Double Blow in the Tropics: A Case of Concurrent Leptospirosis and Scrub Typhus.

A 34-year-old male, with no history of known previous disease, employed at a ginger farm in South India, presented with a four-day history of high-grade fever and headache. Initially, he received symptomatic treatment but was referred due to hypotension and persistent fever. Investigations showed leucocytosis, thrombocytopenia, abnormal liver function tests, renal dysfunction, and elevated C-reactive protein. Positive results were obtained for Leptospira immunoglobulin M (IgM) and scrub typhus IgM tests, indicating a coinfection, reported rarely from this region. Timely clinical suspicion, prompt laboratory diagnosis, and early treatment with doxycycline and broad-spectrum antibiotics are crucial to prevent complications and fatal outcomes in such coinfections.

Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha (TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.

Alternate day versus daily oral iron for treatment of iron deficiency anemia: a randomized controlled trial.

Oral iron is the mainstay of treating iron deficiency anemia. Recent studies indicate better fractional iron absorption with alternate day supplementation. However, the optimal supplementation strategy is unclear. We compared effectiveness of daily versus alternate day supplementation of oral iron for treatment of iron deficiency anemia. This double blind, active control, randomized controlled trial was conducted on two hundred adults having hemoglobin 10 g/dL or less with microcytic hypochromic anemia and/or serum ferritin below 50 ng/mL. They were randomized to receive either two Ferrous sulfate tablets containing 60 mg elemental iron (120 mg total) on alternate days or single tablet of 60 mg elemental iron daily for 8 weeks. Primary outcome was mean change in hemoglobin at week 8 from baseline. Mean hemoglobin was 6.53 (± 1.89) and 6.68 (± 1.89) g/dL in the alternate day and daily arms respectively. Mean change in hemoglobin was + 1.05 ± 1.34 g/dL in alternate day arm and + 1.36 ± 1.51 g/dL in daily arm (p = 0.47) at week 8. There were no statistically significant differences between the arms with respect to any secondary outcome. There is no significant difference between alternate day and daily iron administration in improving hemoglobin. Randomized controlled trials enrolling more participants for longer periods of supplementation and evaluating clinically relevant outcomes like change in hemoglobin may be useful in identifying the ideal dosing strategy.Trial Registration: Clinical Trial Registry of India (CTRI/2019/01/017169).

Otolaryngologists' Initiative for Collaborative Tracheostomy Care: Knowledge, Attitude and Skill in Tracheostomy Care Among Nurses - An Interventional Study from India.

Introduction: Tracheostomy-related adverse events are a global problem, requiring coordinated approach for care of tracheostomised patients. The concept of 'collaborative tracheostomy care' was introduced by Global Tracheostomy Collaborative in 2012. For successful post tracheostomy outcome, nursing care is vital. Data on their knowledge, attitude and skills regarding tracheostomy care including outcome of a structured interventional workshop is not available from India. Methods: A validated questionnaire with items pertaining to knowledge, attitude and skills regarding tracheostomy care was administered to nurses working in intensive care units and wards. Following this, a workshop was conducted for hands-on training in tracheostomy care using didactic lectures, videos and simulation-based training. The participants took a post-test immediately and after three months. Skills were assessed before and three months after the workshop using a checklist. Results: Among 386 participants who attended the pre-test and workshop, 285 (74.2%) underwent post-test immediately and three months later. Overall mean knowledge score (± SD) of the participants in pre-workshop was 6.8 ± 3.5, immediate post-test score was 15.9 ± 2.7 and three months later was 11.6 ± 3.5 (p < 0.001) out of total score 20. The baseline score was significantly higher among ICU nurses. Three months post workshop skill assessment revealed no statistically significant increase in the proportion of participants who performed skills related to suctioning procedure. Conclusion: Knowledge, attitude and practice regarding tracheostomy care is inadequate among nurses. Otolaryngologists-driven structured intervention with didactic lectures, videos and hands-on training can improve all three domains to positively impact outcomes in post tracheostomy patient care. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03682-9.

Cold antibody autoimmune hemolytic anemia following varicella infection.

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare complication of chicken pox. In adults, such AIHA is due to warm antibodies. We report a case of cold antibody AIHA following chicken pox in a young female. Case Report: A 24-year-old female presented with clinical and laboratory features consistent with hemolytic anemia 5 days after the onset of chicken pox. Her hemoglobin levels dropped rapidly during the course of admission from 7.9 to 3.8 g/dL with evidence of ongoing haemolysis in the form of rising total and indirect bilirubin. Peripheral smear revealed red cell agglutinates and erythrophagocytosis. Direct Coomb's test (DCT) was positive for C3d suggesting a cold antibody AIHA. Since test for Donath Landsteiner antibody was negative, and all other tests for common causes of hemolytic anemia were noncontributory, it was presumed to be due to chicken pox. The fulminant course necessitated a short course of oral steroids to which she responded with rise in hemoglobin and no further hemolysis. Two weeks later, her peripheral smear was normal and DCT negative. Conclusion: In patients presenting with acute onset anemia following chicken pox, possibility of cold antibody AIHA must be considered and appropriate testing pursued. Despite lack of empiric evidence, short course of steroids may be beneficial if drop in hemoglobin is rapid with evidence of fulminant hemolysis, showing no abatement after first week.

Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia.

Background: Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer's Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias. Methods: In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations. Results: Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias. Conclusion: Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.

Immunoglobulin G Antibodies to SARS-CoV-2 Among Healthcare Workers at a Tertiary Care Center in South India.

Introduction Healthcare workers (HCWs) are at risk of exposure to SARS-CoV-2. Seroprevalence in this group may offer insights into trends to monitor and revise strategies to prevent transmission. Methods A cross-sectional study was conducted in two phases among healthcare workers at a tertiary care center to detect IgG antibodies to SARS-CoV-2. Seropositivity was calculated during both phases, and possible associations were determined using regression analysis. Results A total of 382 and 168 HCWs took part in the two phases, respectively. IgG antibodies were detected in 13 of 382 (3.4%; 95% confidence interval (CI): 2%-5.7%) and 71 of 168 (42.3%) participants in the first and second phases, respectively. Receiving at least one dose of vaccine (p < 0.001) and age (p = 0.028) were factors associated with the presence of antibodies, while gender, job type, exposure to COVID-19 cases, and comorbidities were not associated with seropositivity. Conclusion Serosurveys among HCWs may help identify transmission patterns and redesign infection control practices in the healthcare setting.

Thrombotic thrombocytopenic purpura as an acute complication of COVID-19.

Introduction: While disseminated intravascular coagulation (DIC) is a serious complication of COVID-19, a close differential in critically ill patients with thrombocytopenia is Thrombotic thrombocytopenic purpura (TTP). Case Report: We describe the case of a middle-aged lady admitted with COVID-19 pneumonia who developed progressive thrombocytopenia, altered sensorium and renal failure. The absence of coagulation abnormalities alerted to the possibility of TTP, strengthened by presence of schistocytes in peripheral smear. Conclusions: This case highlights the need for high index of suspicion and to pay attention to normal tests as well that might give clues to the diagnosis. New onset thrombocytopenia in COVID-19 need not always indicate DIC. A careful examination of peripheral smear may help diagnosing TTP especially if coagulation profile is normal.

Use of Bacopa monnieri in the Treatment of Dementia Due to Alzheimer Disease: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease have been inconclusive. OBJECTIVE: The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease. METHODS: We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease. RESULTS: Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer's Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs. CONCLUSIONS: There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes. TRIAL REGISTRATION: PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421.

Latest Trends in Outcome Measures in Dementia and Mild Cognitive Impairment Trials.

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer's disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

Impact of COVID-19 on Guillain-Barre Syndrome in India: A Multicenter Ambispective Cohort Study.

Introduction/Aims: Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic have reported varied data regarding the incidence of Guillain-Barre syndrome (GBS). The present study investigated demographic and clinical features, management, and outcomes of patients with GBS during a specified period of the COVID-19 pandemic, and compared these features to those of GBS in the previous year. Methods: A multicenter, ambispective cohort study including 26 centers across India was conducted. Data from a pre-COVID-19 period (March 1 to August 31, 2019) were collected retrospectively and collected ambispectively for a specified COVID-19 period (March 1 to August 31, 2020). The study was registered with the Clinical Trial Registry India (CTRI/2020/11/029143). Results: Data from 555 patients were included for analysis: pre-COVID-19 (n = 334) and COVID-19 (n = 221). Males were more commonly affected during both periods (male:female, 2:1). Gastroenteritis was the most frequent antecedent event in 2019 (17.4%), whereas fever was the most common event in 2020 (10.7%). Paraparesis (21.3% versus [vs.] 9.3%, P = 0.001) and sensory involvement (51.1% vs. 41.3%; P = 0.023) were more common during COVID-19 in 2020, whereas back pain (26.3% vs. 18.4%; P = 0.032) and bowel symptoms (20.7% vs. 13.7%; P = 0.024) were more frequent in the pre-COVID period. There was no difference in clinical outcomes between the two groups in terms of GBS disability score at discharge and 3 months after discharge. Independent predictors of disability in the pre-COVID period included areflexia/hyporeflexia, the requirementfor intubation, and time to bulbar weakness; in the COVID-19 period, independent predictors included time from onset to admission, intubation, and intubation requirement. The mortality rate was 2.3% during the entire study period (13/555 cases). Discussion: Results of this study revealed an overall reduction in the frequency of GBS during the pandemic. The lockdown likely reduced the risk for antecedent infections due to social distancing and improved hygiene, which may have resulted in the reduction of the frequency of GBS.

Does management reasoning constitute the backbone of the clinical learning environment?: Conceptual analysis of the existing notions.

Management reasoning is a paradigm whereby learning occurs in a context bound fashion on analysing the biophysical factors existing in the clinical learning environment. In the contemporary medical education forums, much importance is being laid on clinical reasoning and this warrants the appropriate usage of the biomedical knowledge in arriving at the diagnosis. We perceive that clinical reasoning, in pure sense, often doesn't solve the purpose of rendering the best management plan to the patient. This holds stronger when the case is non-linear and highly complex in nature. Management reasoning fills the gap between hypotheses generation, i.e. accomplishing diagnosis and devising management plan. Indeed, it is a complex activity relying on several factors including the physician's perceptual abilities and situated cognition derived from formal and informal learning experiences. In contrast to clinical reasoning, which can be taught using structured scenarios, management reasoning necessitates analysing multitude of factors revolving around a patient and prioritizing those in order to titrate the best possible management plan. This commentary spotlights different dimensions of management reasoning, emphasizes the need of teaching it in the current scenarios, enlists the ways it can be taught, and opens the platform for discussing further on this underemphasized topic.

Dengue Versus Multisystem Inflammatory Syndrome - When the Grey Zone Gets Thinner.

Despite the decline in COVID-19 cases, the potential threat of multisystem inflammatory syndrome (MIS) - a hyperinflammatory response following acute SARS-CoV-2 infection - looms large. Although initially described in children, it is being increasingly reported in adults. In dengue endemic regions, MIS is likely to cause diagnostic dilemma with dengue due to overlapping clinical and laboratory features. We describe a young male with fever, gastrointestinal symptoms, a transient rash, thrombocytopenia, and positive dengue NS1 antigen test. Early onset of thrombocytopenia, significant gastrointestinal symptoms and protracted fever were atypical, raising suspicion of MIS-A in view of a recovery from a recent SARS-CoV-2 infection. However, absence of neurologic and cardiac manifestations, stable hemodynamics, absence of mucosal involvement and negative inflammatory markers helped in managing the patient conservatively as dengue. This case highlights diagnostic challenges faced by clinicians treating suspected dengue in the face of increasing recognition of MIS and need for systematic research to establish diagnostic criteria for MIS-A.

Melioidosis: distinctive clinico-epidemiological characteristics in southern India.

As it is increasingly being reported from India, we carried out a prospective study of patients with culture-proven melioidosis from south India, examining clinical, laboratory features, epidemiological data, risk factors, treatments, outcomes at three and six months, and factors associated with mortality.Between 2014 and 2018, 31 cases were identified. Diabetes (83.9%) and alcohol abuse (58.1%) were common risk factors. Musculoskeletal, skin and soft tissue manifestations together constituted 48.4% of presentations, while 29% had pneumonia. During the intensive phase, 74.2% received one of three recommended antibiotic regimes, but 51.6% did not receive continuation treatment. Pneumonia and lack of continuation treatment were independently associated with a high mortality of 25.8%. Hot spots for melioidosis exist in India, and there is considerable diversity of presentation, including skin, soft tissue, musculoskeletal and neurological involvement. High rates of bacteraemia are shown.

Simulated Randomized Controlled Trial to Learn Critical Appraisal (SiRCA): A Randomized Controlled Study of Effectiveness Among Undergraduate Medical Students.

INTRODUCTION: The ideal method to teach evidence-based medicine (EBM) to medical students is unclear. We determined the effectiveness of a simulated randomized controlled trial (RCT) in improving critical appraisal and EBM skills among medical students compared to traditional training. METHODS: One hundred and eighteen medical students were randomized into two groups. Sixty-one students (immersion arm) were trained in critical appraisal using a simulated RCT aimed at determining efficacy of a "brainy pill" on ability to crack puzzles. Fifty-seven students (traditional group) were trained using a journal club with a checklist. Primary outcome of change in knowledge and skills of critical appraisal and EBM was determined by comparing scores on pre- and post-intervention Fresno tests. RESULTS: Mean age of students was 21.76 (SD - 0.78) years. Seventy (59.3%) were females and 48 (40.7%) males. Mean pre-test scores of traditional and immersion groups were 8.0 (SD - 4.88) and 9.31 (SD - 5.49) respectively and post-test scores were 50.2 (SD - 16.2) and 68.12 (SD - 14.72) respectively (post-intervention mean difference - 17.92; 95% CI 12.26 - 23.57; p<0.0000001). Odds of achieving 65% or more in post-intervention Fresno test score was significantly higher in immersion group (29.8% vs 8.2%; OR 4.76; 95% CI 1.62-13.97; p = 0.001). Perceived competence regarding EBM skills improved significantly in immersion group. CONCLUSIONS: Simulated RCT is effective in imparting critical appraisal and EBM practice skills to medical students. Trainers should consider integrating and reinforcing this approach in EBM curriculum to make learning contextual and immersive.