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Fulltext The effects of angiotensin-converting enzyme gene polymorphism on the progression of immunoglobulin A nephropathy in Malaysian patients

Draman CR, Kong NC, Gafor AH, Rahman AF, Zainuddin S, Mustaffa WM, et al.

Singapore Med J, 2008 Nov;49(11):924-9.
PMID: 19037561

Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients.
Fulltext Knowledge of sexual and reproductive health among adolescents attending school in Kelantan, Malaysia

Ab Rahman A, Ab Rahman R, Ibrahim MI, Salleh H, Ismail SB, Ali SH, et al.

Southeast Asian J Trop Med Public Health, 2011 May;42(3):717-25.
PMID: 21706952

The objectives of this study were to describe the knowledge of sexual and reproductive health among adolescents attending school and to compare the levels of knowledge between males and females and between older and younger groups of adolescents. A cross-sectional study was conducted among 1,034 secondary school students using a self administered validated questionnaire. The items with the fewest correct responses included: whether one can get pregnant after a single act of sexual intercourse (30.4%), whether sexual intercourse causes sexually transmitted diseases (STDs) (12.4%) and whether washing the vagina after sexual intercourse prevents pregnancy (17.0%). Their main source of sexual information was friends (64.4%). An independent t-test revealed the mean knowledge score was significantly higher among females than males on items assessing whether the genitalia may be touched freely by family members, females having attained menarche may become pregnant if having sex, whether pregnancy will occur if there is penetration of the penis into the vagina, whether premarital sexual intercourse causes pregnancy and if there is a relationship between abandoned babies and premarital pregnancies. The mean knowledge score assessing whether pregnancy can be prevented using condoms was higher among males than females. The mean knowledge scores were significantly higher among form four and form five students than forms one, two and three students. Lack of knowledge regarding important aspects of sexual and reproductive health warrant the need to strengthen sexual and reproductive health education.
Distribution of virulence genes in clinical isolates of hospital-associated and community-associated methicillin-susceptible Staphylococcus aureus from Terengganu, Malaysia

Che Hamzah AM, Yeo CC, Puah SM, Chua KH, A Rahman A, Ismail S, et al.

Trop Biomed, 2024 Jun 01;41(2):149-156.
PMID: 39154266 DOI: 10.47665/tb.41.2.003

Staphylococcus aureus is a common bacterial pathogen known to cause various kinds of infections due to its repertoire of virulence factors. This study aimed to investigate the distribution of 19 types of virulence genes among clinical isolates of methicillin-susceptible S. aureus (MSSA) using the polymerase chain reaction. A total of 109 MSSA isolates, i.e., 63 hospital-associated (HA) and 46 community-associated (CA) were collected from Hospital Sultanah Nur Zahirah, the main tertiary hospital in Terengganu, Malaysia, from July 2016 to June 2017. The most frequent virulence genes detected were hla (78.9%, n=86) and hld (78.0%, n=85) encoding hemolysins, lukED (56.9%, n=62) encoding leukotoxin ED, followed by seb (26.6%, n=29) and sea (24.8%, n=27) encoding enterotoxins. Among 34 (31.2%) isolates carrying six or more virulence genes, only five were multidrug resistant (MDR) while the remaining isolates were susceptible. Significant associations were discovered between the hld gene with CA-MSSA (p=0.016) and the seo gene with HA-MSSA (p=0.023). However, there is no significant association between virulence genes among the different types of infection. The clinical MSSA isolates in Terengganu showed high prevalence and high diversity of virulence gene carriage.
Fulltext Tobacco Denormalization Indicator in the Prevalence of Positive Smoker Identity and Its Associated Factors

Ahmad MH, Ibrahim MI, Ab Rahman A, Musa KI, Mohd Zain F, Mohd Zain R, et al.

Int J Environ Res Public Health, 2020 Mar 31;17(7).
PMID: 32244417 DOI: 10.3390/ijerph17072363

Positive smoker identity (PSI) is a construct that evaluates the degree of smokers' positive thoughts, images and feeling about smoking behavior and culture. PSI encompasses the indicators related to tobacco denormalization strategy, which is one of the four WHO tobacco endgame strategies. PSmoQi is a newly validated instrument which could reliably assess PSI. This study's objectives were to determine the prevalence of positive smoker identity and its associated factors using PSmoQi. A sample of 253 smokers from government agencies in Kota Bharu City, Malaysia were recruited using invitation letters sent to their head of agencies. Data collection was done in a briefing session voluntary attended by the smokers. Factors associated with PSI were analyzed using Multiple Logistic Regression. The prevalence of smokers with positive smoker identity was 72.3%. Factors associated with positive smoker identity were older age (Adjusted Odds ratio; AOR: 1.042; 95% confident interval; CI: 1.004, 1.081); p = 0.028), higher smoking self-concept scale Malay version (SSCS-M) score (AOR: 1.216; 95% CI: 1.112, 1.329; p < 0.001), higher heaviness index (AOR: 1.002; 95% CI: 1.001, 1.004; p = 0.011) and lower educational attainment (AOR: 0.458; 95% CI: 0.233, 0.900; p = 0.024). This study shows a high prevalence of PSI among smokers from government agencies in Kota Bharu City. Factors such as age, SSCS-M score, heaviness index and educational attainment influenced the level of positive smoker identity in a smoker. The finding would contribute an evidentiary guideline in screening smokers for smoking cessation clinic enrollment to achieve the best interventional outcome, as well as it would provide an objective indicator for tobacco denormalization status in a population.
Fulltext Quality of Life Among Caregivers of Children with Special Needs in Kelantan, Malaysia: The Importance of Psychosocial Mediators

Isa SNI, Ishak I, Ab Rahman A, Mohd Saat NZ, Che Din N, Lubis SH, et al.

Malays J Med Sci, 2021 Apr;28(2):128-141.
PMID: 33958967 DOI: 10.21315/mjms2021.28.2.12

BACKGROUND: Quality of life (QoL) is an important aspect of well-being for the caregivers of children with disability, making it a noteworthy outcome. Little is known about the challenges faced by the caregivers in Asian countries and its association to their QoL. The purpose of this study was to examine a model describing the relationship between sociodemographic and disability-related factors on caregivers' QoL, mediated by the caregivers' psychosocial factors such as perceived stress, coping skills, and social support.
METHODS: A cross-sectional study was conducted involving caregivers of children with special needs in Kelantan, a state of Peninsular Malaysia. A total of 383 caregivers completed questionnaires measuring sociodemographics, disability-related factors, psychosocial factors and QoL outcome. Structural equation modelling was performed to examine the relations of the variables in the conceptual model.
RESULTS: In the final model, childcare dependency, caregiver's age, financial support, negative perception of stress and maladaptive coping skills were significant predictors of QoL (R 2 = 0.65). Caregiver's age had a direct effect on QoL, while financial support had an indirect effect on QoL via negative perception of stress. Childcare dependency had direct and indirect effects on QoL via negative perception of stress. Higher perceived stress was associated with lower QoL directly and indirectly via maladaptive coping skills. The final model fitted the data well (root mean square error of approximation [RMSEA] = 0.046; CFI = 0.923; χ2/df = 1.798).
CONCLUSION: Intervention strategies to improve the QoL of caregivers should target the family unit and take into account the factors of child's disability, demographic and caregiver's psychosocial status.
Fulltext A comparison of morbidity patterns in public and private primary care clinics in malaysia

Mimi O, Tong SF, Nordin S, Teng CL, Khoo EM, Abdul-Rahman A, et al.

Malays Fam Physician, 2011;6(1):19-25.
PMID: 25606215 MyJurnal

OBJECTIVES: To compare the morbidity patterns in public and private primary care clinics; determine patients' reasons for encounter (RFE) and diagnoses using the ICPC-2, and compare ten commonest diagnoses and RFEs.
METHODS: A cross-sectional study on randomly selected clinics was conducted nationwide. Doctors completed the Patient Encounter Record (PER) for systematically selected encounters for a week.
RESULTS: Response rate was 82.0% (public clinic) and 33% (private clinic) with 4262 encounters and 7280 RFE. Overall, the three commonest disease categories encountered were respiratory (37.2%), general and unspecified (29.5%), and cardiovascular diseases (22.2%). Public and private clinics handled 27% versus 50% acute cases and 20.0% versus 3.1% chronic cases i.e. 33.7 and 5.6 chronic diseases per 100 RFE respectively.
CONCLUSION: Doctors in public clinics saw more chronic and complex diseases as well as pregnancy related complaints and follow-up cases while in private clinics more acute and minor illnesses were seen. Health services should be integrated and support given to co-manage chronic diseases in both sectors.
KEYWORDS: Malaysia; Primary practice; delivery of health care; morbidity pattern; reasons for encounter
Fulltext Identification of psychosocial factors of noncompliance in hypertensive patients

Hassan NB, Hasanah CI, Foong K, Naing L, Awang R, Ismail SB, et al.

J Hum Hypertens, 2006 Jan;20(1):23-9.
PMID: 16177812 DOI: 10.1038/sj.jhh.1001930

This cross-sectional study was aimed to identify the predictors of medication noncompliance in hypertensive patients. The study was conducted at the Family Medicine Clinic, Hospital Universiti Sains Malaysia, Kelantan, Malaysia, which is a university-based teaching hospital. All hypertensive patients aged 40 or over-registered from January to June 2004, who had been on treatment for at least 3 months, were screened. Previously validated self-administered questionnaires were used to assess the compliance and psychosocial factors. A total of 240 hypertensive patients were recruited in the study. Of these, 55.8% were noncompliant to medication. Logistic regression showed that age (adjusted odds ratio (OR): 0.96; 95% confidence interval (CI): 0.92-0.997; P: 0.035), patient satisfaction (adjusted OR: 0.97; 95% CI: 0.93-0.998; P: 0.036) and medication barrier (adjusted OR: 0.95; 95% CI: 0.91-0.987; P: 0.009) were significant predictors of medication noncompliance. Therefore, younger age, poor patient satisfaction and medication barrier were identified as independent psychosocial predictors of medication noncompliant in hypertensive patients.
Fulltext Development and Validation of Positive Smoker Identity Questionnaire (PSmoQi): A New Instrument for Smoking Cessation Correlates

Ahmad MH, Ibrahim MI, Ab Rahman A, Musa KI, Mohd Zin F, Mohd Zain R, et al.

Int J Environ Res Public Health, 2019 01 26;16(3).
PMID: 30691181 DOI: 10.3390/ijerph16030351

Background: The positive smoker identity construct, which was based on West's PRIME Theory, affected the smoking prevalence, quit attempts and cessation success. A validated questionnaire which could measure this rich and complex construct may facilitate prediction models of successful cessation. We aimed to develop and validate a questionnaire that assesses positive smoker identity based on West's PRIME Theory. Method: The initial item pool was developed based on a theoretical framework, empirical literature, existing scales and expert review. The questionnaire was conveniently distributed to 100 smokers. Exploratory factor analysis was utilized to explore domains in the questionnaire. Construct and criterion validity, internal consistency and reliability of the domains were analyzed. Results: The final positive smoker identity questionnaire (PSmoQi) has 26 items under four internally-consistent and reliable domains: Contributory factors, contextual and temporal patterning, identity related to smoking, and behaviour in relation to smoking. The full scale demonstrated good internal consistency (∝ = 0.78), acceptable convergent and divergent validity, and good concurrent validity with the smoker self-concept scale. Conclusion: The current study provides fundamental evidence for the PSmoQi as a valid instrument in research related to smoking cessation and interventional strategy. The PSmoQi contained validated domains which could measure almost a full spectrum of smoking cessation components.
Effect of saffron supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials

Hasani M, Malekahmadi M, Rezamand G, Estêvão MD, Pizarro AB, Heydari H, et al.

Diabetes Metab Syndr, 2021 10 12;15(6):102311.
PMID: 34678576 DOI: 10.1016/j.dsx.2021.102311

BACKGROUND AND AIMS: Possible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes.
METHODS: An electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size.
RESULTS: Eight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: -0.18; 95% CI: -0.34, -0.02; I2 = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: -0.14; 95% CI: -0.36, 0.09; I2 = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: -0.18, 0.46; I2 = 42.9%) compared to placebo.
CONCLUSIONS: Saffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.
Fulltext Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach

Arefin A, Ismail Ema T, Islam T, Hossen S, Islam T, Al Azad S, et al.

J Biomed Res, 2021 Nov 06;35(6):459-473.
PMID: 34857680 DOI: 10.7555/JBR.35.20210111

Lassa hemorrhagic fever, caused by Lassa mammarenavirus (LASV) infection, accumulates up to 5000 deaths every year. Currently, there is no vaccine available to combat this disease. In this study, a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block the α-dystroglycan (α-DG) receptor and prevent LASV influx. Following rigorous absorption, distribution, metabolism, and excretion (ADME) and quantitative structure-activity relationship (QSAR) profiling, molecular docking was conducted with the top ligands against the α-DG receptor. The compounds chrysin, reticuline, and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity. Post-docking analysis revealed that interactions with Arg76, Asn224, Ser259, and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands. Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes. In-depth assessment of root-mean-square deviation (RMSD), root mean square fluctuation (RMSF), polar surface area (PSA), B-Factor, radius of gyration (Rg), solvent accessible surface area (SASA), and molecular surface area (MolSA) values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes. To authenticate the potentialities of the ligands as target-specific drugs, an in vivo study is underway in real time as the continuation of the research.
Fulltext Vaping topography and reasons of use among adults in Klang Valley, Malaysia

Zainol Abidin N, Abidin EZ, Zulkifli A, Syed Ismail SN, Karuppiah K, Amer Nordin AS, et al.

Asian Pac J Cancer Prev, 2018 Feb 26;19(2):457-462.
PMID: 29480664

Background: Consistency and accuracy of results in assessing health risks due to vaping or e-cigarette use are difficult to achieve without established consumption data. The present report covers baseline data on vaping topography and reasons for use among local users in Klang Valley, Malaysia.
Methods: An 80-item survey regarding socio-demographic characteristics, smoking topography and reasons for e-cigarette use was employed to assess e-cigarette users recruited from several public universities and private organisations. The survey questionnaire was self-administered. Data were analysed using statistical software.
Results: Eighty-six current e-cigarette users participated with more than half (51.2%) of them aged ≥ 25 years old. Significant proportions of the sample were single (51.2%), had a tertiary education level (63.5%) and a household income of less than USD1000 per month (65.2%). Median duration of e-cigarette use was less than a year; users drew approximately 50 puffs per day and refilled twice a day. The majority (74%) used e-liquids containing nicotine with a concentration of 6 μg/mL. Daily users spent USD18-23 per month. Reasons for using the e-cigarette included enjoyment of the products (85.9%), perception of lower toxicity than tobacco (87%), and the fact that it was a cheaper smoking alternative (61%).
Conclusion: The data on e-cigarette smoking topography obtained in this study are novel. The reasons of usage were mainly users’ enjoyment of e-cigarettes, preparation for quitting smoking, perception of low toxicity and a healthier smoking substitute and cheapness in the long run. The results establish basic knowledge for the local vaping topography and reference material for future e-cigarette-related research.
Synthesis, characterization and thermoluminescence properties of LiCaPO4 phosphor for ionizing radiation dosimetry

Rahat MR, Mimi HA, Islam SA, Kamruzzaman M, Ferdous J, Begum M, et al.

Appl Radiat Isot, 2023 Dec;202:111047.
PMID: 37782983 DOI: 10.1016/j.apradiso.2023.111047

Many minerals and compounds show thermoluminescence (TL) properties but only a few of them can meet the requirements of an ideal dosimeter. Several phosphate materials have been studied for low-dose dosimetryin recent times. Among the various phosphates, ABPO4-type material shows interesting TL properties. In this study, an ABPO4-type (A = Lithium, B=Calcium) phosphor is synthesized using a modified solid-state diffusion method. Temperature is maintained below 800 °C in every step of phosphor preparation to obtain the pure phase of Lithium calcium phosphate (LiCaPO4). The purpose of this work is to synthesize LiCaPO4 using a simple method, examine its structural and luminescence properties in order to gain a deeper understanding of its TL characteristics. The general TL properties, such as TL glow curve, dose linearity, sensitivity, and fading, are investigated. Additionally, this study aims to determine various kinetic parameters through Glow Curve Deconvolution (GCD) method using the Origin Lab software together with the Chen model. XRD analysis confirmed the phase purity of the phosphor with a rhombohedral structure. Lattice parameters, unit cell volume, grain size, dislocated density, and microstrain were also calculated from XRD data. Raman analysis and Fourier Transform Infrared analysis were used to collect information about molecular bonds, vibrations, identity, and structure of the phosphor. To investigate TL properties and associated kinetic parameters, the phosphor was irradiated with 6.0 MV (photon energy) and 6.0 MeV (electron energy) from a linear accelerator for doses ranging from 0.5 Gy to 6.0 Gy. For both photon and electron energy, TL glow curves have two identical peaks near 200 °C and 240 °C.The TL glow curves for 0.5 Gy-6 Gy are deconvoluted, then fitted with the appropriate model and then calculated the kinetic parameters. Kinetic parameters such as geometric factor (μg), order of kinetics, activation energy (E), and frequency factor (s) are obtained from Chen's peak shape method. The dose against the TL intensity curve shows that the response is almost linear in the investigated dose range. For photon and electron energy, the phosphor is found to be the most sensitive at 2.0 Gy and 4.0 Gy, respectively. The phosphor shows a low fading and after 28 days of exposure, it shows a signal loss of better than 3%. The studied TL properties suggest the suitability of LiCaPO4 in radiation dosimetry and associated fields.
Fulltext Visible and angular interrogation of Kretschmann-based SPR using hybrid Au-ZnO optical sensor for hyperuricemia detection

Mustaffa SN, Md Yatim N, Abdul Rashid AR, Md Yatim N, Pithaih V, Sha'ari NS, et al.

Heliyon, 2023 Dec;9(12):e22926.
PMID: 38125452 DOI: 10.1016/j.heliyon.2023.e22926

Uric acid is a waste product of the human body where high levels of it or hyperuricemia can lead to gout, kidney disease and other health issues. In this paper, Finite Difference Time Doman (FDTD) simulation method was used to develop a plasmonic optical sensor to detect uric acid with molarity ranging from 0 to 3.0 mM. A hybrid layer of gold-zinc oxide (Au-ZnO) was used in this Kretschmann-based Surface Plasmon Resonance (K-SPR) technique with angular interrogation at 670 nm and 785 nm visible optical wavelengths. The purpose of this study is to observe the ability of the hybrid material as a sensing performance enhancer for differentiating between healthy and unhealthy uric acid levels based on the refractive index values from previous study. Upon exposure to 670 nm wavelength, the average sensitivity of this sensor was found to be 0.028°/mM with a linearity of 98.67 % and Q-factor value of 0.0053 mM-1. While at 785 nm, the average sensitivity is equal to 0.0193°/mM with slightly lower linearity at 94.46 % and Q-factor value of 0.0076 mM-1. The results have proven the ability of hybrid material Au-ZnO as a sensing performance enhancer for detecting uric acid when compared with bare Au and can be further explored in experimental work.
Fulltext A multicenter controlled trial on knowledge and attitude about cardiopulmonary resuscitation among secondary school children in Malaysia

Rahman NH, Keng Sheng C, Kamauzaman TH, Md Noh AY, Wahab SF, Zaini IZ, et al.

Int J Emerg Med, 2013;6(1):37.
PMID: 24135122 DOI: 10.1186/1865-1380-6-37

We performed a multicenter controlled trial to assess the knowledge and attitude (KA) about cardiopulmonary resuscitation (CPR) among secondary school children in a district in Malaysia.
Fulltext Relationship of self-reported body size and shape with risk for prostate cancer: A UK case-control study

Aladwani M, Lophatananon A, Robinson F, Rahman A, Ollier W, Kote-Jarai Z, et al.

PLoS One, 2020;15(9):e0238928.
PMID: 32941451 DOI: 10.1371/journal.pone.0238928

INTRODUCTION: Previous evidence has suggested a relationship between male self-reported body size and the risk of developing prostate cancer. In this UK-wide case-control study, we have explored the possible association of prostate cancer risk with male self-reported body size. We also investigated body shape as a surrogate marker for fat deposition around the body. As obesity and excessive adiposity have been linked with increased risk for developing a number of different cancers, further investigation of self-reported body size and shape and their potential relationship with prostate cancer was considered to be appropriate.
OBJECTIVE: The study objective was to investigate whether underlying associations exist between prostate cancer risk and male self-reported body size and shape.
METHODS: Data were collected from a large case-control study of men (1928 cases and 2043 controls) using self-administered questionnaires. Data from self-reported pictograms of perceived body size relating to three decades of life (20's, 30's and 40's) were recorded and analysed, including the pattern of change. The associations of self-identified body shape with prostate cancer risk were also explored.
RESULTS: Self-reported body size for men in their 20's, 30's and 40's did not appear to be associated with prostate cancer risk. More than half of the subjects reported an increase in self-reported body size throughout these three decades of life. Furthermore, no association was observed between self-reported body size changes and prostate cancer risk. Using 'symmetrical' body shape as a reference group, subjects with an 'apple' shape showed a significant 27% reduction in risk (Odds ratio = 0.73, 95% C.I. 0.57-0.92).
CONCLUSIONS: Change in self-reported body size throughout early to mid-adulthood in males is not a significant risk factor for the development of prostate cancer. Body shape indicative of body fat distribution suggested that an 'apple' body shape was protective and inversely associated with prostate cancer risk when compared with 'symmetrical' shape. Further studies which investigate prostate cancer risk and possible relationships with genetic factors known to influence body shape may shed further light on any underlying associations.
Fulltext Epidemiology, clinical ramifications, and cellular pathogenesis of COVID-19 mRNA-vaccination-induced adverse cardiovascular outcomes: A state-of-the-heart review

Almas T, Rehman S, Mansour E, Khedro T, Alansari A, Malik J, et al.

Biomed Pharmacother, 2022 May;149:112843.
PMID: 35325848 DOI: 10.1016/j.biopha.2022.112843

The coronavirus disease 2019 (COVID-19) has overwhelming healthcare systems globally. To date, a myriad of therapeutic regimens has been employed in an attempt to curb the ramifications of a severe COVID-19 infection. Amidst the ongoing pandemic, the advent and efficacious uptake of COVID-19 vaccination has significantly reduced disease-related hospitalizations and mortality. Nevertheless, many side-effects are being reported after COVID-19 vaccinations and myocarditis is the most commonly reported sequelae post vaccination. Majority of these diseases are associated with COVID-19 mRNA vaccines. Various studies have established a temporal relationship between these complications, yet the causality and the underlying pathogenesis remain hypothetical. In this review, we aim to critically appraise the available literature regarding the cardiovascular side effects of the various mRNA vaccines and the associated pathophysiology.
Fulltext Rapid Assessment of Price Instability and Paucity of Medicines and Protection for COVID-19 Across Asia: Findings and Public Health Implications for the Future

Godman B, Haque M, Islam S, Iqbal S, Urmi UL, Kamal ZM, et al.

Front Public Health, 2020;8:585832.
PMID: 33381485 DOI: 10.3389/fpubh.2020.585832

Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic.
Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, et al.

J Pathol, 2023 Aug;260(5):514-532.
PMID: 37608771 DOI: 10.1002/path.6165

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
Fulltext Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.

J Pathol, 2023 Aug;260(5):498-513.
PMID: 37608772 DOI: 10.1002/path.6155

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Fulltext Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.

J Pathol, 2024 Mar;262(3):271-288.
PMID: 38230434 DOI: 10.1002/path.6238

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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