2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities. BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Health Literacy Among Non-Communicable Disease Service Seekers: A Nationwide Finding from Primary Health Care Settings of Bangladesh.

BACKGROUND: Considering the health literacy status of service seekers is crucial while developing programs and policies to improve service delivery in primary health care settings. OBJECTIVE: Our aim was to assess health literacy among adults seeking non-communicable disease (NCD)-related services in primary health care centers (PHC) of Bangladesh and identify its contributing factors and its preventive effect on risky behaviors. METHODS: In this cross-sectional study, 2,793 NCD service seekers were interviewed face-to-face from eight rural and three urban PHCs selected by a multi-stage random sampling method. We used the European Health Literacy Survey Questionnaire to collect data on health literacy. We applied logistic regression analysis to identify the contributing factors related to adequate health literacy. Odds ratios were used to calculate the preventive fraction of health literacy for NCD risk behaviors. KEY RESULTS: Limited health literacy was found among 43% of the respondents. Adequate health literacy was associated with younger age, male sex, having a formal education, living in an extended family, hailing from a high socioeconomic group, and attending urban PHC. After adjusting the sociodemographic factors, the prevalence of smoking, smokeless tobacco usage, and inadequate fruits and vegetables consumption among participants were found to be 25%, 51%, and 18% lower for people with sufficient health literacy. CONCLUSIONS: NCD service seekers have a high rate of inadequate health literacy. Adequate health literacy has the potential to lower the behavioral risk factors of NCDs. [HLRP: Health Literacy Research and Practice. 2024;8(1):e12-e20.].

PLAIN LANGUAGE SUMMARY: This study is the first to address the knowledge gap regarding the state of NCD-related health literacy in Bangladesh. The findings of this study can be used by policymakers to create initiatives that will improve the health literacy of people seeking primary health care for NCDs.

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Background: Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Methods: Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. Results: We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. Discussion: If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. Conclusion: s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Post-discharge quality of life of COVID-19 patients at 1-month follow-up: A cross-sectional study in the largest tertiary care hospital of Bangladesh.

There is increasing evidence of the post-COVID-19 suffering and decreased quality of life in the COVID-19 patients. This study aimed to assess the quality of life and associated factors of COVID-19 patients at one month after discharge from the hospital. This was a cross-sectional study that was conducted at the post-covid clinic of Dhaka Medical College Hospital (DMCH) where RT-PCR-confirmed adult COVID-19 recovered patients were enrolled one month after discharge from the same hospital. They were consecutively selected from January 01 to May 30. A pretested semi-structured questionnaire was used for the data collection for clinical variables. The generic multi-attributable utility instrument EQ-5D-5L was used for assessing health-related quality of life (HRQoL). A total of 563 patients were enrolled in the study. The patients had a mean age with standard deviation (±SD) of 51.18 (±13.49) years and 55.95% were male. The mean (SD) EQ-5D-5L index score and EQ-VAS scores were 0.78 (±0.19) and 70.26 (±11.13), respectively. Overall, 45.77%, 50.99%, 52.79%, 55.14% and 62.16% had problems (slight to extreme) in the mobility, self-care, usual activities, pain/discomfort and anxiety/depression dimensions, respectively. Patients aged ≥60 years had significant problem in mobility (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.07-9.77). Female participants were 5.50 times (95% CI: 2.22-13.62) more likely to have problems in their usual activities. In comparison to urban area, living in a peri-urban setting was significantly associated with problems in mobility (OR 1.89, 95% CI: 1.13-3.20), pain/discomfort (OR 1.82, 95% CI: 1.04-3.12) and anxiety/depression (OR 2.16, 95% CI: 1.22-3.84). Comorbid patients were 1.75 times (95% CI: 1.07-2.85) more likely to report problems in the pain/discomfort dimension. Presence of symptom(s) was associated with problems in self-care (OR 3.27, 95%CI: 1.31-8.18), usual-activity (OR 3.08, 95%CI: 1.21-7.87), pain/discomfort dimensions (OR 2.75, 95%CI: 1.09-6.96) and anxiety/depression (OR 3.35, 95%CI: 1.35-8.30). Specific management strategies should be planned to address the factors associated with low health-related quality of life in post-acute care of COVID-19 patients.

Clinical Presentation of COVID-19 and Antibody Responses in Bangladeshi Patients Infected with the Delta or Omicron Variants of SARS-CoV-2.

The clinical presentation of COVID-19 and the specific antibody responses associated with SARS-CoV-2 variants have not been investigated during the emergence of Omicron variants in Bangladesh. The Delta and Omicron variants were identified by post-PCR melting curve analysis of the spike (S) protein receptor binding domain amplicons. Anti-S-protein immunoglobulin-G anti-nucleocapsid (N)-protein immunoglobulin-G and immunoglobulin-A levels were measured by ELISA. The Delta variant was found in 40 out of 40 (100%) SARS-CoV-2 RT-PCR positive COVID-19 patients between 13 September and 23 October 2021 and Omicron variants in 90 out of 90 (100%) RT-PCR positive COVID-19 patients between 9 January and 10 February 2022. The Delta variant associated with hospitalization (74%, 80%, and 40%) and oxygen support (60%, 57%, and 40%) in the no vaccine, dose-1, and dose-2 vaccinated cases, respectively, whereas the Omicron COVID-19 required neither hospitalization nor oxygen support (0%, p < 0.0001). Fever, cough, and breathlessness were found at a significantly higher frequency among the Delta than Omicron variants (p < 0.001). The viral RNA levels of the Delta variant were higher than that of the Omicron variants (Ct median 19.9 versus 23.85; p < 0.02). Anti-spike protein immunoglobulin-G and anti-N-protein immunoglobulin-G within 1 week post onset of Delta variant COVID-19 symptoms indicate prior SARS-CoV-2 infection. The Delta variant and Omicron BA.1 and BA.2 breakthrough infections in the Dhaka region, at 240 days post onset of COVID-19 symptoms, negatively correlated with the time interval between the second vaccine dose and serum sampling. The findings of lower anti-spike protein immunoglobulin-G reactivity after booster vaccination than after the second vaccine dose suggest that the booster vaccine is not necessarily beneficial in young Bangladeshi adults having a history of repeated SARS-CoV-2 infections.

The polymorphic landscape analysis of GATA1 exons uncovered the genetic variants associated with higher thrombocytopenia in dengue patients.

The current study elucidated an association between gene variants and thrombocytopenia through the investigation of the exonic polymorphic landscape of hematopoietic transcription factor-GATA1 gene in dengue patients. A total of 115 unrelated dengue patients with dengue fever (DF) (N = 91) and dengue hemorrhagic fever (DHF) (N = 24) were included in the study. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. Variants G>A (at chX: 48792009) and C>A (at chX: 4879118) had higher frequency out of 13 variants identified (3 annotated and 10 newly recognized). Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Increased stability of the protein due to substitution of serine by asparagine (S129N at chX: 48792009) may cause increased rigidity followed by reduced structural flexibility which may ultimately disturb the dimerization (an important prerequisite for GATA1 to perform its biological activity) process of the GATA1 protein. This, in turn, may affect the function of GATA1 followed by impaired production of mature platelets which may be reflected by the lower platelet counts in individuals with such variation. In summary, we have identified new variants within the GATA1 gene which were found to be clinically relevant to the outcome of dengue patients and thus, have the potential as candidate biomarkers for the determination of severity and prognosis of thrombocytopenia caused by dengue virus. However, further validation of this study in a large number of dengue patients is warranted. Trial Registration: number SLCTR/2019/037.

Perceptions about Telemedicine among Populations with Chronic Diseases amid COVID-19: Data from a Cross-Sectional Survey.

Chronic diseases, including non-communicable diseases (NCDs), have arisen as a severe threat to health and socio-economic growth. Telemedicine can provide both the highest level of patient satisfaction and the lowest risk of infection during a pandemic. The factors associated with its usage and patient adherence are not visible in Bangladesh's resource-constrained settings. Therefore, this study aimed to identify perceptions about telemedicine among populations with chronic diseases amid the COVID-19 pandemic. A closed-ended self-reported questionnaire was created, and the questionnaire was written, reviewed, and finalized by a public health investigator, a psychiatrist, and an epidemiologist. The data for this study were collected from individuals using simple random sampling and snowball sampling techniques. Ethics approval was granted, and written/verbal consent was taken before interviews. Most of the participants showed a positive attitude towards telemedicine. People aged 35-54 years old and a higher level of education were less frequently associated with willingness to receive telemedicine services for current chronic disease (WRTCCD) than their counterparts. People living in urban areas and lower-income participants were more strongly associated with WRTCCD. Additionally, people who did not lose their earnings due to the pandemic were less strongly associated with WRTCCD. However, the main strength of this research is that it is a broad exploration of patient interest in several general forms of telehealth. In Bangladesh, there are many opportunities for telemedicine to be integrated into the existing healthcare system, if appropriate training and education are provided for healthcare professionals.

Persistence of sleep disturbance among post-COVID patients: Findings from a 2-month follow-up study in a Bangladeshi cohort.

To evaluate the persistence and factors associated with sleep disturbances among COVID-19 patients with a history of sleep disturbances 2 months after discharge from the hospital. A total of 400 patients admitted at Dhaka Medical College Hospital during July and August were diagnosed as suffering from sleep disturbances during their hospital stay using a standardized scale. They were followed up 2 months later through telephone, and a total of 322 participants were interviewed (excluding 63 nonresponders and five deceased) regarding the persistence of disturbances in sleep through a structured questionnaire. Patient demographic, clinical, and epidemiological data including history regarding in-hospital sleep disturbance were retrieved from hospital treatment sheets. Results revealed, 35% of study participants (n = 113) were still experiencing symptoms of sleep disturbances during the interview by telephone. Age (p = 0.015), diabetes mellitus (relative risk [RR]: 1.21; confidence interval [CI]: 1.02-1.42, p = 0.022), on admission SPO2 (p = 0.009), C-reactive protein (CRP) (p = 0.025), serum ferritin (p = 0.014), and d-dimer (p = 0.030) were independently associated with sleep disturbances among participants (p < 0.05). Binary and fitting logistic regression through repeated K folds cross-validation revealed 1.65 (CI: 1.02-2.66), 1.07 (CI: 1.01-1.14), and 1.07 (CI: 1.00-1.15) times higher odds of persistence of sleep disturbances among patients with diabetes mellitus, increased neutrophil, and lymphocyte percentages, respectively. Findings of this study need to be validated and patients should be further followed up with more in-depth studies conducted 6 or 12 months after initial infection, possibly with the help of higher sample size and in-person interview.

Real Time PCR-based diagnosis of human visceral leishmaniasis using urine samples.

Diagnosis of visceral leishmaniasis (VL) through the detection of its causative agents namely Leishmania donovani and L. infantum is traditionally based on immunochromatographic tests, microscopy of bone marrow, spleen aspirates, liver or lymph node and differential diagnosis. While the first process has low specificity, the later one carries the risk of fatal hemorrhage. Over the last decade, multiple Polymerase Chain Reaction (PCR) based diagnosis has been developed using blood and urine sample with a varying degree of sensitivity and specificity, an issue worth improving for precision diagnosis. Earlier, we reported a PCR-based diagnosis of L. donovani in peripheral blood using a novel set of PCR primers with absolute specificity. Using the same set of primers and PCR conditions, here we describe diagnosis of L. donovani from urine, for a non-invasive, rapid and safe diagnosis. Diagnosis of VL was carried out using urine samples collected from clinically diagnosed VL patients (n = 23) of Bangladesh in Real Time PCR. Test results were validated by comparing blood samples from the same set of patients. Sensitivity and specificity of this diagnosis was analyzed using retrospective bone marrow samples, collected earlier from confirmed VL patients (n = 19). The method showed 100% sensitivity in detecting L. donovani in urine and corresponding blood and retrospective bone marrow samples, as well as 100% specificity in control groups. A Real Time PCR-based molecular detection system using urine sample is hereafter presented what could be a, non-invasive approach for VL detection with precision and perfection.

A 2-month post-COVID-19 follow-up study on patients with dyspnea.

BACKGROUND AND AIMS: Dyspnea is one of the most common symptoms associated with the COVID-19 caused by novel coronavirus SARS-CoV-2. This study aimed to assess the prevalence of dyspnea, observe co-variables, and find predictors of dyspnea after 2 months of recovery from COVID-19. METHODS: A total of 377 patients were included in the study based on their responses and clinical findings during initial admission to the hospital with COVID-19. After excluding five deceased patients, a total of 327 patients were interviewed through telephone using a 12-point dyspnea scale and using relevant questions to gauge the patient clinically. Interviews were carried out by trained physicians, and responses were recorded and stored. All analyses were carried out using the statistical programming language R. RESULTS: Of the total 327 participants in the study, 34% had stated that they were suffering from respiratory symptoms even after 2 months of COVID-19. The study demonstrated that patient oxygen saturation level SpO2 (P = .03), D-dimer (P = .001), serum ferritin (P = .006), and the presence and severity of dyspnea are significantly correlated. In addition to that, patient smoking history (P = .012) and comorbidities such as chronic obstructive pulmonary disease (COPD) (P = .021) were found to be statistically significant among groups. CONCLUSION: These findings of this study can be useful for predicting and managing long-term complications of COVID-19.

Molecular and Serological Characterization of the SARS-CoV-2 Delta Variant in Bangladesh in 2021.

Novel SARS-CoV-2 variants are emerging at an alarming rate. The delta variant and other variants of concern (VoC) carry spike (S)-protein mutations, which have the potential to evade protective immunity, to trigger break-through infections after COVID-19 vaccination, and to propagate future waves of COVID-19 pandemic. To identify SARS CoV-2 variants in Bangladesh, patients who are RT-PCR-positive for COVID-19 infections in Dhaka were screened by a RT-PCR melting curve analysis for spike protein mutations. To assess the anti-SARS CoV-2 antibody responses, the levels of the anti-S -proteins IgA and IgG and the anti-N-protein IgG were measured by ELISA. Of a total of 36 RT-PCR positive samples (75%), 27 were identified as delta variants, with one carrying an additional Q677H mutation and two with single nucleotide substitutions at position 23029 (compared to Wuhan-Hu-1 reference NC 045512) in the genome sequence. Three (8.3%) were identified as beta variants, two (5.5%) were identified as alpha variants, three (8.3%) were identified as having a B.1.1.318 lineage, and one sample was identified as an eta variant (B.1.525) carrying an additional V687L mutation. The trend of higher viral load (lower Cp values) among delta variants than in the alpha and beta variants was of borderline statistical significance (p = 0.045). Prospective studies with larger Bangladeshi cohorts are warranted to confirm the emergence of S-protein mutations and their association with antibody response in natural infection and potential breakthrough in vaccinated subjects.

Capacity development and safety measures for health care workers exposed to COVID-19 in Bangladesh.

BACKGROUND: The safety of health care workers (HCWs) in Bangladesh and the factors associated with getting COVID-19 have been infrequently studied. The aim of this study was to address this gap by assessing the capacity development and safety measures of HCWs in Bangladesh who have been exposed to COVID-19 and by identifying the factors associated with respondents' self-reported participation in capacity development trainings and their safety practices. METHODS: This cross-sectional study was based on an online survey of 811 HCWs working at 39 dedicated COVID-19 hospitals in Bangladesh. A pretested structured questionnaire consisting of questions related to respondents' characteristics, capacity development trainings and safety measures was administered. Binary logistic regressions were run to assess the association between explanatory and dependent variables. RESULTS: Among the respondents, 58.1% had been engaged for at least 2 months in COVID-19 care, with 56.5% of them attending capacity development training on the use of personal protective equipment (PPE), 44.1% attending training on hand hygiene, and 35% attending training on respiratory hygiene and cough etiquette. Only 18.1% reported having read COVID-19-related guidelines. Approximately 50% of the respondents claimed that there was an inadequate supply of PPE for hospitals and HCWs. Almost 60% of the respondents feared a high possibility of becoming COVID-19-positive. Compared to physicians, support staff [odds ratio (OR) 4.37, 95% confidence interval (CI) 2.25-8.51] and medical technologists (OR 8.77, 95% CI 3.14-24.47) were more exhausted from working in COVID-19 care. Respondents with longer duty rosters were more exhausted, and those who were still receiving infection prevention and control (IPC) trainings were less exhausted (OR 0.54, 95% CI 0.34-0.86). Those who read COVID-19 guidelines perceived a lower risk of being infected by COVID-19 (OR 0.44, 95% CI 0.29-0.67). Compared to the respondents who strongly agreed that hospitals had a sufficient supply of PPE, others who disagreed (OR 2.68, 95% CI 1.31-5.51) and strongly disagreed (OR 5.05, 95% CI 2.15-11.89) had a higher apprehension of infection by COVID-19. CONCLUSION: The findings indicated a need for necessary support, including continuous training, a reasonable duty roster, timely diagnosis of patients, and an adequate supply of quality PPE.

Antibiotic Prescribing Patterns at COVID-19 Dedicated Wards in Bangladesh: Findings from a Single Center Study.

BACKGROUND: As evidence is mounting regarding irrational and often unnecessary use of antibiotics during the COVID-19 pandemic a cross-sectional Point Prevalence Survey (PPS) (in accordance with WHO guideline) was conducted across COVID-19 dedicated wards in Dhaka Medical College and Hospital (DMCH). METHODOLOGY: Antibiotic usage data were collected from 193 patients at different COVID-19 dedicated wards at DMCH on 11 June 2020. Comparisons in antibiotic usage were made between different groups using Pearson chi-square and Fisher's exact test. RESULT: Findings reveal all surveyed patients (100%) were receiving at least one antibiotic with 133 patients (68.91%) receiving multiple antibiotics. Overall, patients presenting with the severe disease received more antibiotics. Third-generation cephalosporins (i.e. ceftriaxone) (53.8%), meropenem (40.9%), moxifloxacin (29.5%), and doxycycline (25.4%) were the four most prescribed antibiotics among surveyed patients. Diabetes mellitus (DM) was independently associated with multiple antibiotic prescribing. Abnormal C-reactive protein (CRP) and serum d-dimer were linked with higher odds of multiple antibiotic prescribing among study patients. CONCLUSION: Prevalence of multiple antibiotic prescriptions was high among severely ill patients and those with abnormal CRP and d-dimer levels. Data regarding the quality of antibiotic prescribing were lacking.

Detection of Anti-Nucleocapsid Antibody in COVID-19 Patients in Bangladesh Is not Correlated with Previous Dengue Infection.

BACKGROUND: The assessment of antibody responses to severe acute respiratory syndrome coronavirus-2 is potentially confounded by exposures to flaviviruses. The aims of the present research were to determine whether anti-dengue antibodies affect the viral load and the detection of anti-coronavirus nucleocapsid (N)-protein antibodies in coronavirus infectious disease 2019 (COVID-19) in Bangladesh. METHODS: Viral RNA was evaluated in swab specimens from 115 COVID-19 patients by real-time reverse transcription polymerase chain reaction (rT-PCR). The anti-N-protein antibodies, anti-dengue virus E-protein antibodies and the dengue non-structural protein-1 were determined in serum from 115 COVID-19 patients, 30 acute dengue fever pre-COVID-19 pandemic and nine normal controls by ELISA. RESULTS: The concentrations of viral RNA in the nasopharyngeal; Ct median (95% CI); 22 (21.9-23.3) was significantly higher than viral RNA concentrations in oropharyngeal swabs; and 29 (27-30.5) p < 0.0001. Viral RNA concentrations were not correlated with-dengue IgG levels. The anti-nucleocapsid antibodies were IgA 27% positive and IgG 35% positive at days 1 to 8 post-onset of COVID-19 symptoms versus IgA 0% and IgG 0% in dengue patients, p < 0.0001. The levels of anti- nucleocapsid IgA or IgG versus the levels of anti-dengue IgM or IgG revealed no significant correlations. CONCLUSIONS: Viral RNA and anti-nucleocapsid antibodies were detected in COVID-19 patients from dengue-endemic regions of Bangladesh, independently of the dengue IgG levels.

Investigation of the efficacy and safety of eltrombopag to correct thrombocytopenia in moderate to severe dengue patients - a phase II randomized controlled clinical trial.

BACKGROUND: The dengue-infected patients with or without hemorrhagic manifestations, typically exhibit moderate to severe thrombocytopenia. A thrombopoietin receptor agonist - eltrombopag has been efficacious in correcting thrombocytopenia in patients with various pathological conditions including immune thrombocytopenia, chronic liver disease, and severe aplastic anemia. This study investigated the efficacy and safety of eltrombopag to correct dengue-mediated thrombocytopenia. METHODS: In this open-label, randomized controlled phase-II trial, patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) having platelet (PLT) count lower than 100 × 109/L without comorbidity, pregnancy, and liver abnormalities were enrolled in Dhaka Medical College Hospital, Better Life Hospital and AMZ hospital, Dhaka, Bangladesh. Between October 10, 2019, and December 30, 2019, 123 DF and DHF patients were assessed for eligibility to be enrolled in the trial. Fourteen patients were excluded as they failed to fulfill the inclusion criteria (N = 6) or refused to participate in the trial (N = 8). Finally, 109 patients were randomly assigned to either Group 1, (N = 36), Group 2 (N = 37), or Control-group (N = 36) in a 1:1:1 ratio. Two doses of eltrombopag - 25 mg/day and 50 mg/day were administered to Group-1 and Group-2 patients, respectively whereas the control-group patients received standard dengue treatment without eltrombopag. The management of all enrolled patients was according to WHO guidelines. The randomization procedure was performed by using a computerized system (STATA Inc.). CBC and immature platelet fraction (IPF) were monitored from Day-0 to Day-7. Absolute immature platelet count (A-IPC) was calculated from PLT count and IPF for each patient. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured on Day-0 and Day-4 and an Ultrasonogram (USG) of the abdomen was performed on Day-4 and Day-7 for each patient. The efficacy of eltrombopag as the primary outcome of the trial was investigated by the proportion of patients with recovered platelet count receiving eltrombopag with corrected platelet count (platelet count above the lower normal limit: 150 × 109/L) on Day-7 of the enrollment as compared to the Control-group. As the secondary outcomes, the reduction of bleeding tendency in response to eltrombopag as well as the safety of eltrombopag in dengue patients were assessed. The safety was evaluated in case of adverse events, liver function enzymes AST/ALT levels and USG. This trial is registered with the international clinical trial registry, number SLCTR/2019/037. RESULTS: A total of 101 patients including 77 DF and 24 DHF patients completed the trial as eight patients left the trial without completing the follow-up. Patients of the different groups were compared with respect to mean age (26±8, 30±10 and 30±9 years for, Group-1,-2 and Control-group, respectively) (p-value= 0.23) and basal PLT count (Group-1: 58±24 × 109; Group-2: 52±29 × 109 and control-group: 55±30 × 109) (p-value= 0.63). The mean PLT counts for Group-1 (332 × 109/L ± 92) and Group-2 (371 × 109/L ± 111) were significantly higher than control-group (194 × 109/L ± 96) on Day-7 (adjusted p-value= 1.15 × 10-06 for Group-1 vs. Control-group, and adjusted p-value= 1.82 × 10-08 for Group-2 vs. Control-group).). On Day-7, 91% of Group-1 (N = 30) and Group-2 (N = 32) patients who received eltrombopag achieved primary endpoint of PLT count above than lower normal limit (150 × 109/L) (Group-1: 91%, OR: 8.33, 95% CI: 2.11 to 32.80, p-value: 0.0024 and Group-2: 91%, OR: 8.89, 95% CI: 2.26 to 34.89, p-value: 0.0017) compared to 55% (N = 18) of control-group patients who did not receive eltrombopag. The bleeding manifestations for thirteen out of fourteen grade-II DHF patients were subsided within Day-7 who received eltrombopag, whereas four out of ten grade-II DHF patients with PLT counts lower than the lower normal limit in the control group showed intermittent bleeding symptoms throughout the trial period. Mean A-IPC but not IPF was significantly higher for eltrombopag-treated groups in comparison to the Control-group. The frequency of the most common adverse events (vomiting and diarrheal tendencies) was similar in the treated-and control-groups (N = 5, 15%, and N = 3, 9% for Group-1 and -2, respectively vs. N = 4, 12% in the Control-group). Ten (30%) patients of Group-1 and, fourteen (40%) patients of Group-2 showed increased AST (U/L) as opposed to nine patients (27%) in the Control-group. Increased ALT levels were observed for three (9%), nine (26%), and seven (21%) patients belonging to the Group-1, -2, and Control-group, respectively. PLT counts higher than the upper normal limit (450 × 109/L) on Day-7 were observed for seven patients who were administered the higher dose (50 mg/day) in contrast to the three patients receiving the lower dose (25 mg/day). USG reports did not show thrombosis events in any of the patients. INTERPRETATION: The trial revealed that the administration of eltrombopag in a short regimen for three days was efficacious to restore the PLT count in DF and DHF patients. The higher number of A-IPCs in eltrombopag treated patients underscored the possible mode of action of eltrombopag through stimulating megakaryopoiesis in dengue patients. The trial hints toward the positive effect of eltrombopag in the cessation of bleeding manifestation. Administration of the lower dose (25 mg/day) of eltrombopag was shown to be safer and equally efficacious to the higher dose (50 mg/day) in treating dengue-infected patients.

Convalescent plasma transfusion therapy in severe COVID-19 patients- a safety, efficacy and dose response study: A structured summary of a study protocol of a phase II randomized controlled trial.

OBJECTIVES: General: To assess the safety, efficacy and dose response of convalescent plasma (CP) transfusion in severe COVID-19 patients Specific: a. To identify the appropriate effective dose of CP therapy in severe patients b. To identify the efficacy of the therapy with their end point based on clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality c. To assess the clinical improvement after CP transfusion in severe COVID-19 patients d. To assess the laboratory improvement after CP transfusion in severe COVID-19 patients TRIAL DESIGN: This is a multicentre, multi-arm phase II Randomised Controlled Trial. PARTICIPANTS: Age and sex matched COVID-19 positive (by RT-PCR) severe cases will be enrolled in this trial. Severe case is defined by the World Health Organization (W.H.O) clinical case definition. The inclusion criteria are 1. Respiratory rate > 30 breaths/min; PLUS 2. Severe respiratory distress; or SpO2 ≤ 88% on room air or PaO2/FiO2≤ 300 mm of Hg, PLUS 3. Radiological (X-ray or CT scan) evidence of bilateral lung infiltrate, AND OR 4. Systolic BP < 90 mm of Hg or diastolic BP <60 mm of Hg. AND/OR 5. Criteria 1 to 4 AND or patient in ventilator support Patients' below18 years, pregnant and lactating women, previous history of allergic reaction to plasma, patients who have already received plasma from a different source will be excluded. Patients will be enrolled at Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital, Dhaka medical college hospital (DMCH) and Mugda medical college hospital (MuMCH). Apheretic plasma will be collected at the transfusion medicine department of SHNIBPS hospital, ELISA antibody titre will be done at BSMMU and CMBT and neutralizing antibody titre will be checked in collaboration with the University of Oxford. Patients who have recovered from COVID-19 will be recruited as donors of CP. The recovery criteria are normality of body temperature for more than 3 days, resolution of respiratory symptoms, two consecutively negative results of sputum SARS-CoV-2 by RT-PCR assay (at least 24 hours apart) 22 to 35 days of post onset period, and neutralizing antibody titre ≥ 1:160. INTERVENTION AND COMPARATOR: This RCT consists of three arms, a. standard care, b. standard care and 200 ml CP and c. standard care and 400 ml CP. Patients will receive plasma as a single transfusion. Intervention arms will be compared to the standard care arm. MAIN OUTCOMES: The primary outcome will be time to clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality. The secondary outcome would be improvement of laboratory parameters after therapy (neutrophil, lymphocyte ratio, CRP, serum ferritin, SGPT, SGOT, serum creatinine and radiology), length of hospital stay, length of ICU stay, reduction in proportion of deaths, requirement of ventilator and duration of oxygen and ventilator support. RANDOMISATION: Randomization will be done by someone not associated with the care or assessment of the patients by means of a computer generated random number table using an allocation ratio of 1:1:1. BLINDING (MASKING): This is an open level study; neither the physician nor the patients will be blinded. However, the primary and secondary outcome (oxygen saturations, PaO2/FiO2, BP, day specific laboratory tests) will be recorded using an objective automated method; the study staff will not be able to influence the recording of these data. NUMBER TO BE RANDOMISED (SAMPLE SIZE): No similar study has been performed previously. Therefore no data are available that could be used to generate a sample size calculation. This phase II study is required to provide some initial data on efficacy and safety that will allow design of a larger study. The trial will recruit 60 participants (20 in each arm). TRIAL STATUS: Protocol version 1.4 dated May 5, 2020 and amended version 1.5, dated June 16, 2020. First case was recruited on May 27, 2020. By August 10, 2020, the trial had recruited one-third (21 out of 60) of the participants. The recruitment is expected to finish by October 31, 2020. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT04403477 . Registered 26 May, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trial's website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Knowledge, attitudes, and practices toward the novel coronavirus among Bangladeshis: Implications for mitigation measures.

The current novel coronavirus (nCoV) pandemic, COVID-19, was first reported in December 2019 in Wuhan, China, and has spread globally, causing startling loss of life, stalling the global economy, and disrupting social life. One of the challenges to contain COVID-19 is convincing people to adopt personal hygiene, social distancing, and self-quarantine practices that are related to knowledge, attitudes, and practices (KAP) of the residents of respective countries. Bangladesh, a densely populated country with a fast-growing economy and moderate literacy rate, has shown many hiccups in its efforts to implement COVID-19 policies. Understanding KAP may help policy makers produce informed decisions. This study assessed KAP in relation to COVID-19 in Bangladesh. An online survey using a pre-tested questionnaire conducted in late March 2020 attained 1,837 responses across Bangladesh. Ultimately, 1,589 completed responses were included in a statistical analysis to calculate KAP scores and their interrelations with sociodemographic variables. The overall KAP was poor, with only 33% of the participants demonstrating good knowledge, whereas 52.4% and 44.8% of the subjects showed good attitudes and practices, respectively. Sociodemographic factors had strong bearings on the KAP scores. Significantly higher KAP scores were evident in females over males, among aged 45 years and older over younger participants, and among retired workers and homemakers over students and public service employees. This study indicated a panic fuelled by poor understanding of COVID-19 associated facts and the need for the government to ensure more granular and targeted awareness campaigns in a transparent and factual manner to foster public confidence and ensure more meaningful public participation in mitigation measures. This study provides a KAP baseline regarding COVID-19 among Bangladeshis.