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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

This research aimed to reveal teachers' opinions about how the grammar-teaching process is related to the acquisitions in the curriculum, activities, and acquisitions presented in the textbooks teaching in mother tongue, the study reviewed different textbooks from four publishers, Cem, Sonuç, Koza, and Ministry of National Education (MEB) publications prepared for the 2018 primary school Turkish language course curriculum and Education Information Network (EBA) of the Turkish Ministry of Education. Moreover, opinions of ten primary school teachers who have taught all grades regarding the teaching process for grammar acquisition were investigated. The study conducted a case study method, which is one of the qualitative research techniques. Besides, a document analysis was conducted to obtain the research findings. Structured interview protocol and document review were used as the data collection tool. The findings of the study revealed that acquisition in the learning areas of reading and writing for grammar in the curriculum was not clearly and transparently identified, and the limits of the teaching framework were not specified. The study findings also revealed that information was transferred only in the majority of the grammar activities in the textbooks. Also, classroom teachers reported that they used different methods on the subjects they could embody in the teaching process, but they claimed to have difficulties in teaching abstract concepts.

Abstract Conjugated polymers are promising tools to differentiate various types of semiconducting single-walled carbon nanotubes (s-SWCNTs). However, their synthesis is challenging. Insufficient control over molecular weights, and unpredictive/unrepeatable batches hinder possible applications and scale-up. Furthermore, commercial homogeneous catalysts often require inert conditions and are almost impossible to recycle. To overcome these problems, we present a nanocatalyst consisting of magnetic nickel nanowires decorated with highly active palladium nanoparticles. A two-step wet chemical reduction protocol with the assistance of sonochemistry was employed to obtain a heterogeneous catalyst capable of conducting step-growth Suzuki polycondensation of a fluorene-based monomer. Additionally, we enhanced the performance of our catalytic system via controlled microwave irradiation, which significantly shortened the reaction time from 3 d to only 1 h. We studied the influence of the main process parameters on the yield and polymer chain length to gain insight into phenomena occurring in the presence of metallic species under microwave irradiation. Finally, the produced polymers were used to extract specific s-SWCNTs by conjugated polymer extraction to validate their utility.

The study aims is to determine the experiences of primary school teachers in terms of teaching Turkish to the students who are not native Turkish speakers. In the study, phenomenology pattern, one of the qualitative research patterns, was used. Participants were determined by the criterion-based sampling method. The participants of the research consisted of 36 primary school teachers who had Syrian and Afghan refugees in their class. The research data were collected through a semi-structured interview form developed by the researchers. Content analysis technique was used in the analysis of the data. It was observed that most of the participants felt insufficient in teaching Turkish to students who had different native languages, had problems in applying, measuring and evaluating teaching methods and course activities, and had language problems with them. In the study, the difficulties experienced in teaching Turkish to Syrian and Afghan refugee students who were not native Turkish speakers were presented and the suggestions about what to do in the education process related to these difficulties were provided. It was concluded that in the education process of the teachers, students and families should take Turkish language courses. Moreover, in addition to the Turkish courses in teaching Turkish, it was reported that the primary school teachers stated that it would be helpful to do social activities with students who have language problems, to provide counseling services for them, and to prearrange distribution of the students to each classroom. It was concluded that special activities should be carried out in the verbal communication learning area.

ABSTRACT Dementia poses a significant societal and health challenge in the 21st century, with many hospitalized patients experiencing dementia without a documented diagnosis. Objective: To evaluate the prevalence of dementia and its associated risk factors among older patients admitted to hospitals. Methods: The study included older patients (≥ 60 years) admitted to medical departments of a general hospital in three major Iranian cities. Researchers utilized the Activities of Daily Living-Instrumental Activities of Daily Living (ADL-IADL) scale, the Geriatric Depression Scale (GDS), the Mini-Cog test, the 4 A’s test (4AT), and the Abbreviated Mental Test Score (AMTS). Among the 420 recruited older inpatients, 228 (54.3%) were female. Results: The mean age of participants was 71.39 years (standard deviation ±7.95), with 30.7% diagnosed with major neurocognitive disorder (dementia). The likelihood of dementia exhibited statistically significant correlations with gender, age, number of children, and occupation. Conclusions: Screening older individuals for cognitive impairment upon hospital admission holds the potential to prevent adverse outcomes and enhance the quality of treatment for patients concurrently dealing with dementia.

Transcatheter aortic valve replacement (TAVR) has become the treatment option for symptomatic severe aortic stenosis patients across all risk profiles. Despite remarkable advancements in technology and operator experience, the occurrence of periprocedural stroke remains a significant concern, predominantly attributed to thromboembolic events in the immediate postprocedural period. To optimize patient outcomes, various strategies have been developed to minimize the risk of stroke, encompassing comprehensive preprocedural planning, effective management of comorbidities, utilization of cerebral embolic protection devices, and tailored medical therapy. This comprehensive review summarizes the currently available strategies for mitigating periprocedural stroke post-TAVR and provides insights into future directions.

Background: There are studies available on the prevalence of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) in hospitalized patients but not on the incidence of CAM in post-discharge patients. The aim of our study was to find the incidence of CAM in the patients discharged from a COVID hospital. Material and Methods: Adult patients with COVID discharged between March 1, 2021 and June 30, 2021 were contacted and enquired about sign and symptoms of CAM. Data of all included patients were collected from electronic records. Results: A total of 850 patients responded, among which 59.4% were males, 66.4% patients had co-morbidities, and 24.2% had diabetes mellitus. Around 73% of patients had moderate to severe disease and were given steroids; however, only two patients developed CAM post discharge. Conclusion: The incidence of CAM post discharge was low in our study, which could be attributed to protocolized therapy and intensive monitoring.

In this study, it was aimed to evaluate the reading performances of 2nd, 3rd and 4th graders. The study was designed in a scanning model. The research was conducted with 2nd, 3rd and 4th grade students studying in Bayburt, Turkey. The appropriate reading rates, reading speeds and reading errors of the students were examined by asking them to read a narrative text appropriate to their class. The texts were selected from the books distributed to the schools by the Ministry of National Education. Error Analysis Inventory was used to diagnose reading difficulties of students and to collect data about their reading performances. It was used to determine the reading levels of the readers individually. The present study is important since it identify students with reading difficulties and determines the necessary programs to overcome these difficulties.

First language literacy is a prerequisite both for proper formal education and second language learning. When children start school, not all of them succeed in learning reading perfectly; for some of them, it may take more time to reach the desired reading proficiency. This study aimed to examine the relationship between the first language oral reading behaviors of poor readers among 3rd graders. For this purpose, reading comprehension levels and reading behaviors along with eye movements of eight poor readers were investigated. A narrative text suitable for the grade level was utilized to determine the reading skills and analyzed through IRI and Ekwall and Shanker Reading Inventory. Additionally, the eye movements of 8 adult skilled readers were recorded for comparison. Reading speed, word recognition rates, reading errors and comprehension scores were analyzed along with dwell time, fixations and total time spent on each word. Results showed that poor readers had viable difficulties in comprehension and made frequent reading errors which were also accompanied by a low word recognition rate. Poor readers also exhibited inflated eye movement parameters when compared to adult skilled readers. The results were discussed regarding poor reading ability, dyslexia and possible pedagogical interventions.

Background: COVID-19 infections among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccinated individuals are of clinical concern, especially in those requiring hospitalization. Such real-world data on ChAdOx1 nCoV-19- and BBV152-vaccinated individuals are scarce. Hence, there is an urgent need to understand their clinical profile and outcomes. Methods: A 1:1 pair-matched study was performed among vaccinated and unvaccinated COVID-19 patients admitted between March 2021 and June 2021 at a tertiary care centre in New Delhi, India. The vaccinated group (received at least one dose of ChAdOx1 nCoV-19 or BBV152) was prospectively followed till discharge or death and matched [for age (±10 years), sex, baseline disease severity and comorbidities] with a retrospective group of unvaccinated patients admitted during the study period. Paired analysis was done to look for clinical outcomes between the two groups. Results: The study included a total of 210 patients, with 105 in each of the vaccinated and unvaccinated groups. In the vaccinated group, 47 (44.8%) and 58 (55.2%) patients had received ChAdOx1 nCoV-19 and BBV152, respectively. However, 73 patients had received one dose and 32 had received two doses of the vaccine. Disease severity was mild in 36.2%, moderate in 31.4% and severe in 32.4%. Two mortalities were reported out of 19 fully vaccinated individuals. All-cause mortality in the vaccinated group was 8.6% (9/105), which was significantly lower than the matched unvaccinated group mortality of 21.9% (23/105), p = 0.007. Vaccination increased the chances of survival (OR = 3.8, 95% CI: 1.42–10.18) compared to the unvaccinated group. Conclusion: In the second wave of the pandemic predominated by delta variant of SARS CoV-2, vaccination reduced all-cause mortality among hospitalized patients, although the results are only preliminary.

Abstract Plain English summary The World Health Organization (WHO) provides a framework (ICD-MM) to classify pregnancy-related deaths systematically, which enables global comparison among countries. We compared the classification of pregnancy-related deaths in Suriname by the attending physician and by the national maternal death review (MDR) committee and among the MDR committees of Suriname, Jamaica and the Netherlands. There were 89 possible pregnancy-related deaths in Suriname between 2010 and 2014. Nearly half (47%) were classified differently by the Surinamese MDR committee as compared to the classification of the attending physicians. All three MDR committees agreed that 18% (n = 16/89) of the cases were no maternal deaths. Out of the remaining 73 cases, there was disagreement regarding whether 15% (n = 11) were maternal deaths. The Surinamese and Jamaican MDR committees achieved greater consensus in classification than the Surinamese and the Netherlands MDR committees. The Netherlands MDR committee classified more deaths as unspecified than Surinamese and the Jamaican MDR committees. Underlying causes that achieved a high level of agreement among the three committees were abortive outcomes and obstetric hemorrhage, while little agreement was reported for unspecified and other direct causes. The issues encountered during maternal death classification using the ICD-MM guidelines included classification of suicide during early pregnancy; when to assume pregnancy without objective evidence; how to count maternal deaths occurring outside the country of residence; the relevance of direct or indirect cause attribution; and how to select the underlying cause when direct and indirect conditions or multiple comorbidities co-occur. Addressing these classification barriers in future revisions of the ICD-MM guidelines could enhance the feasibility of maternal death classification and facilitate global comparison. Background Insight into the underlying causes of pregnancy-related deaths is essential to develop policies to avert preventable deaths. The WHO International Classification of Diseases-Maternal Mortality (ICD-MM) guidelines provide a framework to standardize maternal death classifications and enable comparison in and among countries over time. However, despite the implementation of these guidelines, differences in classification remain. We evaluated consensus on maternal death classification using the ICD-MM guidelines. Methods The classification of pregnancy-related deaths in Suriname during 2010–2014 was compared in the country (between the attending physician and the national maternal death review (MDR) committee), and among the MDR committees from Suriname, Jamaica and the Netherlands. All reviewers applied the ICD-MM guidelines. The inter-rater reliability (Fleiss kappa [κ]) was used to measure agreement. Results Out of the 89 cases certified by attending physicians, 47% (n = 42) were classified differently by the Surinamese MDR committee. The three MDR committees agreed that 18% (n = 16/89) of these cases were no maternal deaths, and, therefore, excluded from further analyses. However, opinions differed whether 15% (n = 11) of the remaining 73 cases were maternal deaths. The MDR committees achieved moderate agreement classifying the deaths into type (direct, indirect and unspecified) (κ = 0.53) and underlying cause group (κ = 0.52). The Netherlands MDR committee classified more maternal deaths as unspecified (19%), than the Jamaican (7%) and Surinamese (4%) committees did. The mutual agreement between the Surinamese and Jamaican MDR committees (κ = 0.69 vs κ = 0.63) was better than between the Surinamese and the Netherlands MDR committees (κ = 0.48 vs κ = 0.49) for classification into type and underlying cause group, respectively. Agreement on the underlying cause category was excellent for abortive outcomes (κ = 0.85) and obstetric hemorrhage (κ = 0.74) and fair for unspecified (κ = 0.29) and other direct causes (κ = 0.32). Conclusions Maternal death classification differs in Suriname and among MDR committees from different countries, despite using the ICD-MM guidelines on similar cases. Specific challenges in applying these guidelines included attribution of underlying cause when comorbidities occurred, the inclusion of deaths from suicides, and maternal deaths that occurred outside the country of residence.

Background Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Non-interpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. Methods Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culture-positive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. Results A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). Conclusion The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

Plasmodium infections are co-endemic with infections caused by other agents of acute febrile illnesses, such as dengue virus (DENV), chikungunya virus, Leptospira spp., and Orientia tsutsugamushi. However, co-infections may influence disease severity, treatment outcomes, and development of drug resistance. When we analyzed cases of acute febrile illness at the All India Institute of Medical Sciences, New Delhi, India, from July 2017 through September 2018, we found that most patients with malaria harbored co-infections (Plasmodium mixed species and other pathogens). DENV was the most common malaria co-infection (44% of total infections). DENV serotype 4 was associated with mild malaria, and Leptospira was associated with severe malaria. We also found the presence of P. knowlesi in our study population. Therefore, in areas with a large number of severe malaria cases, diagnostic screening for all 4 DENV serotypes, Leptospira, and all Plasmodium species should be performed.

Abstract Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.

Abstract Background Our study aims to evaluate the current perinatal registry, analyze national childbirth outcomes and study ethnic disparities in middle-income country Suriname, South America. Methods A nationwide birth registry study was conducted in Suriname. Data were collected for 2016 and 2017 from the childbirth books of all five hospital maternity wards, covering 86% of all births in the country. Multinomial regression analyses were used to assess ethnic disparities in outcomes of maternal deaths, stillbirths, teenage pregnancy, cesarean delivery, low birth weight and preterm birth with Hindustani women as reference group. Results 18.290 women gave birth to 18.118 (98%) live born children in the five hospitals. Hospital-based maternal mortality ratio was 112 per 100.000 live births. Hospital-based late stillbirth rate was 16 per 1000 births. Stillbirth rate was highest among Maroon (African-descendent) women (25 per 1000 births, aOR 2.0 (95%CI 1.3–2.8) and lowest among Javanese women (6 stillbirths per 1000 births, aOR 0.5, 95%CI 0.2–1.2). Preterm birth and low birthweight occurred in 14 and 15% of all births. Teenage pregnancy accounted for 14% of all births and was higher in Maroon women (18%) compared to Hindustani women (10%, aOR 2.1, 95%CI 1.8–2.4). The national cesarean section rate was 24% and was lower in Maroon (17%) than in Hindustani (32%) women (aOR 0.5 (95%CI 0.5–0.6)). Cesarean section rates varied between the hospitals from 17 to 36%. Conclusion This is the first nationwide comprehensive overview of maternal and perinatal health in a middle income country. Disaggregated perinatal health data in Suriname shows substantial inequities in outcomes by ethnicity which need to be targetted by health professionals, researchers and policy makers.

Context: Nontuberculous mycobacteria (NTM) are ubiquitous mycobacteria present in environment and generally affect patients with either structural lung disease or immunosuppression and commonly involve lungs, lymph node, or skin. Materials and Methods: Between July 2016 and February 2019, 18 cases of NTM were diagnosed and their relevant clinical, diagnostic, and treatment details were recorded after taking informed consent. Results: We report 18 cases of NTM involving lungs (n = 11), skin and soft tissue (n = 3), joint (n = 2), genitourinary (n = 1), and central nervous system (n = 1). History of immunosuppression was present in two patients, whereas history of some form of intervention was seen in six patients. Mycobacterium fortuitum group (n = 5) was the most commonly isolated organism, followed by Mycobacterium avium complex (n = 4), Mycobacterium abscessus (n = 3), Mycobacterium kansasii (n = 2), and Mycobacterium chelonae (n = 1). In two patients, M. chelonae and M. abscessus were isolated in succession. Of these 18 patients, clinical response was present in 15 of the patients. Diagnosis and treatment of NTM in resource limited settings is extremely challenging. Conclusion: Most of the patients with NTM are misdiagnosed and are treated as tuberculosis in India, sometimes with a multidrug resistance regimen, which results in significant morbidity and mortality. We present these cases to shed some light on the epidemiology of NTM in this part of India.

Background: Mutations in atpE gene or transcriptional repressor Rv0678 gene associated with inhibition of adenosine 5′-triphosphate synthase and upregulation of efflux pumps, respectively, may potentially lead to in vitro resistance to bedaquiline. This is the first study from India, which looks at mutations associated with this novel drug. Methods: In 2019 (January to June), a total of 68 laboratory-confirmed pre-extensively drug-resistant tuberculosis (XDR-TB) (fluoroquinolone resistant [n = 52] and second-line injectables resistant [n = 12]) and 4 × DR-TB culture specimens were included. All specimens were evaluated for genetic analysis using predesigned primers of atpE and Rv0678 genes. Results: Among the pre-XDR-TB isolates (n = 64), there were no mutations found in either atpE or Rv0678. However, among the XDR-TB isolates (n = 4), one specimen (25%) was found to be associated with a mutation in atpE gene at position 49, resulting in the amino acid leucine replaced by proline (L-49-P). No mutations were observed with the Rv0678 gene. Conclusion: In this study, genetic analysis showed that only one-fourth XDR-TB isolates had a mutation in the atpE gene; there were no other mutations found in the Rv0678 gene. To the best of our knowledge, this novel mutation (L-49-P) in atpE gene is being reported for the first time in northern India.

BACKGROUND: Latin America and the Caribbean is the region with the highest prevalence of hypertensive disorders of pregnancy worldwide. In Suriname, where the stillbirth rate is the second highest in the region, it is not yet known which maternal factors contribute most substantially. OBJECTIVE: The aims of this study in Suriname were to (1) study the impact of different types of maternal morbidity on adverse perinatal outcomes and (2) study perinatal birth outcomes among women with severe hypertensive disorders of pregnancy. STUDY DESIGN: A case-control study was conducted between March 2017 and February 2018 during which time all hospital births (86% of total) in Suriname were included. We identified babies with adverse perinatal outcomes (perinatal death or neonatal near miss) and women with severe maternal morbidity (according to the World Health Organization Near Miss tool). Stillbirths and early neonatal deaths (

Abstract Background Obstetric guidelines are useful to improve the quality of care. Availability of international guidelines has rapidly increased, however the contextualization to enhance feasibility of implementation in health facilities in low and middle-income settings has only been described in literature in a few instances. This study describes the approach and lessons learned from the ‘bottom-up’ development process of context-tailored national obstetric guidelines in middle-income country Suriname. Methods Local obstetric health care providers initiated the guideline development process in Suriname in August 2016 for two common obstetric conditions: hypertensive disorders of pregnancy (HDP) and post partum haemorrhage (PPH). Results The process consisted of six steps: (1) determination of how and why women died, (2) interviews and observations of local clinical practice, (3) review of international guidelines, (4) development of a primary set of guidelines, (5) initiation of a national discussion on the guidelines content and (6) establishment of the final guidelines based on consensus. Maternal enquiry of HDP- and PPH-related maternal deaths revealed substandard care in 90 and 95% of cases, respectively. An assessment of the management through interviews and labour observations identified gaps in quality of the provided care and large discrepancies in the management of HDP and PPH between the hospitals. International recommendations were considered unfeasible and were inconsistent when compared to each other. Local health care providers and stakeholders convened to create national context-tailored guidelines based on adapted international recommendations. The guidelines were developed within four months and locally implemented. Conclusion Development of national context-tailored guidelines is achievable in a middle-income country when using a ‘bottom-up’ approach that involves all obstetric health care providers and stakeholders in the earliest phase. We hope the descriptive process of guideline development is helpful for other countries in need of nationwide guidelines.

A 54-year-old female, known case of hypertension and diabetes mellitus (controlled), was admitted with prolonged fever for 1½ months. On evaluation, fever workup was inconclusive and multiple cultures were negative. On re-assessment of history, she gave a history of cardiac catheterization 1 month back. Further evaluation revealed aortic valve vegetation on two-dimensional echo with raised beta-D glucan levels. She was managed with antifungal therapy followed by valve replacement surgery. The patient improved following the management and is doing fine. This case highlights the importance of detailed history-taking and evaluation. It also highlights the not uncommon occurrence of fungal endocarditis in patients with healthcare contact and the role of biomarkers as surrogate in case of culture-negative endocarditis.

P-glycoprotein, an ATP-binding cassette (ABC) transporter, extrudes a large variety of xenobiotics from the cell which protects tissues from toxins. Here authors solve a pair of X-ray structures of homodimeric P-glycoprotein and resolve structural elements proposed to participate in the mechanism of the transporter.

BACKGROUND: The Sustainable Development Goal target 3.1 aims to reduce the global maternal mortality ratio to less than 70 per 100,000 live births. Great disparities reported in maternal mortality ratio between and within countries make this target unachievable. To gain more insight into such disparities and to monitor and describe trends, confidential enquiries into maternal deaths are crucial. OBJECTIVE: We aimed to study the trend in maternal mortality ratio, causes, delay in access and quality of care, and “lessons learned” in Suriname, over almost 3 decades with 3 confidential enquiries into maternal deaths and provide recommendations to prevent maternal deaths. STUDY DESIGN: The third national confidential enquiry into maternal deaths was conducted between 2015 and 2019 in Suriname by prospective, population-based surveillance and multidisciplinary systematic maternal death review. Subsequently, a comparative analysis with previous confidential enquiry into maternal deaths was performed: confidential enquiry into maternal deaths I (a prospective study, 1991–1993) and confidential enquiry into maternal deaths II (a retrospective study, 2010–2014). RESULTS: We identified 62 maternal deaths and recorded 48,881 live births (maternal mortality ratio, 127/100,000 live births) between 2015-2019. Of the women who died, 14 of 62 (23%) were in poor condition when entering a health facility, whereas 11 of 62 (18%) died at home or during transportation. The maternal mortality ratio decreased over the years, (226 [n=64]; 130 [n=65]; and 127 [n=62]), with underreporting rates of 62%, 26%, and 24%, respectively in confidential enquiry into maternal deaths I, II and III. Of the women deceased, 36 (56%), 37 (57%), and 40 (63%) were of African descent; 46 (72%), 45 (69%), and 47 (76%) died after birth; and 47 (73%), 55 (84%), and 48 (77%) died in the hospital, respectively, in confidential enquiries into maternal deaths I, II, and III. Significantly more women were uninsured in confidential enquiry into maternal deaths III (15 of 59 [25%,]) than in confidential enquiry into maternal deaths II (0%) and I (6 of 64 [9%]). Obstetrical hemorrhage was less often the underlying cause of death over the years (19 of 64 [30%], vs 13 of 65 [20%], vs 7 of 62 [11%]), whereas all other obstetrical causes occurred more often in confidential enquiry into maternal deaths III (eg, suicide [0; 1 of 65 (2%); 5 of 62 (8%)]) and unspecified deaths (1 of 64 [2%]; 3 of 65 [5%]; and 11 of 62 [18%] in confidential enquiry into maternal deaths I, II and III respectively). Maternal deaths were preventable in nearly half of the cases in confidential enquiry into maternal deaths II (28 of 65) and III (29 of 62). Delay in quality of care occurred in at least two-thirds of cases (41 of 62 [65%], 47 of 59 [80%], and 47 of 61 [77%]) over the years. CONCLUSION: Suriname's maternal mortality rate has decreased throughout the past 3 decades, yet the trend is too slow to achieve the Sustainable Development Goal 3.1. Preventable maternal deaths can be reduced by ensuring high-quality facility-based obstetrical and postpartum care, universal access to care especially for vulnerable women (of African descent and low socioeconomic class), and by addressing specific underlying causes of maternal deaths.

Background Suriname has one of the highest stillbirth rates in Latin America and the Caribbean. To facilitate data comparison of perinatal deaths, the World Health Organization developed the International Classification of Diseases-10 Perinatal Mortality (ICD-PM). Objective We aimed to (1) assess characteristics and risk indicators of women with a stillbirth, (2) determine the timing and causes of stillbirths according to the ICD-PM with critical evaluation of its application and (3) propose recommendations for the reduction of stillbirths in Suriname. Methods A hospital-based, nation-wide, cross-sectional study was conducted in all hospitals within Suriname during one-year (2017). The medical files of stillbirths (gestation ≥28 weeks/birth weight ≥1000 grams) were reviewed and classified using ICD-PM. We used descriptive statistics and multiple logistic regression analyses. Results The stillbirth rate in Suriname was 14.4/1000 births (n=131 stillbirths, n=9089 total births). Medical files were available for 86% (n=113/131) of stillbirths. Women of African descent had the highest stillbirth rate and two times the odds of stillbirth (OR 2.1, 95%CI 1.4–3.1) compared to women of other ethnicities. One third (33%, n=37/113) of stillbirths occurred after hospital admission. The timing was antepartum in 85% (n=96/113), intrapartum in 11% (n=12/113) and unknown in 4% (n=5/113). Antepartum stillbirths were caused by hypoxia in 46% (n=44/96). In 41% (n=39/96) the cause was unspecified. Maternal medical and surgical conditions were present in 50% (n=57/113), mostly hypertensive disorders. Conclusion Stillbirth reduction strategies in Suriname call for targeting ethnic disparities, improving antenatal services, implementing perinatal death audits and improving diagnostic post-mortem investigations. ICD-PM limited the formulation of recommendations due to many stillbirths of ‘unspecified’ causes. Based on our study findings, we also recommend addressing some challenges with applying the ICD-PM. Abbreviations CTG: Cardiotocography; ENAP: Every Newborn Action Plan (ENAP); ICD-PM: The WHO application of ICD-10 to deaths during the perinatal period – perinatal mortality; SBR: Stillbirth rate; SGA: Small for gestational age; WHO: World Health Organization; LMIC: Low- and middle-income countries; FHR: foetal heart rate.

BackgroundPostpartum hemorrhage (PPH) is the leading cause of direct maternal mortality globally and in Suriname. We aimed to study the prevalence, risk indicators, causes, and management of PPH to identify opportunities for PPH reduction.MethodsA nationwide retrospective descriptive study of all hospital deliveries in Suriname in 2017 was performed. Logistic regression analysis was applied to identify risk indicators for PPH (≥ 500ml blood loss). Management of severe PPH (blood loss ≥1,000ml or ≥500ml with hypotension or at least three transfusions) was evaluated via a criteria-based audit using the national guideline.ResultsIn 2017, the prevalence of PPH and severe PPH in Suriname was 9.2% (n = 808/8,747) and 2.5% (n = 220/8,747), respectively. PPH varied from 5.8% to 15.8% across the hospitals. Risk indicators associated with severe PPH included being of African descent (Maroon aOR 2.1[95%CI 1.3-3.3], Creole aOR 1.8[95%CI 1.1-3.0]), multiple pregnancy (aOR 3.4[95%CI 1.7-7.1]), delivery in Hospital D (aOR 2.4[95%CI 1.7-3.4]), cesarean section (aOR 3.9[95%CI 2.9-5.3]), stillbirth (aOR 6.4 [95%CI 3.4-12.2]), preterm birth (aOR 2.1[95%CI 1.3-3.2]), and macrosomia (aOR 2.8 [95%CI 1.5-5.0]). Uterine atony (56.7%, n = 102/180[missing 40]) and retained placenta (19.4%, n = 35/180[missing 40]), were the main causes of severe PPH. A criteria-based audit revealed that women with severe PPH received prophylactic oxytocin in 61.3% (n = 95/155[missing 65]), oxytocin treatment in 68.8% (n = 106/154[missing 66]), and tranexamic acid in 4.9% (n = 5/103[missing 117]).ConclusionsPPH prevalence and risk indicators in Suriname were similar to international and regional reports. Inconsistent blood loss measurement, varied maternal and perinatal characteristics, and variable guideline adherence contributed to interhospital prevalence variation. PPH reduction in Suriname can be achieved through prevention by practicing active management of the third stage of labor in every birth and considering risk factors, early recognition by objective and consistent blood loss measurement, and prompt treatment by adequate administration of oxytocin and tranexamic acid according to national guidelines.

Abstract Background Although public reporting of hospital performance is becoming common, it remains uncertain whether public reporting leads to improvement in clinical outcomes. This study was conducted to evaluate whether enrollment in a quality reporting project is associated with improvement in quality of care for patients with acute myocardial infarction. Methods We conducted a quasi-experimental study using hospital census survey and national inpatient database in Japan. Hospitals enrolled in a ministry-led quality reporting project were matched with non-reporting control hospitals by one-to-one propensity score matching using hospital characteristics. Using the inpatient data of acute myocardial infarction patients hospitalized in the matched hospitals during 2011–2013, difference-in-differences analyses were conducted to evaluate the changes in unadjusted and risk-adjusted in-hospital mortality rates over time that are attributable to intervention. Results Matching between hospitals created a cohort of 30,220 patients with characteristics similar between the 135 reporting and 135 non-reporting hospitals. Overall in-hospital mortality rates were 13.2% in both the reporting and non-reporting hospitals. There was no significant association between hospital enrollment in the quality reporting project and change over time in unadjusted mortality (OR, 0.98; 95% CI, 0.80–1.22). In 28,168 patients eligible for evaluation of risk-adjusted mortality, enrollment was also not associated with change in risk-adjusted mortality (OR, 0.98; 95% CI, 0.81–1.17). Conclusions Enrollment in the quality reporting project was not associated with short-term improvement in quality of care for patients with acute myocardial infarction. Additional efforts may be necessary to improve quality of care.

Fungal rhinosinusitis is not very uncommon in diabetic patients, but Scedosporium apiospermum as a cause of this infection is rare. We report a case of fungal rhinosinusitis by Scedosporium spp. in a diabetic male along with literature review. The patient is on voriconazole, with adequate therapeutic response after 6 months of follow up.

Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) holds enormous potential for the structure determination of proteins for which it is difficult to produce large and high-quality crystals. SFX has been applied to various systems, but rarely to proteins that have previously unknown structures. Consequently, the majority of previously obtained SFX structures have been solved by the molecular replacement method. To facilitate protein structure determination by SFX, it is essential to establish phasing methods that work efficiently for SFX. Here, selenomethionine derivatization and mercury soaking have been investigated for SFX experiments using the high-energy XFEL at the SPring-8 Angstrom Compact Free-Electron Laser (SACLA), Hyogo, Japan. Three successful cases are reported of single-wavelength anomalous diffraction (SAD) phasing using X-rays of less than 1 Å wavelength with reasonable numbers of diffraction patterns (13 000, 60 000 and 11 000). It is demonstrated that the combination of high-energy X-rays from an XFEL and commonly used heavy-atom incorporation techniques will enable routine de novo structural determination of biomacromolecules.

Abstract Background The fifth Millennium Development Goal (MDG-5) aimed to improve maternal health, targeting a maternal mortality ratio (MMR) reduction of 75% between 1990 and 2015. The objective of this study was to identify all maternal deaths in Suriname, determine the extent of underreporting, estimate the reduction, audit the maternal deaths and assess underlying causes and substandard care factors. Methods A reproductive age mortality survey was conducted in Suriname (South-American upper-middle income country) between 2010 and 2014 to identify all maternal deaths in the country. MMR was compared to vital statistics and a previous confidential enquiry from 1991 to 1993 with a MMR 226. A maternal mortality committee audited the maternal deaths and identified underlying causes and substandard care factors. Results In the study period 65 maternal deaths were identified in 50,051 live births, indicating a MMR of 130 per 100.000 live births and implicating a 42% reduction of maternal deaths in the past 25 years. Vital registration indicated a MMR of 96, which marks underreporting of 26%. Maternal deaths mostly occurred in the urban hospitals (84%) and the causes were classified as direct (63%), indirect (32%) or unspecified (5%). Major underlying causes were obstetric and non-obstetric sepsis (27%) and haemorrhage (20%). Substandard care factors (95%) were mostly health professional related (80%) due to delay in diagnosis (59%), delay or wrong treatment (78%) or inadequate monitoring (59%). Substandard care factors most likely led to death in 47% of the cases. Conclusion Despite the reduction in maternal mortality, Suriname did not reach MDG-5 in 2015. Steps to reach the Sustainable Development Goal in 2030 (MMR ≤ 70 per 100.000 live births) and eliminate preventable deaths include improving data surveillance, installing a maternal death review committee, and implementing national guidelines for prevention and management of major complications of pregnancy, childbirth and puerperium.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%–50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein–Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.

BACKGROUND:Sepsis was the main cause of maternal mortality in Suriname, a middle-income country. Objective of this study was to perform a qualitative analysis of the clinical and management aspects of sepsis-related maternal deaths with a focus on the 'golden hour' principle of antibiotic therapy. METHODS:A nationwide reproductive age mortality survey was performed from 2010 to 2014 to identify and audit all maternal deaths in Suriname. All sepsis-related deaths were reviewed by a local expert committee to assess socio-demographic characteristics, clinical aspects and substandard care. RESULTS:Of all 65 maternal deaths in Suriname 29 (45%) were sepsis-related. These women were mostly of low socio-economic class (n = 23, 82%), of Maroon ethnicity (n = 14, 48%) and most deaths occurred postpartum (n = 21, 72%). Underlying causes were pneumonia (n = 14, 48%), wound infections (n = 3, 10%) and endometritis (n = 3, 10%). Bacterial growth was detected in 10 (50%) of the 20 available blood cultures. None of the women with sepsis as underlying cause of death received antibiotic treatment within the first hour, although most women fulfilled the diagnostic criteria of sepsis upon admission. In 27 (93%) of the 29 women from which sufficient information was available, substandard care factors were identified: delay in monitoring in 16 (59%) women, in diagnosis in 17 (63%) and in treatment in 21 (78%). CONCLUSION:In Suriname, a middle-income country, maternal mortality could be reduced by improving early recognition and timely diagnosis of sepsis, vital signs monitoring and immediate antibiotic infusion (within the golden hour).

Zika virus (ZIKV) is an arthropod-borne flavivirus that presents with acute febrile illness associated with rash, arthralgia and conjunctivitis. After years of sporadic reports in Africa, the three major outbreaks of this disease occurred in Yap Islands (2007), French Polynesia (2013–14) and South Americas (2015–16). Although, serological surveys suggested the presence of ZIKV in India in 1950s, cross-reactivity could not be ruled out. The first four proven cases of ZIKV from India were reported in 2017. This was followed by major outbreaks in the states of Rajasthan and Madhya Pradesh in 2018. Fortunately, the outbreaks in India were not associated with neurological complications. These outbreaks in India highlighted the spread of this disease beyond geographical barriers owing to the growing globalization, increased travel and ubiquitous presence of its vector, the Aedes mosquito. In this review, we discuss the epidemiology, clinical features and management of ZIKV in India. [ABSTRACT FROM AUTHOR]

We present a rare case of multiple infections coexisting together. This is one of the rarest cases of four infections which coexisted together in our patient. It is an alarming for the physicians to be aware of such infections as early prompt diagnosis can be lifesaving.