The yield of tuberculosis contact investigation on relapsed TB patients and analysis of associated risk factors: Singapore's experience.

The yield of contact investigation on relapsed tuberculosis (TB) cases can guide strategies and resource allocation in the TB control programme. We conducted a retrospective cohort study to review the yield of contact investigation in relapsed TB cases and identify factors associated with TB infection (TBI) among close contacts of relapsed TB cases notified between 2018 and 2022 in Singapore. TB infection positivity was higher among contacts of relapsed cases which were culture-positive for Mycobacterium tuberculosis complex compared to those who were only polymerase chain reaction (PCR)-positive (14.8% vs. 12.3%). On multivariate analysis, after adjusting for age and gender of the index, gender, and existing comorbidities of contacts, factors independently associated with TBI were culture and smear positivity of the index (AOR 1.41, 95%CI 1.02-1.94), higher odds with every 10 years of increase in age compared to contacts below aged 30, contacts who were not Singapore residents (AOR 2.09, 95%CI 1.46-2.97), and household contacts (AOR 2.19, 95%CI 1.44-3.34). Although the yield of screening was higher for those who were culture-positive compared to only PCR-positive relapsed cases, contact tracing for only PCR-positive cases may still be important in a country with moderate TB incidence, should resources allow.

The floating hip injury: a descriptive study and case-control analysis.

PURPOSE: A "floating hip" (FH) injury is a rare injury describing the simultaneous ipsilateral fracture of the femur and pelvis or acetabulum (P/A). We describe our experience with patients presenting with FH injuries and compare them to controls with similar P/A fractures but without femoral involvement. METHODS: Medical records and radiographs of FH patients and controls presenting to our tertiary centre between 2015 and 2020 were reviewed. Follow-up data from outpatient clinical records were also extracted. The control group were extensively matched by age, sex, body mass index, fracture classification and energy of injury. RESULTS: From 1392 recorded P/A fractures, 42 FH cases were identified (average age 39 years, 78.6% males). The most common femoral fracture was the midshaft (35.7%), followed by the neck of femur (26.2%). 90.5% of FH injuries were due to high-energy mechanisms. 64.3% of P/A fractures, and 100% of femoral fractures were managed surgically. Compared to controls, FH cases were more likely to have additional orthopaedic injuries (73.8% vs. 40.5%, p = 0.002), more total theatre admissions (mean 2.5 vs. 1.19, p < 0.001), longer hospital stays (28.3 vs. 14.9 days, p = 0.02), and a higher rates of post-op complications (53.8% vs. 20%, p = 0.025). CONCLUSIONS: We report differences in the presentation, management, and outcomes of FH injuries versus controls, even after extensive matching for confounders. These differences may inform future treatment strategies for the FH injury.

Comparison of the patients with diabetes mellitus using either insulin or oral antidiabetic drug in terms of difficult laryngoscopy: A randomized controlled study.

Aim: We aimed to evaluate the differences in the difficult laryngoscopy as a general anesthetic component in patients with Diabetes Mellitus (DM) using either insulin or oral antidiabetic drug (OADD). Materials and Methods: This study was planned for a total of 230 patients including DM patients and non-DM patients as a control group who would undergo elective surgery between 30.01.2020-30.04.2020. Age, gender, body mass index (BMI), Mallampati scores, thyromental distance (TMD), inter-incisor distance (IID), and neck extension measurements were noted. Preoperative HbA1C levels, DM type, diagnosis time, and duration of insulin or OADD use were recorded. Patients without DM (Group C), patients using insulin (Group I), and patients using OADD (Group D) were separated respectively. Cormack-Lehane (CL) classification of the airway, number of laryngoscopic attempts, intubation success at the first attempt, intubation duration, performance of backward-upward-rightward pressure (BURP) maneuver, and requirement of use of different airway equipment were compared between the groups. Results: The data of 192 patients were compared. The mean IID (mm) was lower in Groups I and D than C. It was the lowest in Group I. Presence of neck extension of more than 30° in Groups I and D was lower than C. Classification of CL in Groups I and D was higher than C. Number of laryngoscopic attempts was higher in Groups I and D than C. Intubation success at the first attempt was lower in Groups I and D than C. The intubation duration was longer in Groups I and D than C. It was the longest in Group I. The more BURP maneuvering was required in Groups I and D than C. In Groups I and D, the number of uses of different airway equipment was higher than in Group C. The rate of using a videolaryngoscope (VL) in Group I was higher than in Groups D and C. Conclusion: Difficult laryngoscopy was more common in DM patients. Moreover, in patients with DM using insulin, VL use was more often and intubation duration was longer than in patients with DM using OADD.

Large transmission cluster of acute hepatitis C identified among HIV-positive men who have sex with men in Bangkok, Thailand.

A rapidly emerging and highly concentrated hepatitis C virus (HCV) outbreak has recently been observed among both acute and chronic HIV-positive men who have sex with men (MSM) in Bangkok, Thailand. NS5B regions of the HCV genome were amplified using nested PCR and sequenced. Phylogenetic inference was constructed by Maximum Likelihood methods and clusters were identified with support and genetic distance thresholds of 85% and of 4.5%. Forty-eight (25 acute HIV and 23 chronic HIV) MSM with incident HCV infection were included in the analysis. HCV genotype (GT) was 85% GT 1a and 15% GT 3a or 3b. Median age at HCV diagnosis was 34 (interquartile range, 28-41) years. 83.3% (40/48) had history of syphilis infection and 36% (16/44) reported crystal methamphetamine use. Only 2 (4%) reported ever injecting drugs, both crystal methamphetamine. In the phylogenetic clustering analysis, 83% belonged to one of two clusters: one large (75%) and one small (8%) cluster. All clusters were GT 1a. MSM with acute HIV infection were more likely to be in a cluster (92%) than those with chronic infection (74%). HCV screening should be regularly performed for MSM in ART clinics, and offering direct-acting antiviral agents to all MSM with HCV infection might contain the HCV epidemic from expanding further.

Haemorrhagic transformation following ischaemic stroke: A retrospective study.

The aim of this study was to identify the prevalence of haemorrhagic transformation (HT) in patients with ischaemic stroke, and evaluate its association with medical comorbidities, stroke subtypes, premorbid medication, and long-term survival. To achieve this, we performed a retrospective analysis of 527 consecutive stroke rehabilitation patients. Of these, 102 (19.4%) developed HT. Older patients, and those with large artery strokes, had a higher risk of HT. Forty-one patients received alteplase (rtPA), of which 15 (36.6%) developed HT. A total of 129 (24.5%) patients were taking aspirin prior to their stroke and, of these, 39 (30.2%) developed HT. Twenty-three (4.36%) patients were taking vitamin k antagonists, prior to stroke, of which 14 (60.9%) developed HT. There were 102 patients (19.35%) with underlying atrial fibrillation, of whom 55 (53.9%) developed HT. Patients with known ischaemic heart disease had an increased risk of HT, and patients with HT had significantly lower total cholesterol levels (4.96 vs. 5.34) and lower LDL cholesterol levels (3.20 vs. 3.5). In conclusion, older age, atrial fibrillation, treatment with oral anticoagulants and antiplatelet medications prior to stroke, low total and LDL cholesterol, and rtPA use, are all associated with HT. Survival was not affected by the presence of HT.

Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation at the organ level alters microvascular shear stress, impairing angiogenesis. A computational model of placental vasculature predicted elevated placental micro-vascular shear stress in FGR placentae (0.2 Pa in severe FGR vs 0.05 Pa in normal placentae). Endothelial cells cultured under predicted FGR shear stresses migrated significantly slower and with greater persistence than in shear stresses predicted in normal placentae. These cell behaviors suggest a dominance of vessel elongation over branching. Taken together, these results suggest (1) poor vascular development increases vessel shear stress, (2) increased shear stress induces cell behaviors that impair capillary branching angiogenesis, and (3) impaired branching angiogenesis continues to drive elevated shear stress, jeopardizing further vascular formation. Inadequate vascular branching early in gestation could kick off this cyclic loop and continue to negatively impact placental angiogenesis throughout gestation.

Proceedings of the Inaugural Strategy Meeting for the Establishment of a Southeast Asia Regional Therapeutic Plasma Exchange Consortium for Neurological Disorders.

In conjunction with the third regional Southeast Asian (SEA) therapeutic plasma exchange (TPE) conference in Kuala Lumpur, Malaysia, 25 clinicians and researchers from SEA and South Asian countries attended the inaugural strategy meeting for the establishment of a regional TPE consortium for neurological disorders. The primary objective was to establish regional collaboration to improve delivery of TPE services in SEA. A pre-meeting survey was conducted to gather insights on disease spectrum, contextual practice challenges, and the need for a regional TPE consensus. Challenges identified include limited healthcare funding in support of diagnostic workup, TPE therapy, as well as development of clinical infrastructure and expertise capacity building. There was favorable interest in developing a working plan contextualized to this region. Strategies to overcome challenges were discussed. This included the need for a comprehensive referral system and network of regional TPE centers suited to local needs, supported by innovative TPE delivery programs.

Diabetes mellitus burden among people living with HIV from the Asia-Pacific region.

INTRODUCTION: Comorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new-onset DM among PLHIV in Asian settings. METHODS: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM. RESULTS AND DISCUSSION: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p < 0.001) compared to <2010, older age (41 to 50 years: HR = 2.46, 95% CI 1.39 to 4.36, p  = 0.002; and >50 years: HR = 4.19, 95% CI 2.12 to 8.28, p < 0.001) compared to <30 years, body mass index (BMI) >30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2 , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006). CONCLUSIONS: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.

Persistence of meticillin-resistant Staphylococcus aureus carriage in re-admitted patients.

A retrospective cohort study was conducted to investigate the duration and risk factors for persistence of meticillin-resistant Staphylococcus aureus (MRSA) colonization among known carriers who were re-admitted to hospital. MRSA carriage persisted in a high proportion of known carriers up to two years after their last date of discharge, and re-admission screening should be performed for at least this duration. A targeted screening approach should focus on older patients with a history of long inpatient stays, who are at higher risk of persistent carriage. Timely discharge planning is important in reducing the risk of persistent MRSA colonization among known carriers.

[Diagnosis and treatment of orbital cellulitis]. / Diagnostiek en behandeling van orbitale cellulitis.

Orbital cellulitis is a rare disease usually caused by sinusitis. Generally, the prognosis of both preseptal cellulitis and orbital cellulitis is favourable. Radiological distinction should be made between an orbital abscess and subperiosteal empyema. Theoretically, empyema is more accessible to antibiotics and, as it arises in a pre-existing anatomical space, it needs less aggressive treatment than an abscess. In contrast, the wall of an abscess created by the bacteria is scarcely permeable to antibiotics. Indications for surgical drainage should be based on clinical findings and not on Chandler's classification. Loss of vision, an unresponsive pupil or a densely packed orbit are indications for immediate surgical drainage. Drainage of an orbital abscess may speed up recovery.

Risk assessment and laboratory investigation of respiratory illness in travellers returning to Singapore 2012-2015: experience from the MERS-CoV Surveillance Programme.

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV), Singapore has enhanced its national surveillance system to detect the potential importation of this novel pathogen. Using the guidelines from the Singapore Ministry of Health, a suspect case was defined as a person with clinical signs and symptoms suggestive of pneumonia or severe respiratory infection with breathlessness, and with an epidemiological link to countries where MERS-CoV cases had been reported within the preceding 14 days. This report describes a retrospective review of 851 suspected MERS-CoV cases assessed at the adult tertiary-care hospital in Singapore between September 2012 and December 2015. In total, 262 patients (31%) were hospitalized. All had MERS-CoV infection ruled out by RT-PCR or clinical assessment. Two hundred and thirty (88%) of the hospitalized patients were also investigated for influenza virus by RT-PCR. Of these, 62 (27%) tested positive for seasonal influenza. None of the patients with positive influenza results had been vaccinated in the year prior to hospital admission. Ninety-three (36%) out of the 262 hospitalized patients had clinical and/or radiological evidence of pneumonia. This study demonstrates the potential benefits of pre-travel vaccination against influenza and pneumococcal disease.

Imaging in knee osteoarthritis.

PURPOSE OF REVIEW: Osteoarthritis is the most prevalent and disabling disease still necessitating research in pathogenic mechanisms, predictors of disease progression and responsive techniques to detect the slow structural changes within a short time frame. In this scenario, imaging modalities are essential. With recent advancements in technology and availability of large longitudinal datasets, tremendous advances are occurring. The present review discusses and summarizes recent original publications in this area. RECENT FINDINGS: MRI has been the most popular modality used to evaluate the different roles of structural disorders in incident knee osteoarthritis, to compare predictability of individual features of semiquantitative scores for knee replacement and to formulate different disease progression models. More ultrasound studies have been published, including the proposed semiquantitative scoring system by the Outcome Measures in Rheumatoid Arthritis Clinical Trial group. SUMMARY: As more advanced emerging technologies are developed in imaging, there are great opportunities to formulate new incident and prediction osteoarthritis models and to discover tissue-targeted disease-modifying drugs.

Vancomycin-resistant enterococci with reduced daptomycin susceptibility in Singapore: prevalence and associated factors.

Prevalence of vancomycin-resistant enterococci (VRE) and use of daptomycin are increasing in Asia. To determine the prevalence of daptomycin non-susceptible enterococci (DNSE) and understand factors associated with reduced daptomycin susceptibility in VRE, we conducted a case-control study in a 1600-bed adult tertiary hospital in Singapore. All VRE isolates from inpatients in 2012 were tested for daptomycin susceptibility. Patients with VRE isolates of daptomycin minimum inhibitory concentration (MIC) ⩾3 µg/ml were classified as daptomycin-reduced susceptible VRE (DRS-VRE) and those with daptomycin MIC 4 µg/ml (DNSE). About half (135, 55%) had reduced susceptibility to daptomycin (MIC 3-4 µg/ml). None in the DS-VRE group had prior exposure to daptomycin. After adjusting for age, gender, comorbidity, hospitalization duration, surgical history, indwelling device use, and duration of antibiotic exposure in the prior 3 months, >1 movement between wards [odds ratio (OR) 0·35, 95% confidence interval (CI) 0·16-0·74, P = 0·006] and minocycline resistance (OR 0·45, 95% CI 0·25-0·84, P = 0·011) were independently associated with DRS-VRE. Our study suggests that daptomycin exposure, >1 movement between wards, and resistance to minocycline, were associated with reduced daptomycin susceptibility in VRE.

Length of stay an important mediator of hospital-acquired methicillin-resistant Staphylococcus aureus.

Hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is becoming increasingly established in Asian hospitals. The primary aim of this study was to decompose the risk factors for HA-MRSA based on conceptual clinical pathways. The secondary aim was to show the amount of effect attributable to antibiotic exposure and total length of stay before outcome (LBO) so that institutions can manage at-risk patients accordingly. A case-control study consisting of 1200 inpatients was conducted in a large tertiary hospital in Singapore between January and December 2006. Results from the generalized structural equation model (GSEM) show that LBO [adjusted odds ratio (aOR) 14·9, 95% confidence interval (CI) 8·7-25·5], prior hospitalization (aOR 6·2, 95% CI 3·3-11·5), and cumulative antibiotic exposure (aOR 3·5, 95% CI 2·3-5·3), directly affected HA-MRSA acquisition. LBO accounted for the majority of the effects due to age (100%), immunosuppression (67%), and surgery (96%), and to a lesser extent for male gender (22%). Our model enabled us to account and quantify effects of intermediaries. LBO was found to be an important mediator of age, immunosuppression and surgery on MRSA infection. Traditional regression approaches will not only give different conclusions but also underestimate the effects. Hospitals should minimize the hospital stay when possible to reduce the risk of MRSA.

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high.

HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting.

Antiretroviral treatment failure has been defined by immunological failure (IF) in some resource-limited settings whereas defining by virological failure (VF) has been widely used in developed countries. There is limited comparison of the levels of HIV-1 drug resistance between using VF and IF for the diagnosis of treatment failure. A retrospective cohort study was conducted among HIV-1-infected patients failing first-line antiretroviral therapy (ART). Of 95 patients, median CD4 and HIV-1 RNA were 158 cells/mm(3) and 10,200 copies/mL, respectively. Patients in the IF group had higher HIV-1 RNA than those in VF group (23,820 versus 9510 copies/mL, P = 0.008). Nucleoside reverse transcriptase inhibitor (NRTI)-, non-NRTI- and protease inhibitor-resistance-associated mutations (RAMs) were observed in 57.9%, 94.7% and 5.3%, respectively. Q151M, a multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P = 0.032). Using IF to diagnose treatment failure is associated with higher HIV-1 RNA levels and a higher rate of Q151M, which can limit the options for second-line ART.

Incidental head and neck findings on MRI in young healthy volunteers: prevalence and clinical implications.

We determined the prevalence and clinical relevance of incidental brain and head and neck findings in young healthy volunteers with MR imaging. We retrospectively analyzed the MR images obtained from 203 healthy young adult volunteers (mean age, 21.9 years; range, 18-35 years). The prevalence of the categories of findings (no referral necessary, routine referral, urgent referral, and immediate referral) was scored by a head and neck radiologist or neuroradiologist. We found a high prevalence of incidental brain and head and neck abnormalities (9.4% and 36.7%, respectively); 4.4% of the brain findings and 5.5% of the head and neck findings were classified as in need of referral. Only 1 incidental finding classified as in need of referral (a skull lesion consistent with fibrous dysplasia) was actually referred at the time of the study (5.2%). These findings suggest that a high prevalence of incidental findings is common in healthy young volunteers, though the clinical implications are negligible.

Serotonin and dopamine transporters in relation to neuropsychological functioning, personality traits and mood in young adult healthy subjects.

BACKGROUND: Serotonin and dopamine neurotransmitter systems are implicated in the regulation of mood, cognition and personality traits and their dysfunction is thought to be implicated in diverse psychopathologies. However, in healthy subjects the relationship between the serotonin and dopamine systems and neuropsychological functioning and personality traits is not clearly established. In the present study we investigated whether neuropsychological functioning, personality traits and mood states of a group of healthy subjects are associated with in vivo measures of serotonin transporters (SERTs) and dopamine transporters (DATs). METHOD: A total of 188 young healthy subjects underwent neuropsychological and subjective measurements of memory function, depression and impulsivity. Participants' SERT and DAT availability in predefined regions of interest were assessed using single photon emission computed tomography (SPECT) with the radiotracer [123I]ß-CIT. Individual magnetic resonance imaging (MRI) scans served as anatomic reference. RESULTS: We did not find any significant association between SERT or DAT availability and neuropsychological test performance or self-reported impulsivity and mood. There were no significant sex differences in SERT or DAT availability, but men performed significantly better on some tests of visuospatial functioning than women. CONCLUSIONS: Robust negative findings for striatal DAT availability seriously question earlier findings of positive associations between DAT availability and cognitive functions in healthy subjects. Our results also suggest that subcortical SERT availability is not associated with the neuropsychological functions and personality traits assessed. In summary, the present study suggests that neuropsychological and personality measurements in young healthy people are not associated with subcortical SERT or striatal DAT availabilities in the brain.