The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

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.

Efficacy and safety of adjunctive treatment with perampanel in epilepsy patients.

INTRODUCTION: Epilepsy is a neurological disease with high global prevalence. Almost one-third of epilepsy patients continue having seizures despite adequate treatment. Perampanel has been widely used in the Western countries as an adjunctive therapy for both generalized and focal seizures. Owing to its high cost, the use of perampanel is limited in our country. MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital. RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects. CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.

Characteristics of electroencephalogram changes and correlation with seizures in hospitalised patients.

INTRODUCTION: Electroencephalogram (EEG) is an important investigational tool that is widely used in the hospital settings for numerous indications. The aim was to determine factors associated with abnormal EEG and its clinical correlations in hospitalised patients. MATERIALS AND METHODS: Patients with at least one EEG recording were recruited. The EEG and clinical data were collated. RESULTS: Two hundred and fifty patients underwent EEG and 154 (61.6%) were found to have abnormal EEG. The abnormal changes consist of theta activity (79,31.6%), delta activity (20, 8%), focal discharges (41,16.4%) and generalised discharges (14, 5.6%). Older patients had 3.481 higher risk for EEG abnormalities, p=0.001. Patients who had focal seizures had 2.240 higher risk of having EEG abnormalities, p<0.001. Low protein level was a risk for EEG abnormalities, p=0.003. CONCLUSION: This study emphasised that an abnormal EEG remains a useful tool in determining the likelihood for seizures in a hospital setting. The risk factors for EEG abnormality in hospitalised patients were age, focal seizures and low protein level. The EEG may have an important role as part of the workup in hospitalised patients to aid the clinician to tailor their management in a holistic manner.

Factors related to prehospital delay and decision delay among acute stroke patients in a district hospital, Malaysia.

INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients. MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment. RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay. CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.

A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020.

OBJECTIVE: This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future. METHOD: A total of 3087 articles and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references. RESULTS: The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future. CONCLUSION: This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.

Silent microaspirations: The forerunner to the diagnosis of bulbar onset myasthenia gravis in a young woman.

Recurrent pneumonia warrants a diligent work-up to identify the underlying cause that perpetuates the disease process. Insidious bulbar dysfunction is arguably the most devastating as it would be diagnosed late after significant pulmonary complications due to chronic micro-aspiration. Bulbar disorder should be considered as the potential aetiology of recurrent pulmonary infections in the young population after excluding immunodeficiency disorder and respiratory anatomical anomaly. This report illustrates a rare case of bulbar onset myasthenia gravis which manifested as focal bronchiolectasis due to recurrent undiagnosed aspiration pneumonia three years earlier. Absence of hallmark features of Myasthenia Gravis (MG) such as ptosis, opthalmoplegia and proximal muscle weakness contributed to the diagnostic delay and challenges in this case. The diagnosis was established with the collaboration of multidisciplinary teams. Subsequent correct therapeutic interventions resulted in remarkable recovery in functional status and prevented her from further aspiration in the long run.

Effectiveness and tolerability of Perampanel in children, adolescents and young adults with refractory epilepsy: A UK national multicentre study.

PURPOSE: Perampanel is one of the latest antiepileptic drugs (AEDs) approved for the treatment of focal and generalised epilepsy in individuals with epilepsy aged 12 years and older. There is sparse data on the use of Perampanel in children under 12. We conducted a study amongst paediatric neurologists in the United Kingdom to investigate its effectiveness and tolerability as an adjunctive therapy in children of all ages with refractory epilepsy. METHODS: Data was collected via an online questionnaire sent to paediatric neurologists in the UK. Data gathered, prospective in 62 (64.5%) and retrospective in 34 (35.5%) patients, included changes in seizure frequency from baseline and unwanted effects at 3, 6 and 12 months follow-up. Only patients with a minimum follow-up of six months were included. RESULTS: Ninety six patients (48 females) with refractory epilepsy from 11 of 29 tertiary centres were included. Median [IQR] (range) age was 14 years 11 months [12 years, 16 years 6 months] (11 months-24 years 5 months). Seventy three (76%) had focal epilepsy, sixteen (17%) generalised, and seven (7%) patients both generalised and focal epilepsy. The responder rate, ≥50% seizure reduction from baseline, was 19% for all seizure types at both 6 and 12 months, 19% and 24% for focal seizures, and 25% and 7% for generalised seizures at these time points respectively. The retention rate was 42% at 12 months. Treatment was discontinued due to unwanted effects in 29 (36.7%) of the 79 patients with follow-up data available up to 12 months: 30% due to challenging behaviour, 14% dizziness, and 7.6% somnolence. CONCLUSION: Perampanel was fairly effective in a heterogeneous group of 96 children and adolescents with very refractory epilepsy. The rate of adverse events leading to discontinuation was considerable in this group.

Role of high resolution ultrasound in ulnar nerve neuropathy.

AIM: This study was conducted to measure the cross sectional area (CSA) of the ulnar nerve (UN) in the cubital tunnel and to evaluate the role of high-resolution ultrasonography in the diagnosis of ulnar nerve neuropathy (UNN). MATERIALS AND METHODS: This was a cross sectional study with 64 arms from 32 patients (34 neuropathic, 30 nonneuropathic). Diagnosis was confirmed by nerve conduction study and electromyography. The ulnar nerves were evaluated with 15MHz small footprint linear array transducer. The ulnar nerve CSA was measured at three levels with arm extended: at medial epicondyle (ME), 5cm proximal and 5cm distal to ME. Results from the neuropathic and nonneuropathic arms were compared. Independent T-tests and Pearson correlation tests were used. P value of less than 0.05 was considered significant. RESULTS: Mean CSA values for the UN at levels 5cm proximal to ME, ME and 5cm distal to ME were 0.055, 0.109, 0.045 cm(2) respectively in the neuropathic group and 0.049, 0.075, 0.042 cm2 respectively in the non-neuropathic group. The CSA of the UN at the ME level was significantly larger in the neuropathic group, with p value of 0.005. However, there was no statistical difference between the groups at 5cm proximal and distal to the ME, with p values of 0.10 and 0.35 respectively. CONCLUSION: There is significant difference in CSA values of the UN at ME between the neuropathic and non-neuropathic groups with mean CSA value above the predetermined 0.10cm(2) cut-off point. High-resolution ultrasonography is therefore useful to diagnose and follow up cases of elbow UNN.

Measuring the cost of care in benign prostatic hyperplasia using time-driven activity-based costing (TDABC).

BACKGROUND: Determining '"value'" in health care, defined as outcomes per unit cost, depends on accurately measuring cost. We used time-driven activity-based costing (TDABC) to determine the cost of care in men with benign prostatic hyperplasia (BPH) - a common urologic condition. METHODS: We implemented TDABC across the entire care pathway for BPH including primary and specialist care in both inpatient and outpatient settings. A team of expert stakeholders created detailed process maps, determined space and product costs, and calculated personnel capacity cost rates. A model pathway was derived from practice guidelines and calculated costs were applied. RESULTS: Although listed as 'optional' in practice guidelines, invasive diagnostic testing can increase costs by 150% compared with the standalone urology clinic visit. Of five different surgical options, a 400% cost discrepancy exists between the most and least expensive treatments. CONCLUSIONS: TDABC can be used to measure cost across an entire care pathway in a large academic medical center. Sizable cost variation exists between diagnostic and surgical modalities for men with BPH. IMPLICATIONS: As financial risk is shifted toward providers, understanding the cost of care will be vital. Future work is needed to determine outcome discrepancy between the diagnostic and surgical modalities in BPH.

Use of patient ethnography to support quality improvement in benign prostatic hyperplasia.

BACKGROUND: Patient-centeredness is a primary aim of quality improvement (QI) but optimal strategies to achieve that goal remain elusive. Benign prostatic hyperplasia (BPH) is one of the commonest urologic diagnoses and significantly affects quality of life. Patient ethnography is an emerging qualitative method of observation and dynamic interviews to understand the context through which the patient experiences care. We implemented patient ethnography to support our QI infrastructure and improve patient-centeredness in BPH. PROBLEM: Little is known about how to measure whether processes of care are patient-centered. We did not know whether the care processes our patients experienced provided value from their perspective. GOALS: We sought to discover previously unrecognized components of care that patients perceived to be of low value. Our primary goal was to develop QI initiatives that targeted low-value themes identified in the ethnography. Our secondary goal was a rapid rollout of three targeted initiatives. STRATEGY: We used a 4-step patient ethnography: (1) created detailed process maps to define phases of care, (2) interviewed patients, (3) synthesized transcript data in focus groups using the Crawford Slip method, and (4) targeted undesirable components of care for QI. Semi-structured interviews with seven representative patients identified low-value themes. Focus groups, comprised of primary care physicians, case coordinators, nurses, and urologists, evaluated the interview transcripts and generated improvement opportunities prioritized based on feasibility, patient value, scalability, and innovation. We used affinity mapping and priority matrix techniques to prioritize QI opportunities. RESULTS: We identified five low-value themes from the patient interviews and developed corresponding QI opportunities. These included issues surrounding the referral and consultation process as well as postoperative care, especially home urinary catheter maintenance. Six months after completing the ethnography three of five targeted improvement opportunities had been implemented.

Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease.

UNLABELLED: Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the development of motor fluctuations and dyskinesia. We studied the prevalence and predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients with PD. METHODS: This is a cross-sectional study involving 95 patients with PD on uninterrupted levodopa therapy for at least 6 months. The instrument used was the UPDRS questionnaires. The predictors of dyskinesia were determined using multivariate logistic regression analysis. RESULTS: The mean age was 65.6 ± 8.5 years. The mean onset age was 58.5 ± 9.8 years. The median disease duration was 6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other ethnic groups. Eighty-one percent of patients with dyskinesia had clinical fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001), higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p = 0.005) than patients without dyskinesia. The three significant predictors of dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients was 44%. The most significant predictors were duration of levodopa therapy, total daily levodopa dose, and onset age.

Prevalence of depression in stroke patients with vascular dementia in universiti kebangsaan malaysia medical center.

OBJECTIVE: Depression among patients with vascular dementia is frequently overlooked and potentially causes significant morbidity. There is limited data in Malaysia on the subject and this study was conducted to determine the prevalence of depression in vascular dementia (VaD) in UKMMC. METHODS: This was a cross-sectional study involving diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria and who had a mini mental state examination (MMSE) score of less than 26. All patients were interviewed, examined clinically and their previous brain computer tomography (CT) were reviewed. The prevalence of depression was determined using the Cornell scale of depression. RESULTS: A total of 76 patients were recruited with a mean age of 70.5 ± 9.5 years. The median duration of illness was 2.0 (1.0-4.8) years. The prevalence of depression in the study population was 31.6%. The patients with depression had a significant older mean age (74.5±8.7 years old) compared to those without depression (68.6±9.4 years old). Patients with large artery stroke of less than 3 years had significant higher frequency of depression (53.6%) compared to patients with small artery stroke (23.8%) and patients with right sided large artery stroke had significantly higher frequency of depression compared to left (70% vs. 44.4%). Median MMSE score (17.0) for depressed patients was significantly lower compared with median MMSE score (22.5) for non depressed patients. Median Barthel Index (30.0) for depressed patients was significantly lower compared with median Barthel score for non depressed patients. CONCLUSIONS: Depression was prevalent among post stroke patients with VaD in UKMMC particularly for patients with older age, large artery stroke, right sided large artery stroke, low MMSE score and low Barthel Index. Early recognition of high risk patients is important in the holistic management of patients to prevent significant morbidity arising from depression.

Implications of immunosuppressive agents in cardiovascular risks and carotid intima media thickness among lupus nephritis patients.

INTRODUCTION: Patients with systemic lupus erythematosus, particularly with lupus nephritis (LN), are at risk of premature cardiovascular (CV) disease. OBJECTIVE: To determine the association between immunosuppressive medications, traditional CV risk factors and carotid intima media thickness (CIMT) among patients with LN. METHODOLOGY: This was a cross-sectional study in which consecutive LN patients attending the Nephrology/SLE Clinic were evaluated for traditional CV risk factors. Detailed information on their treatment was obtained from their medical records. CIMT, an excellent marker of subclinical atherosclerosis, was measured by B Mode carotid ultrasound. RESULTS: A total of 82 patients with LN with a mean age of 33.9 ± 9.8( )years were recruited. More than half had hypertension (n = 55, 67.1%) and dyslipidemia (n = 43, 52.4%) as traditional CV risks. Longer history and higher cumulative dose of corticosteroids were associated with hypertension, but use of intravenous methylprednisolone was associated with lower systolic and diastolic blood pressure and lower serum total cholesterol and triglyceride levels (p < 0.05 each). Hydroxychloroquine use was associated with lower total serum cholesterol and serum low-density lipoprotein levels (p < 0.05). Although the use of cyclosporine A (CyA) was associated with hypertension (p < 0.05), those who received a lower cumulative dose of CyA had thicker CIMT (r (s) = -0.33, p =0.01) and CyA use remained an independent predictor of CIMT during linear regression analysis. There were no associations between CIMT and cumulative dose and duration of steroids, hydroxychloroquine, azathioprine, mycophenolic acid and cyclophosphamide. CONCLUSION: Aggressive treatment of severe LN and the use of CyA as a steroid-sparing agent may have protective effects against premature atherosclerosis.

Lack of association of ABCB1 haplotypes on five loci with response to treatment in epilepsy.

Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.

Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy.

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.