Factors associated with prehospital delay in acute myocardial infarction in Maldives.

BACKGROUND: Acute myocardial infarction (AMI) is the top cause of death in Maldives. Our study aims to determine the prehospital delay and its associated factors in AMI patients in Maldives. METHODS: A cross-sectional study was conducted with 127 patients, divided into early (≤ 6 h) and delayed (> 6 h) presenters to the hospital. The data collection for the study was carried out by interviewing AMI patients, focusing on their socio-demographic characteristics, coronary artery disease risk factors, clinical symptoms, situational factors, and behavioral and cognitive responses to symptoms. RESULTS: The median onset-to-door time was 230 (IQR 420) minutes. The mean age of AMI patients was 50.9 (SD ± 12.9) years old, and 39.4% of them had delayed presentation to the hospital. Smokers (adj OR = 0.3; 95% CI: 0.1, 0.9; P = 0.047) and those with previous episodes of chest pain or AMI (adj OR = 0.2; 95% CI: 0.03, 0.91; P = 0.038) were significant factors for early presentation to the hospital, while denial of symptoms (adj OR = 29.3; 95% CI: 1.6, 547.2; P = 0.024) and lack of knowledge (adj OR = 7.2; 95% CI: 1.77, 29.43; P = 0.006) led to a delayed decision to seek treatment. Situational factors such as onset at the workplace (adj OR = 5.8; 95% CI: 1.24, 26.83; P = 0.025) had lower odds of delay, whereas referral cases (adj OR = 7.7; 95% CI: 1.9, 30.94; P = 0.004) and use of sea ambulance (adj OR = 11.1; 95% CI: 2.8, 43.8; P = 0.001) were prone to delay in presentation to the hospital. CONCLUSION: Sea ambulance, referral cases, lack of knowledge, and denial of symptoms are significant factors associated with prehospital delay among patients with AMI. Public awareness about the benefits of early presentation and improvement of the means of transportation between islands is suggested to improve emergency cardiac care in the country.

Putative Pathogenic Genes of Leptospira interrogans and Leptospira weilii Isolated from Patients with Acute Febrile Illness.

Leptospirosis is an important worldwide tropical disease caused by pathogenic Leptospira spp. The determination of virulence genes is important, as it influences patients' clinical manifestations and clinical outcomes. This case report focused on detecting the pathogenic genes of Leptospira in association with the clinical manifestations of patients at the Hospital Universiti Sains Malaysia, Malaysia, who presented with acute febrile illness. Two cases were found and, to the best of our knowledge, these were the first two cases in Malaysia in which patients presented with febrile illness were associated with successful Leptospira isolation from clinical samples. Both clinical isolates were identified by 16S rRNA sequencing as Leptospira weilii and Leptospira interrogans, respectively, and they were classified as pathogenic Leptospira by the presence of different pathogenic genes, based on a polymerase chain reaction (PCR) amplification of targeted genes. This report emphasizes that different infecting Leptospira species and the presence of different virulence factors cause a slight difference in clinical manifestations and laboratory findings of leptospirosis. Genomic sequencing and annotation revealed the detection of classical leptospiral virulence factor genes that were otherwise missed using PCR for detection of Leptospira weilii genome B208.

A Performance Assessment Study of Different Clinical Samples for Rapid COVID-19 Antigen Diagnosis Tests.

Accurate diagnosis to limit the spread of SARS-CoV-2 is crucial for the clinical management of this lethal infection. Recently, many low-cost and easy-to-use rapid test kits (RTK) have been developed in many countries for the massive screening of SARS-CoV-2. Thus, evaluating the accuracy and reliability of an RTK is critical. The current study was conducted on 157 individuals to evaluate the performance accuracy of rapid SARS-CoV-2 antigen detection kits using different clinical samples compared with qRT-PCR results. Nasopharyngeal swabs were collected from patients for qRT-PCR and RTK tests, and then buccal and nasal, and nasal swabs were collected for RTK tests separately. The nasal and buccal swabs showed high sensitivity (98%) and specificity (100%) compared with the qRT-PCR results. Meanwhile, for nasal, the sensitivity was 96% with 98% specificity, and nasopharyngeal swabs showed 98% sensitivity and 94% specificity. Fisher's exact test revealed statistical significance (p < 0.05) between nasopharyngeal, nasal and buccal, and nasal swabs compared with qRT-PCR results. The study concludes that different clinical samples used for the rapid diagnosis of SARS-CoV-2 showed high sensitivities and specificities compared with qRT-PCR. The RTKs using nasal and buccal, nasopharyngeal, and nasal swabs are valuable tools for the early detection of SARS-CoV-2, especially when molecular detections are available with limited access and a high infectivity rate, when the timely detection of virus cases is urgently needed. These types of clinical samples are effective to be used by RTKs for surveillance among community and healthcare workers.

Supradiaphragmatic central venous catheter malposition detection using the parasternal long-axis echocardiographic view and dextrose 50% contrast solution: A pilot study.

Background: Contrast-enhanced ultrasonography (CEUS) using saline was studied to detect supradiaphragmatic central venous catheter malposition. Commonly used echocardiographic views are apical 4-chamber (A4c) and subcostal views. However, this standard method is not feasible in certain situations. We explored the feasibility of the right ventricle inflow parasternal long axis (RVI-PLAX) echocardiographic view and dextrose 50% (D50%) contrast solution for detecting supradiaphragmatic central venous catheter malposition. Method: This pilot study screened 60 patients who underwent ultrasound-guided supradiaphragmatic central venous catheter insertion. We compared the investigators' guidewire's J-tip detection, D50% rapid atrial swirl sign (RASS) findings on the RVI-PLAX view and the central venous catheter tip on chest radiograph. We also compared the mean capillary blood sugar level before and after the 5 ml D50% flush. Results: No guidewire J-tips were detected from the RVI-PLAX view. The first and second investigators' diagnosis of central venous catheter malposition detected on RVI-PLAX CEUS achieved an almost perfect agreement (κ = 1.0 (95% confidence interval (CI): 0.90 to 1.0), p < .0001). The RVI-PLAX CEUS was not able to detect two central venous catheter malpositions (one atrial malposition and one left brachiocephalic vein venous catheter malposition). The capillary blood sugar was significantly elevated (8.96 mmol/L vs. 9.75 mmol/L) after D50% flush (p < 0.005) with no complications reported within 30 minutes after the D50% flush. Conclusion: RVI-PLAX view should not be used for guidewire detection. CEUS using D50% and RVI-PLAX view are potentially useful tools in detecting central venous catheter malposition. Further studies comparing them with conventional methods are needed.

Performance Validation of COVID-19 Self-Conduct Buccal and Nasal Swabs RTK-Antigen Diagnostic Kit.

The antigen rapid diagnostic test (Ag-RDT) is an immunodiagnostic test that detects the presence of viral proteins (antigens) expressed by the COVID-19 virus in a sample from a patient's respiratory tract. This study focused on evaluating the performance of self-conduct buccal and nasal swabs RTK-antigen test compared to nasopharyngeal swab RTK-based COVID-19 diagnostic assays, Panbio™ COVID-19 Ag Rapid Test Device (Nasopharyngeal) (Abbott Rapid Diagnostics Jena GmbH, Jena, Germany) used in hospitals for first-line screening. The sensitivity and specificity of the paired RTK-Ag test in detecting the an-tigen were calculated at 96.4% and 100%, respectively. Fisher exact tests showed the association between nasopharyngeal swabs RTK-Ag assay and buccal-nasal swabs RTK-Ag from ProdetectTM is significant (p-values < 0.001). The result showed that a self-conducted buccal and nasal RTK-antigen rapid test by the patients is comparable to the results obtained from a rapid test device conducted by trained medical personnel using a nasopharyngeal swab.

Hiding in plain sight: Diagnosing pleural tuberculosis using lung ultrasound.

INTRODUCTION: Diagnosing pleural tuberculosis can be difficult in patients with ambiguous presentation, especially in resource-limited health centres. Thus, lung ultrasound had been studied as a novel method in helping clinicians to diagnose this condition. CASE PRESENTATION: A 48-year-old woman presented with worsening dyspnoea and orthopnoea for one week. She had also experienced weight loss, minimal dry cough and right-sided pleuritic chest pain for several weeks. A chest radiograph showed a right lower zone pleural effusion with no apparent lung consolidation. Lung ultrasound showed a right apical consolidation and right lower zone septated pleural effusion. Pleural fluid investigations showed exudative features of mixed lymphocytic, mesothelial and neutrophilic cellular components. Tuberculin skin test was strongly positive. She was subsequently treated for pleural tuberculosis. One month after treatment, her symptoms had improved considerably. DISCUSSION: Lung ultrasound has been found to be more effective than chest radiograph in detecting consolidation and diagnosing pneumonia. The portability and efficacy of today's ultrasound machines, including the handheld types, show that lung ultrasound is a practical, reliable and valuable diagnostic tool in managing pulmonary conditions including tuberculosis, provided that the operators are adequately trained. CONCLUSION: Lung ultrasound in tuberculosis is the next frontier for clinicians and researchers.

Ketamine-propofol (Ketofol) for procedural sedation and analgesia in children: a systematic review and meta-analysis.

OBJECTIVES: The aim of this review is to elucidate the efficacy and side effects of ketofol in comparison to other anaesthetic agents during procedural sedation and analgesia. METHOD: The Cochrane Central Register of Controlled Trials (1996 to Feb 2019) and MEDLINE (1966 to Feb 2019) were searched, including the related randomised control trials and reviewed articles to find unpublished trials or trials not obtained via electronic searches. Inclusion criteria for the studies included comparing recovery time, recording clinician satisfaction, and assessing the adverse effects of ketofol. RESULTS: Eleven trials consisting of a total of 1274 patients met our criteria and were included in this meta-analysis. Five trials compared ketofol with a single agent, while six trials compared ketofol with combined agents. While comparing between ketofol and a single agent (either ketamine or propofol), ketofol showed significant effect on recovery time (MD: -9.88, 95% CI: - 14.30 to - 5.46; P = 0.0003; I2 = 92%). However, no significant difference was observed while comparing ketofol with combined agents (RR: 0.75, 95% CI: - 6.24 to 7.74; P < 0.001; I2 = 98%). During single-agent comparison, ketofol showed no significant differences in terms of clinician satisfaction (RR: 2.86, 95% CI: 0.64 to 12.69; P = 0.001; I2 = 90%), airway obstruction (RR: 0.72, 95% CI: 0.35 to 11.48; P = 0.81; I2 = 0%), apnoea (RR: 0.9, 95% CI: 0.33 to 2.44; P = 0.88; I2 = 0%), desaturation (RR: 1.11, 95% CI: 0.64 to 1.94; P = 0.28; I2 = 21%), nausea (RR: 0.52, 95% CI: 0.91 to 1.41; P = 0.2; I2 = 38%), and vomiting (RR: 0.63, 95% CI: 0.25 to 1.61; P = 0.18; I2 = 42%). During comparison with combined agents, ketofol was more effective in reducing hypotension (RR: 4.2, 95% CI: 0.2 to 0.85; P = 0.76; I2 = 0%), but no differences were observed in terms of bradycardia (RR: 0.70, 95% CI: 0.14 to 03.63; P = 0.09; I2 = 53%), desaturation (RR: 1.9, 95% CI: 0.15 to 23.6; P = 0.11; I2 = 61%), and respiratory depression (RR: 1.98, 95% CI: 0.18 to 21.94; P = 0.12; I2 = 59%). CONCLUSION: There is low certainty of evidence that ketofol improves recovery time and moderate certainty of evidence that it reduces the frequency of hypotension. There was no significant difference in terms of other adverse effects when compared to other either single or combined agents. TRIAL REGISTRATION: PROSPERO CRD42019127278 .

Leptospiral Culture without 5'-Fluorouracil Revealed Improved Leptospira Isolation from Febrile Patients in North-Eastern Malaysia.

Objectives: Isolation of Leptospira by culture represents a definitive growth and confirmation of the disease, yet it is hampered with its nature of slow growth. With slight modification of culture method, the study aims to isolate and characterize Leptospira spp. from patients with acute febrile illness. Methods: A total of 109 blood samples were collected from patients with acute febrile illness that presented at the Emergency Department of Hospital Universiti Sains Malaysia, Malaysia. Clinical samples were subjected to Leptospira IgM Rapid test, microscopic agglutination test (MAT), isolation by culture method, and direct real-time PCR test. For leptospiral isolation, the samples (whole blood and deposit from spun plasma) were cultured into modified Ellinghausen McCullough Johnson Harris (EMJH) media with and without 5'-fluorouracil (5-FU). In every culture positive sample, partial 16S rRNA gene sequencing was performed for molecular identification of the isolates. Phylogenetic analysis was carried out to determine the genetic relatedness among the isolates. An inhibition of 5-FU study was performed on Leptospirainterrogans serovar Canicola with different concentrations to compare the growth detection of the tested Leptospira with or without 5-FU within 7 days of incubation. Results: Leptospirosis was diagnosed in 14.7% of patients with acute febrile illness. Two Leptospira spp. (n = 2/109, 1.85%) were successfully isolated from whole blood and deposit from spun plasma samples. B004 and B208 samples were positive at day 11 and day 7, respectively, in EMJH media without addition of 5-FU. Sample B004 was identified as Leptospira interrogans and B208 as Leptospira weilli. Phylogenetic analysis confirmed that both of them were within pathogenic group and they were not related. The 5-FU inhibition study revealed that additional of 5-FU at final concentration of 200 µg/mL to EMJH media demonstrated an inhibitory effect on the growth of the tested strain Conclusion: Isolation of Leptospira spp. using EMJH media without addition of 5'-fluorouracil resulted in a better outcome. Two pathogenic Leptospira isolates were successfully cultivated from patients with acute febrile illness that were genetically not related.

Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.

RATIONALE: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question. OBJECTIVES: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia. METHODS: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02). CONCLUSIONS: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

An 11-Year Analysis of Emergency Presentations of Melioidosis in Northeastern Malaysia.

A neglected tropical disease, melioidosis is known to have variability in clinical presentations. Here, we described clinical features that should alert the physicians on the possibility of melioidosis. In this review of 86 cases from 2001 to 2011, the common presentations of melioidosis in the Emergency Department (ED), Hospital Universiti Sains Malaysia were; male gender (79.1 %), in working age group (47.8 ± 15.2 year-old), worked in contact with soil (73.3 %), presented with fever (91.9 %), in rainy season (55.8 %), have underlying diabetes mellitus (79.1 %), have leukocytosis (67.4 %) and high blood glucose (62.8 %) during presentation. In 34.9 % of cases, the antimicrobials were initiated at the ED and only 10.5 % include antimelioid drugs. Thirty-one patients (36.0 %) died due to melioidosis and 51.6 % of this were within 48 h of admission. Despite high mortality rate, the clinical awareness on the possibility of melioidosis among emergency physicians is still low and need to be strengthened.

Overexpression of DNA methyltransferase 1 (DNMT1) protein in astrocytic tumour and its correlation with O6-methylguanine-DNA methyltransferase (MGMT) expression.

BACKGROUND: The relationship between DNA methyltransferase (DNMT) and O6-methylguanine-DNA methyltransferase (MGMT) in mediating tumorigenesis is still poorly understood. This study was carried out to investigate a correlation between DNMT1 and MGMT immunoexpression in astrocytic tumour samples. METHODS: Formalin-fixed paraffin embedded tissues of astrocytic tumour patients was obtained from an observational study conducted in Hospital Universiti Sains Malaysia (USM), which was performed from January 1997 until May 2012. Patient's histological information was retrieved from the accessible Pathology Registry. Immunohistochemistry (IHC) staining was performed to assess DNMT1 and MGMT expressions in patients' tumours. RESULTS: Our data showed that DNMT1 was highly expressed in high grade astrocytic tumours. A multiple regression analysis demonstrated a significant association of DNMT1 overexpression with tumour grade III and IV (GIII: OR=5.802; 95% CI: 1.059, 31.785; p value=0.043; GIV: OR=40.663; 95% CI=4.069, 406.347; p value=0.002). The MGMT protein was downregulated in tumours with higher grade as evident by a reduction mean H-score for MGMT expression from GI to GIV [28.36 ± 43.88, 28.08 ± 33.67, 26.00 ± 48.70 and 16.20 ± 35.61]. However, a good negative correlation was observed between DNMT1 and MGMT in high grade tumour [Spearman correlation test: r=-0.561, p value ≤ 0.001 in percentage expression and r=-0.576, p value ≤ 0.001 in H score]. CONCLUSION: DNMT1 overexpression was seen correlated with a reduction of MGMT protein expression in high grade astrocytic tumour. Understanding the role of these markers could be important to overcome astrocytic tumour aggresiveness.

Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast.

BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

A multicenter controlled trial on knowledge and attitude about cardiopulmonary resuscitation among secondary school children in Malaysia.

BACKGROUND: 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. METHODS: This was a prospective intervention study. The primary endpoint of the study was to determine the level of KA about resuscitation after CPR training. The six schools and classes from selected schools were chosen by randomization among the form three and four classes using sealed envelopes. A fully validated questionnaire consisting of three sections (sociodemographic, knowledge and attitude) was given to the pupils before and 2 weeks after the intervention. The intervention group was given a lecture, video show, pamphlet and 1-h practical session on CPR training. The control group received a placebo in order to overcome the learning effect. The maximum scores for the knowledge and attitude sections were 72 and 28, respectively. Repeated measures ANOVA analysis was used for specific objectives to determine the changes in knowledge and attitude level pre- and post-intervention for both study groups. P-values less than 0.05 were taken as significant at 95% confidence intervals. RESULTS: The mean (SD) total knowledge scores for the intervention (n = 216) and control (n = 252) groups were 62.43 (13.68) and 62.29 (12.11), respectively (maximum score 72) (p > 0.05). On the other hand, the mean (SD) total attitude scores for the intervention and the control groups were 19.33 (4.51) and 17.85 (4.52), respectively (maximum score 28) (p < 0.001). There were significant differences in mean knowledge and attitude scores between the intervention and control groups with regard to time (pre- and post-intervention). The mean difference in knowledge and attitude scores between both study groups was 8.31 (p < 0.001) and 2.39 (p < 0.001), respectively. CONCLUSIONS: The level of knowledge and attitudes of secondary school children was shown to be acceptable prior to the intervention. Furthermore, a brief CPR training program improved their level of knowledge and attitudes significantly as compared to those who had never been trained.

Keratinous inclusion cyst of oesophagus: unusual finding.

Cysts of the oesophagus are unusual findings and they are classified according to the embryological site of origin. It may represent inclusion cysts, retention cysts and developmental cysts. We present a case of keratinous inclusion cyst of the lower oesophagus in a 71-year-old Malay woman who presented with dyspepsia and severe epigastric pain. An oesophago-gastro-duodenoscopy demonstrated a sliding hiatus hernia with whitish ulcer-like lesion at the lower oesophagus. Biopsy from the lesion revealed a keratinous inclusion cyst. The patient was given pantoprazole and put on regular follow-up for monitoring any other development.