Impact of Diabetes in COVID-19 Associated Mucormycosis and its Management: A Non-Systematic Literature Review.

BACKGROUND: COVID-19 has become extremely dangerous manifesting itself in a variety of forms ranging from a simple flu-like illness to death. COVID-19 associated mucormycosis (CAM) is a global threat with diabetes being a major contributor. OBJECTIVE: This review aims to give a clear picture of the impact of hyperglycemia in CAM along with its management. METHODS: Google and Google Scholar were searched and studies that addressed the impact of diabetes in CAM were considered for this review. We also performed a bibliographic search of the specific article to find additional studies. RESULTS: A series of events such as unregulated activation of innate immune system modification, pro-inflammatory M1 macrophages activation, and the depletion of natural killer cell activity is very common in patients with COVID-19. In addition, the exacerbated cytokine syndrome and hyperinflammatory response may elevate the severity of this condition, which further leads to higher mortality. The impaired immune phase which follows provide the niche for increased infection among diabetic patients making them more prone towards developing mucormycosis and associated infections. Early detection, surgical debridement, and appropriate medical treatment with antifungals and hypoglycaemic agents may help control the infection and associated morbidity and mortality. COVID-19 drugs, hypoglycaemic agents, antifungals, and comorbidities have all been associated with adverse side effects and drug interactions. CONCLUSION: Clinicians should be well aware of this deadly disease and manage COVID-19, diabetes, and mucormycosis through individualized treatment regimens to improve patient outcomes.

Systematic review and meta-analysis of global prevalence of neurotoxic and hemotoxic snakebite envenomation.

Background: The World Health Organization estimates that there are approximately 5.4 million snakebites and 1.8-2.7 million cases of envenomation, with 81 410-137 880 deaths each year worldwide. Aims: To estimate the prevalence of neurotoxic and haemotoxic snakebite envenomation through a comprehensive systematic review and meta-analysis. Methods: We searched Medline/PubMed, Scopus and Cochrane Library up to January 2021 using keywords such as snakebite and snake envenomation. Bibliographic and random searches were also performed. Prospective or retrospective observational studies and randomized controlled trials were included for the review. Results: We included 271 of 9711 studies published between 1963 and 2020. The pooled prevalence of snakebite from 188 studies with a total of 207 235 participants showed the highest prevalence in North America (69.20%; 95% confidence interval, CI: 57.06-81.34%) and lowest in Africa (28.10%; 95% CI: 22.22-33.98%). There was a pooled prevalence of 24.94% (95% CI: 22.84-27.03%) for haemotoxicity, with a highest prevalence of coagulopathy (43.76%; 95% CI: 33.15-54.37%). The overall prevalence of neurotoxicity was 38.20% (95% CI: 31.88-44.53%), with a highest prevalence of ptosis (53.57%; 95% CI: 38.51-68.62%). Conclusion: There was a higher prevalence of snakebites in North America. The most prevalent haemotoxicity and neurotoxicity were coagulopathy and ptosis, respectively. The overall quality of evidence was good with a non-significant publication bias.

Role of human leukocyte antigen in anti-epileptic drugs-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis: A meta-analysis.

PURPOSE: Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR). RESULTS: We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77. CONCLUSION: Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.

Artificial intelligence in differentiating tropical infections: A step ahead.

BACKGROUND AND OBJECTIVE: Differentiating tropical infections are difficult due to its homogenous nature of clinical and laboratorial presentations among them. Sophisticated differential tests and prediction tools are better ways to tackle this issue. Here, we aimed to develop a clinician assisted decision making tool to differentiate the common tropical infections. METHODOLOGY: A cross sectional study through 9 item self-administered questionnaire were performed to understand the need of developing a decision making tool and its parameters. The most significant differential parameters among the identified infections were measured through a retrospective study and decision tree was developed. Based on the parameters identified, a multinomial logistic regression model and a machine learning model were developed which could better differentiate the infection. RESULTS: A total of 40 physicians involved in the management of tropical infections were included for need analysis. Dengue, malaria, leptospirosis and scrub typhus were the common tropical infections in our settings. Sodium, total bilirubin, albumin, lymphocytes and platelets were the laboratory parameters; and abdominal pain, arthralgia, myalgia and urine output were the clinical presentation identified as better predictors. In multinomial logistic regression analysis with dengue as a reference revealed a predictability of 60.7%, 62.5% and 66% for dengue, malaria and leptospirosis, respectively, whereas, scrub typhus showed only 38% of predictability. The multi classification machine learning model observed to have an overall predictability of 55-60%, whereas a binary classification machine learning algorithms showed an average of 79-84% for one vs other and 69-88% for one vs one disease category. CONCLUSION: This is a first of its kind study where both statistical and machine learning approaches were explored simultaneously for differentiating tropical infections. Machine learning techniques in healthcare sectors will aid in early detection and better patient care.

Ciprofloxacin-induced cutaneous adverse drug events: a systematic review of descriptive studies.

OBJECTIVES: Ciprofloxacin (CIPRO) is a fluroquinolone class antibiotic used commonly for the treatment of various acute and chronic bacterial infections. However, recently there is increase in the case reports of CIPRO-induced Cutaneous Adverse Drug Reactions (CADRs). We aim to systematically review all the descriptive studies of CIPRO induced CADRs. METHODS: Medline (via PubMed) was searched without any language or date restriction from inception to March 2019 using search terms of "Ciprofloxacin" and "Cutaneous reactions." We included only the descriptive studies, which elucidate the CADRs experienced by the patients following the administration of CIPRO. Two reviewers involved in study selection, data extraction and quality assessment of the included studies. Discrepancies were resolved by consensus between the reviewers. RESULTS: Thirty-nine studies (out of 446) were found to be eligible for the final inclusion. The dose of CIPRO among the included studies was ranging from 500 to 1,000 mg/day and duration of treatment was between 7 and 10 days. The most common CADRs observed were toxic epidermal necrolysis, Stevens-Johnson syndrome, fixed drug eruptions, bullous fixed drug reaction, acute generalized pustulosis, erythema multiforme, drug rash with eosinophilia and systemic symptoms and erythema nodosum. CONCLUSIONS: Management of the CIPRO-induced CADRs is recommended with the complete cessation of the CIPRO, followed by supportive management with oral or topical glucocorticoids, emollients, and topical moisturizers. CIPRO is likely to cause CADRs, physicians should be vigilant while prescribing it to the patients.

Linezolid Induced Skin Reactions in a Multi Drug Resistant Infective Endocarditis Patient: A Rare Case.

RATIONALE: Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here, we present a rare case report of LNZ induced CARs in a MDR IE patient. CASE REPORT: A 24-year-old female patient was admitted to the hospital with chief complaints of fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days. She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient was prescribed corticosteroids along with other supportive care. Her reactions completely subsided and infection got controlled following 1 month of therapy. CONCLUSION: Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover, strengthened spontaneous reporting is required for better quantification.

Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies.

PURPOSE: Recently, there have been an increased number of reports on levetiracetam (LEV) induced cutaneous adverse drug reactions (CADRs). We aimed to identify and critically evaluate all the descriptive studies on LEV induced-CADRs and to describe the possible clinical manifestations, management, and treatment outcomes of the condition. METHODOLOGY: PubMed and grey literature databases were searched from inception to June 2019 without any restriction. We also performed a bibliographic search for additional studies. Only descriptive studies on LEV-induced CADRs were included for our review. Study selection, data abstraction and quality assessment were performed by two contributors independently and disagreements were settled through consensus or through discussion with a third reviewer. RESULTS: Data from 24 out of 88 studies, which included 25 patients (12 female and 13 male) aged from 40 weeks to 73 years, were reviewed. Patients received between 500 mg/day to 3000 mg/day of LEV. Drug reaction with eosinophilia and systemic symptoms syndrome, Steven-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, generalised hyperpigmentation and leucocytoclastic vasculitis were observed among the included patients. Immediate cessation of LEV, providing supportive care and use of topical antihistamines and anti-inflammatory drugs appeared to be the mainstay of management, and all patients were found to have recovered. CONCLUSION: Clinicians should be aware of the possible CADRs induced by LEV to avoid the development of a potentially fatal condition. Immediate withdrawal of the drug and supporting care seem to be effective in the management of the CADRs. REGISTRATION NUMBER: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019141002.