SwasthGarbh: A smartphone App for improving the quality of antenatal care and ameliorating maternal-fetal health.

The utility of telemedicine in healthcare has been brought to the forefront by the COVID-19 pandemic. 'SwasthGarbh' (Healthy Pregnancy) is a multi-functional, interactive smartphone application for providing antenatal care and real-time medical support to all pregnant women (especially those in rural areas and/or do not have easy access to doctors). A randomized controlled trial (n = 150) demonstrates its utility in improving the quality of antenatal care, reducing obstetric/medical complications and achieving a positive pregnancy experience. The test group (patients registered on the App) showed a significantly higher number of mean (± SD) antenatal visits (7.0 ± 1.5 vs. 5.7 ± 1.8; P<0.001) as well as better compliance with the WHO visit protocol (87.2% vs. 69.8%, P<0.001) and antenatal investigations (73.2% vs. 41.7%, P<0.001) in comparison to the control group (followed-up conventionally), respectively. Furthermore, substantial reduction in medical (38.0% vs. 55.5%, P = 0.04) and obstetric (52.1% vs. 59.7%, P = 0.36) complications during pregnancy as well as significant improvement in mean (± SD) maternal systolic BP (118.9 ± 11.8 vs. 123.4 ± 14.2 mmHg; P = 0.046), diastolic BP (76.0 ± 8.4 vs. 80.0 ± 10.9 mmHg; P = 0.02) and hemoglobin (11.5 ± 1.4 vs. 10.9 ± 1.4 g/dL; P = 0.03) parameters at delivery was observed in the test group compared to the controls, respectively. All the above mentioned positive clinical outcomes were the result of the provision of high quality antenatal care, timely detection of complications, prompt medical assistance and improved medication adherence. This is first pregnancy App that provides instantaneous access to doctor's advice and is clinically endorsed as well as credible.

Bioactive compounds in Layacha brown rice (Oryza sativa L.) improve immune responses in mice via activation of transcription factor Nrf2

Dysregulated or weak immunity is caused by ageing, chemo-radiotherapy, COVID-19, infections, steroids, pollutants and toxins. Bioactive foods are required for boosting immunity. In the present study, nine rice (Oryza sativa L.) varieties were selected from the repository of 23,250 Indian germplasm accessions. The immunomodulatory effects of these rice varieties were assessed in vitro and in vivo. Layacha-rice-methanolic-extract (Larimex) significantly enhanced innate (>20%) and adaptive (>10%) immune responses evinced from higher bacterial phagocytosis by macrophages, increased mitogen-induced T-cell proliferation (11%) and scavenged reactive oxygen species (ROS) (70–80%). Larimex activated transcription factor Nrf2 and its downstream genes Nqo1, Ho1 and Txnrd1 in immune cells. Larimex significantly improved immune responses (>20%) only in cells from wild type but not Nrf2 knock-out mice indicating its causal role in boosting immunity. Untargeted metabolomics of Layacha rice showed preponderance of metabolic pathways and bioactive compounds, which activate Nrf2 in mammalian cells. Layacha rice can be a suitable food for boosting immunity.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19.

Metabolic associated fatty liver disorder (MAFLD) characterizes the contributing etiologies (i.e., type 2 diabetes mellitus, metabolic syndrome, overweight) of individuals with fatty liver disease that affects 1/3rd of the world population. In 2020, the coronavirus disease 2019 (COVID-19) crisis was unprecedented, and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2. MAFLD patients are frequently obese with added metabolic menace like diabetes, hypertension, and dyslipidemia leading to greater jeopardy of COVID-19. MAFLD patients are 4 to 6-fold more prone towards infections. COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin. Hence, MAFLD in COVID-19 patients worsens the condition significantly. The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission. Direct hepatic injury, enhanced levels of inflammatory cytokines, declined hepatic mitochondrial activity, and compromised immunity are considered as some underlying mechanisms. The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients. The review systematically analyzes the effect of striking two worldwide pandemics (MAFLD and COVID-19) together in the present era.

COVID Vaccines vs. Viral Evolution: Who will Win the Battle?

The emergence of new variants seems to perpetually prolong the COVID-19 pandemic. On top of that, the waning of vaccine protection is further thwarting our efforts to end it. Our article discusses the incessant question raging in everybody's mind: Are we ever going to win?

Hypoxia induces dichotomous and reversible attenuation of T cell responses through reactive oxygen species-dependent phenotype redistribution and delay in lymphoblast proliferation.

As T cells transit between blood, lymphoid organs, and peripheral tissues, they experience varied levels of oxygen/hypoxia in inflamed tissues, skin, intestinal lining, and secondary lymphoid organs. Critical illness among COVID-19 patients is also associated with transient hypoxia and attenuation of T cell responses. Hypoxia is the fulcrum of altered metabolism, impaired functions, and cessation of growth of a subset of T cells. However, the restoration of normal T cell functions following transient hypoxia and kinetics of their phenotype-redistribution is not completely understood. Here, we sought to understand kinetics and reversibility of dichotomous T cell responses under sustained and transient hypoxia. We found that a subset of activated T cells accumulated as lymphoblasts under hypoxia. Further, T cells showed the normal expression of activation markers CD25 and CD69 and inflammatory cytokine secretion but a subset exhibited delayed cell proliferation under hypoxia. Increased levels of reactive oxygen species (ROS) in cytosol and mitochondria were seen during dichotomous and reversible attenuation of T cell response under hypoxia. Cell cycle analysis revealed maximum levels of cytosolic and mitochondrial ROS in dividing T cells (in S, G2, or M phase). Hypoxic T cells also showed specific attenuation of activation induced memory phenotype conversion without affecting naïve and activated T cells. Hypoxia-related attenuation of T cell proliferation was also found to be reversible in an allogeneic leukocyte specific mixed lymphocyte reaction assay. In summary, our results show that hypoxia induces a reversible delay in proliferation of a subset of T cells which is associated with obliteration of memory phenotype and specific increase in cytosolic/mitochondrial ROS levels in actively dividing subpopulation. Thus, the transient reoxygenation of hypoxic patients may restore normal T cell responses.

Hit or miss: The Dilemma of Specimen Selection for Microbiological Diagnosis of Rhino-Orbital-Cerebral- COVID-Associated Mucormycosis (ROCM-CAM).

BACKGROUND: We diagnosed various cases of rhino-orbital-cerebral- COVID-associated Mucormycosis (ROCM-CAM) during India's second wave of COVID-19. This helped formulate novel suggestions for improving laboratory output, applicable anywhere in the world. METHOD: To diagnose ROCM-CAM by microbiological methods, we used direct microscopy and conventional culture on various clinical samples within the shortest turn-around time. DESIGN: Prospective single-center observational study Participants: patients with ROCM-CAM Results: Of 113 suspected cases of ROCM-CAM during May 2021, direct microscopy and culture could confirm the disease in 87.61% and 44.25% of patients, respectively. The highest pathogen isolation was seen from maxillary bone fragments, FESS-guided biopsy from pterygopalatine fossae, nasal turbinates and nasal mucosal biopsy. Direct microscopy could diagnose the disease in almost 40% of patients within 24 hours and 60% within two days. Conventional cultures yielded Rhizopus spp. (86%) as the commonest fungal pathogen followed by Mucor spp. (12%) within 7 days. Deep tissue biopsies are more useful for rapid diagnosis than superficial specimens. Routine fungal cultures can supplement case detection and help prognosticate survivors. CONCLUSION: The management of ROCM is a surgical emergency. The diagnosis of the condition must therefore be prompt and precise. Despite ongoing antifungal therapy, nasal mucosal tissue, FESSguided, and intra-operative tissue biopsies showed the pathogen's highest diagnostic yield. The diagnostic index improved further when multiple (4-5) high-quality specimens were collected. Nasal swabs and crusts, among the most commonly requested specimens worldwide, were found to have an overall low diagnostic potential.

Cardiac assessment of patients during post COVID-19 recovery phase: a prospective observational study.

Introduction: The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It usually presents as a respiratory syndrome but also known to cause many cardiovascular complications during acute phase. However, little is documented about cardiac complications during the post COVID-19 recovery phase. Therefore, this prospective observational study was planned to evaluate cardiovascular effects of the disease in patients recovering from COVID-19. Methods: This was a prospective observational study with a total of 63 patients presenting at 6-month follow-up in post COVID-19 outpatient clinics. Patients with known cases of underlying ischemic heart disease, cardiomyopathy, or any other cardiac disorder, and patients with chronic lung disorder or severe anemia were excluded. Results: Dyspnea was the most common presenting complaint. In biochemical parameters, none of them showed any significant difference between these two groups including NT pro BNP, ferritin, CK-MB. But NT pro BNP was high in moderate/severe cases, especially those having reduced ejection fraction. On echocardiographic evaluation, LVEF was low in moderate/severe group patients (59.7% vs. 51.1%, p < 0.0001). LV diastolic dysfunction was also observed more commonly in moderate/severe group patients (55.9% vs. 86.2%, p = 0.009). There was no significant difference in RV function assessment parameters. Conclusion: Patients in the moderate/severe group during index hospitalization for COVID-19 should be followed up with NT Pro BNP and echocardiography. This may help in early recognition of heart failure during follow-up of COVID-19 patients.

"When all else fails you have to come to the emergency department": Overarching lessons about emergency care resilience from frontline clinicians in Pacific Island countries and territories during the COVID-19 pandemic.

The COVID-19 pandemic continues to test health systems resilience worldwide. Low- and middle-income country (LMIC) health care systems have considerable experience in disasters and disease outbreaks. Lessons from the preparedness and responses to COVID-19 in LMICs may be valuable to other countries.This policy paper synthesises findings from a multiphase qualitative research project, conducted during the pandemic to document experiences of Pacific Island Country and Territory (PICT) frontline clinicians and emergency care (EC) stakeholders. Thematic analysis and synthesis of enablers related to each of the Pacific EC systems building blocks identified key factors contributing to strengthened EC systems.Effective health system responses to the COVID-19 pandemic occurred when frontline clinicians and 'decision makers' collaborated with respect and open communication, overcoming healthcare workers' fear and discontent. PICT EC clinicians demonstrated natural leadership and strengthened local EC systems, supporting essential healthcare. Despite resource limitations, PICT cultural strengths of relational connection and innovation ensured health system resilience. COVID-19 significantly disrupted services, with long-tail impacts on non-communicable disease and other health burdens.Lessons learned in responding to COVID-19 can be applied to ongoing health system strengthening initiatives. Optimal systems improvement and sustainability requires EC leaders' involvement in current decision-making as well as future planning. Search strategy and selection criteria: Search strategy and selection criteria We searched PubMed, Google Scholar, Ovid, WHO resources, Pacific and grey literature using search terms 'emergency care', 'acute/critical care', 'health care workers', 'emergency care systems/health systems', 'health system building blocks', 'COVID-19', 'pandemic/surge event/disease outbreaks' 'Low- and Middle-Income Countries', 'Pacific Islands/region' and related terms. Only English-language articles were included. Funding: Phases 1 and 2A of this study were part of an Epidemic Ethics/World Health Organization (WHO) initiative, supported by Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z. Copyright of the original work on which this publication is based belongs to WHO. The authors have been given permission to publish this manuscript. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions or policies of WHO. Co-funding for this research was received from the Australasian College for Emergency Medicine Foundation via an International Development Fund Grant. RM is supported by a National Health and Medical Research Council (NHMRC) Postgraduate Scholarship and a Monash Graduate Excellence Scholarship. GOR is supported by a NHMRC Early Career Research Fellowship. CEB is supported by a University of Queensland Development Research Fellowship. None of these funders played any role in study design, results analysis or manuscript preparation.

Lessons from the frontline: Leadership and governance experiences in the COVID-19 pandemic response across the Pacific region.

Background: Universal access to safe, effective emergency care (EC) during the COVID-19 pandemic has illustrated its centrality to healthcare systems. The 'Leadership and Governance' building block provides policy, accountability and stewardship to health systems, and is essential to determining effectiveness of pandemic response. This study aimed to explore the experience of leadership and governance during the COVID-19 pandemic from frontline clinicians and stakeholders across the Pacific region. Methods: Australian and Pacific researchers collaborated to conduct this large, qualitative research project in three phases between March 2020 and July 2021. Data was gathered from 116 Pacific regional participants through online support forums, in-depth interviews and focus groups. A phenomenological approach shaped inductive and deductive data analysis, within a previously identified Pacific EC systems building block framework. Findings: Politics profoundly influenced pandemic response effectiveness, even at the clinical coalface. Experienced clinicians spoke authoritatively to decision-makers; focusing on safety, quality and service duty. Rapid adaptability, past surge event experience, team-focus and systems-thinking enabled EC leadership. Transparent communication, collaboration, mutual respect and trust created unity between frontline clinicians and 'top-level' administrators. Pacific cultural assets of relationship-building and community cohesion strengthened responses. Interpretation: Effective governance occurs when political, administrative and clinical actors work collaboratively in relationships characterised by trust, transparency, altruism and evidence. Trained, supported EC leadership will enhance frontline service provision, health security preparedness and future Universal Health Coverage goals. Funding: Epidemic Ethics/World Health Organization (WHO), Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z. Co-funding: Australasian College for Emergency Medicine Foundation, International Development Fund Grant.

Lessons from the frontline: Documenting the experiences of Pacific emergency care clinicians responding to the COVID-19 pandemic.

Low- and middle-income countries (LMICs) across the Pacific region have been severely impacted by the COVID-19 pandemic, and emergency care (EC) clinicians have been on the frontline of response efforts. Their responsibilities have extended from triage and clinical management of patients with COVID-19 to health system leadership and coordination. This has exposed EC clinicians to a range of ethical and operational challenges.This paper describes the context and methodology of a rapid, collaborative, qualitative research project that explored the experiences of EC clinicians in Pacific LMICs during the COVID-19 pandemic. The study was conducted in three phases, with data obtained from online regional EC support forums, key informant interviews and focus group discussions. A phenomenological approach was adopted, incorporating a hybrid inductive and deductive thematic analysis. Research findings, reported in other manuscripts in this collection, will inform multi-sectoral efforts to improve health system preparedness for future public health emergencies. Funding: Epidemic Ethics/World Health Organization (WHO) initiative, supported by Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z (Phases 1 and 2A) and an Australasian College for Emergency Medicine Foundation International Development Fund Grant.

Lessons from the frontline: Documenting the pandemic emergency care experience from the Pacific region - Infrastructure and equipment.

Background: The COVID-19 pandemic highlighted challenges for all health systems worldwide. This research aimed to explore the impact of COVID-19 across the Pacific especially with regards to emergency care (EC) and clinicians' preparations and responses. Methods: A collaboration of Australia and Pacific researchers conducted prospective qualitative research over 18 months of the pandemic. In this three phase study data were gathered from Emergency Clinicians and stakeholders through online support forums, in-depth interviews and focus groups. A phenomenological methodological approach was employed to explore the lived experience of participants. This paper discusses the findings of the study regarding the EC building block of 'Infrastructure and Equipment.' Findings: Pre-existing infrastructure and equipment were not sufficient to help control the pandemic. Adequate space and correct equipment were essential needs for Pacific Island emergency clinicians, with donations, procurement and local ingenuity required for suitable, sustainable supplies and facilities. Adequate personal protective equipment (PPE) conferred a sense of security and increased Health Care Workers willingness to attend to patients. Interpretation: Investing in adequate infrastructure and appropriate equipment is crucial for an effective response to the COVID-19 pandemic. The sustainability of such investments in the Pacific context is paramount for ongoing EC and preparation for future surge responses and disasters. Funding: Phases 1 and 2A of this study were part of an Epidemic Ethics/World Health Organization (WHO) initiative, supported by Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z. Co-funding for this research was received from the Australasian College for Emergency Medicine Foundation via an International Development Fund Grant.

Lessons from the frontline: The value of emergency care processes and data to pandemic responses across the Pacific region.

Background: Emergency care (EC) addresses the needs of patients with acute illness and injury, and has fulfilled a critical function during the COVID-19 pandemic. 'Processes' (e.g. triage) and 'data' (e.g. surveillance) have been nominated as essential building blocks for EC systems. This qualitative research sought to explore the impact of the pandemic on EC clinicians across the Pacific region, including the contribution of EC building blocks to effective responses. Methods: The study was conducted in three phases, with data obtained from online support forums, key informant interviews and focus group discussions. There were 116 participants from more than 14 Pacific Island Countries and Territories. A phenomenological approach was adopted, incorporating inductive and deductive methods. The deductive thematic analysis utilised previously identified building blocks for Pacific EC. This paper summarises findings for the building blocks of 'processes' and 'data'. Findings: Establishing triage and screening capacity, aimed at assessing urgency and transmission risk respectively, were priorities for EC clinicians. Enablers included support from senior hospital leaders, previous disaster experience and consistent guidelines. The introduction of efficient patient flow processes, such as streaming, proved valuable to emergency departments, and checklists and simulation were useful implementation strategies. Some response measures impacted negatively on non-COVID patients, and proactive approaches were required to maintain 'business as usual'. The pandemic also highlighted the value of surveillance and performance data. Interpretation: Developing effective processes for triage, screening and streaming, among other areas, was critical to an effective EC response. Beyond the pandemic, strengthening processes and data management capacity will build resilience in EC systems. Funding: Phases 1 and 2A of this study were part of an Epidemic Ethics/World Health Organization (WHO) initiative, supported by Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z. Co-funding for this research was received from the Australasian College for Emergency Medicine Foundation via an International Development Fund Grant.

Lessons from the frontline: The COVID-19 pandemic emergency care experience from a human resource perspective in the Pacific region.

Background: This study explores emergency care (EC) and other frontline healthcare worker (HCW) experiences responding to the COVID-19 pandemic in the Pacific region. The crisis has reinforced the crucial role well-trained, resourced, and supported EC providers play in supporting vital health systems and services in all global regions not only during 'business as usual' periods, but in times of tremendous stress and surge. Methods: Qualitative data were collected from EC providers and relevant stakeholders in three research phases in 2020 and 2021. Data on the World Health Organization's (WHO) Human Resources Building Block, adapted for the Pacific EC context, was thematically analysed. Key findings were further analysed to identify enablers and barriers to effective EC pandemic management. Findings: 116 participants from across the Pacific region participated in this study. Five themes emerged: (1) EC providers performed multiple pandemic roles; (2) Importance of authorities' valuing frontline HCWs; (3) HCW mental health and exhaustion; (4) HCW tension managing stigma, personal/professional expectations, and chronic health needs; and (5) Building health and human resource capacity. Interpretation: This study significantly contributes to the limited scientific literature on HCW experiences responding to COVID-19 across the Pacific. Recommendations arising out of this research align with consensus priorities and standards that were identified pre-pandemic by health stakeholders across the Pacific for enhancing EC system development. With limited HCWs available for many Pacific nations, it is imperative the dignity and welfare of local HCWs is genuinely prioritised. Funding: Epidemic Ethics/WHO, Foreign, Commonwealth and Development Office/Wellcome Grant 214711/Z/18/Z. Co-funding: Australasian College for Emergency Medicine Foundation, International Development Fund Grant.

COVID-19 cases and their outcome among patients with uncommon co-existing illnesses: A lesson from Northern India

Introduction Newer coexisting conditions should be identified in order to modify newer risk factors. Aim was to identify patients with non-classical or less common coexisting conditions in patients infected of COVID 19. Method Single centred study from June 2020 to May 2021 at a tertiary centre in North India. A preformed questionnaire was used to record clinical and laboratory parameters and to identify cases which are in addition to CDC list and Indian data. Results 0.67% (46) cases out of 6832 patients were identified to have non-classical coexisting illness. It was divided into 2 groups-infections A (60.1%) and non-infections B (39.9%). Group A included-tuberculosis- pulmonary (14.3%) & extra pulmonary (32.9%), bacterial (25.0%) viral infections [dengue, hepatitis B & C] (14.3%), HIV disease (10.7%) and malaria (3.6%). Group B included- organ transplant (27.8%), autoimmune [myasthenia gravis, polymyositis, psoriasis] (22.6%), haematologic [Haemophilia, ITP, Aplastic anaemia, APML, CML] (27.8%), uncommon malignancies [disseminated sacral chordoma and GTN] (11.1%) and snakebite (11.1%). Serum Procalcitonin was not helpful for diagnosis of bacterial infection in COVID-19 disease. Group A had significantly longer duration of illness, hepatitis and elevated CRP. The mortality in group A & B were 32.1% and 43.8% respectively. Death in non-severe COVID cases was in tetanus and snakebite. 30.7% death among tuberculosis patients. More than 70% of deaths were attributable to COVID 19 in both the groups. Conclusion In Indian settings, comorbidities like tuberculosis and bacterial infections can precipitate severe COVID 19 unlike other parts of the world where tuberculosis is relatively uncommon.

SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021.

Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing. Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, ∼ 46% of people remained susceptible, contributing to subsequent waves of infection.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

COVID-19: Finally on Wane, with Reduced Lethality.

As most of the countries have already passed the peaks of the second or third wave of infections, COVID-19 is (finally) on the wane and will soon touch the baseline persistence with a reduced death rate. The Case Fatality Ratio (CFR) or lethality is presently only ~2.0%, which is relatively low in comparison to the high of 14% in April 2020. More importantly, the lethality in healthy people is 20 times lower. In addition, successful vaccination programs are currently underway in several countries. Thus, although new pathogenic variants as well as a few isolated cases of resurgence, will continue to emerge, the worst seems to be over and we will surely win this battle soon.