A Randomized Double-blind Study to Assess the Skin Irritation and Sensitization Potential of a Once-weekly Donepezil Transdermal Delivery System in Healthy Volunteers.

BACKGROUND: A once-weekly donepezil transdermal delivery system (TDS; Adlarity; Corium, LLC) is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer type. METHODS: In this placebo-controlled, randomized, double-blind phase 1 trial, healthy volunteers aged 40 years or older were randomized to receive a placebo and donepezil TDS and were evaluated for the primary endpoints of skin irritation and sensitization potential. Skin irritation was scored. RESULTS: Two hundred fifty-six participants were randomized and received ≥1 dose of any treatment. After the first weekly TDS application, no skin irritation or minimal irritation was evident between donepezil and placebo TDSs. At the third weekly TDS application, for donepezil TDS, the average of the mean combined skin irritation score was 0.55 of a possible maximum of 7, indicating none to minimal skin irritation, and for placebo, the score was 0.19, indicating no skin irritation. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS. CONCLUSION: Once-weekly 5-mg/d donepezil TDS demonstrated minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential.

Extent of knowledge and attitudes on plagiarism among undergraduate medical students in South India - a multicentre, cross-sectional study to determine the need for incorporating research ethics in medical undergraduate curriculum.

BACKGROUND: Undergraduate medical students in India participate in various research activities However, plagiarism is rampant, and we hypothesize that it is the lack of knowledge on how to avoid plagiarism. This study's objective was to measure the extent of knowledge and attitudes towards plagiarism among undergraduate medical students in India. METHODS: It was a multicentre, cross-sectional study conducted over a two-year period (January 2018 - December 2019). Undergraduate medical students were given a pre-tested semi-structured questionnaire which contained: (a) Demographic details; (b) A quiz developed by Indiana University, USA to assess knowledge; and (c) Attitudes towards Plagiarism (ATP) questionnaire. RESULTS: Eleven medical colleges (n = 4 government medical colleges [GMCs] and n = 7 private medical colleges [PMCs]) participated. A total of N = 4183 students consented. The mean (SD) knowledge score was 4.54 (1.78) out of 10. The factors (adjusted odds ratio [aOR]; 95% Confidence interval [CI]; p value) that emerged as significant predictors of poor knowledge score were early years of medical education (0.110; 0.063, 0.156; < 0.001) and being enrolled in a GMC (0.348; 0.233, 0.463; < 0.001).The overall mean (SD) scores of the three attitude components namely permissive, critical and submissive norms were 37.56 (5.25), 20.35 (4.20) and 31.20 (4.28) respectively, corresponding to the moderate category. CONCLUSION: The overall knowledge score was poor. A vast majority of study participants fell in the moderate category of attitude score. These findings warrant the need for incorporating formal training in the medical education curriculum.

Detection of New Delhi Metallo-ß-lactamase 1 and Cephalosporin Resistance Genes Among Carbapenem-Resistant Enterobacteriaceae in Water Bodies Adjacent to Hospitals in India.

The prevalence of carbapenem resistance among bacterial isolates from selected water bodies receiving hospital effluents and adjoining aquaculture farms in Kerala, India, was studied. Klebsiella pneumoniae followed by Escherichia coli, Klebsiella oxytoca, Enterobacter aerogenes and Acinetobacter baumannii were the predominant isolates. Antibiotic sensitivity of these isolates was determined by Kirby-Bauer disc diffusion method. Nearly 60% of the Enterobacteriaceae isolates screened were multidrug resistant of which 16.6% were carbapenem resistant. The carbapenem-resistant Enterobacteriaceae were further screened for the presence of New Delhi metallo ß-lactamase-1 and cephalosporin resistance encoding genes. All NDM-1 isolates were highly resistant to carbapenem, cephalosporin, aminoglycosides, quinolones, tetracycline, and sulphonamides. K. pneumoniae harboring blaNDM-1 gene and E. coli isolates with blaCTX-M-15 and blaSHV-11 genes were detected in hospital discharge points. In aquaculture farms too, carbapenem-resistant K. pneumoniae with blaNDM-1 gene and E. coli isolates with blaCTX-M-15 were observed, although there was no use of antibiotics in these farms. However, other carbapenemase genes such as blaTEM, blaVIM, blaIMP and blaGIM were not detected in any of these isolates. The results suggest the increased prevalence of carbapenem-resistant Enterobacteriaceae in the water bodies receiving hospital effluent and its dissemination to adjacent aquaculture farms, posing a serious threat to public health.

New Classification System for Cleft Alveolus: A Computed Tomography-based Appraisal.

AIM: The present study proposed a new classification system based on computed tomography (CT) scan appraisal; this enables the surgeon to identify the extent of the defect and helps to execute the proper treatment plan. BACKGROUND: Various terminologies and classifications were proposed to understand developmental defects. But none of the existing classifications/nomenclatures used the preoperative radiographic evaluation (i.e., computed tomography scan-CT scan) in the management and prognosis. Various treatments were advocated and practiced successfully for the surgical correction of lip and palate. MATERIALS AND METHODS: The available CT scans from archives of the Department of Radiology and Oral and Dental Surgery were evaluated (retrospectively) for cleft alveolus and its morphology as per the proposal. The English language literature was searched in the MEDLINE database without date restriction to revise existing literature on numerous classification systems/nomenclatures using MeSH keywords related to cleft lip, palate, alveolus, developmental disturbance, facial clefts, and classification. Existing classification systems were revisited with a note on the drawbacks. After careful examination of morphological patterns of all clefts, the new CT scan-based alveolar cleft classification is proposed depending on the extent of cleft. RESULTS: The literature revealed a total of twenty-nine classifications of cleft lip and palate starting from the year 1922 to the year 2015, but none exclusively classified the cleft alveolus based on CT scan observations. The observation of three thousand CT scans showed five types of cleft alveolus, depending on the extent of involvement. CONCLUSION: The CT scan-based classification is essential to the surgeon for successful surgical planning of cleft alveolus. The proposed classification is clinically relevant in this digital era for relating surgical outcomes. The three-dimensional viewing of a defect is essential for the surgeon for virtual planning. This paper provides a CT scan-based classification for universal acceptance in this era of digital technology, and CT scan aids in achieving these goals. CLINICAL SIGNIFICANCE: The new proposal is based on preoperative evaluation of cleft using a CT scan. CT scan imaging provides a clear picture of the cleft in three dimensions for the operating surgeon. Advanced technology-enhanced surgical management modalities like CAD/CAM guided templates to support graft for successful management. The classification system will help the medical and surgical fraternity in various aspects. The three-dimensional modeling of defect and printing of a defect model using additive manufacturing technology helps the surgeon for presurgical visualization and virtual planning in a better way. This strategy of defect classification using a CT scan will help obtain better clinical outcomes and patient satisfaction.

Transversus abdominis plane block supplementation during iliac crest bone graft harvesting - Effect on postoperative pain.

BACKGROUND AND AIMS: Transversus abdominis plane (TAP) block is a technique proposed to minimise pain after anterior iliac crest bone harvesting. This study aims to evaluate the postoperative pain in patients who receive ultrasound-guided TAP block to supplement routine wound infiltration. MATERIAL AND METHODS: A total of 143 patients aged between 6 and 22 years were randomised into two groups. Patients in group A received supplemental TAP block on the same side. Patients in group B received local anesthetic wound infiltration alone. Pain scores were compared at the first and 24th postoperative hours. RESULTS: TAP block significantly reduced pain and delirium in the immediate postoperative period. The mean FLACC (Face, Legs, Activity, Cry, Consolability) score after 10 min was 0.8 in group A versus 1.8 in group B (P = 0.001). The mean Watcha scale at 10 min was 1.0 in group A versus 1.2 in group B (P = 0.001). After 24 h, 81.7% of patients in group A had no pain versus 59.7% in group B (P = 0.004). The incidence of intolerable pain at 24 h was 5.6% in group B versus 0% in group A (P = 0.04). Cumulative ambulation scores were significantly better in group A (P < 0.05). There was a strong and positive correlation between the analgesia and ability to ambulate comfortably at 24 h postop (Pearson's coefficient 0.95). CONCLUSION: Supplemental ultrasound-guided TAP block given intraoperatively reduces the postoperative pain. The incidence of emergence delirium was low. These patients were also able to ambulate earlier.

Deployment of a Short, Single-Opening Endoscopic Clip Versus a Long, Reopening Endoscopic Clip in Clinical Practice.

BACKGROUND: Endoscopic clips vary in their designs and costs. Clip wastage is a common problem, and this is dependent on the success of its deployment. AIMS: The aim of this study is to compare the rates of successful deployment between two different commonly used endoscopic clips. METHODS: A single-center, retrospective study was conducted. Endoscopy reports of patients with clips deployed over 24 months were reviewed. We compared a long-pronged, reopening endoscopic clip (type A: Resolution clip; Boston Scientific, Natick, MA, USA) versus a short-pronged, single-opening clip (type B: QuickClip2; Olympus Medical Systems Corp, Japan). The main outcome was clip deployment success rate. Secondary outcomes were predictors of successful deployment, cost, and wastage. RESULTS: Of 14,690 endoscopic cases, 472 clips (171 type A and 301 type B) were deployed in 262 procedures. Type A clips had a significantly higher successful deployment rate (147/171, 86.0 %) than type B clips (221/301, 73.4 %) (p = 0.002). On multivariate analysis, variables independently associated with successful deployment included using type A clips (OR 2.07, 95 % CI 1.20-3.55; p = 0.009) and clips placed in the lower gastrointestinal tract (OR 3.48, 95 % CI 1.64-7.40; p = 0.001). The cost of using type A clips was higher than type B clips (p < 0.001). Type B clips were associated with more wastage (p = 0.049). CONCLUSIONS: Long-pronged, reopening clips (type A) have a better deployment rate than short-pronged, single-opening clips (type B). Although type A clips had less wastage, the cost per procedure was higher.

A report of 2 patients with transient blindness following Le Fort I osteotomy and a review of past reported cases.

Blindness following a LeFort I osteotomy is a rare but extremely serious complication. Ten cases have been reported to date. None of these patients recovered vision. Optic neuropathy is believed to be the cause but the exact mechanism has not been settled. We report the first, and the only two, documented cases of complete loss of vision that recovered subsequently. The first patient was a 19-year-old male with repaired bilateral cleft lip and palate. He developed loss of vision in the right eye on the second postoperative day. The second patient was a 22-year-old male with repaired unilateral cleft lip and palate. He developed complete loss of vision in the left eye on the day of surgery. Both these patients underwent ongoing studies, which did not show any abnormalities. Both were treated with methylprednisolone. Both the patients gradually showed improvement in their vision. The first patient recovered normal vision several months postoperatively. The second patient's vision improved to 4/60 by 4 months postoperatively. We discuss the probable mechanisms of optic nerve injury and also the possible reasons why sight was restored in these patients. This is a rare but serious complication following a fairly common procedure. Through this article we wish to create an awareness of this complication and also a possible way of avoiding such a disaster.

Detection of lung cancer and stages via breath analysis using a self-made electronic nose device.

BACKGROUND: Breathomics is an emerging area focusing on monitoring and diagnosing pulmonary diseases, especially lung cancer. This research aims to employ metabolomic methods to create a breathprint in human-expelled air to rapidly identify lung cancer and its stages. RESEARCH DESIGN AND METHODS: An electronic nose (e-nose) system with five metal oxide semiconductor (MOS) gas sensors, a microcontroller, and machine learning algorithms was designed and developed for this application. The volunteers in this study include 114 patients with lung cancer and 147 healthy controls to understand the clinical potential of the e-nose system to detect lung cancer and its stages. RESULTS: In the training phase, in discriminating lung cancer from controls, the XGBoost classifier model with 10-fold cross-validation gave an accuracy of 91.67%. In the validation phase, the XGBoost classifier model correctly identified 35 out of 42 patients with lung cancer samples and 44 out of 51 healthy control samples providing an overall sensitivity of 83.33% and specificity of 86.27%. CONCLUSIONS: These results indicate that the exhaled breath VOC analysis method may be developed as a new diagnostic tool for lung cancer detection. The advantages of e-nose based diagnostics, such as an easy and painless method of sampling, and low-cost procedures, will make it an excellent diagnostic method in the future.

Time to positivity of blood cultures causing candidemia and its relation to mortality.

Background and Objectives: Early diagnosis of candidemia is of vital importance in reducing mortality and morbidity. The main objective of the study was to determine the TTP (Time to Positivity) of different species of Candida causing bloodstream infection and to see whether TTP can help differentiate Candida glabrata which is frequently fluconazole resistant from Fluconazole sensitive Candida. Materials and Methods: TTP (Time to positivity) and AAT (Appropriate Antifungal therapy) were noted for Blood cultures becoming positive for Candida. Presence of Risk factors for candidemia like prolonged ICU stay, neutropenia, Total Parenteral Nutrition (TPN), use of steroids , broad spectrum antibiotics, use of Central Venous Catheter, Foleys catheter were also analyzed. Results: The most frequent isolates were Candida parapsilosis, Candida tropicalis and Candida albicans. The median TTP for all Candida isolates in our study was 34 hours. The diagnostic sensitivity of TTP for detecting C. glabrata and C. tropicalis in patients with candidemia was 88% and 85% respectively. TTP showed that there was no difference in survival between TTP <24 hrs. and > 24hrs. Initiation of antifungal therapy <24 hours and > 24hrs after onset of candidemia had no association with survival. Conclusion: Longer TTP maybe predictive of C. glabrata while shorter TTP may be predictive of C. tropicalis. In our study we found that fluconazole resistant Candida causing blood stream infection is quite unlikely if the TTP of the isolate is <48hrs.

Formulating a Community-Centric Indicator Framework to Quantify One Health Drivers of Antibiotic Resistance: A Preliminary Step towards Fostering 'Antibiotic-Smart Communities'.

Antibiotic resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through the 'One Health' approach is essential to complement top-down measures. However, the absence of objective criteria to measure the performance of ABR interventions in community settings makes it difficult to mobilize interest and investment for such interventions. An exercise was therefore carried out to develop an indicator framework for this purpose. A comprehensive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was carried out by global experts on ABR, looking at appropriateness, feasibility, and validity. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management, and Water Sanitation and Hygiene (WASH) domains. The indicator framework was piloted in the panchayat (located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating that the framework is sensitive to change. The indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use the framework with minimal training. It is hoped that, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community as part of National Action Plan on AMR.

Public perception and community-level impact of national action plans on antimicrobial resistance in Vietnam.

Objectives: Vietnam was the first country from the WHO Western Pacific Region to adopt a national action plan (NAP) on antimicrobial resistance (AMR) in 2013. The multilayered nature of AMR requires coordination across 'One Health' sectors, dedicated financing, multistakeholder involvement, and widespread community engagement to implement the action plans. This study explores the perceived impact of NAP implementation at the community level. Methods: Key informant interviews (KIIs) were used for data collection during 2021. An interview tool was used for the KIIs and purposive sampling was used to identify study participants from Vietnam. The study participants were those engaged with a substantial scale of antimicrobial usage, diagnosis of infections or concerned with antimicrobial content in effluents in their professional life. Twelve KIIs were conducted with participants from human health, animal health and the environmental sector. The data were entered into Microsoft Excel, and manifest and latent content analysis was done. Results: The analysis highlighted themes such as limited public awareness of AMR, ongoing capacity building and quality assurance initiatives, implementation of guidelines and regulations for AMR containment, sustained investment in improving infrastructure, and challenges relating to accountability whilst prescribing and selling antibiotics. Conclusions: There were many positive critical developments during the NAP implementation period in Vietnam towards AMR mitigation. For better impact, there is a need to revitalize the implementation machinery of NAPs by improving the enforcement capacity of regulations, cross-sectoral collaboration and promoting community ownership.

Design and evaluation of oral formulation for apixaban.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

The role of Schedule H1 and Red Line campaign in improving antibiotic use in India.

Purpose: Over-the-counter (OTC) sale of antibiotics have contributed to the growing threat of antibiotic resistance. The Government of India has instituted regulatory measures, such as Schedule H1 and public campaigns such as Red Line Campaign, to limit such sales. This study was conducted to assess the perceptions of stakeholders regarding their effectiveness. Methods: To assess Schedule H1, pharmacists who own retail pharmacies in the state of Kerala, India, were interviewed using a pre-prepared question guide. In the next phase, healthcare professionals and patients in a hospital were shown the Red Line on an antibiotic blister pack and asked about its significance. Finally, 100 patients were shown a blister pack of Amoxicillin, and asked to identify the medicine or its use. Results: It was observed that there is poor awareness about antibiotic regulations and a perception of laxity in enforcement. Regarding the Red Line, only 7% of healthcare professionals could describe its significance and none among patients. Among the 100 patients who were shown Amoxicillin, only 42 could identify it as an antibiotic or describe its use. Conclusions: There is a general perception that regulations are poorly enforced and all are not aware of the Red Line campaign including healthcare professionals. Greater awareness at all levels about appropriate antibiotic use through prescriptions followed by greater efforts towards regulatory implementation and compliance should form parts of a multi-modal strategy to contain OTC sales of antibiotics. This will greatly help to aid physicians in improving overall healthcare through safe and effective prescribing.

Central Variant Posterior Reversible Encephalopathy Syndrome in a Pregnant Woman With Eclampsia: A Case Report.

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological diagnosis characterized by acute or subacute neurological symptoms. A 27-year-old woman at 35 weeks of pregnancy, who presented with generalized tonic-clonic seizures had persistently low Glasgow Coma Scale (GCS) score after delivery of the baby. Magnetic Resonance Imaging (MRI) of the brain showed T-2 Fluid Attenuated Inversion Recovery (FLAIR) hyperintensities in the brainstem, bilateral medial cerebellar hemispheres, bilateral medial temporal lobes, bilateral thalami, lentiform and caudate nuclei, and bilateral fronto-parieto-occipital lobes. There was diffusion restriction in bilateral caudate nuclei, left thalamus and right frontal lobe, and microhemorrhages in the left thalamus. These findings were suggestive of central variant PRES. She improved with strict blood pressure control and anti-edema measures. A repeat MRI brain on day 10 showed significant improvement, and she had no residual neurological deficits. The central variant of PRES is a rare entity that has to be considered in a patient presenting with neurological deficits in the setting of uncontrolled blood pressure, eclampsia, immunomodulatory medication use, or renal failure. While most patients with PRES fully recover with timely therapy targeted at reversing the primary cause, some may have residual neurological deficits or rarely, die.

Lunate dislocations: anatomy, diagnosis and management.

Lunate dislocation is an uncommon but serious wrist injury, often resulting from a high energy mechanism of trauma. Advanced trauma life support protocols should be followed to diagnose and treat concomitant life-threatening pathology. Thorough neurovascular and soft tissue examination is required to identify open wounds and median nerve dysfunction, including acute onset carpal tunnel syndrome. Imaging is undertaken to appreciate injury severity, which is graded by the Mayfield classification. Closed reduction in the emergency department is the initial management, which alleviates pressure on neurovascular structures. Definitive management is surgical, most commonly via open reduction and direct ligamentous stabilisation. The aims of surgery are to restore anatomical carpal alignment and maintain stability, allowing repair and healing of the important wrist ligaments. Medium-to long-term functional outcomes are adequate, with most patients returning to work within 6 months. However, progressive radiographic midcarpal arthrosis is common, as well as permanent loss of grip strength, range of motion and chronic pain. This article considers the anatomy, diagnosis and management of acute lunate and perilunate dislocations.

Extent of awareness and attitudes on plagiarism among post-graduate resident doctors and junior medical faculty in India: a cross-sectional, multicentric study.

OBJECTIVES: Though dissertation is mandatory for postgraduates (PG), it is unknown if adequate knowledge on plagiarism exists at that level. Thus, we intended to study the knowledge and attitude towards plagiarism among junior doctors in India. DESIGN: Cross-sectional study SETTING: PG medical residents and Junior faculty from various teaching institutions across south India. PARTICIPANTS: A total of N=786 doctors filled the questionnaires of which approximately 42.7% were from government medical colleges (GMCs) and the rest from private institutions. METHODS: Participants were given a pretested semistructured questionnaire which contained: (1) demographic details; (2) a quiz developed by Indiana University, USA to assess knowledge and (3) Attitudes towards Plagiarism Questionnaire (ATPQ). OUTCOME MEASURES: The Primary outcome measure was knowledge about plagiarism. The secondary outcome measure was ATPQ scores. RESULTS: A total of N=786 resident doctors and junior faculty from across 11 institutions participated in this study. Of this, 42.7% were from GMCs and 60.6% were women. The mean (SD) knowledge score was 4.43 (1.99) out of 10. The factors (adjusted OR; 95% CI; p value) that emerged as significant predictors of knowledge were number of years in profession (-0.181; -0.299 to -0.062; 0.003), no previous publication (0.298; 0.099 to 0.498; 0.003) and working in a GMC (0.400; 0.106 to 0.694; 0.008). The overall mean (SD) scores of the three attitude components were: Permissive attitudes-37.33 (5.33), critical attitudes -20.32 (4.82) and subjective norms-31.05 (4.58), all of which corresponded to the moderate category. CONCLUSION: Participants lacked adequate knowledge on how to avoid plagiarism suggesting a need for a revamp in medical education curriculum in India by incorporating research and publication ethics.

Challenges in Implementing Antimicrobial Stewardship Programmes at Secondary Level Hospitals in India: An Exploratory Study.

Introduction: Implementing a sustainable and effective Antimicrobial Stewardship (AMS) programme in secondary level hospitals, in Low-Middle Income Country (LMIC) contexts, has numerous challenges. It is important to understand these challenges so that the stewardship initiatives can be tailored according to the unique requirements thrown up by these healthcare facilities. This study explores the experiences of implementing AMS in secondary level hospitals in the state of Kerala, India. Methods: A qualitative study was planned to map the challenges in implementing AMS in the secondary level hospitals. Toward the end of the 1 year followup period, the nodal officers at each hospital were interviewed using a semi-structured interview guide. The in-depth interviews were transcribed and later subjected to content analysis using N-Vivo 11.0, a popular software tool used for qualitative analysis. Results: Many physicians cite perceived patient satisfaction as one of the reasons for increased antibiotic use, as many patients consider antibiotics as standard of care. Also, the distance traveled by the patient and advancing age are factors which increase antibiotic use. The physician factors which determine use include empiric treatment needs, outbreak of diseases, absence of education programmes in antibiotic usage to fill in the knowledge gap and fear of litigation. The promotional activities by companies and antibiotics being a major source of income for small hospitals, affects use patterns. The factors which determine antibiotic selection includes conformism, experience of the physician, perceived resistance to certain antibiotics, emergence of specific diseases, and promotional activities related to antimicrobial agents. The challenges in implementing a sustainable stewardship programme is multifactorial. It includes competition between doctors, time constraints faced by physicians, absence of a champion, sub-optimal interdepartmental cooperation, absence of supporting facilities, dysfunctional regulatory systems, and unreliability of antibiograms. Discussion: AMS in resource-limited setting is going to be a challenge, especially in terms of financing, access to technologies and capacity building. Political and regulatory willpower of international partnerships should be effectively harnessed for designing solutions for LMIC contexts. Also, models for stewardship from elsewhere should undergo an adaptation process before implementation in low resource settings.

Low-Shot Deep Learning of Diabetic Retinopathy With Potential Applications to Address Artificial Intelligence Bias in Retinal Diagnostics and Rare Ophthalmic Diseases.

Importance: Recent studies have demonstrated the successful application of artificial intelligence (AI) for automated retinal disease diagnostics but have not addressed a fundamental challenge for deep learning systems: the current need for large, criterion standard-annotated retinal data sets for training. Low-shot learning algorithms, aiming to learn from a relatively low number of training data, may be beneficial for clinical situations involving rare retinal diseases or when addressing potential bias resulting from data that may not adequately represent certain groups for training, such as individuals older than 85 years. Objective: To evaluate whether low-shot deep learning methods are beneficial when using small training data sets for automated retinal diagnostics. Design, Setting, and Participants: This cross-sectional study, conducted from July 1, 2019, to June 21, 2020, compared different diabetic retinopathy classification algorithms, traditional and low-shot, for 2-class designations (diabetic retinopathy warranting referral vs not warranting referral). The public domain EyePACS data set was used, which originally included 88 692 fundi from 44 346 individuals. Statistical analysis was performed from February 1 to June 21, 2020. Main Outcomes and Measures: The performance (95% CIs) of the various AI algorithms was measured via receiver operating curves and their area under the curve (AUC), precision recall curves, accuracy, and F1 score, evaluated for different training data sizes, ranging from 5120 to 10 samples per class. Results: Deep learning algorithms, when trained with sufficiently large data sets (5120 samples per class), yielded comparable performance, with an AUC of 0.8330 (95% CI, 0.8140-0.8520) for a traditional approach (eg, fined-tuned ResNet), compared with low-shot methods (AUC, 0.8348 [95% CI, 0.8159-0.8537]) (using self-supervised Deep InfoMax [our method denoted as DIM]). However, when far fewer training images were available (n = 160), the traditional deep learning approach had an AUC decreasing to 0.6585 (95% CI, 0.6332-0.6838) and was outperformed by a low-shot method using self-supervision with an AUC of 0.7467 (95% CI, 0.7239-0.7695). At very low shots (n = 10), the traditional approach had performance close to chance, with an AUC of 0.5178 (95% CI, 0.4909-0.5447) compared with the best low-shot method (AUC, 0.5778 [95% CI, 0.5512-0.6044]). Conclusions and Relevance: These findings suggest the potential benefits of using low-shot methods for AI retinal diagnostics when a limited number of annotated training retinal images are available (eg, with rare ophthalmic diseases or when addressing potential AI bias).

Chromobacterium violaceum causing deadly sepsis.

Infections caused by Chromobacterium violaceum are extremely rare but can be relatively fatal in septicemia. We report a case of a 76 year old female who presented with pustules in the skin and later developed into septicemia. She succumbed to the illness despite escalating the antibiotic therapy to meropenem. To the best of our knowledge this is the 16th case report from India.

Current Orthognathic Practice in India: Do We Need to Change?

The last decade or so has seen paradigm shifts in the various aspects of orthognathic surgery. A lot of these changes are to do with digitalization of the orthodontic-surgical workflow, optimization of surgery-first protocols, virtual surgical planning-based 3D printing solutions and changing patient-health-care dynamics. The aim of this article is to provide evidence-based recommendations that are both practical and economically viable for the current orthognathic practice in India.