appropriateness, guideline compliance, and prescribing patterns of antimicrobial use among medical patients in two tertiary hospitals in Malaysia to benchmark practice.
METHODOLOGY: A prospective hospital-wide point prevalence survey was carried out by a multidisciplinary team in April 2019 at the University Malaya Medical Centre (UMMC) and the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia. Data was collected from the patient's electronic medical records and recorded using the Hospital National Antimicrobial Prescribing Survey toolkit developed by the National Centre for Antimicrobial Stewardship, Australia.
RESULTS: The appropriateness of prescriptions was 60.1% (UMMC) and 67% (HCTM), with no significant difference between the two hospitals. Compliance with guidelines was 60.0% (UMMC) and 61.5% (HCTM). Amoxicillin-clavulanic acid was the most commonly prescribed antimicrobial (UMMC = 16.9%; HCTM = 11.9%).
CONCLUSIONS: The appropriateness of antimicrobial prescribing in medical wards, compliance with guidelines, and prescribing patterns were similar between the two hospitals in Malaysia. The survey identified several areas of prescribing that would need targeted AMS interventions.
Infertility and cortisol: a systematic review

Karunyam BV, Abdul Karim AK, Naina Mohamed I, Ugusman A, Mohamed WMY, Faizal AM, et al.

Front Endocrinol (Lausanne), 2023;14:1147306.
PMID: 37455908 DOI: 10.3389/fendo.2023.1147306

INTRODUCTION: Stress and infertility form a complex relationship. In line with this, various stress-related biological markers have been investigated in infertility.
METHODS: This systematic review was performed using PRISMA guidelines (i) to report whether cortisol is highly present in infertile patients compared to fertile control; (ii) to report whether there is any significant difference in the cortisol level in infertile subjects that conceive and those that didn't at the end of assisted reproduction treatments. Original articles involving human (male and female) as subjects were extracted from four electronic databases, including the list of references from the published papers. Sixteen original full-length articles involving male (4), female (11), and both genders (1) were included.
RESULTS: Findings from studies that compared the cortisol level between infertile and fertile subjects indicate that (i) Male: three studies reported elevated cortisol level in infertile patients and one found no significant difference; (ii) Female: four studies reported increased cortisol level in infertile subjects and three studies found no significant difference. Findings from studies that measured the cortisol level from infertile patients that conceived and those that didn't indicate that (i) Male: one study reported no significant difference; (ii) Female: one study reported elevated cortisol in infertile patients that conceived, whereas two studies reported increased cortisol in infertile patients that was unable to conceive. Five studies found no significant difference between the groups.
DISCUSSION: In the present review we only included the cortisol value that was measured prior to stimulation or IVF treatment or during natural or spontaneous cycles, despite this, there are still variations in the sampling period, assessment techniques and patients' characteristics. Hence, at present, we are still unable to conclude that cortisol is significantly elevated in infertile patients. We warrant future studies to standardize the time of biological sample collection and other limitations that were addressed in the review to negate the unwanted influencing factors.
Testosterone is associated with age-related changes in bone health status, muscle strength and body composition in men

Chin KY, Soelaiman IN, Naina Mohamed I, Shahar S, Teng NI, Suhana Mohd Ramli E, et al.

Aging Male, 2012 Dec;15(4):240-5.
PMID: 23098182 DOI: 10.3109/13685538.2012.724740

OBJECTIVE: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass.
MATERIALS AND METHODS: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging.
RESULTS: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05).
CONCLUSION: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.
Fulltext Physical function assessment of older adults with lower body fractures at 3 months post-discharge from hospital

Ibrahim N', Sharkawi Ahmad M, Zulfarina MS, Zaris SNASM, Nor Azlin ZA, Naina Mohamed I, et al.

Ther Clin Risk Manag, 2019;15:201-210.
PMID: 30774356 DOI: 10.2147/TCRM.S189748

Background and purpose: Physical function assessment can be performed to assess functional mobility among older adults, especially after a traumatic incident such as lower body fracture (LBF). The objective of this study was to evaluate physical function of older patients with LBF after 3 months of discharge from the hospital.
Patients and methods: A total of 89 patients were followed up at the discharge phase. Four independent variables were tested: age, sex, type of fracture, and use of a walking aid before fracture. Mobility and strength were assessed with the Timed Up and Go (TUG) test and hand-grip strength (HGS) test, respectively.
Results: The majority of the patients were ≥65 years old (64%), female (61.8%), of Chinese ethnicity (50.6%), and had a hip fracture (51.7%). The mean time for TUG test was 26.11 seconds, while mean HGS was 19.02 kg. We found significant differences in TUG test scores with respect to all independent variables tested: age (P=0.026), sex (P=0.011), fracture type (P<0.001), and use of a walking aid before fracture (P=0.004). Significant differences were also detected in HGS test scores with respect to all independent variables tested: age (P<0.001), sex (P<0.001), fracture type (P<0.001), and use of a walking aid before fracture (P=0.035).
Conclusion: Increasing age, female sex, having a hip fracture, and use of a walking aid before fracture predicted reduction in the physical function and strength among older adults with LBF.
Fulltext Phytochemical Analysis, Antioxidant and Bone Anabolic Effects of Blainvillea acmella (L.) Philipson

Abdul Rahim R, Jayusman PA, Lim V, Ahmad NH, Abdul Hamid ZA, Mohamed S, et al.

Front Pharmacol, 2021;12:796509.
PMID: 35111063 DOI: 10.3389/fphar.2021.796509

Blainvillea acmella (L.) Philipson [Asteraceae] (B. acmella) is an important medicinal plant native to Brazil, and it is widely known as a toothache plant. A plethora of studies have demonstrated the antioxidant activities of B. acmella and few studies on the stimulatory effects on alkaline phosphatase (ALP) secretion from bone cells; however, there is no study on its antioxidant and anabolic activity on bone cells. The study aimed to evaluate the phytochemical contents of aqueous and ethanol extracts of B. acmella using gas chromatography mass spectrometry (GCMS) and liquid chromatography time of flight mass spectrometry (LCTOFMS) along with the total phenolic (TPC) and flavonoid (TFC) contents using Folin-Ciocalteu and aluminum colorimetric methods. The extracts of B. acmella leaves were used to scavenge synthetic-free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The bone anabolic effects of B. acmella extracts on MC3T3-E1 cells were measured with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoium bromide (MTT) at 1, 3, 5, and 7 days, Sirius-red and ALP at 7 and 14 days, and Alizarin Red S at 14 and 21 days. Comparatively, ethanol extract of B. acmella (BaE) contributed higher antioxidant activities (IC50 of 476.71 µg/ml and 56.01 ± 6.46 mg L-ascorbic acid/g against DPPH and FRAP, respectively). Anabolic activities in bone proliferation, differentiation, and mineralization were also higher in B. acmella of ethanol (BaE) than aqueous (BaA) extracts. Positive correlations were observed between phenolic content (TPC and TFC) to antioxidant (ABTS and FRAP) and anabolic activities. Conversely, negative correlations were present between phenolic content to antioxidant (DPPH) activity. These potential antioxidant and bone anabolic activities in BaE might be due to the phytochemicals confirmed through GCMS and LCTOFMS, revealed that terpenoids of α-cubebene, cryophyllene, cryophyllene oxide, phytol and flavonoids of pinostrobin and apigenin were the compounds contributing to both antioxidant and anabolic effects in BaE. Thus, B. acmella may be a valuable antioxidant and anti-osteoporosis agent. Further study is needed to isolate, characterize and elucidate the underlying mechanisms responsible for the antioxidant and bone anabolic effects.
Fulltext Safety and efficacy of oil palm phenolic supplementation in improving lipid profile among hyperlipidemic adults: a phase 2, randomized, double-blind, placebo-controlled clinical trial

Muhammad Ismail Tadj NB, Ibrahim NI, Tg Abu Bakar Sidik TMI, Zulfarina MS, Haji Mohd Saad Q, Leow SS, et al.

Front Pharmacol, 2023;14:1190663.
PMID: 37484009 DOI: 10.3389/fphar.2023.1190663

Introduction: Oil palm phenolic (OPP) is an antioxidant aqueous palm oil by-product and contains a high amount of phenolics. OPP has been proven to have many therapeutical benefits, and one of them is as an antihyperlipidemic agent. The previous phase 1 clinical trial proved OPP was safe to be orally consumed by healthy volunteers and yielded a good lipid profile. Thus, this phase 2 clinical trial was conducted to determine the effectiveness of OPP in improving the lipid profile among hyperlipidemic subjects. Methods: A parallel, placebo-controlled, randomized, double-blinded clinical trial was conducted for 2 months on 50 hyperlipidemic subjects aged 20-50 years old. The subjects were randomly distributed to two treatment arms with 25 participants each: control/placebo (11 males and 14 females) and 250 mg of OPP (10 males and 15 females). The subjects were required to consume one capsule per day for 60 days. Fasting blood sampling for routine blood profile (hematology, liver function, renal function, and lipid) analysis and a medical examination were conducted at baseline, day 30, and day 60. t-test analysis was used to compare the difference between two test groups. Results: The baseline lipid profile between control group (TC, 5.78 ± 0.52 mmol/L; LDL, 3.88 ± 0.51 mmol/L; HDL, 1.30 ± 0.25; TG, 1.30 ± 0.82), and 250 mg OPP (TC, 5.76 ± 0.54 mmol/L; LDL, 3.82 ± 0.59 mmol/L; HDL, 1.37 ± 0.34; TG, 1.25 ± 0.54) is insignificant. No serious adverse events (SAEs) were reported. No abnormality in fasting blood parameters in all groups was found. Compared to the control group among male participants, the 250 mg OPP group showed an improved serum triglyceride level. There were no statistically significant changes in all blood parameters from day 1 to day 60 with the exception of triglyceride level. Conclusion: The absence of SAEs reported and no abnormal findings in biochemistry and hematology results suggested that the 250 mg OPP was safe to be taken by hyperlipidemic patients with a high probability of reducing triglyceride level in hyperlipidemic male patients The outcomes from this phase II trial suggest that by incorporating OPP supplements into the diet may be a promising strategy for individuals with hyperlipidemia to improve their lipid profiles and reduce cardiovascular risk. However, more research is needed to fully understand the mechanisms of action and establish the long-term efficacy and safety of OPP supplementation in larger scale. Limitation: Small samples size hence lack of diversity (25 subjects per groups) and early sharing of treatment-response results. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04573218.
Fulltext Point Prevalence Survey of Antimicrobial Use in a Malaysian Tertiary Care University Hospital

Jamaluddin NAH, Periyasamy P, Lau CL, Ponnampalavanar S, Lai PSM, Ramli R, et al.

Antibiotics (Basel), 2021 May 04;10(5).
PMID: 34064457 DOI: 10.3390/antibiotics10050531

Antimicrobial resistance remains a significant public health issue, and to a greater extent, caused by the misuse of antimicrobials. Monitoring and benchmarking antimicrobial use is critical for the antimicrobial stewardship team to enhance prudent use of antimicrobial and curb antimicrobial resistance in healthcare settings. Employing a comprehensive and established tool, this study investigated the trends and compliance of antimicrobial prescribing in a tertiary care teaching hospital in Malaysia to identify potential target areas for quality improvement. A point prevalence survey method following the National Antimicrobial Prescribing Survey (NAPS) was used to collect detailed data on antimicrobial prescribing and assessed a set of quality indicators associated with antimicrobial use. The paper-based survey was conducted across 37 adult wards, which included all adult in-patients on the day of the survey to form the study population. Of 478 patients surveyed, 234 (49%) patients received at least one antimicrobial agent, with 357 antimicrobial prescriptions. The highest prevalence of antimicrobial use was within the ICU (80%). Agents used were mainly amoxicillin/β-lactamase inhibitor (14.8%), piperacillin/β-lactamase inhibitor (10.6%) and third-generation cephalosporin (ceftriaxone, 9.5%). Intravenous administration was ordered in 62.7% of prescriptions. Many antimicrobials were prescribed empirically (65.5%) and commonly prescribed for pneumonia (19.6%). The indications for antimicrobials were documented in the patients' notes for 80% of the prescriptions; however, the rate of review/stop date recorded must be improved (33.3%). One-half of surgical antimicrobial prophylaxis was administered for more than 24 h. From 280 assessable prescriptions, 141 (50.4%) were compliant with guidelines. Treating specialties, administration route, class of antimicrobial, and the number of prescriptions per patient were contributing factors associated with compliance. On multivariate analysis, administering non-oral routes of antimicrobial administration, and single antimicrobial prescription prescribed per patient was independently associated with non-compliance. NAPS can produce robust baseline information and identifying targets for improvement in antimicrobial prescribing in reference to current AMS initiatives within the tertiary care teaching hospital. The findings underscore the necessity to expand the AMS efforts towards reinforcing compliance, documentation, improving surgical prophylaxis prescribing practices, and updating local antibiotic guidelines.
Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review

Kumar J, Naina Mohamed I, Mohamed R, Ugusman A, Muzaimi M, Mohamed W, et al.

Front Pharmacol, 2024;15:1428492.
PMID: 39086393 DOI: 10.3389/fphar.2024.1428492

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.
Fulltext Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture

Iskandar K, Molinier L, Hallit S, Sartelli M, Hardcastle TC, Haque M, et al.

Antimicrob Resist Infect Control, 2021 03 31;10(1):63.
PMID: 33789754 DOI: 10.1186/s13756-021-00931-w

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.
Assessment of antimicrobial prescribing patterns, guidelines compliance, and appropriateness of antimicrobial prescribing in surgical-practice units: point prevalence survey in Malaysian teaching hospitals

Jamaluddin NAH, Periyasamy P, Lau CL, Ponnampalavanar S, Lai PSM, Loong LS, et al.

Front Pharmacol, 2024;15:1381843.
PMID: 38720771 DOI: 10.3389/fphar.2024.1381843

Objectives: This study sought to investigate the quality of antimicrobial prescribing among adult surgical inpatients besides exploring the determinants of non-compliance and inappropriate prescribing to inform stewardship activities. Methods: A cross-sectional point prevalence study employing Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) was conducted in April 2019 at two teaching hospitals in Malaysia. Results: Among 566 surgical inpatients, 44.2% were receiving at least one antimicrobial, for a total of 339 prescriptions. Antimicrobials belonging to the World Health Organization's Watch group were observed in 57.8% of cases. Both hospitals exhibited similar types of antimicrobial treatments prescribed and administration routes. A significant difference in antimicrobial choice was observed between hospitals (p < 0.001). Hospital with electronic prescribing demonstrated better documentation practice (p < 0.001). Guidelines compliance, 32.8% (p = 0.952) and appropriateness, 55.2% (p = 0.561) did not significantly differ. The major contributors of inappropriateness were incorrect duration, (15%) and unnecessary broad-spectrum coverage, (15.6%). Non-compliance and inappropriate prescribing were found to be 2 to 4 times significantly higher with antimicrobial prophylaxis prescription compared to empirical therapy. Conclusion: Antimicrobial stewardship efforts to improve appropriate surgical prescribing are essential. These initiatives should prioritize surgical prophylaxis prescribing, focusing on reducing unnecessarily prolonged use and broad-spectrum antimicrobials, raising awareness among prescribers and promoting proper documentation.

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