Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

V ˙ Lamax: determining the optimal test duration for maximal lactate formation rate during all-out sprint cycle ergometry.

PURPOSE: This study aimed to ascertain the optimal test duration to elicit the highest maximal lactate formation rate ( V ˙ Lamax), whilst exploring the underpinning energetics, and identifying the optimal blood lactate sampling period. METHODS: Fifteen trained to well-trained males (age 27 ± 6 years; peak power: 1134 ± 174 W) participated in a randomised cross-over design completing three all-out sprint cycling tests of differing test durations (10, 15, and 30 s). Peak and mean power output (W and W.kg-1), oxygen uptake, and blood lactate concentrations were measured. V ˙ Lamax and energetic contributions (phosphagen, glycolytic, and oxidative) were determined using these parameters. RESULTS: The shortest test duration of 10 s elicited a significantly (p = 0.003; p < 0.001) higher V ˙ Lamax (0.86 ± 0.17 mmol.L-1.s-1; 95% CI 0.802-0.974) compared with both 15 s (0.68 ± 0.18 mmol.L-1.s-1; 95% CI 0.596-0.794) and 30 s (0.45 ± 0.07 mmol.L-1.s-1; 95% CI 0.410-0.487). Differences in V ˙ Lamax were associated with large effect sizes (d = 1.07, d = 3.15). We observed 81% of the PCr and 53% of the glycolytic work completed over the 30 s sprint duration was attained after 10 s. BLamaxpost were achieved at 5 ± 2 min (ttest 10 s), 6 ± 2 min (ttest 15 s), and 7 ± 2 min (ttest 30 s), respectively. CONCLUSION: Our findings demonstrated a 10 s test duration elicited the highest V ˙ Lamax. Furthermore, the 10 s test duration mitigated the influence of the oxidative metabolism during all-out cycling. The optimal sample time to determine peak blood lactate concentration following 10 s was 5 ± 2 min.

Dietary habits and physical activity during the third wave of the COVID-19 pandemic: associated factors, composite outcomes in a cross-sectional telephone survey of a Chinese population, and trend analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created many challenges for Hong Kong residents attempting to maintain healthy lifestyle habits. This study aimed to measure the prevalences of unhealthy dietary habits and physical inactivity levels in Hong Kong Chinese, identify associated factors, and conduct a time trend analysis during the third wave of the COVID-19 pandemic. METHODS: A cross-sectional telephone survey was conducted in Hong Kong by simple random sampling. The survey comprised socio-demographic characteristics, clinical information, the Hong Kong Diet Score (HKDS), smoking and alcohol consumption, and a Chinese version of the International Physical Activity Questionnaire Short Form. The composite outcome was low HKDS, physical inactivity, smoking, and alcohol consumption. We used 14 Health Behaviour Survey reports from 2003 to 2019 to establish a trend analysis regarding fruit and vegetable consumption, physical activity level, smoking, and alcohol consumption. RESULTS: We performed 1500 complete telephone surveys with a response rate of 58.8%. Most participants were older adults (≥65 years, 66.7%), women (65.6%), and married (77.9%). The HKDS was significantly lower in men, single individuals, low-income participants, alcohol drinkers, and patients with diabetes mellitus or renal disease. Participants who were single, undergoing long-term management of medical diseases, or had diabetes or renal diseases exhibited greater likelihood of physical inactivity. CONCLUSION: Prevalences of unhealthy lifestyle habits were high among men, single individuals, and chronic disease patients during the third wave of the COVID-19 pandemic in Hong Kong. The adoption of physical activity habits tended to decrease in the past two decades.

A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Prevalence and Correlates of Caregiver Anxiety in Family Caregivers of Patients With Advanced Cancer: a Cross-Sectional Study in a Palliative Care Unit in Hong Kong.

OBJECTIVES: To assess the prevalence of caregiver anxiety and to identify correlates of caregiver anxiety in family caregivers of patients with advanced cancer in a palliative care unit in Hong Kong. METHODS: Family caregivers of patients admitted to the palliative care ward for the first time between July 2019 and September 2019 were screened for recruitment. Caregiver demographics (age, sex, marital status, occupation, education level, housing condition, relationship with the patient, known diagnosis of anxiety or depression, and Charlson comorbidity index) were collected, as were caregiver understanding of patient's diagnosis and prognosis, perceived patient's distress, frequency of witnessing confusion or delirium of patients in past month, perceived adequacy of psychological support (other than general social support), and perceived anxiety towards patient's approaching death. Caregiver anxiety was assessed using the 7-item Generalised Anxiety Disorder scale (GAD-7). Caregiver depression status was assessed using the 9-item Patient Health Questionnaire (PHQ-9). Caregiver psychological well-being was assessed using the 11-item Psychological Well-being Scale for Family Caregivers (PWS-C). Caregiver overall burden was assessed using the Chinese version of the 13-item Modified Caregiver Strain Index (C-M-CSI). RESULTS: 70 caregivers (of 66 patients) were included, with a response rate of 98.6%. 16 (22.9%) caregivers had moderate to severe anxiety (GAD-7 score of ≥10). The GAD-7 score was higher in female caregivers than in male caregivers (mean rank: 39.26 vs 27.83, p = 0.026). 26 (37.1%) caregivers had depression (PHQ-9 score of ≥7). The GAD-7 score of caregivers was associated with the PHQ-9 score (rs = 0.834, p < 0.01), the four subscales of PWS-C: social support (rs = -0.308, p = 0.01), life meaning (rs = -3.30, p < 0.01), emotional distress (rs = 0.615, p < 0.01), and caregiver inadequacy (rs = 0.41, p < 0.01), and the C-M-CSI score for caregiver overall burden (rs = 0.332, p < 0.01). In multiple linear regression, predictors for GAD-7 score were the PHQ-9 score, caregiver's feeling of anxiety towards patient's approaching death, and caregiver sex. CONCLUSIONS: 22.9% of family caregivers of patients with advanced cancer have moderate to severe anxiety. Anxiety of caregivers was associated with depression, caregiver's feeling of anxiety towards patient's approaching death, psychological support, and life meaning. All these are potentially amendable by interventions. A structured screening of anxiety in family caregivers of patients with advanced cancer should be considered as routine practice.

Novel strain-level resolution of Crohn's disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing.

The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn's disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn's disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn's disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

Basal Cell Carcinoma Surgery in general practice: Is there a role for the local General Practitioner?

Basal cell carcinoma (BCC) is a common disease of the skin caused principally by prolonged solar radiation exposure. It is normally a malignancy with favorable prognostic features and is potentially curable by standard excision. In White populations with high disease incidence, general practitioners (GPs) play a vital role in diagnosing and managing BCC, including surgical excision. Dedicated care at the primary care level by adequately trained GPs is conceivably cost effective for the health system and more convenient for the patient. In Asia and other parts of the world with low incidence, this valuable role of GPs may appear to be inconsequential. In this regard, any justification for the involvement of local GPs in BCC surgery is debatable. This article aims to provide a clinical update on essential information relevant to BCC surgery and advance understanding of the intricate issues of making a treatment decision at the primary care level. CASE REPORT: Madam Tan, a 71-year-old Malaysian Chinese lady, otherwise healthy, presented to her local GP with a complaint of a nodule over the left cheek that had been there for more than a decade. Her concern was that the lesion was growing and had become conspicuous. She had spent most of her life as a farmer working in her orchard.Upon examination, she had an obvious dome-shaped nodule over the left cheek measuring approximately 1.8 cm in diameter. The lesion was firm, pigmented, well-demarcated, and slightly ulcerated at the top. Clinically, she was diagnosed with a pigmented nodular basal cell carcinoma of the left cheek. Examination of the systems was unremarkable.She requested that the consulting GP remove the growth. The cost for specialist treatment and waiting time at the local hospital were her concerns. CLINICAL QUESTIONS: Can the basal cell skin cancer be excised safely and effectively in the local primary care setting? What are the crucial preoperative concerns?

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

BACKGROUND: The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. METHODS: A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. RESULTS: Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I2=93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I2=98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. CONCLUSIONS: Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy.

Could patient-controlled thirst-driven fluid administration lead to more rapid rehydration than clinician-directed fluid management? An early feasibility study.

BACKGROUND: Fluid management is a major factor determining perioperative outcome, yet in reality, fluid administration practice is variable. Thirst however, is a highly sensitive and reliable indicator of fluid deficits. We explored the use of thirst sensation to trigger i.v. fluid boluses to guide individualized fluid management. METHODS: We performed a randomised double crossover trial on 16 healthy male volunteers, of mean age 31 yr and BMI 24.4 kg m-2. Twice, after administrations of oral furosemide (40 mg) and 12 h of oral fluid restriction, participants received a 4-h i.v. fluid infusion. In the experimental arm, participants pressed a trigger to relieve their thirst, administering a 200 ml bolus. In the control arm, i.v. fluid was infused following National Institute for Health and Clinical Excellence (NICE) guidelines at 1.25 ml kg-1 h-1 with a clinician delivered 500 ml i.v. bolus in response to clinical signs of dehydration. Plasma osmolality and urine specific gravity were measured before and after each infusion. RESULTS: More fluid was infused in response to thirst than by adherence to NICE guidelines, with a mean difference of 743 ml (P=0.0005). Thirst-driven fluid administration was fitted to an exponential function of time, plateauing after a mean half-life of 98.8 min. In the experimental arm there was a greater reduction in urine specific gravity and thirst score with mean differences 0.0053 g cm-3 (P=0.002) and 3.3 (P=0.003), respectively. Plasma osmolality demonstrated no fluid overload. CONCLUSIONS: A system delivering i.v. fluid in response to subjective thirst corrects fluid deficits in healthy participants. A clinical feasibility study will assess the potential use of this system in the perioperative setting. CLINICAL TRIAL REGISTRATION: NCT 03176043.

Prevalence of hepatitis C infection and its associated factors in healthy adults without identifiable route of transmission.

While hepatitis C virus (HCV) infection is long known to be associated with parenteral exposure, the specific route of transmission is not identified in a proportion of infected patients. Taking blood donors as the surrogate of healthy adults in the community in Hong Kong, we identified 91 HCV-infected donors (≤0.02% positive rate) in 2014-2016, of whom 46 were recruited in a mixed-method study to examine their transmission routes. A majority (75%) of the recruited donors were HCV RNA positive, with the predominant subtypes being 1b and 6a. From the results of the structured self-administered questionnaire and in-depth interviews, only 14 (30%) recruited donors could be traced to past history of contaminated blood transfusion (n = 9) or injection drug use (n = 5). Case-control analyses with 3 different control groups were performed to examine factors associated with HCV infection in multivariable analyses. High-risk sexual behaviour, body piercing, intramuscular injection and vaccine inoculation abroad, having lived abroad for >3 months were significantly associated with HCV in donors with otherwise nonidentifiable source of infection. While the specific route of transmission cannot be established for each person, associations with multiple parenteral exposures outside Hong Kong were observed. The World Health Organization has advocated for the global elimination of HCV by 2030. With a high proportion of HCV-infected persons who are unaware of their infections, HCV elimination could be hard to achieve.

Comparison between FEV1/FEV6 and FEV1/FVC as screening of chronic obstructive pulmonary disease.

OBJECTIVE: To compare FEV1/FEV6 to the standard spirometry (FEV1/FVC) as a screening tool for COPD. METHODS: This cross-sectional study was conducted at Hospital Tuanku Fauziah, Perlis, Malaysia from August 2015 to April 2016. FEV1/FEV6 and FEV1/FVC results of 117 subjects were analysed. Demographic data and spirometric variables were tabulated. A scatter plot graph with Spearman's correlation was constructed for the correlation between FEV1/FEV6 and FEV1/FVC. The sensitivity, specificity, positive and negative predictive values of FEV1/FEV6 were determined with reference to the gold standard of FEV1/FVC ratio <0.70. Receiver-operator characteristic (ROC) curve analysis and Kappa statistics were used to determine the FEV1/FEV6 ratio in predicting an FEV1/FVC ratio <0.70. RESULTS: Spearman's correlation with r = 0.636 (P<0.001) was demonstrated. The area under the ROC curve was 0.862 (95% confidence interval [CI]: 0.779 - 0.944, P<0.001). The FEV1/FEV6 cut-off with the greatest sum of sensitivity and specificity was 0.75. FEV1/FEV6 sensitivity, specificity, positive and negative predictive values were 93.02%, 67.74%, 88.89% and 77.78% respectively. There was substantial agreement between the two diagnostic cut-offs (κ = 0.634; 95% CI: 0.471 - 0.797, P<0.001) CONCLUSIONS: The FEV1/FEV6 ratio can be considered to be a good alternative to the FEV1/FVC ratio for screening of COPD. Larger multicentre study and better education on spirometric techniques can validate similar study outcome and establish reference values appropriate to the population being studied.