Search results for: symptomatic visceral leishmaniasis

Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Wai Yan Shih, Sau Man Wong, Wing Chung Chang, Wai Chi Chan

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Background: Late-life depression is associated with significant consequences. Although symptomatic reduction is achievable through pharmacological interventions, older adults are more vulnerable to the side effects than their younger counterparts. In addition, drugs do not address underlying cognitive dysfunctions such as rumination and reduced autobiographical memory specificity (AMS), both shown to be maladaptive coping styles that are associated with a poorer prognosis in depression. Considering how aging is accompanied by cognitive, psychological and physical changes, the interplay of these age-related factors may potentially aggravate and interfere with these depressive cognitive dysfunctions in late-life depression. Special care should, therefore, be drawn to ensure these cognitive dysfunctions are adequately addressed. Aim: This randomized controlled trial aims to examine the effect of mindfulness-based cognitive therapy (MBCT) on depressed older adults, and whether the potential benefits of MBCT are mediated by improvements in rumination and AMS. Method: Fifty-seven participants with an average age of 70 years old were recruited from multiple elderly centers and online mailing lists. Participants were assessed with: (1) Hamilton depression scale, (2) ruminative response scale, (3) autobiographical memory test, (4) mindful attention awareness scale, and (5) Montreal cognitive assessment. Eligible participants with mild to moderate depressive symptoms and normal cognitive functioning were randomly allocated to an 8-week MBCT group or active control group consisting of a low-intensity exercise program and health education. Post-intervention assessments were conducted after the 8-week program. Ethics approval was given by the Institutional Review Board of the University of Hong Kong/Hospital Authority. Results: Mixed-factorials ANOVAs demonstrated significant time x group interaction effects for depressive symptoms, AMS, and dispositional mindfulness. A marginally significant interaction effect was found for rumination. Simple effect analyses revealed a significant reduction in depressive symptoms for the both the MBCT group (mean difference = 7.1, p = .000), and control group (mean difference = 2.7, p = .023). However, only participants in the MBCT group demonstrated improvements in rumination, AMS, and dispositional mindfulness. Bootstrapping-based mediation analyses showed that the effect of MBCT in alleviating depressive symptoms was only mediated by the reduction in rumination. Conclusions: The findings support the use of MBCT as an effective intervention for depressed older adults, considering the improvements in depressive symptoms, rumination, AMS and dispositional mindfulness despite their age. Reduction in ruminative tendencies plays a major role in the cognitive mechanism of MBCT.

Keywords: mindfulness-based cognitive therapy, depression, older adults, rumination, autobiographical memory specificity

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Authors: Jagmeet S. Kanwal, Julia F. Langley

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Music can heal the body, but a mechanistic understanding of this phenomenon is lacking. This study explores the effects of music presentation on neurologic and physiologic responses leading to metabolic changes in the human body. The mind and body co-exist in a corporeal entity and within this framework, sickness ensues when the mind-body balance goes awry. It is further hypothesized that music has the capacity to directly reset this balance. Two lines of inquiry taken together can provide a mechanistic understanding of this phenomenon 1) Empirical evidence for a sound-sensitive pressure sensor system in the body, and 2) The notion of a “healing center” within the brain that is activated by specific patterns of sounds. From an acoustics perspective, music is spatially distributed as pressure waves ranging from a few cm to several meters in wavelength. These waves interact and propagate in three-dimensions in unique ways, depending on the wavelength. Furthermore, music creates dynamically changing wave-fronts. Frequencies between 200 Hz and 1 kHz generate wavelengths that range from 5'6" to 1 foot. These dimensions are in the range of the body size of most people making it plausible that these pressure waves can geometrically interact with the body surface and create distinct patterns of pressure stimulation across the skin surface. For humans, short wavelength, high frequency (> 200 Hz) sounds are best received via cochlear receptors. For low frequency (< 200 Hz), long wavelength sound vibrations, however, the whole body may act as an ideal receiver. A vast array of highly sensitive pressure receptors (Pacinian corpuscles) is present just beneath the skin surface, as well as in the tendons, bones, several organs in the abdomen, and the sexual organs. Per the available empirical evidence, these receptors contribute to music perception by allowing the whole body to function as a sound receiver, and knowledge of how they function is essential to fully understanding the therapeutic effect of music. Neuroscientific studies have established that music stimulates the limbic system that can trigger states of anxiety, arousal, fear, and other emotions. These emotional states of brain activity play a crucial role in filtering top-down feedback from thoughts and bottom-up sensory inputs to the autonomic system, which automatically regulates bodily functions. Music likely exerts its pleasurable and healing effects by enhancing functional and effective connectivity and feedback mechanisms between brain regions that mediate reward, autonomic, and cognitive processing. Stimulation of pressure receptors under the skin by low-frequency music-induced sensations can activate multiple centers in the brain, including the amygdala, the cingulate cortex, and nucleus accumbens. Melodies in music in the low (< 600 Hz) frequency range may augment auditory inputs after convergence of the pressure-sensitive inputs from the vagus nerve onto emotive processing regions within the limbic system. The integration of music-generated auditory and somato-visceral inputs may lead to a synergistic input to the brain that promotes healing. Thus, music can literally heal humans through “touch” as it energizes the brain’s autonomic system for restoring homeostasis.

Keywords: acoustics, brain, music healing, pressure receptors

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Authors: Fayez Hanna, Viet Tran

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A 20 years old lady- primigravida 6 weeks pregnant with unremarkable past history, presented to the emergency department at the Royal Hobart Hospital, Tasmania, Australia, with hyperemesis gravidarum associated with, dehydration and complicated with hematemesis and chest pain resistant. Accordingly, we conducted laboratory investigations which revealed: FBC: WBC 23.9, unremarkable U&E, LFT, lipase and her VBG showed a pH 7.4, pCo2 36.7, cK+ 3.2, cNa+ 142. The decision was made to do a chest X-ray (CXR) after explaining the risks/benefit of performing radiographic investigations during pregnancy and considering the patient's plan for the termination of the pregnancy as she was not ready for motherhood for shared decision-making and consent to look for pneumoperitoneum to suggest perforated viscus that might cause the hematemesis. However, the CXR showed pneumomediastinum but no evidence of pneumoperitoneum or pneumothorax. Consequently, a decision was made to proceed with CT oesophagography with imaging pre and post oral contrast administration to identify a potential oesophageal tear since it could not be excluded using a plain film of the CXR. The CT oesophagography could not find a leak for the administered oral contrast and thus, no oesophageal tear could be confirmed but could not exclude the Mallory-Weiss tear (lower oesophageal tear). Further, the CT oesophagography showed an extensive pneumomediastinum that could not be confirmed to be pulmonary in origin noting the presence of bilateral pulmonary interstitial emphysema and pneumothorax in the apex of the right lung that was small. The patient was admitted to the Emergency Department Inpatient Unit for monitoring, supportive therapy, and symptomatic management. Her hyperemesis was well controlled with ondansetron 8mg IV, metoclopramide 10mg IV, doxylamine 25mg PO, pyridoxine 25mg PO, esomeprazole 40mg IV and oxycodone 5mg PO was given for pain control and 2 litter of IV fluid. The patient was stabilized after 24 hours and discharged home on ondansetron 8mg every 8 hours whereas the patient had a plan for medical termination of pregnancy. Three weeks later, the patient represented with nausea and vomiting complicated by a frank hematemesis. Her observation chart showed HR 117- other vital signs were normal. Pathology showed WBC 14.3 with normal U&E and Hb. The patient was managed in the Emergency Department with the same previous regimen and was discharged home on same previous regimes. Five days later, she presented again with nausea, vomiting and hematemesis and was admitted under obstetrics and gynaecology for stabilization then discharged home with a plan for surgical termination of pregnancy after 3-days rather than the previously planned medical termination of pregnancy to avoid extension of potential oesophageal tear. The surgical termination and follow up period were uneventful. The case is considered rare as pneumomediastinum is a very rare complication of hyperemesis gravidarum where vomiting-induced barotrauma leads to a ruptured oesophagus and air leak into the mediastinum. However no rupture oesophagus in our case. Although the combination of pneumothorax and pneumomediastinum without oesophageal tear was reported only 8 times in the literature, but none of them was due to hyperemesis gravidarum.

Keywords: Pneumothorax, pneumomediastinum, hyperemesis gravidarum, pneumopericardium

Procedia PDF Downloads 102

Authors: Yifan Lu, Ying Cui, Ying Zhu, Edward S. Lu, Rebecca Zeng, Rohan Bajaj, Raviv Katz, Rongrong Le, Jay C. Wang, John B. Miller

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Purpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcome and is associated with an increased risk of cerebral stroke and cardiovascular events. Fluorescein angiography (FA) is the traditional diagnostic tool for RAO; however, wide-field swept-source optical coherence tomography angiography (WF SS-OCTA), as a nascent imaging technology, is able to provide quick and non-invasive angiographic information with a wide field of view. In this study, we looked for associations between OCT-A vascular metrics and visual acuity in patients with prior diagnosis of RAO. Methods: Patients with diagnoses of central retinal artery occlusion (CRAO) or branched retinal artery occlusion (BRAO) were included. A 6mm x 6mm Angio and a 15mm x 15mm AngioPlex Montage OCT-A image were obtained for both eyes in each patient using the Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm x 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. The average measurement of the central foveal subfield, inner ring, and outer ring was calculated for each parameter. Non-perfusion area (NPA) was manually measured using 15mm x 15mm Montage images. A linear regression model was utilized to identify a correlation between the imaging metrics and visual acuity. A P-value less than 0.05 was considered to be statistically significant. Results: Twenty-five subjects were included in the study. For RAO eyes, there was a statistically significant negative correlation between vision and retinal thickness as well as superficial capillary plexus vessel density (SCP VD). A negative correlation was found between vision and deep capillary plexus vessel density (DCP VD) without statistical significance. There was a positive correlation between vision and choroidal thickness as well as choroidal volume without statistical significance. No statistically significant correlation was found between vision and the above metrics in contralateral eyes. For NPA measurements, no significant correlation was found between vision and NPA. Conclusions: This is the first study to our best knowledge to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between various retinal vascular imaging metrics and visual outcomes. Further investigations should explore the associations between these imaging findings and cardiovascular risk as RAO patients are at elevated risk for symptomatic stroke. The results of this study provide a basis to understand the structural changes involved in visual outcomes in RAO. Furthermore, they may help guide management of RAO and prevention of cerebral stroke and cardiovascular accidents in patients with RAO.

Keywords: OCTA, swept-source OCT, retinal artery occlusion, Zeiss Plex Elite

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Authors: Hansraj Bookun, Rachel Xuan, Angela Tan, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos, Jim Iliopoulos

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Introduction: Complex endovascular aortic aneursymal repairs with fenestrated and branched endografts require customised devices to exclude the pathology while reducing morbidity and mortality, which was historically associated with open repair of complex aneurysms. Such endovascular procedures have predominantly been performed in a large volume dedicated tertiary centres. We present here our nine year multidisciplinary experience with this technology in an Australian tertiary centre. Method: This was a cross-sectional, single-centre observational study of 670 patients who had undergone complex endovascular aortic aneurysmal repairs with conventional endografts, fenestrated endografts, and iliac-branched devices from January 2010 to July 2019. Descriptive statistics were used to characterise our sample with regards to demographic and perioperative variables. Homogeneity of the sample was tested using multivariant regression, which did not identify any statistically significant confounding variables. Results: 670 patients of mean age 74, were included (592 males) and the comorbid burden was as follows: ischemic heart disease (55%), diabetes (18%), hypertension (90%), stage four or greater kidney impairment (8%) and current or ex-smoking (78%). The main indications for surgery were elective aneurysms (86%), symptomatic aneurysms (5%), and rupture aneurysms (5%). 106 patients (16%) underwent fenestrated or branched endograft repairs. The mean length of stay was 7.6 days. 2 patients experienced reactionary bleeds, 11 patients had access wound complications (6 lymph fistulae, 5 haematoms), 11 patients had cardiac complications (5 arrhythmias, 3 acute myocadial infarctions, 3 exacerbation of congestive cardiac failure), 10 patients had respiratory complications, 8 patients had renal impairment, 4 patients had gastrointestinal complications, 2 patients suffered from paraplegia, 1 major stroke, 1 minor stroke, and 1 acute brain syndrome. There were 4 vascular occlusions requiring further arterial surgery, 4 type I endoleaks, 4 type II endoleaks, 3 episodes of thromboembolism, and 2 patients who required further arterial operations in the setting of patient vessels. There were 9 unplanned returns to the theatre. Discussion: Our numbers of 10 years suggest that we are not a dedicated high volume centre focusing on aortic repairs. However, we have achieved significantly low complication rates. This can be attributed to our multidisciplinary approach with the intraoperative involvement of skilled interventional radiologists and vascular surgeons as well as postoperative protocols with particular attention to spinal cord protection. Additionally, we have a ratified perioperative pathway that involves multidisciplinary team discussions of patient-related factors and lesion-centered characteristics, which allows for holistic, patient-centered care.

Keywords: aneurysm, aortic, endovascular, fenestrated

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Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

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Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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Authors: Vijayabhaskar Reddy Kandula, Peter Provost Taillac, Balasubramanya M. A., Ram Krishnan Nair, Gokul Toshnival, Vibhu Dhawan, Vijaya Karanam, Buffy Cramer

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Introduction: The lack of Emergency Care Services (ECS) is a cause of extensive and serious public health problems in low- and middle-income countries (LMIC), Many LMIC countries have ambulance services that allow timely transfer of ill patients but due to poor care during the ‘Golden Hour’ many deaths occur which are otherwise preventable. Lack of adequate training as evidenced by a study in India is a major reason for poor care during the ‘Golden Hour’. Adapting developed country models which includes staffing specialty-trained doctors in emergency care, is neither feasible nor guarantees cost-effective ECS. Methods: Based on our assessment and felt needs by first-line doctors providing emergency care in 2014, Rajiv Gandhi Health Sciences University’s JeevaRaksha Trust in partnership with the University of Utah, USA, designed, piloted and successfully implemented a 4-day Comprehensive-Emergency Care and Life Support course (C-ECLS) for allopathic doctors. 1730 doctors completed the 4-day course between June 2014 and December- 2020. Subsequently, we conducted a survey to investigate the utilization rates and usefulness of the training. 1662 were contacted but only 309 completed the survey. The respondents had the following designations: Senior faculty (33%), junior faculty (25), Resident (16%), Private-Practitioners (8%), Medical-Officer (16%) and not-working (11%). 51% were generalists (51%) and the rest were specialists (>30 specialties). Results: 97% (271/280) felt they are better doctors because of C-ECLS. 79% (244/309) reported that training helped to save life- specialists more likely than generalists (91% v/s 68%. P<0.05). 64% agreed that they were confident of managing COVID-19 symptomatic patients better because of C-ECLS. 27% (77) were neutral; 9% (24) disagreed. 66% agreed that training helps to be confident in managing COVID-19 critically ill patients. 26% (72) were neutral; 8% (23) disagreed. Frequency of use of C-ECLS skills: Hemorrhage-control (70%), Airway (67%), circulation skills (62%), Safe-transport and communication (60%), managing critically ill patients (58%), cardiac arrest (51%), Trauma (49%), poisoning/animal bites/stings (44%), neonatal-resuscitation (39%), breathing (36%), post-partum-hemorrhage and eclampsia (35%). Among those who used the skills, the majority (ranging from (88%-94%) reported that they were able to apply the skill more effectively because of ECLS training. Conclusion: JeevaRaksha’s C-ECLS is the world’s first comprehensive training. It improves the confidence of front-line doctors and enables them to provide quality care during the ‘Golden Hour’ of emergency. It also prepares doctors to manage unknown emergencies (e.g., COVID-19). C-ECLS was piloted in Morocco, and Uzbekistan and implemented countrywide in Bhutan. C-ECLS is relevant to most settings and offers a replicable model across LMIC.

Keywords: comprehensive emergency care and life support, training, capacity building, low- and middle-income countries, developing countries

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Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

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Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: A. Bhatt, C. Bassi, H. Farragher, J. Musk

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Background: All medicines placed on the EU market are legally required to be accompanied by labeling and package leaflet, which provide comprehensive information, enabling its safe and appropriate use. Mock-ups with results of assessments using a target patient group must be submitted for a marketing authorisation application. Consumers need confidence in non-prescription, OTC medicines in order to manage their minor ailments and umbrella brands assist purchasing decisions by assisting easy identification within a particular therapeutic area. A number of regulatory agencies have risk management tools and guidelines to assist in developing umbrella brands for OTC medicines, however assessment and decision making is subjective and inconsistent. This study presents an evaluation in the UK following the US FDA warning concerning methaemoglobinaemia following 21 reported cases (11 children under 2 years) caused by OTC oral analgesics containing benzocaine. METHODS: A standard face to face, 25 structured task based user interview testing methodology using a standard questionnaire and rating scale in consumers aged 15-91 years, was conducted independently between June and October 2015 in their homes. Whether individuals could discriminate between the labelling, safety information and warnings on cartons and PILs between 3 different OTC medicines packs with the same umbrella name was evaluated. Each pack was presented with differing information hierarchy using, different coloured cartons, containing the 3 different active ingredients, benzocaine (oromucosal spray) and two lozenges containing 2, 4, dichlorobenzyl alcohol, amylmetacresol and hexylresorcinol respectively (for the symptomatic relief of sore throat pain). The test was designed to determine whether warnings on the carton and leaflet were prominent, accessible to alert users that one product contained benzocaine, risk of methaemoglobinaemia, and refer to the leaflet for the signs of the condition and what to do should this occur. Results: Two consumers did not locate the warnings on the side of the pack, eventually found them on the back and two suggestions to further improve accessibility of the methaemoglobinaemia warning. Using a gold pack design for the oromucosal spray, all consumers could differentiate between the 3 drugs, minimum age particulars, pharmaceutical form and the risk factor methaemoglobinaemia. The warnings for benzocaine were deemed to be clear or very clear; appearance of the 3 packs were either very well differentiated or quite well differentiated. The PIL test passed on all criteria. All consumers could use the product correctly, identify risk factors ensuring the critical information necessary for the safe use was legible and easily accessible so that confusion and errors were minimised. Conclusion: Patients with known methaemoglobinaemia are likely to be vigilant in checking for benzocaine containing products, despite similar umbrella brand names across a range of active ingredients. Despite these findings, the package design and spray format were not deemed to be sufficient to mitigate potential safety risks associated with differences in target populations and contraindications when submitted to the Regulatory Agency. Although risk management tools are increasingly being used by agencies to assist in providing objective assurance of package safety, further transparency, reduction in subjectivity and proportionate risk should be demonstrated.

Keywords: labelling, OTC, risk, user testing

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Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu

Abstract:

INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.

Keywords: neurology, chronic, progressive, ophthalmoplegia

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Authors: Elena Parmentier, Henrik Endeman

Abstract:

Introduction: Large mediastinal masses often present with diagnostic and clinical challenges due to compression of the respiratory and hemodynamic system. We present a case of a mediastinal mass with symptomatic mechanical compression of the trachea, resulting in challenging airway management. Methods: We present a case of 66-year-old male, complaining of progressive dysphagia. Initial esophagogastroscopy revealed a stenosis secondary to external compression, biopsies were inconclusive. Additional CT scan showed a large mediastinal mass of unknown origin, situated between the vertebrae and esophagus. Symptoms progressed and patient developed dyspnea and stridor. A new CT showed quick growth of the mass with compression of the trachea, subglottic to just above the carina. A tracheal covered stent was successfully placed. Endobronchial ultrasound revealed a large irregular mass without tracheal invasion, biopsies were taken. 4 days after stent placement, the patients’ condition deteriorated with worsening of stridor, dyspnea and desaturation. Migration of the tracheal stent into the right main bronchus was seen on chest X ray, with obstruction of the left main bronchus and secondary atelectasis. Different methods have been described in the literature for tracheobronchial stent removal (surgical, endoscopic, fluoroscopyguided), our first choice in this case was flexible bronchoscopy. However, this revealed tracheal compression above the migrated stent and passage of the scope occurred impossible. Patient was admitted to the ICU, high-flow nasal oxygen therapy was started and the situation stabilized, giving time for extensive assessment and preparation of the airway management approach. Close cooperation between the intensivist, pulmonologist, anesthesiologist and otorhinolaryngologist was essential. Results: In case of sudden deterioration, a protocol for emergency situations was made. Given the increased risk of additional tracheal compression after administration of neuromuscular blocking agents, an approach with awake fiberoptic intubation maintaining spontaneous ventilation was proposed. However, intubation without retrieval of the tracheal stent was found undesirable due to expected massive shunting over the left atelectatic lung. As rescue option, assistance of extracorporeal circulation was considered and perfusionist was kept on standby. The patient stayed stable and was transferred to the operating theatre. High frequency jet ventilation under general anesthesia resulted in desaturations up to 50%, making rigid bronchoscopy impossible. Subsequently an endotracheal tube size 8 could be placed successfully and the stent could be retrieved via bronchoscopy over (and with) the tube, after which the patient was reintubated. Finally, a tracheostomy (Shiley™ Tracheostomy Tube With Cuff, size 8) was placed, fiberoptic control showed a patent airway. Patient was readmitted to the ICU and could be quickly weaned of the ventilator. Pathology was positive for rhabdomyosarcoma, without indication for systemic therapy. Extensive surgery (laryngectomy, esophagectomy) was suggested, but patient refused and palliative care was started. Conclusion: Due to meticulous planning in an interdisciplinary team, we showed a successful airway management approach in this complicated case of critical airway compression secondary to a rare rhabdomyosarcoma, complicated by tracheal stent migration. Besides presenting our thoughts and considerations, we support exploring other possible approaches of this specific clinical problem.

Keywords: airway management, rhabdomyosarcoma, stent displacement, tracheal stenosis

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