Changes in the epidemiology and clinical manifestations of human immunodeficiency virus-associated tuberculosis in Hong Kong.

INTRODUCTION: Human immunodeficiency virus (HIV)-associated tuberculosis (TB) remains an important health challenge worldwide. Although TB prevalence has decreased in the general population, there is limited information regarding temporal trends in the incidence of HIV-associated TB in Hong Kong. There are also insufficient data regarding changes in clinical manifestation patterns among HIV-associated TB patients over time. This study aimed to describe temporal trends in the epidemiology and clinical manifestations of HIV-associated TB in Hong Kong. METHODS: We retrospectively reviewed data regarding HIV-associated TB patients that were reported to the TB-HIV Registry of the Department of Health during the period 2007 to 2020. Trends of TB as a primary acquired immunodeficiency syndrome (AIDS)-defining illness, as well as changes in demographic features and clinical manifestations of HIV-associated TB during this period were examined using Cochran-Armitage trend test. RESULTS: A decreasing trend was observed in the proportion of all reported cases of AIDS in which TB was a primary AIDS-defining illness during the study period. The proportions of female patients and patients with extrapulmonary involvement significantly increased, whereas the proportions of ever-smokers and patients with sputum smear positivity significantly decreased during the same period. A decreasing trend was observed in the proportion of patients with pulmonary TB in which the lower zone was the predominant site of lung parenchymal lesions. Among patients with a diagnosis of HIV infection before TB, an increasing trend was observed in the proportion of patients receiving antiretroviral therapy. CONCLUSION: Important temporal changes were observed in the epidemiology and clinical manifestations of HIV-associated TB. These results highlight the need for continued surveillance regarding the patterns of demographic features and clinical manifestations to inform policymakers when planning control strategies for HIV-associated TB.

Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

Management of patent foramen ovale in embolic stroke of undetermined source patients: Malaysian experts' consensus.

INTRODUCTION: About 20 to 40% of ischaemic stroke causes are cryptogenic. Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic stroke which is diagnosed based on specific criteria. Even though patent foramen ovale (PFO) is linked with the risk of stroke, it is found in about 25% of the general population, so it might be an innocent bystander. The best way to treat ESUS patients with PFO is still up for discussion. MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities. RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.

Diagnostic performance of prospective same-day 18F-FDG PET/MRI and 18F-FDG PET/CT in the staging and response assessment of lymphoma.

BACKGROUND: Accurate staging and response assessment are essential for prognosis and to guide treatment in patients with lymphoma. The aim of this study was to compare the diagnostic performance of FDG PET/MRI versus FDG PET/CT in adult patients with newly diagnosed Hodgkin and Non- Hodgkin lymphoma. METHODS: In this single centre study, 50 patients were prospectively recruited. FDG PET/MRI was performed after staging FDG PET/CT using a single injection of 18F-FDG. Patients were invited to complete same-day FDG PET/MRI with FDG PET/CT at interim and end of treatment response assessments. Performance was assessed using PET/CT as the reference standard for disease site identification, staging, response assessment with Deauville score and concordance in metabolic activity. RESULTS: Staging assessment showed perfect agreement (κ = 1.0, P = 0) between PET/MRI and PET/CT using Ann Arbor staging. There was excellent intermodality correlation with disease site identification at staging (κ = 0.976, P < 0.001) with FDG PET/MRI sensitivity of 96% (95% CI, 94-98%) and specificity of 100% (95% CI, 99-100%). There was good correlation of disease site identification at interim assessment (κ = 0.819, P < 0.001) and excellent correlation at end-of-treatment assessment (κ = 1.0, P < 0.001). Intermodality agreement for Deauville scores was good at interim assessment (κ = 0.808, P < 0.001) and excellent at end-of-treatment assessment (κ = 1.0, P = 0). There was good-excellent concordance in SUV max and mean between modalities across timepoints. Minimum calculated radiation patient effective dose saving was 54% between the two modalities per scan. CONCLUSION: With high concordance in disease site identification, staging and response assessment, PET/MR is a potentially viable alternative to PET/CT in lymphoma that minimises radiation exposure.

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Using satellite imagery to evaluate precontact Aboriginal foraging habitats in the Australian Western Desert.

Modern satellite imaging offers radical new insights of the challenges and opportunities confronting traditional Aboriginal ecology and land use in Australia's Western Desert. We model the likely dynamics of historic and precontact desert land use using Earth observation data to identify the distribution of suitable foraging habitats. Suitability was modelled for an ideal environmental scenario, based on satellite observations of maximal water abundance, vegetation greenness, and terrain ruggedness. Our model shows that the highest-ranked foraging habitats do not align with land systems or bioregions that have been used in previous reconstructions of Australian prehistory. We identify impoverished desert areas where unsuitable foraging conditions have likely persisted since early in the last glacial cycle, and in which occupation would always have been rare. These findings lead us to reconsider past patterns of land use and the predicted archaeological signature of earlier desert peoples.

Initial clinical experience of patient-specific QA of treatment delivery in online adaptive radiotherapy using a 1.5 T MR-Linac.

Purpose. This study aims to evaluate the performance of a commercial 1.5 T MR-Linac by analyzing its patient-specific quality assurance (QA) data collected during one full year of clinical operation.Methods and Materials. The patient-specific QA system consisted of offline delivery QA (DQA) and online calculation-based QA. Offline DQA was based on ArcCHECK-MR combined with an ionization chamber. Online QA was performed using RadCalc that calculated and compared the point dose calculation with the treatment planning system (TPS). A total of 24 patients with 189 treatment fractions were enrolled in this study. Gamma analysis was performed and the threshold that encompassed 95% of QA results (T95) was reported. The plan complexity metric was calculated for each plan and compared with the dose measurements to determine whether any correlation existed.Results. All point dose measurements were within 5% deviation. The mean gamma passing rates of the group data were found to be 96.8 ± 4.0% and 99.6 ± 0.7% with criteria of 2%/2mm and 3%/3mm, respectively. T95 of 87.4% and 98.2% was reported for the overall group with the two passing criteria, respectively. No statistically significant difference was found between adaptive treatments with adapt-to-position (ATP) and adapt-to-shape (ATS), whilst the category of pelvis data showed a better passing rate than other sites. Online QA gave a mean deviation of 0.2 ± 2.2%. The plan complexity metric was positively correlated with the mean dose difference whilst the complexity of the ATS cohort had larger variations than the ATP cohort.Conclusions. A patient-specific QA system based on ArcCHECK-MR, solid phantom and ionization chamber has been well established and implemented for validation of treatment delivery of a 1.5 T MR-Linac. Our QA data obtained over one year confirms that good agreement between TPS calculation and treatment delivery was achieved.

Thermal behavior of spin-current generation in PtxCu1-x devices characterized through spin-torque ferromagnetic resonance.

High temperature studies of spin Hall effect have often been neglected despite its profound significance in real-world devices. In this work, high temperature spin torque ferromagnetic resonance measurement was performed to evaluate the effects of temperature on the Gilbert damping and spin Hall efficiency of PtxCu1-x. When the temperature was varied from 300 K to 407 K, the Gilbert damping was relatively stable with a change of 4% at composition x = 66%. Alloying Pt and Cu improved the spin Hall efficiency of Pt75Cu25/Co/Ta by 29% to a value of 0.31 ± 0.03 at 407 K. However, the critical switching current density is dependent on the ratio between the Gilbert damping and spin Hall efficiency and the smallest value was observed when x = 47%. It was found that at this concentration, the spin transparency was at its highest at 0.85 ± 0.09 hence indicating the importance of interfacial transparency for energy efficient devices at elevated temperature.

Local anaesthetic delivery regimens for peripheral nerve catheters: a systematic review and network meta-analysis.

There are numerous possible techniques for delivering local anaesthetic through peripheral nerve catheters. These include continuous infusions, patient-controlled boluses and programmed intermittent boluses. The optimal delivery regimen of local anaesthetic is yet to be conclusively established. In this review, we identified prospective trials of delivery regimens through peripheral nerve catheters. Our primary outcome was visual analogue scale scores for pain at 48 h. Secondary outcomes were: visual analogue scores at 24 h; patient satisfaction scores; rescue opioid use; local anaesthetic consumption; and nausea and vomiting. Network meta-analysis was used to compare these outcomes. Predefined sub-group analyses were performed. Thirty-three studies enrolling 1934 participants were included. In comparison with continuous infusion, programmed intermittent boluses improved visual analogue pain scores at both 48 and 24 h, the weighted mean difference (95%CI) being -0.63 (-1.12 to -0.14), p = 0.012 and -0.48 (-0.92 to -0.03), p = 0.034, respectively. Programmed intermittent boluses also improved satisfaction scores, the weighted mean difference (95%CI) being 0.70 (0.10-1.31), p = 0.023, and reduced rescue opioid use, the weighted mean difference (95%CI) in oral morphine equivalent at 24 h being -23.84 mg (-43.90 mg to -3.77 mg), p = 0.020. Sub-group analysis revealed that these findings were mostly confined to lower limb and truncal catheter studies; there were few studies of programmed intermittent boluses for upper limb catheters. Programmed intermittent boluses may provide optimal delivery of a local anaesthetic through peripheral nerve catheters. Further research is warranted, particularly to delineate the differences between upper and lower limb catheter locations, which will help clarify the clinical relevance of these findings.

Comparing the outcome of monitored anaesthesia care and local anaesthesia for carpal tunnel syndrome surgery by neurosurgeons.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the commonest median nerve entrapment neuropathy of the hand, up to 90% of all nerve compression syndromes. The disease is often treated with conservative measures or surgery. The senior author initially intended to treat his own neurosurgical patients concurrently diagnosed with carpal tunnel syndrome in 2014, subsequently, he began to pick up more referrals from the primary healthcare group over the years. This has led to the setup of a peripheral and spine clinic to act as a hub of referrals. OBJECTIVE: Department of Neurosurgery Sarawak aimed to evaluate the surgical outcome of carpal tunnel release done over five years. METHODS: The carpal tunnel surgeries were done under local anaesthesia (LA) given by neurosurgeons (Bupivacaine 0.5% or Lignocaine 2%). Monitored anaesthesia care (MAC) was later introduced by our hospital neuroanaesthetist in the beginning of 2018 (Target-controlled infusion propofol and boluses of fentanyl). We looked into our first 17 cases and compared these to the two anaesthesia techniques (LA versus MAC + LA) in terms of patient's pain score based on visual analogue scale (VAS). RESULTS: Result showed MAC provided excellent pain control during and immediately after the surgery. None experienced anaesthesia complications. There was no difference in pain control at post-operation one month. Both techniques had equal good clinical outcome during patients' clinic follow up. CONCLUSION: Neurosurgeons provide alternative route for CTS patients to receive surgical treatment. Being a designated pain free hospital, anaesthetist collaboration in carpal tunnel surgery is an added value and improves patients overall experience and satisfaction.

Recommendations on prevention and screening for colorectal cancer in Hong Kong.

Colorectal cancer is the commonest cancer in Hong Kong. The Cancer Expert Working Group on Cancer Prevention and Screening was established in 2002 under the Cancer Coordinating Committee to review local and international scientific evidence, assess and formulate local recommendations on cancer prevention and screening. At present, the Cancer Expert Working Group recommends that average-risk individuals aged 50 to 75 years and without significant family history consult their doctors to consider screening by: (1) annual or biennial faecal occult blood test, (2) sigmoidoscopy every 5 years, or (3) colonoscopy every 10 years. Increased-risk individuals with significant family history such as those with a first-degree relative diagnosed with colorectal cancer at age ≤60 years; those who have more than one first-degree relative diagnosed with colorectal cancer irrespective of age at diagnosis; or carriers of genetic mutations associated with familial adenomatous polyposis or Lynch syndrome should start colonoscopy screening earlier in life and repeat it at shorter intervals.

Multiple sclerosis and neuromyelitis optica spectrum disorders in Malaysia: A comparison in different ethnic groups.

We performed a retrospective observational analytical study looking at the frequencies and characteristics of multiple sclerosis(MS) and neuromyelitis optica spectrum disorders(NMOSD) in consecutive patients with idiopathic inflammatory demyelinating disease (IIDDs) attending three centers (2009-2017). Of 523 patients with IIDDs, there were 173 patients with NMOSD and 230 patients with MS. The percentage of NMOSD: IIDDs was 33%. The percentage of NMOSD:Total MS and NMOSD cohort was 43%. Of 141 seropositive NMOSD patients, 134(95%) were from the three main ethnic groups. The percentage of seropositive NMOSD to IIDDs and to combined MS and NMOSD was 26.9% and 35% respectively. Ratios of MS to NMOSD were nearly equal at 1.3 to 1.0, reinforcing the high ratio of NMOSD to MS in Asia. Nearly half of the Chinese cohort were seropositive ie; 71/141 (50%) with the remainder being Malays; 56/141 (39.7%) and Indians; 7/141 (5%). Amongst the other indigenous groups seropositivity was seen in 2 each of Iban, Bajau, Kadazan descent as well as one of Bidayuh origin. Comparatively, seropositivity in NMOSD is commoner amongst the Chinese compared to the Malays (p ≤ 0.005) and Indians, p ≤ 0.05 with ratios as high as 10:1. In the MS group of 230 subjects, 123(53.5%) were Malays (ratio of MS:NMOSD of 2:1), 41(17.8%) were Chinese, (ratio of MS:NMOSD of 0.5:1.0) and 54 (23.5%)were Indians (ratios of MS:NMOSD of 5:1 amongst the Indians). The remainder from East Malaysia were made up of 2 each of Kadazans, Ibans and Bajaus including 3 each of Bidayuh and Eurasian descent. Comparatively, in the NMOSD and MS cohorts a female preponderance was noted more so amongst Chinese NMOSD patients, with rare familial occurrence in both but more in Malay MS/NMOSD patients. This study also highlighted some of the inter-ethnic differences in presentation of MS and NMOSD amongst the 3 main ethnic races in Malaysia and confirms indigenous races having MS/NMOSD which needs further research. It also reviewed current literature on similar inter-ethnic differences world wide. To conclude, MS and NMOSD are the commonest demyelinating diseases seen in Malaysia with interesting inter-ethnic differences and similarities.

Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Recommendations on prevention and screening for breast cancer in Hong Kong.

In Hong Kong, breast cancer is the most common cancer among women and poses a significant health care burden. The Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) was set up in 2002 by the Cancer Coordinating Committee to review and assess local and international scientific evidence, and to formulate recommendations for cancer prevention and screening. After considering the local epidemiology, emerging scientific evidence, and local and overseas screening practices, the CEWG concluded that it was unclear whether population-based breast cancer screening did more harm than good in local asymptomatic women at average risk. The CEWG considers that there is insufficient evidence to recommend for or against population-based mammography screening for such individuals. Women who consider breast cancer screening should be adequately informed about the benefits and harms. The CEWG recommends that all women adopt primary preventive measures, be breast aware, and seek timely medical attention for suspicious symptoms. For women at high risk of breast cancer, such as carriers of confirmed BRCA1/2 deleterious mutations and those with a family history of breast cancer, the CEWG recommends that they seek doctor's advice for annual mammography screening and the age at which the process should commence. Additional annual screening by magnetic resonance imaging is recommended for confirmed BRCA1/2 mutation carriers or women who have undergone radiation therapy to the chest between the age of 10 and 30 years. Women at moderate risk of breast cancer should discuss with doctors the pros and cons of breast cancer screening before making an informed decision about mammography screening every 2 to 3 years.

The Framingham risk score underestimates the risk of cardiovascular events in the HER2-positive breast cancer population.

INTRODUCTION: Patients with breast cancer (bca) who overexpress her2 (the human epidermal growth factor receptor 2) are at risk for cardiotoxicity when treated with anthracycline-based chemotherapy and her2-targeted agents. The Framingham risk score (frs) is a validated tool that stratifies patients into high-, intermediate-, or low-risk groups and calculates their 10-year risk of developing cardiovascular disease (cvd) based on past medical history, systolic blood pressure, and measurement of serum lipids. We retrospectively analyzed patients with her2-positive bca to determine whether the frs predicts adverse cardiovascular (CV) events or cardiotoxicity in patients treated using anthracyclines or her2-targeted therapy, or both. METHODS: The frs was determined for patients with bca referred to The Ottawa Hospital Cardiology-Oncology Clinic from October 2008 to August 2014. The patients were stratified into high (≥20%), intermediate (10%-20%), and low (<10%) 10-year cv risk groups. Primary outcomes included cvd-related hospitalizations and deaths, and cardiotoxicity [drop in left ventricular ejection fraction (lvef) of >10% to a lvef ≤50%]. RESULTS: Of the 152 patients included in the analysis (median follow-up: 40.7 months; range: 3.5-263 months), 47 (31%) were classified as high risk; 36 (24%), as intermediate risk; and 69 (45%), as low-risk. The number of cvd-related hospitalizations and deaths was 22, for an overall prevalence of 14%, with significantly more events occurring in high-risk than in low-risk patients (odds ratio: 4.18; 95% confidence limits: 1.47, 11.89). The frs predicted a 10-year risk of any cv event of 11.2% and underestimated the actual rate of cv events in the entire cohort. High frs was not associated with cardiotoxicity (p = 0.82). CONCLUSIONS: In a population of patients with her2-positive bca referred to a cardiology-oncology clinic, the frs does not accurately predict the risk of cv events or cardiotoxicity.