The Zwolle experience with left bundle branch area pacing using stylet-driven active fixation leads.

AIMS: Left bundle branch area pacing (LBBAP) is a novel physiological pacing modality and is regarded as a viable alternative to His bundle pacing. LBBAP has mostly been performed with the lumen-less permanent pacing lead (SelectSecure™ Model 3830, Medtronic, Inc.) with a fixed helix. The aim of this study was to compare the non-stylet driven lumen-less lead (LLL) (Medtronic 3830) with a standard stylet-driven active fixation lead (SDL) (Tendril™ STS Model 2088TC-38, Abbott Laboratories) in terms of lead parameters, procedural success and complication rates. METHODS: Patients receiving a LBBA pacemaker in the Isala Hospital, The Netherlands, were prospectively enrolled. The majority received a standard right ventricular (RV) lead as backup, the implanter chose between LLL and SDL for the LBBAP lead. RESULTS: The study included 94 patients with a mean follow-up of 30 weeks. 30/31 LLL procedures were successful, compared with 62/63 in the SDL group. Including the participants that lost LBBAP during follow-up resulted in success rates of 90.3% for LLL versus 96.8% for SDL, P = 0.199. Mean number of deployments was significantly lower in the SDL group compared with the LLL group (2 ± 2.3 versus 4 ± 3.4, P = 0.005), implantation and procedural times were comparable. Pacing thresholds were low and remained low in both groups (at last follow-up 0.8 ± 0.30 V for LLL versus 0.6 ± 0.20 V for SDL). Complication rates did not differ significantly between both groups, P = 0.805. CONCLUSION: LBBAP using SDL is feasible and has comparable success rates with lower number of deployments of the active fixation screw.

Outcomes of traumatic brain injury in the patient of 60 years and above: a single centre retrospective study.

INTRODUCTION: The elderly is at risk for traumatic brain injury (TBI), but local data on their morbidity and mortality outcomes was lacking. This study aims to assess the outcome in mortality and functional outcome, Glasgow Outcome Scale (GOS) and factors associated with poor outcomes in patients with TBI more than 60 years old. MATERIALS AND METHODS: This single centre retrospective cohort study was carried out involving patients age 60 years old and above with TBI between June 2018 to May 2021. The mortality and GOS at hospital discharge, 30th day, and 90th day of trauma were analysed. The simple logistic regression (SLR) and multiple logistic regression (MLR) were performed to determine factors associated with poor outcomes and mortality. RESULTS: A total of 248 patients were analysed. The mean age was 67.5 ± 6.31 years. 156 (62.9%), 26 (10.5%), and 66 (26.6%) had mild, moderate, and severe TBI, respectively. The overall mortality rate was 9.7% and the median(IQR) GOS score were 4(2); p<0.001 at hospital discharge, 30th day and 90th day. There was significant difference in GOS outcomes after 90 days χ2(2) = 136.76 p<0.001. Upon MLR, there was a significant association of polytrauma, Adj. OR 11.04 (2.503-48.711); p < 0.002 and TBI severity: moderate TBI, Adj. OR 71.44(13.028-391.782); p < 0.001 and severe TBI, Adj OR 2533.51 (213.050-30127.644); p<0.001 towards poor outcome. However, only severity of TBI: moderate TBI, Adj. OR 19.48 (1.899-199.094); p=0.012 and severe TBI, Adj OR 26.42 (2.864-243.722); p=0.004 is associated with mortality. CONCLUSION: Polytrauma and moderate-severe head injury are associated with poor outcomes and moderate-severe head injury is associated with high mortality.

Clinical characteristics, attendance outcomes and deaths of homeless persons in the emergency department: implications for primary health care and community prevention programmes.

OBJECTIVES: Persons experiencing homelessness (PEH) are known to be often excluded from primary health care and community prevention programmes leading to high use of hospital emergency departments (EDs). This study aimed to identify demographic features, clinical characteristics and attendance outcomes of PEH presenting to ED. STUDY DESIGN: Analysis of routinely collected data set. METHODS: Clinical presentations and drug prescription data of PEH who presented a major ED in the West Midlands region of England from 2014 to 2019 were extracted and analysed using descriptive and inferential statistics. RESULTS: During the study period, 3271 of 596,198 presentations were made by PEH; 74% PEH attendees were male. Drug- and alcohol-related conditions, as well as pain and injury constituted the most frequent reasons for presentation, contributing to over half of all presentations. A significantly higher proportion of males (n = 481, 20.3%) presented with drug and alcohol problems than females (n = 93, 11.2%) (P ≤ 0.001). However, pain was the primary reason for presentation for twice as many female patients (n = 189, 22.8%) compared with males (n = 305, 12.9%) (P < 0.001). Nearly one in five left the ED before being assessed and a total of 39 patients (1.2%) died in the ED and 785 (24.0%) required in-patient admissions to the same hospital. CONCLUSIONS: Drug, alcohol and pain including the need of opioid analgesics constituted the majority of presentations made by PEH in ED. The observed rate of death of PEH in ED is 12 times higher than the general population. A very high proportion of PEH also leave the ED before being treated. Future research should focus on strengthening community interventions, particularly to improve access to those at risk of dual diagnoses of substance misuse and mental health problems. Interventions involving multisector collaborations are needed to improve seamless discharge from ED and minimise repeat attendance. Gender differences in the nature of presentations and ED outcomes needs to be investigated further.

The use of magnetic resonance phase-contrast cine in Chiari malformation with syringomyelia.

INTRODUCTION: Chiari malformation (CM) is a disorder of mesodermal origin and is commonly associated with syringomyelia. Foramen magnum decompression is the first-line of standard treatment in symptomatic patients with a confirmed radiographic diagnosis. Magnetic resonance (MR) cine allows accurate evaluation of cerebrospinal fluid (CSF) physiology at the craniovertebral junction but often this is under-utilised in Malaysia. METHODS: In this series, we looked into nine cases of CM with syringomyelia from clinical and radiological perspective before and after surgery. The radiological parameters were herniated tonsillar length, syrinx: cord ratio, syrinx length and diameter. Flow velocity and morphologic changes in Chiari were illustrated. RESULTS: Seven patients showed either reduction in syrinx length, syrinx: cord ratio or both postoperatively. Clinical recovery somewhat varied in motor and sensory symptoms. Four patients gained better functional grade in modified Rankin scale (MRS) while the rest remained similar. The study highlighted the advantage of CSF flow dynamics information over MR anatomical radiographic improvement in addressing the neurologic and functional recovery. We also discussed the practicality of cine sequence in preoperative patient selection, syrinx analysis and postoperative flow evaluation in anticipation of clinical outcome. CONCLUSION: Phase-contrast cine MRI is a useful tool dictated by resource availability. We recommend its routine use in preoperative analysis and subsequent observational follow-up after surgery.

Cerebral venous sinus thrombosis: review of cases in a single centre in Malaysia.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a potentially fatal neurological condition. However, due to the non-specific clinical and radiological features of CVST, it can sometimes result in a delay in the diagnosis and subsequent management. The aim of this study was to evaluate the demography, risk factors and one-year outcome of CVST patients treated in Hospital Universiti Sains Malaysia. METHODS: In this retrospective study, we reviewed the cases diagnosed with CVST admitted to our centre from January 2011 until November 2015. RESULTS: A total of 15 patients were included in this review. The patterns of imaging findings as well as risk factors for CVST is discussed with a review of the literature and current management practices. One year followed-up showed full recovery (Glasgow Outcome Scale (GOS) of 5) in 10 cases (66.7%), whereas 4 cases (26.7%) with GOS of 4 (three cases with neurological deficits, and 1 case with mild symptom. There was one case of mortality in this study secondary to sepsis during hospitalisation. The presenting symptoms were mainly headache, focal neurology deficits, seizure and altered sensorium. Risk factors identified were oral contraceptive pills usage, chronic sinuses or ear infections, and obesity. Initial computed tomography (CT) scan showed various findings and haemorrhagic infarct was one of the common findings. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) revealed majority of the patients had occlusion at two or more venous sinus sites. No patients had new or recurrent intracranial haemorrhage following initiation of anticoagulation therapy. CONCLUSION: Thus it is considerable safe to start anticoagulation therapy in CVST patients including those with intracranial haemorrhage. We propose further neuroimaging to avoid missed diagnosis of CVST in patient presented with recent onset headache and CT evidence of unusual cerebral infarction.

Unique product quality considerations in vaccine development, registration and new program implementation in Malaysia.

This review aims to present the unique considerations for manufacturing and the regulation of new vaccines in Muslim-populated countries such as Malaysia. Our specific objectives are to highlight vaccine production and the ingredients of concern, summarize the current mechanism for ruling and recommendations on new vaccines, outline the different steps in decision-making on incorporating a new vaccine into the National Immunization Program, describe its issues and challenges, and explore the commercial viability and challenges of producing local permissible (halal) vaccines. Through this review, we hope readers understand that alternatives are present to replace ingredients of concern in vaccines. Halal certification and introduction of a new vaccine into a program are strictly conducted and health-care providers must be prepared to educate the public on this. At the same time, it is hoped that the production of halal vaccine in Malaysia will promote self-reliance in Muslim-populated countries.

Experimental data on compressive and flexural strengths of coir fibre reinforced foamed concrete at elevated temperatures.

Quantifying the elevated temperature strengths of cement-based material is crucial to the design of building structural systems for fire resistance purpose. This paper collates a database of elevated temperature axial compressive and flexural strengths of coir fibre reinforced foamed concrete exposed to heating temperatures of 105 °C, 200 °C, 300 °C, 400 °C, 500 °C, 600 °C, 700 °C and 800 °C. There were four densities of foamed concrete of 700, 1100, 1500 and 1900 kg/m3 were prepared and tested. The untreated coir fibre was added in foamed concrete in percentages of 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% by mix volume fraction. The database can aid in prediction of elevated temperature strengths of fibre reinforced foamed concrete which can be exploited to assist manufacturers to develop their products without having to perform numerous large-scale elevated temperature tests in the future.

Stroke in pregnancy.

Stroke is uncommon among young adults. However, the incidence of stroke among young women increases with pregnancy during peripartum and postpartum periods. The relative risk of suffering from haemorrhagic stroke was three times higher than ischemic stroke during these periods when compared with antenatal period. Neuroimaging should be prioritized in order to establish diagnosis and to facilitate treatment in a patient with suspected acute stroke. Prophylaxic anticoagulants should be used in high risk patients. Treatments of acute stroke in pregnant women include anti-platelet and thrombolytic agents. Further studies should be carried as there is lack of high level of evidences to formulate clear guideline for the management of stroke during pregnancy.

A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder.

Here we report a 12 year old male with an extreme presentation of spastic paraplegia along with autism and dysmorphisms. Whole exome sequencing identified a predicted pathogenic pair of missense variants in SPAST at the same chromosomal location, each with a different alternative allele, while a chromosome microarray identified a 1.73 Mb paternally inherited copy gain of 1q21.1q21.2 resulting in a blended phenotype of both Spastic paraplegia 4 and 1q21.1 microduplication syndrome. We believe that the extreme phenotype observed is likely caused by the presence of cells which contain only mutant SPAST, but that the viability of the patient is possible due mosaicism of mutant alleles observed in different proportions across tissues.

Enhancing the growth performance of replacement female breeder goats through modification of feeding program.

AIM: The study was conducted at a smallholder goat farm located in Labu, Negeri Sembilan, Malaysia. The objective of this study was to evaluate the effect of proper feeding program on growth performances of replacement breeder goats. MATERIALS AND METHODS: A total of 30 healthy female boer cross goats at the age of 4 months old with average initial live body weight (BW) of 20.05±0.5 kg were used for on-farm feeding trial to evaluate the growth performance as preparation for breeding purposes. The experimental goats were divided into two groups of 15 animals each labeled as control and treatment groups, which were kept under intensive farming system. Goats in control group were fed with normal routine feeding protocol practiced by the farmer, while goats in the treatment group were fed with new feed formulation. Throughout the experimental period, on-farm monitoring and data collection were carried out. Initial BW and body condition score (BCS) were recorded before the start of the experiment while final BW and BCS were gained after 7 months of the experimental period. Average daily gain (ADG) was calculated after the experiment end. Data on BW, ADG, and BCS were recorded from both groups for every 2 weeks and reported monthly. The feed intake for the control group was 2.8 kg/animal/day which practiced by the farmer and 3.2 kg/animal/day as new feed formulation for the treatment group. RESULTS: After 7 months of the experimental period, final BW shows an improvement in treatment group (39.1±1.53 kg) compared with control group (32.3±1.23 kg). The ADG in treatment group also gives promising result when comparing with control group. Goats in treatment group significantly attained better ADG than control group which were 126.7 g/day and 83.3 g/day, respectively. For the BCS, goats in the treatment group had shown an improvement where 86.67% (13 out of 15) of the group had BCS ≥3 (1-5 scoring scale) and only 66.67% (10 out of 15) of the control group had BCS ≥3. CONCLUSION: Therefore, it was concluded that implementation of proper feeding program as shown in treatment group give promising result to improve the growth performance of replacement breeder goats which can be adopted by the farmers to improve farm productivity.

Sediment deposit thickness and its effect on critical velocity for incipient motion.

The understanding of how the sediment deposit thickness influences the incipient motion characteristic is still lacking in the literature. Hence, the current study aims to determine the effect of sediment deposition thickness on the critical velocity for incipient motion. An incipient motion experiment was conducted in a rigid boundary rectangular flume of 0.6 m width with varying sediment deposition thickness. Findings from the experiment revealed that the densimetric Froude number has a logarithmic relationship with both the thickness ratios ts/d and ts/y0 (ts: sediment deposit thickness; d: grain size; y0: normal flow depth). Multiple linear regression analysis was performed using the data from the current study to develop a new critical velocity equation by incorporating thickness ratios into the equation. The new equation can be used to predict critical velocity for incipient motion for both loose and rigid boundary conditions. The new critical velocity equation is an attempt toward unifying the equations for both rigid and loose boundary conditions.

The application of One Health concept to an outdoor problem-based learning activity for veterinary students.

BACKGROUND: The One Health (OH) approach, which seeks to bring together human and animal health, is particularly suited to the effective management of zoonotic diseases across both sectors. To overcome professional silos, OH needs to be taught at the undergraduate level. Here, we describe a problem-based learning activity using the OH approach that was conducted outdoors for 3rd-year veterinary students in Malaysia. MATERIALS AND METHODS: A total of 118 students, divided into two groups, completed the activity which spanned 1½ days at a deer park adjacent to a wilderness area. Students were asked to evaluate the activity using an online survey that had quantitative and qualitative components. RESULTS: Response rate was 69.5%. The activity was rated excellent by 69.5% and good by 30.4%. Levels of satisfaction were high on a range of criteria. 97.5% of students intended to take action in their studies as a result of what they had learned. CONCLUSIONS: Delivery of an outdoor problem-based learning activity using OH approach was very successful in terms of participation, knowledge delivery and understanding, and the willingness of students to integrate OH into their future practice. For the improvement of future programs, the involvement of other disciplines (such as Medical, Biology, Biotechnology, Biomedical, and Public Health) is being considered.

Association of apical rocking with super-response to cardiac resynchronisation therapy.

BACKGROUND: Super-responders to cardiac resynchronisation therapy (CRT) show an exceptional improvement in left ventricular ejection fraction (LVEF). Previous studies showed that apical rocking was independently associated with echocardiographic response to CRT. However, little is known about the association between apical rocking and super-response to CRT. OBJECTIVES: To determine the independent association of LV apical rocking with super-response to CRT in a large cohort. METHODS: A cohort of 297 consecutive heart failure patients treated with primary indication for CRT-D were included in an observational registry. Apical rocking was defined as motion of the left ventricular (LV) apical myocardium perpendicular to the LV long axis. 'Super-response' was defined by the top quartile of LVEF response based on change from baseline to follow-up echocardiogram. Best-subset regression analysis identified predictors of LVEF super-response to CRT. RESULTS: Apical rocking was present in 45 % of patients. Super-responders had an absolute mean LVEF increase of 27 % (LVEF 22.0 % ± 5.7 at baseline and 49.0 % ± 7.5 at follow-up). Apical rocking was significantly more common in super-responders compared with non-super-responders (76 and 34 %, P < 0.001). In univariate analysis, female gender (OR 2.39, 95 % CI 1.38-4.11), lower LVEF at baseline (OR 0.91 95 % CI 0.87-0.95), non-ischaemic aetiology (OR 4.15, 95 % CI 2.33-7.39) and apical rocking (OR 6.19, 95 % CI 3.40-11.25) were associated with super-response. In multivariate analysis, apical rocking was still strongly associated with super-response (OR 5.82, 95 % CI 2.68-12.61). Super-responders showed an excellent clinical prognosis with a very low incidence of heart failure admission, cardiac mortality and appropriate ICD therapy. CONCLUSION: Apical rocking is independently associated with super-response to CRT.

Lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations.

To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns.

Estimating the transmissibility of H5N1 and the effect of vaccination in Indonesia.

The spread of H5N1 avian influenza continues to pose an economic burden and a public health risk worldwide. Despite this, estimates of the transmissibility of infection exist in only a handful of settings and vary considerably. Using final size methods and flock-level infection data from a field trial of mass vaccination, we obtained the first estimates of the transmissibility of infection between and within flocks in Indonesia. We also found that outbreaks in areas designated as vaccination zones were less transmissible than in non-vaccination zones. However, this reduction is only comparable with a limited degree of protective vaccination coverage. Quantifying the overall effect of vaccination in these zones remains challenging. However, this result would appear to imply that, although the interventions applied in vaccination zones were not sufficient to completely prevent transmission in all areas, when outbreaks occur, they are less transmissible than those in areas where vaccination was not applied. This could be either a direct or an indirect effect of vaccination. Given the dynamism of small-scale poultry production in Indonesia, more regular vaccination may be required to ensure that infection is fully controlled in vaccination zones.

Studies on cigarette smoke induced oxidative DNA damage and reduced spermatogenesis in rats.

In the present work, the effect of exposure to cigarette smoke on male fertility in rats, as characterized by changes in the relative weight of sex organs, epididymal sperm count, activity of marker enzymes and DNA damage was evaluated. Exposure of rats to cigarette smoke caused a gradual decrease in total body weight gain and relative weight of the epididymis and seminal vesicles by 30 and 40% respectively. Epididymal sperm count was reduced significantly by 25% (P 0.05) after 2 weeks and by 41% (P 0.001) after 4 weeks of exposure. Exposure to cigarette smoke had reduced the activity of sorbitol dehydogenase by 18% (P < or = 0.05) and increased the activity of lactate dehydrogenase by 28% (P < or = 0.05). The changes in both key enzymes were significant, which reflected the inhibitory effect of cigarette smoke on spermatogenesis and sperm maturation. The toxic effect of exposure could be explained partially due to induction of DNA damage and oxidative stress as shown by the significant increase in serum 8-hydroxy-2'-deoxyguanosine from 22.83 to 37.33 ng ml(-1) blood.

Pharmacogenetics of warfarin in a paediatric population: time in therapeutic range, initial and stable dosing and adverse effects.

Warfarin is used in paediatric populations, but dosing algorithms incorporating pharmacogenetic data have not been developed for children. Previous studies have produced estimates of the effect of polymorphisms in Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) on stable warfarin dosing, but data on time in therapeutic range, initial dosing and adverse effects are limited. Participants (n=97) were recruited, and routine clinical data and salivary DNA samples were collected from all participants and analysed for CYP2C9*2, *3 and VKORC1-1639 polymorphisms.VKORC1 -1639 was associated with a greater proportion of the first 6 months' treatment time spent within the target International Normalised Ratio (INR) range, accounting for an additional 9.5% of the variance in the proportion of time. CYP2C9*2 was associated with a greater likelihood of INR values exceeding the target range during the initiation of treatment (odds ratio (OR; per additional copy) 4.18, 95% confidence interval (CI) 1.42, 12.34). CYP2C9*2 and VKORC1-1639 were associated with a lower dose requirement, and accounted for almost 12% of the variance in stable dose. VKORC1-1639 was associated with an increased likelihood of mild bleeding complications (OR (heterozygotes vs homozygotes) 4.53, 95% CI 1.59, 12.93). These data show novel associations between VKORC1-1639 and CYP2C9*2 and INR values in children taking warfarin, as well as replicating previous findings with regard to stable dose requirements. The development of pharmacogenomic dosing algorithms for children using warfarin has the potential to improve clinical care in this population.

Halal and kosher slaughter methods and meat quality: a review.

There are many slaughter procedures that religions and cultures use around the world. The two that are commercially relevant are the halal and kosher methods practiced by Muslims and Jews respectively. The global trade in red meat and poultry produced using these two methods is substantial, thus the importance of the quality of the meat produced using the methods. Halal and kosher slaughter per se should not affect meat quality more than their industrial equivalents, however, some of their associated pre- and post-slaughter processes do. For instance, the slow decline in blood pressure following a halal pre-slaughter head-only stun and neck cut causes blood splash (ecchymosis) in a range of muscles and organs of slaughtered livestock. Other quality concerns include bruising, hemorrhages, skin discoloration and broken bones particularly in poultry. In addition to these conventional quality issues, the "spiritual quality" of the meat can also be affected when the halal and kosher religious requirements are not fully met during the slaughter process. The nature, causes, importance and mitigations of these and other quality issues related to halal and kosher slaughtering and meat production using these methods are the subjects of this review.