We assessed the effectiveness of an educational intervention in reducing antibiotic prescribing in public primary care clinics in Malaysia. Twenty-nine medical officers in nine clinics received an educational intervention consisting of academic detailing from the resident Family Medicine Specialist, as well as an information leaflet. The antibiotic prescribing rates were assessed for six months - three months before and three months after the intervention. A total of 28,562 prescriptions were analyzed. Among participating doctors, general antibiotic prescribing rates for pre- and post-intervention phases were 14.3% and 11.0% (post-intervention vs pre-intervention RR 0.77, 95% CI 0.72 to 0.83). The URTI-specific antibiotic prescribing rates for pre- and post-intervention phases were 27.7% and 16.6%, respectively (post-intervention vs pre-intervention RR 0.60, 95% CI 0.54 to 0.66). No significant change in antibiotic prescribing rates was observed among primary care practitioners who did not participate in the study. This low cost educational intervention using both active and passive strategies focusing on URTI produced a statistically significant (and clinically important) reduction in antibiotic prescribing.
Study site: Klinik Kesihatan, Negeri Sembilan, Malaysia
A complex HIV-1 unique recombinant form involving subtypes CRF01_AE, B, and B' was recently identified from an injecting drug user in Malaysia. A total of 13 recombination breakpoints were mapped across the near-full-length genome of isolate 10MYPR226, indicating the increasingly diverse molecular epidemiology and frequent linkage among various high-risk groups.
Three strains of HIV-1 unique recombinant forms (URFs) descended from subtypes B, B', and CRF01_AE were identified among people who inject drugs in Kuala Lumpur, Malaysia. These three URFs shared a common recombination breakpoint in the reverse transcriptase region, indicating frequent linkage within the drug-injecting networks in Malaysia.
Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.
Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing.
Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.
The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.
The prevalence of pain complaints as a reason for patient-doctor encounters in the local primary care setting is unknown. We performed a cross-sectional survey of such encounters in one public primary care clinic (KK) and 17 general practice clinics (GP), from the city of Seremban, Negeri Sembilan, Malaysia. Reasons for visits were recorded by doctors in KK and medical students in GP using a structured questionnaire. Morbidity data was coded using the International Classification of Primary Care (ICPC-2). A total of 2234 encounters were recorded (80.9% from KK, 19.1% from GP). The overall prevalence of pain complaints was 31.9% with a significant difference between the two cohorts (KK 28.7% and GP 45.2%, p<0.001). Musculoskeletal pain complaints were more common in KK than GP (40.9% versus 29.7%, p<0.05). Of the 3 main ethnic groups in Malaysia (Malay, Chinese and Indian) the Indian patients at KK had the highest prevalence of pain complaints and the Chinese at the GP had the lowest. Thus pain was a common complaint in the two different primary care settings studied. Some of the differences observed are probably due to the differences in the healthcare seeking behaviour of patients consulting at these two settings as well as differences in the payment systems.
Inefficient metered-dose inhaler (MDI) technique results in poor drug delivery, suboptimal disease control a possibility of inhaled medication overuse. The MDI technique of 134 government hospital and clinic followed-up adult asthmatic patients followed-up in a government hospital and a heath clinic was pragmatically assessed based on the 3 obligatory steps of adequate lip seal, appropriate hand-breath coordination and sufficient breath holding after inhalation. The relationship between technique efficiency and frequency of daily short-acting beta2-agonist (SABA) use via the MDI and asthma exacerbations over a 12-month period was also assessed. Fifty-six patients (42%) had inefficient MDI technique. All demographic and asthma-related variables between the 'efficient' and 'inefficient' technique groups of patients were comparable except for significantly longer mean years of MDI use in the 'efficient' technique group [mean (SD): 10 (7) vs. 7 (5); p=0.003]. There were no significant differences between the two groups in relation to frequency of daily SABA use or asthma exacerbations over the past 12 months. Despite having been available in Malaysia for a considerable period of time, the MDI device is still poorly handled by a large proportion of adult asthmatic patients. Changing to other more user-friendly devices or use of spacer devices to facilitate delivery should be considered for these patients.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Klinik Kesihatan Seremban, Malaysia
Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.
We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.
An indirect ELISA was used to detect antibodies against outer membrane protein preparations (OMPs) from Salmonella typhi. Sera from patients with a definitive diagnosis of typhoid fever (TF) gave a mean absorbance reading, at 414 nm, of 1.52 +/- 0.23 as compared to 0.30 +/- 0.11 for sera from healthy individuals. This gave a positive to negative ratio of absorbance readings of approximately 5.1. Suspected TF patients (no isolation of S. typhi), with positive and negative Widal titers had mean absorbance readings of 1.282 +/00.46 and 0.25 +/- 0.19, respectively. Sera from patients with leptospirosis, rickettsial typhus, dengue fever, and other infections gave mean absorbances of 0.20 +/- 0.08, 0.24 +/- 0.08, 0.27 +/- 0.08, and 0.31 +/- 0.16, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 94%, 80% and 100%, respectively. The antibody response detected in the definitive TF cases was predominantly IgG in nature and no cross-reactivity was seen with OMP preparations extracted from E. coli. Variable reactivity was noted with OMP preparations obtained from other Salmonella spp. Three major OMPs are presented in the antigen preparation and strong binding of positive sera was detected to all three bands.
Antibiotic prescribing by primary care doctors has received renewed interest due to the continuing emergence of antibiotic resistance and the attendant cost to healthcare. We examined the antibiotic prescribing rate in relation to selected socio-demographic characteristics of the prescribers at the Seremban Health Clinic, a large public primary care clinic, designated for teaching, in the state of Negeri Sembilan, Malaysia. Data were obtained from: (1) retrospective review of prescriptions for the month of June 2002 and (2) a questionnaire survey of prescribers. A total of 10667 prescriptions were reviewed. The overall antibiotic prescribing rate was 15%; the rate (16%) was higher for the general Outpatient Department (OPD) than the 3% for the Maternal & Child Health Clinic (MCH). The antibiotic prescription rates for upper respiratory tract infection (URTI) were 26% and 16%, respectively, for the OPD and MCH. Half of all the antibiotic prescriptions were for URTI making prescribing for URTI an appropriate target for educational intervention. The URTI-specific antibiotic prescription rate did not correlate with the prescribers' intention to specialise, patient load, perceived patient's expectation for an antibiotic, or the score for knowledge of streptococcal tonsillitis. Prescribing behaviours and record-keeping practices requiring correction were identified.
Study site: Klinik Kesihatan Seremban, Negeri Sembilan, Malaysia
Purpose Criminalization of drug use in Malaysia has concentrated people who inject drugs (PWID) and people living with HIV into prisons where health services are minimal and HIV-related mortality is high. Few studies have comprehensively assessed the complex health needs of this population. The paper aims to discuss these issues. Design/methodology/approach From October 2012 through March 2013, 221 sequentially selected HIV-infected male prisoners underwent a comprehensive health assessment that included a structured history, physical examination, and clinically indicated diagnostic studies. Findings Participants were mostly PWID (83.7 percent) and diagnosed with HIV while incarcerated (66.9 percent). Prevalence of hepatitis C virus (90.4 percent), untreated syphilis (8.1 percent), active (13.1 percent), and latent (81.2 percent) tuberculosis infection was several fold higher than non-prisoner Malaysian adults, as was tobacco use (71.9 percent) and heavy drinking (30.8 percent). Most (89.5 percent) were aware of their HIV status before the current incarceration, yet few had been engaged previously in HIV care, including pre-incarceration CD4 monitoring (24.7 percent) or prescribed antiretroviral therapy (ART) (16.7 percent). Despite most (73.7 percent) meeting Malaysia's criteria for ART (CD4 <350 cells/ μL), less than half (48.4 percent) ultimately received it. Nearly one-quarter (22.8 percent) of those with AIDS (<200 cells/ μL) did not receive ART. Originality/value Drug addiction and communicable disease comorbidity, which interact negatively and synergistically with HIV and pose serious public health threats, are highly prevalent in HIV-infected prisoners. Interventions to address the critical shortage of healthcare providers and large gaps in treatment for HIV and other co-morbid conditions are urgently needed to meet the health needs of HIV-infected Malaysian prisoners, most of whom will soon transition to the community.
Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.
The Malaysian Clinical Practice Guidelines (CPG) for Management of Dementia (second edition) was launched in April 2010 by the Ministry of Health Malaysia. A training programme for the management of dementia, involving all categories of staff working at primary and secondary centres, was implemented to ensure that care delivery for people with dementia was in accordance with the guidelines. The study aimed to look into improving knowledge and understanding of dementia following training, and to evaluate the effectiveness of the training programme using a clinical audit indicator recommended in the guidelines.
This research aimed to determine HIV prevalence, risk behaviour and knowledge of transmission methods among men who have sex with men (MSM) in Kuala Lumpur, Malaysia. Venue-day-time sampling (VDTS) was applied to identify venues where men congregate to solicit sex from other men. Participants recruited from clubs, massage parlours, saunas and one park self-completed a computerized behavioural questionnaire, were administered an oral rapid HIV test and given the opportunity to return later to receive full counselling and learn their HIV status. A total of 517 men were enrolled into the study. The majority were Malays (47.0%) and Chinese (43.7%). Twenty tested HIV positive (3.9%). Significant predictors of HIV infection included having unprotected anal sex with a casual partner (44.9% of participants, odds ratio [OR] = 2.99; 95% confidence interval [CI] 1.13-7.90; P = 0.027), having unprotected receptive anal sex (27.9%, OR = 2.71; 95% CI 1.10-6.54; P = 0.030) and having group sex (33.3%, OR = 3.95; 95% CI 1.55-10.09; P = 0.004). One in five participants (20.1% and 19.5%) did not believe that HIV could be transmitted through insertive or receptive anal sex, respectively. Risk behaviour is high and knowledge of HIV transmission methods was low among MSM in Kuala Lumpur. Future prevention efforts should focus on providing risk reduction education to this community.
Human mononuclear cells pre-labeled with [3H]arachidonic acid were shown to release metabolites following in vitro addition of heat-killed Salmonella typhi (HKST). The amount of label released was significantly higher than that seen with live S. typhi (LST). Addition of increasing amounts of HKST resulted in an increased release of metabolites. Enzyme immunoassay of the culture supernatants revealed that the bulk of the metabolite released was prostaglandin E2 (PGE2). Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) were not detectable in the culture supernatants. The significance and implications of these results are discussed.