Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

A qualitative study of social accountability translation: from mission to living it.

BACKGROUND: Medical schools are increasingly adopting socially accountable mission and curricula, the realisation of which are dependent on engaging individuals to embody the mission's principles in their everyday activities as doctors. However, little is known about how graduates perceive the efforts taken by their medical school to sensitise them to social accountability values, and how they translate this into their working lives. Our aim was to explore and understand graduate perceptions of how their medical school influenced them to embody a social accountability mission in their working lives. METHODS: This was a qualitative interview study carried out with graduates/alumni [n = 51] of Christian Medical College, Vellore [CMCV], India, a school with a long-established and explicit social-accountability mission. Data coding and analysis were initially inductive and thematic using Braun and Clarke's six step framework. MacIntyre's virtue ethics theory framed secondary analysis, allowing us to consider the relationships between individual and contextual factors. RESULTS: Our participants perceived that CMCV invested heavily in selecting personal qualities aligned with the CMCV mission. They saw that these qualities were reinforced through various practices: [e.g., placements in resource limited and/or remote and rural settings]; community engagement and expectations [e.g., student self-governance]; role modelling [staff and more senior students]. Much emphasis was placed on sustaining these traditions and practices over time, creating a strong sense of identity and belonging among participants, traditions which were fostered further by the alumni network and continued engagement with CMCV post-graduation. CONCLUSIONS: Ensuring social accountable medical education depends on alignment and interactions over time between context and structures, systems and human agents. Further studies are needed to extend understanding of how students from diverse contexts experience socially accountable medical education and translate their educational experience into their thinking and practice after graduation.

Core sepsis-related competencies for medical students: an international consensus by Delphi technique.

BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

Prognostication and Prediction of Outcomes in Patients with Organophosphorus and Carbamate Poisoning: A Prospective Cohort Study.

Background: Organophosphorus (OP) and carbamate poisoning are significant concerns in developing nations. This study evaluates the effectiveness of the ChE check mobile, a cholinesterase-rapid bedside diagnostic test, in the diagnosis and management of OP and carbamate poisoning. Materials and methods: We conducted this prospective observational study, involving patients with OP and carbamate poisoning over 1 year (June 2016 to June 2017) at a single tertiary care center. Levels of RBC cholinesterase (E-AChE), butyl cholinesterase (BChE), and various other determinants were systematically coded and analyzed. Results: The study population (n = 60) consisted primarily of males (n = 43; 71.7%), with a mean age of 30.6 (SD: 13.7) years. Monocrotophos (n = 10; 20.4%) and carbofuran (n = 4; 8.1%) were the commonest OP and carbamate compounds, respectively. The median initial atropinization dose was 10 (IQR: 0, 61.5) mg, with a median total administered atropine dose of 116 (IQR: 32, 320) mg. A significant negative correlation was found between E-AChE levels and both the initial atropinization dose (ρ: -0.653, p-value < 0.001) and total atropine requirement (ρ: -0.659, p-value < 0.001) during admission. An E-AChE cut-off of 4 units/g hemoglobin provided an area under the curve of 0.73 (sensitivity: 80.0%, specificity: 68.6%, p-value < 0.001) for predicting moderate to severe peradeniya organophosphorus poisoning. Conclusion: The check mobile device can be a valuable tool for prognosticating patients. There was a significant correlation between low E-AChE levels and the atropine requirement and severity. How to cite this article: Jha A, Hazra D, Yadav B, Zachariah A, Alex R. Prognostication and Prediction of Outcomes in Patients with Organophosphorus and Carbamate Poisoning: A Prospective Cohort Study. Indian J Crit Care Med 2024;28(2):141-147.

Clinical Spectrum of Mercury Poisoning in India: Case-series from a Poison Control Center.

BACKGROUND: Mercury is a naturally occurring heavy metal that finds wide application in industrial and household settings. It exists in three chemical forms which include elemental (Hg0 ), inorganic mercurous (Hg+) or mercuric (Hg++) salts, and organic compounds. All forms are highly toxic, particularly to the nervous, gastrointestinal, and renal systems. Common circumstances of exposure include recreational substance use, suicide or homicide attempts, occupational hazards, traditional medicines, and endemic food ingestions as witnessed in the public health disasters in Minamata Bay, Japan and in Iraq. Poisoning can result in death or long-term disabilities. Clinical manifestations vary with chemical form, dose, rate, and route of exposure. AIMS AND OBJECTIVES: To summarize the incidence of mercury poisoning encountered at an Indian Poison Center and use three cases to highlight the marked variations observed in clinical manifestations and long-term outcomes among poisoned patients based on differences in chemical forms and routes of exposure to mercury. MATERIALS AND METHODS: A structured retrospective review of the enquiry-database of the Poison Information Center and medical records of patients admitted between August 2019 and August 2021 in a tertiary care referral center was performed. All patients with reported exposure to mercury were identified. We analyzed clinical data and laboratory investigations which included heavy metal (arsenic, mercury, and lead) estimation in whole blood and urine samples. Additionally, selected patients were screened for serum voltage-gated potassium ion channels (VGKC)- contactin-associated protein-like 2 (CASPR2) antibodies. Three cases with a classical presentation were selected for detailed case description. RESULTS: Twenty-two cases were identified between August 2019 and August 2021. Twenty (91%) were acute exposures while two (9%) were chronic. Of these, three representative cases have been discussed in detail. Case 1 is a 3.5-year-old girl who was ought to the emergency department with suspected elemental-mercury ingestion after biting a thermometer. Clinical examination was unremarkable. Chest and abdominal radiography revealed radiodense material in the stomach. Subsequent serial radiographs documented distal intestinal transit of the radiodense material. The child remained asymptomatic. This case exemplifies the largely nontoxic nature of elemental mercury ingestion as it is usually not absorbed from the gastrointestinal tract. Case 2 is a 27-year-old lady who presented with multiple linear nodules over both upper limbs after receiving a red intravenous injection for anemia. Imaging revealed metallic-density deposits in viscera and bones. Nodular biopsy was suggestive of mercury granulomas. A 24-hour urine mercury levels were elevated. She was advised chelation therapy with oral dimercaptosuccinic acid (DMSA). Case 3 is a 22-year-old lady who presented with acrodynia, neuromyotonia, tremulousness, postural giddiness, tachycardia, and hypertension for 2 months, associated with intractable, diffuse burning pain over the buttocks and both lower limbs, 1 month after completing a 3-week course of traditional medications for polycystic ovarian syndrome. A 24-hour urine normetanephrine levels and mercury levels were markedly elevated. Serum anti-VGKC antibodies were present. She was treated with glucocorticoids and oral DMSA with a favorable clinical response. CONCLUSIONS: The clinical manifestations of mercury toxicity are highly variable depending on the source, form, and route of mercury exposure and are related to its toxicokinetics.

Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study.

Introduction: The effectiveness of gastric lavage in organophosphorus (OP) poisoning has not been established. We assessed the ability of gastric lavage to remove OP insecticides as a preliminary stage in assessing effectiveness. Patients and methods: Organophosphorus poisoning patients presenting within 6 hours were included, irrespective of prior gastric lavage. A nasogastric tube was placed and gastric contents aspirated, followed by at least three cycles of gastric lavage with 200 mL of water. Samples from the initial aspirate and the first three lavage cycles were sent for identification and quantification of the OP compounds. Patients were monitored for complications of gastric lavage. Results: Around 42 patients underwent gastric lavage. Eight (19.0%) patients were excluded from the study because of a lack of analytical standards for ingested compounds. Insecticides were detectable in the lavage samples of 24 of 34 (70.6%) patients. Lipophilic OP compounds were detected in 23 of 24 patients, while no hydrophilic OP compounds could be detected in six patients with reported ingestion of hydrophilic compounds. For chlorpyrifos poisoning (n = 10), only 0.65 mg (SD 1.2) of the estimated ingested amount (n = 5) of 8,600 mg (SD 3,200) was recovered by gastric lavage. The mean proportion of the compound removed by initial gastric aspirate was 79.4% and subsequent three cycles removed 11.5, 6.6, and 2.7%. Conclusion: Lipophilic OP insecticides could be quantified in the stomach contents of OP poisoning patients with the first aspiration or lavage being most effective. The amount removed was very low; hence, routine use of gastric lavage for OP poisoning patients arriving within 6 hours is unlikely to be beneficial. How to cite this article: Mathansingh AJ, Jose A, Fleming JJ, Abhilash KPP, Chandiraseharan VK, Lenin A, et al. Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study. Indian J Crit Care Med 2023;27(6):397-402.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Bedside lung ultrasonography: comparison with chest radiography (BLUR), a diagnostic study in a developing country.

BACKGROUND: This study determines the diagnostic utility of lung ultrasonography (LUS) in a medical ward in a developing country. In a low resource country like India, we hope that use of lung ultrasound in primary and secondary hospitals will assist in earlier and better bedside diagnosis. METHODS: This prospective diagnostic study was done to test the diagnostic accuracy of LUS against a composite reference standard, which included clinical history and examination, basic laboratory investigations, imaging and the diagnosis at discharge. We evaluated 321 consecutive patients, admitted in our medical wards with an LUS within 24 hours of the chest radiograph being done. FINDINGS: Between August 2016 and August 2017, we enrolled 321 patients. The sensitivity and specificity of the LUS for all pathologies were found to be 82.5% (76.50 to 87.20) and 78.2% (69.09 to 85.26) respectively. A subgroup analysis including the patients in whom CT was part of the composite reference standard showed sensitivity and specificity of 87.9% and 92.9% for all lung pathologies. It was found that there was superior sensitivity and specificity of LUS compared with chest radiograph in a subgroup analysis of pulmonary oedema and acute respiratory distress syndrome (ARDS). INTERPRETATION: We found that the LUS was better than chest radiograph and as good as CT in most pathologies, especially pulmonary oedema and ARDS. We believe that training in the basics of bedside LUS must be part of the medical curriculum and a low-cost ultrasound machine must be made available in medical wards, so that clinical diagnosis can be supplemented with this tool. In a low resource setting like India, where access to chest radiograph and CT may be difficult particularly in a rural setup, expertise in LUS would be helpful in easy bedside diagnosis and saving cost on a CT scan.

Secondary hospital rotation of postgraduate trainees: A pilot study.

Background: Postgraduate (PG) training in general medicine requires reorientation to meet the healthcare needs of India. In this pilot study, we designed a secondary hospital (SH) posting for medicine PGs to sensitize them to the practice of medicine and challenges in a rural SH setting. Methods: PG trainees in general medicine were sent for a 2-week rotation to select SHs. A faculty coordinator from the teaching hospital facilitated the programme. The SH faculty used qualitative tools to assess the performance of the trainees. The trainees also evaluated the programme using open- and close-ended questionnaires. Results: Eighteen PG trainees in general medicine were posted to six rural SHs. Data analysis showed that the training exposure provided sensitization to the challenges of medical practice in such settings and the need to be multicompetent. Seventeen (94%) trainees felt that they gained insight into the issues that are specific for practice at an SH and >80% expressed confidence about the knowledge and skills gained during that exposure to enhance medical practice in a resource-limited setting. They were also sensitized to various issues of secondary care including skills of multi-competence, the ability to handle a wide variety of cases with limited investigations, a cost-effective approach, decision-making on referrals, procedural competence and flexibility to adapt to new situations. Conclusion: A short SH posting can positively sensitize PGs to the practice of medicine and challenges in secondary care settings.

Renal outcomes among snake-envenomed patients with acute kidney injury in southern India.

Background: . Acute kidney injury (AKI) is a common complication of snake envenomation. However, the long-term renal outcomes of such patients are not well defined. We aimed to determine the proportion of patients who developed AKI, characterize the presenting syndromes and ascertain the long-term resolution of AKI. Methods: . We did a cohort study with prospective follow- up from two centres in southern India. All admitted patients >15 years of age with snake envenomation and serum creatinine ≥1.5 mg/dl over the past 10 years were identified through their discharge summaries. These patients were prospectively contacted, interviewed telephonically and requested to come for a hospital review. Results: . Of the 866 patients screened, 1 84 developed AKI (21.2%). Among these, 53% had combined renal, haematological and neurological manifestations; 33.6% required admission to the intensive care unit and 38% were dialysed. On follow-up of hospital records the creatinine of 49% of patients had normalized. Of those admitted, 36% were contacted and none had a known renal disease or were on dialysis. Among these, 16 patients came to the hospital for review and only 2 had an elevated creatinine. The total mortality was 1 4. Conclusion: . AKI is an important cause of morbidity with snake envenomation and a proportion will require dialysis. The mortality in our study was low and long-term renal outcomes were relatively good.

Evaluation of a distance learning academic support program for medical graduates during rural hospital service in India.

BACKGROUND: Christian Medical College (CMC), Vellore, India, a tertiary care hospital, designed a year-long Fellowship in Secondary Hospital Medicine (FSHM) for CMC graduates, with the aim to support them during rural service and be motivated to consider practicing in these hospitals. The FSHM was a blend of 15 paper-based distance learning modules, 3 contact sessions, community project work, and networking. This paper reports on the evaluation of the FSHM program. METHODS: The curriculum development process for the FSHM reflected the six-step approach including problem identification, needs assessment, formulating objectives, selecting educational strategies, implementation, and evaluation. Telephone interviews with students were conducted to determine if the program motivated them to consider working in smaller hospitals. RESULTS: Qualitative data analysis showed that the program motivated the FSHM students to consider practicing in secondary hospitals by creating awareness of challenging opportunities and instilling confidence to provide good quality clinical care with limited resources. DISCUSSION: We propose rural service for MBBS graduates, supported by a blend of on-site and distance education as a model for medical education.

Posaconazole: an emerging therapeutic option for invasive rhino-orbito-cerebral mucormycosis.

Posaconazole has significant activity against the Mucormycetes. However, data are limited on the clinical efficacy of posaconazole for treating rhino-orbito-cerebral mucormycosis (ROCM). The aim of this study is to assess the efficacy and safety of posaconazole in patients with ROCM. We included 12 consecutive adult patients admitted with ROCM and treated with posaconazole between January 2010 and February 2015. The main outcome of the study was the overall success rate (i.e. either complete or partial response) at the end of treatment. We also assessed serum posaconazole concentrations in a subgroup of patients. Of the 12 patients who received posaconazole, eight patients (66.6%) had complete resolution with median follow-up of 6.5 months (range 2-24 months). Two patients (16.6%) had significant reduction of disease and two (16.6%) had marked residual disease on follow-up. Uncontrolled diabetes was the predisposing factor in all except one patient. One patient developed diarrhoea on posaconazole, which settled without discontinuation of the drug. Posaconazole appears to be a safe and effective antifungal agent in diabetic patients with ROCM, especially in those who have toxicity with polyene therapy.

Supraphysiological 25-hydroxy vitamin D3 level at admission is associated with illness severity and mortality in critically ill patients.

We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37% (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5% (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75% (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5% (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7% (95% confidence interval 1.2-11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

Anergy to purified protein derivative and chronic energy deficiency in sputum-positive pulmonary tuberculosis: Dynamic assessment at baseline and treatment completion.

Background: Tuberculosis (TB) remains a high burden disease in India. Nutrition plays a pivotal role in holistic recovery of the same. Methods: Patients with sputum positive pulmonary TB were consecutively recruited into the study aimed to observe the incidence of under nutrition and anergy purified protein derivative (PPD). Anthropometry and PPD testing were done at baseline. Patients were followed-up at 6 months, with PPD intradermal test repeated to study tuberculin conversion. Nutritional recovery, tuberculin conversion, and determination of persistent anergy were the outcomes of interest. Results: Of the 134 patients enrolled in the study, 43.2% were anergic to PPD at baseline. While 50.8% patients had normal body mass index (BMI), 14.2%, 9.7%, and 25.4% had chronic energy deficiency (CED) Grades I, II, and III, respectively. BMI at baseline showed a positive linear correlation with PPD response (r = 0.44, P < 0.001), and anergy was associated with CED (odds ratio - 3.25, P = 0.001). Forty-six patients completed follow-up and 19.6% showed anergy to PPD. At follow-up, 69.6% had normal BMI. Overall, there was an improvement in anthropometry and PPD reactivity in patients at 6 months, compared to baseline assessment. Conclusion: Anergy was significantly associated with CED at baseline in patients with TB. While most patients had an improvement in nutritional status and PPD reactivity, a small subset of patients had persistent anergy. Recovery from TB is multifactorial and its determinants include microbiological cure, nutritional status, and immunological recovery.

Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

Are physicians ready for precision antibiotic prescribing? A qualitative analysis of the acceptance of artificial intelligence-enabled clinical decision support systems in India and Singapore.

OBJECTIVES: Artificial intelligence (AI)-driven clinical decision support systems (CDSSs) can augment antibiotic decision-making capabilities, but physicians' hesitancy in adopting them may undermine their utility. We conducted a cross-country comparison of physician perceptions on the barriers and facilitators in accepting an AI-enabled CDSS for antibiotic prescribing. METHODS: We conducted in-depth interviews with physicians from the National Centre for Infectious Diseases (NCID), Singapore, and Christian Medical College Vellore (CMCV), India, between April and December 2022. Our semi-structured in-depth interview guides were anchored on Venkatesh's UTAUT model. We used clinical vignettes to illustrate the application of AI in clinical decision support for antibiotic prescribing and explore medico-legal concerns. RESULTS: Most NCID physicians felt that an AI-enabled CDSS could facilitate antibiotic prescribing, while most CMCV physicians were sceptical about the tool's utility. The hesitancy in adopting an AI-enabled CDSS stems from concerns about the lack of validated and successful examples, fear of losing autonomy and clinical skills, difficulty of use, and impediment in work efficiency. Physicians from both sites felt that a user-friendly interface, integration with workflow, transparency of output, a guiding medico-legal framework, and training and technical support would improve the uptake of an AI-enabled CDSS. CONCLUSION: In conclusion, the acceptance of AI-enabled CDSSs depends on the physician's confidence with the tool's recommendations, perceived ease of use, familiarity with AI, the organisation's digital culture and support, and the presence of medico-legal governance of AI. Progressive implementation and continuous feedback are essential to allay scepticism around the utility of AI-enabled CDSSs.

Clinical and Genomic Evolution of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections over Two Time Periods at a Tertiary Care Hospital in South India: A Prospective Cohort Study.

INTRODUCTION: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. METHODS: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014-2015; C2, 2021-2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. RESULTS: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-ß-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. CONCLUSIONS: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.