Systematic review on current antiviral therapy in COVID-19 pandemic.

INTRODUCTION: Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19. METHODS: An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included. RESULTS: Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community. DISCUSSION: In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.

Knowledge, Attitude and Practice of Undergraduate Medical Students of Bangladesh Regarding COVID-19 and its Vaccination.

Medical students are one of the socially active, reliable, and persuading population of information, prevention and control, and incentive of vaccination to stop the current pandemic situation. Consequently, knowing the status of medical students' knowledge, about symptoms, and transmission of disease, prevention of COVID-19 and their attitudes towards a vaccine is important. This multi-center cross-sectional descriptive study was one of the first ones in Bangladesh among the undergraduate medical students who completed pathology, microbiology, and pharmacology. The study was conducted from March to April 2021, using a convenience sampling method in twelve government and non-government medical colleges. Among 1132 who completed the questionnaire, and 15 students from different centers were excluded from the pre-testing and face validation. The age of the 1117 respondents were 22 to 23 years, of which the majority of the respondents were female 749 (67.0%), and 368 (33.0%) were male. Almost all participants had correct knowledge (84.1%) about the symptoms of COVID-19. But 59.2% had wrong knowledge about transmission of disease by an afebrile person. Above 60.0 % of the participants have worn a facial mask when contacting people, refrained from shaking hands, washed hands, avoided people with signs and symptoms suggestive of COVID-19, and avoided crowded places as a practice of prevention. 37.6% of medical students showed positive attitudes about the participation of management of a COVID-19 patient. Most of the participants' decided to have a vaccine depending on its availability. But 31.5% had trust in natural immunity rather than vaccination. Most undergraduate Medical college students understood the basic information, possessed a positive attitude, and presented good practice towards the COVID-19 and vaccination. They play a crucial role in motivation and acceptance of vaccines among the general citizen to fight back against the pandemic in the country with limited resources.

Vaccination against COVID-19 in Bangladesh: Perception and Attitude of Healthcare Workers in COVID-dedicated Hospitals.

Healthcare professionals are the crucial and influencing source of information for vaccines and their communication among patients and communities that can accelerate successful vaccination in a country. This cross-sectional study was one of the first and foremost ones in Bangladesh to observe the basic perception and attitudes towards vaccination against COVID-19 among the healthcare workers (HCWs) - doctors, interns, nurses, ward boys, cleaners, and medical technologists of major COVID-dedicated hospitals. The cross-sectional questionnaire-based study was conducted in February 2021 among 550 HCWs to assess the perception and attitude towards vaccination against COVID-19. The study participants were targeted as the priority group for COVID-19 vaccination, working in two major COVID-dedicated hospitals, Holy Family Red Crescent Medical College Hospital (HF-center), and Sheikh Russel National Gastro-liver Institute and Hospital (SR-center) in Dhaka, Bangladesh during the pandemic. The questionnaire was structured with a three-point scale of responses from 'true', 'false', and 'do not know'. The responses were calculated on point-score as +1 for the correct response, -1 for the wrong response, and 0 for 'do not know' with an overall highest and the lowest possible score of +5 to -5. Absolute (n) and relative frequencies (%) were presented for qualitative variables, while quantitative variables were presented as mean (± standard deviation). Chi-square test was done for univariate analysis of qualitative variables and Student's t-test for quantitative variables. With the 95.27% response rate, including 204 males and 320 were female and the male: female ratio was 1: 1.56. The majority of the participants were doctors (45.8%) followed by nurses (27.9%), and MLSS (26.3%) respectively. The respondents were between 18 to 64 years of age with a mean of 36.17±10.94 years. Most of the respondents (95.99%) responded correctly about the cost-free availability of a vaccine against COVID-19 in the country, 87.40% preferred vaccination as safe and effective. Again 29.77% HCWs think the vaccine might not be safe or effective due to emergency authorization. Only 38.93% of respondents could respond correctly about the necessity of vaccines for children, 31.10% think the vaccination was not required instead of natural immunity. The positive perception and attitude of the frontline HCWs in COVID-dedicated hospitals in Bangladesh are crucial which will positively influence motivation and wide acceptance among the general population for the attainment of the nationwide vaccination program, and adopt effective strategic modification to minimize the gaps for a low-middle income country like Bangladesh with its resource constrain.

Systematic Review on Apolipoprotein E: A Strong Genetic Cause of Hemorrhagic Stroke.

Stroke is one of the commonest causes of mortality among the world. Hemorrhagic stroke accounts nearly 15% of all the strokes. Different risk factors have been identified, of them hypertension, anti-coagulation therapy and previous history of ischemic strokes are significant. Regarding the genetic causes of intracerebral hemorrhage (ICH) monogenic causes play a small role. It was found that Apolipoprotein E (APOE) gene has a strong association with ICH. This is a 299 amino acids long protein located in chromosome 19. APOE has three alleles, they are epsilon 2, 3 and 4. Total 10 meta-analysis were reviewed in this article which involved 52,705 participants. When looking for the association, ∈2 and ∈4 showed positive and ∈3 showed negative association with ICH. Association of ∈4 (OR mean 1.77) was stronger than that of ∈2 (OR mean 1.71).

Systematic Review on Repurposing Use of Favipiravir Against SARS-CoV-2.

The sudden outbreak of a novel coronavirus in 2019 in Wuhan, China, that rapidly provoked a global concern, marked as the third attack of corona virus in the human society that affected the global healthcare system as well as the global economy. Until and unless an effective vaccine is discovered against the virus, the pharmacological intervention by different antivirals is in the run for remedy. The aim of this systematic review was to evaluate the role of favipiravir along with its safety and efficacy for the patients who are suffering from severe acute respiratory distress syndrome due to CoronaVirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE for randomized controlled trials (RCTs), cilicaltrial.com for registered on going trails to evaluate the pros and cons of using favipiravir in COVID-19. After vigorous searching, screening and sorting of 314 articles for completed and published scientific evidences in electronic database, there were only 2 completed and published randomized control trials (RCT) and 17 ongoing or unpublished trials found until June 2020. The main outcome measures were viral clearance, clinical improvement and adverse events reported and published on 147 patients infected with SARS-CoV2. The 2 completed RCTs showed significantly better treatment effects on disease progression, viral clearance, improved the latency to relief for pyrexia and cough on favipiravir treated patients. Adverse effects caused Favipiravir are mild and manageable. Although 9 more RCTs and cohort studies are supposed to be completed by this time that may unveil some evidence for use of anti-RNA-viral drug favipiravir against influenza or Ebola to re-purposing against COVID-19 as adopted in different treatment guidelines.

Mode of presentation and mortality amongst patients hospitalized with heart failure? A report from the First Euro Heart Failure Survey.

BACKGROUND: Heart failure is heterogeneous in aetiology, pathophysiology, and presentation. Despite this diversity, clinical trials of patients hospitalized for HF deal with this problem as a single entity, which may be one reason for repeated failures. METHODS: The first EuroHeart Failure Survey screened consecutive deaths and discharges of patients with suspected heart failure during 2000-2001. Patients were sorted into seven mutually exclusive hierarchical presentations: (1) with cardiac arrest/ventricular arrhythmia; (2) with acute coronary syndrome; (3) with rapid atrial fibrillation; (4) with acute breathlessness; (5) with other symptoms/signs such as peripheral oedema; (6) with stable symptoms; and (7) others in whom the contribution of HF to admission was not clear. RESULTS: The 10,701 patients enrolled were classified into the above seven presentations as follows: 260 (2%), 560 (5%), 799 (8%), 2479 (24%), 1040 (10%), 703 (7%), and 4691 (45%) for which index-admission mortality was 26%, 20%, 10%, 8%, 6%, 6%, and 4%, respectively. Compared to those in group 7, the hazard ratios for death during the index admission were 4.9 (p ≤ 0.001), 4.0 (p < 0.001), 2.2 (p < 0.001), 2.1 (p < 0.001), 1.4 (p < 0.04) and 1.4 (p = 0.04), respectively. These differences were no longer statistically significant by 12 weeks. CONCLUSION: There is great diversity in the presentation of heart failure that is associated with very different short-term outcomes. Only a minority of hospitalizations associated with suspected heart failure are associated with acute breathlessness. This should be taken into account in the design of future clinical trials.

An Echocardiographic Study of the Right Ventricular Diastolic Function in Systemic Hypertension and Its Relation with the Left Ventricular Homologous Changes.

Diastolic dysfunction is a major predictor of mortality and morbidity in hypertensive patients. Not only LV, the RV is also expected to be affected in this overall procedure. To observe the Echocardiographic changes of diastolic function of the RV in systemic HTN and their relation with similar parameters of the LV was the objective. TDI was used in association with standard Doppler modality. In this cross-sectional study, 50 hypertensive subjects were studied who were devoid of any other conditions that may influence the diastolic function of the RV from 01 May 2012 to 31 October 2012 at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. In addition to 2D and M-mode evaluation, standard Doppler and pulsed tissue Doppler assessment of both ventricles were performed. Measurements were obtained for diastolic as well as systolic function of both ventricles. The RV diastolic parameters were impaired in both standard Doppler and tissue Doppler analysis in association with LV parameters. Systolic functions (LV FS and RV TAPSE) were preserved. Doppler-derived tricuspid peak E and E/A were related negatively to septal thickness, but tissue Doppler-derived RV Em/Am showed negative association with both RVAWT and septal thickness. RV RTm was related positively to RVAWT. The RV diastolic parameters showed positive relation with the LV similar parameters both in standard Doppler (E peak velocity, E/A ratio and EDT) and tissue Doppler (Em peak velocity, Em/Am and PCTm) assessment. So, in systemic HTN, LV diastolic dysfunction is also associated with diastolic disturbances of the RV. Pulsed tissue Doppler is a useful tool to detect the changes. RV diastolic parameters correlate well with those of the LV. Prolongation of the active relaxation (RTm) phase of RV is due to its increased wall thickness.

Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases.

BACKGROUND: Costello syndrome (CS) is a rare multiple congenital abnormality syndrome, associated with failure to thrive and developmental delay. One of the more distinctive features in childhood is the development of facial warts, often nasolabial and in other moist body surfaces. Individuals with CS have an increased risk of malignancy, suggested to be about 17%. Recently, mutations in the HRAS gene on chromosome 11p13.3 have been found to cause CS. METHODS: We report here the results of HRAS analysis in 43 individuals with a clinical diagnosis of CS. RESULTS: Mutations were found in 37 (86%) of patients. Analysis of parental DNA samples was possible in 16 cases for both parents and in three cases for one parent, and confirmed the mutations as de novo in all of these cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases. CONCLUSIONS: These results confirm that CS is caused, in most cases, by heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major phenotypic features by mutation suggests a potential correlation between malignancy risk and genotype, which is highest for patients with an uncommon (G12A) substitution. These results confirm that mutation testing for HRAS is a reliable diagnostic test for CS.

Assessment of Subvalvular Apparatus in Patients with Rheumatic Mitral Stenosis: Comparison between 2D and 3D Echocardiography.

Mitral valve is the most involved valve in rheumatic heart disease especially in the form of mitral stenosis. Treatment options of mitral stenosis depend upon pattern, extent & the severity of disease and echocardiography has the key role in this area. Severity of involvement of subvalvular apparatus (SVA) is an important factor for determining the treatment option. 2D echocardiography (2DE) is conventionally used. With the advancement of echocardiographic technology 3D echocardiography (3DE) would offer better assessment of subvalvular apparatus. This study compared transthoracic 2D versus 3D echocardiography for assessment of SVA in chronic rheumatic mitral valve disease. This cross sectional observational study was done in University cardiac centre, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from May 2012 to October 2012. In this study, considering all ethical issues, data were collected from 50 subjects who underwent transthoracic 2D and 3D echocardiography for the assessment of extent and severity of mitral stenosis. Accurate measurement of Mitral valvular area is very important in assessment of severity, which is found similar by both 2DE (0.98±0.24cm²) and 3DE (0.92 ±0.23cm²). But assessment of subvalvular involvement especially chordal adhesion can be done better by 3DE (p<0.001). This observation suggests superiority of 3DE for assessment of SVA in chronic rheumatic mitral stenosis. The result of the study demonstrates that 3DE is superior to 2DE for the assessment of SVA in chronic rheumatic mitral stenosis.

De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models.

Acrocallosal syndrome (ACS) is characterised by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. The condition overlaps with Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominant disorder that results from mutations in the GLI3 gene. Here we report a child with agenesis of the corpus callosum and severe retardation, both cardinal features of ACS and rare in GCPS, who has a mutation in GLI3. Since others have excluded GLI3 in ACS, we suggest that ACS may represent a heterogeneous group of disorders that, in some cases, may result from a mutation in GLI3 and represent a severe, allelic form of GCPS. The finding is important for counselling families with suspected ACS.

Ultrastructural and molecular analysis of Bowman's layer corneal dystrophies: an epithelial origin?

PURPOSE: Two mutations (R555Q and R124L) in the BIGH3 gene have been described in anterior or Bowman's layer dystrophies (CDB). The clinical, molecular, and ultrastructural findings of five families with CDB was reviewed to determine whether there is a consistent genotype:phenotype correlation. METHODS: Keratoplasty tissue from each patient was examined by light and electron microscopy (LM and EM). DNA was obtained, and exons 4 and 12 of BIGH3 were analyzed by polymerase chain reaction and single-stranded conformation polymorphism/heteroduplex analysis. Abnormally migrating products were analyzed by direct sequencing. RESULTS: In two families with type I CDB (CDBI), the R124L mutation was defined. There were light and ultrastructural features of superficial granular dystrophy and atypical banding of the "rod-shaped bodies" ultrastructurally. Patients from three families with "honeycomb" dystrophy were found to carry the R555Q mutation and had characteristic features of Bowman's dystrophy type II (CDBII). CONCLUSIONS: There is a strong genotype:phenotype correlation among CBDI (R124L) and CDBII (R555Q). LM and EM findings suggest that epithelial abnormalities may underlie the pathology of both conditions. The findings clarify the confusion over classification of the Bowman's layer dystrophies.

Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.

PURPOSE: Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis. METHODS: Seventy-six patients with different forms of anterior segment dysgenesis were classified clinically. DNA was obtained and screened by means of polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing. RESULTS: Eight of 76 patients had mutations within the PITX2 gene. Anterior segment phenotypes show wide variability and include a phenocopy of aniridia and Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations and splice-site and homeobox mutations, confirming that haploinsufficiency the likely pathogenic mechanism in the majority of cases. CONCLUSIONS: There is significant phenotypic variability in patients with PITX2 mutations, both within and between families. Developmental glaucoma is common. The umbilical and dental abnormalities are highly penetrant, define those at risk of carrying mutations in this gene, and guide mutation analysis. In addition, there is a range of other extraocular manifestations.

Pulverulent cataract with variably associated microcornea and iris coloboma in a MAF mutation family.

AIMS: To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, MAF. METHODS: Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features. RESULTS: The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10-10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient. CONCLUSION: The bZIP transcription factor MAF is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in MAF may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.

Problem based learning.

PBL, an educational format, stimulates active and life long learning. PBL improves the motivation of students, stimulates integration of disciplines, small group learning; improves clinical reasoning, problem-solving and decision making. It has been introduced increasingly in the curricula of a number of countries in South-East Asia, viz. Thailand, India, Myanmar and Nepal. We feel that the seed of PBL should be sown in the soil of the Undergraduate Medical Curriculum in Bangladesh urgently.

Turner syndrome: a case of gonadal dysgenesis.

An eighteen years old girl came from Ishargang, Mymensingh complaining of short stature, absence of development of breast, lack of menstruation and other secondary sex characters. She was found in infantile appearance with a height of 123 cm, body weight of 28 kg. She had short, broad, webbed neck, cuvitus valgus, absence of development of breast, axillary and public hairs with infantile external genitalia. Hormonal profile revealed high level of LH and FSH, low level of estrogens. Ultrasonography revealed uterine hypoplasia and ill defined gonadal streaks, Karyotype showed typical 45, X0 pattern. She was diagnosed as a case of gonadal dysgenesis due to Turner syndrome.

Constitutional delay of growth and puberty is not commonly associated with mutations in the acid labile subunit gene.

OBJECTIVES: Constitutional delay of growth and puberty (CDGP) is a common clinical condition that may be inherited as an autosomal dominant, recessive or X-linked trait. However, single-gene defects underlying CDGP have not yet been identified. A small number of children (to date 10) with modest growth failure and in the majority delayed puberty, a phenotype similar to that of CDGP, have been reported to carry mutations in the IGF acid labile subunit (IGFALS) gene which encodes the ALS, a part of the ternary complex carrying IGF-I in the circulation. The aim of our study was to screen a well-characterised CDGP cohort exhibiting a range of growth retardation and pubertal delay for pathogenic sequence variants in IGFALS. DESIGN AND METHODS: We used denaturing high performance liquid chromatography (dHPLC) to screen for IGFALS mutations in DNA samples from 90 children (80 males) with CDGP of predominantly White European origin. DNA fragments generating abnormal waveforms were directly sequenced. RESULTS: No IGFALS mutation was identified in the coding sequences or exon-intron boundaries in our CDGP cohort. One abnormal waveform pattern in dHPLC in 15 children with CDGP was found to represent a recognised synonymous single-nucleotide polymorphism of the coding transcript in the second exon in residue 210 of IGFALS. CONCLUSIONS: IGFALS sequence variants are unlikely to be a common association with pubertal delay in children with CDGP.

A heterozygous c-Maf transactivation domain mutation causes congenital cataract and enhances target gene activation.

MAF, one of a family of large Maf bZIP transcription factors, is mutated in human developmental ocular disorders that include congenital cataract, microcornea, coloboma and anterior segment dysgenesis. Expressed early in the developing lens vesicle, it is central to regulation of lens crystallin gene expression. We report a semi-dominant mouse c-Maf mutation recovered after ENU mutatgenesis which results in the substitution, D90V, at a highly conserved residue within the N-terminal 35 amino-acid minimal transactivation domain (MTD). Unlike null and loss-of-function c-Maf mutations, which cause severe runting and renal abnormalities, the phenotype caused by the D90V mutation is isolated cataract. In reporter assays, D90V results in increased promoter activation, a situation similar to MTD mutations of NRL that also cause human disease. In contrast to wild-type protein, the c-Maf D90V mutant protein is not inhibited by protein kinase A-dependent pathways. The MTD of large Maf proteins has been shown to interact with the transcriptional co-activator p300 and we demonstrate that c-Maf D90V enhances p300 recruitment in a cell-type dependent manner. We observed the same for the pathogenic human NRL MTD mutation S50T, which suggests a common mechanism of action.

Locus heterogeneity in autosomal dominant congenital external ophthalmoplegia (CFEOM).

Congenital external ophthalmoplegia (CFEOM) is an uncommon autosomal dominant condition that has previously been mapped to the pericentromeric region of chromosome 12 in seven families with no evidence of locus heterogeneity. We report three families with typical CFEOM. One family does not map to this region of chromosome 12 or to other chromosomal locations implicated in disorders of lid or ocular movement. Recombinants in two CFEOM families potentially help to reduce the size of the candidate region on chromosome 12.

A novel hereditary developmental vitreoretinopathy with multiple ocular abnormalities localizing to a 5-cM region of chromosome 5q13-q14.

BACKGROUND: To undertake a clinical and molecular analysis of a previously unpublished kindred with a phenotypically distinct vitreoretinopathy characterized by associated ocular developmental abnormalities. DESIGN: Family genetic study. PARTICIPANTS: A total of 23 members, both affected and unaffected, of 1 kindred with vitreoretinopathy. METHOD: Individuals within the kindred were examined clinically and blood samples taken for DNA analysis. Genetic analysis was performed for the proximal region of chromosome 5q by means of polymerase chain reaction (PCR). MAIN OUTCOME MEASURES: Detection of vitreoretinopathy and associated abnormalities. RESULTS: This novel, hereditary vitreoretinopathy, showing the classic features of vitreous pathology and early-onset retinal detachments, was associated with a variety of ocular developmental abnormalities, including posterior embryotoxon, congenital glaucoma, iris hypoplasia, congenital cataract, ectopia lentis, microphthalmia, and persistent hyperplastic primary vitreous. There were no associated systemic features. Genetic mapping with markers from the proximal region of 5q13-q14 showed linkage to a 5-cM region between the markers D5S626 and D5S2103. CONCLUSIONS: The 5-cM region is within that implicated in the etiology of both Wagner and erosive vitreoretinopathies. This suggests that this novel condition may be allelic, refines the genetic mapping for vitreoretinopathies that map to 5q13-q14, and implicates a gene important not only in vitreous production but also in early ocular development.