Technology, Training, and Task Shifting at the World's Largest Mass Gathering in 2025: An Opportunity for Antibiotic Stewardship in India.

The role of antibiotic overuse in intensifying selection pressures and contributing to the emergence of antimicrobial resistance is well established. The Kumbh Mela, a religious festival that occurs in 4 Indian cities of spiritual significance, is the world's largest mass gathering, attracting over 80 million pilgrims in 2013. Digital syndromic surveillance from the 2013 and 2015 Melas demonstrated a consistent pattern of antibiotic overuse, with an antibiotic prescribing rate of up to 31% for all patient encounters. As preparations for the 2025 Kumbh Mela begin, task shifting, point-of-care diagnostic and digital tools, robust clinician training, and community awareness can promote the restrained and evidence-based use of antibiotics, minimizing the potential for the emergence of antimicrobial resistance at the world's largest mass gathering.

Clinico-Epidemiologic Characteristics of Patients Reported in the Mycotic Infections in COVID-19 Registry.

We update results from the Mycotic Infections in COVID-19 (MUNCO) Registry, May-September 2021. Data collection from May to September 2021 yielded 728 cases from India, Nepal, Bangladesh, Thailand, and the United States. The cases consisted of mostly mucormycosis (97.6%), primarily rhinocerebral, and were analyzed to investigate clinical characteristics associated with negative outcomes. Patients were mostly diabetic (85%) and male (76%), with significant mortality (11.7%). All patients received treatment of coronavirus disease 2019 (COVID-19) as well as antifungal treatment. The crude mortality rate was 11.3% for mucormycosis and 22.7% formixed infections. This study demonstrates the utility of online databases in the collection of high-caliber data.

Evaluating the effect and user satisfaction of an adapted and translated mobile health application ASTHMAXcel© among adults with asthma in Pune, India.

OBJECTIVE: ASTHMAXcel© is a mobile application previously shown to improve asthma knowledge, control, and quality of life. In this study, we translated the application to Marathi for pilot testing in Pune, India in order to evaluate its impact on user satisfaction and asthma knowledge among adult asthma patients. METHODS: ASTHMAXcel© was adapted to Marathi with the help of asthma patients and clinicians from Bharati Hospital. 57 different asthma patients were then recruited and received the Asthma Knowledge Questionnaire (AKQ), Asthma Control Questionnaire (ACQ), and Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) to complete at baseline. Study participants then completed the adapted ASTHMAXcel© application. Post-intervention, participants filled out a post-AKQ and Questionnaire for User Interface Satisfaction (QUIS). A subset of participants was also interviewed for qualitative feedback. Paired t-tests and Pearson's correlation were used for statistical analysis. RESULTS: Mean AKQ improved from 5.0+/-2.4 to 12.4+/-1.6 (p = 0.0001). QUIS results revealed that participants were highly satisfied with the application, scoring an average of 50 out of 54 maximum points. Better baseline asthma control was correlated with greater overall experience with the application (-0.110, p = 0.0417). Finally, the qualitative feedback revealed four themes for future refinement. CONCLUSION: The adapted version of ASTHMAXcel© was linked to significant improvement in patient asthma knowledge and a high level of user satisfaction. These results support the potential utility of mHealth applications in promoting guideline-based asthma care in India. However, further studies are needed to establish a causal relationship between ASTHMAXcel© and improved clinical outcomes.

Factors Associated with Mortality in Coronavirus-Associated Mucormycosis: Results from Mycotic Infections in COVID-19 (MUNCO) Online Registry.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. METHODS: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. RESULTS: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02-1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01-11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82-0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09-0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93-24.36, p = ≤0.0001). CONCLUSION: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study.

COVID-19 Therapeutics: Improvise-Adapt-Learn.

"In the midst of chaos, there is also opportunity"-Sun Tzu, The Art of War [...].

Social, political, and economic determinants of access to biologics: A scoping review of structural determinants in the clinical disparities literature.

BACKGROUND: The number of biologics among new medication approvals is increasing. Social, political, and economic factors influence access to these expensive medications. Disparities in access to new medications can exacerbate health disparities. The notion of "structural determinants" provides a theoretical framework for broadly evaluating the integration of upstream social, political, and economic determinants in the clinical study of access. OBJECTIVE: To review the literature on access to FDA approved biologic medications with particular focus on the integration of social, political, and economic determinants into study design and interpretation. METHODS: We used PRISMA guidelines to review studies on racial and socioeconomic disparities in biologic access through August 2020. We assessed whether the design or interpretation of studies considered key economic determinants of access: the biologics supply chain, trade agreements, patents, drug research and development, insurance reimbursement, and non-insurance drug policies. RESULTS: 100 studies met our inclusion criteria. Sixty-six studies considered insurance reimbursement, but trade law, patents, and other key economic determinants were rarely considered. The literature focuses on a small number of older biologics. CONCLUSIONS: A small number of studies model the integration of structural determinants into clinical research on access to biologics, but overall this literature has many limitations and lacks integration of structural determinants. Increased interdisciplinary collaboration, availability of manufacturer data, and use of disease registries can help create structurally grounded understandings of the relationship between the political economy of expensive medications and clinical disparities.

Quantitative B and T cell abnormalities in four patients presenting with mucormycosis and prior asymptomatic COVID-19 infection.

India saw an unprecedented and rapid rise of invasive coronavirus-associated mucormycosis (CAM) during the delta COVID-19 surge. There is little known about the pathophysiology and if there is a direct causation between the COVID-19 infection and invasive CAM. While the traditional risk factors such as uncontrolled diabetes and other immunocompromising conditions are recognised, there could be several COVID-19-induced phenomena that may predispose the patients to develop CAM and are yet unrecognised. It has been proposed that prior severe COVID-19 is associated with invasive CAM. This could be due to the increased use of immunomodulators or the direct effects of the COVID-19 infection. We report four patients with CAM during the delta surge who did not have prior known COVID-19 infection but on subsequent testing had positive antibodies suggesting past asymptomatic infection. We report the quantitative abnormalities in lymphocyte subsets in all four patients and report CD19+ B cell lymphopenia and reduced percentage of CD27+ CD45RA+ naïve helper T cells. CAM may occur in patients after asymptomatic COVID-19 infection, in the absence of systemic corticosteroid and immunomodulator use, and may reflect underlying immune abnormalities possibly attributable to or unmasked by prior COVID-19 infection.

Current Effective Therapeutics in Management of COVID-19.

The current pandemic due to the SARS-CoV-2 virus has caused irreparable damage globally. High importance is placed on defining current therapeutics for Coronavirus Disease 2019 (COVID-19). In this review, we discuss the evidence from pivotal trials that led to the approval of effective therapeutics in the treatment and prevention of COVID-19. We categorize them as effective outpatient and inpatient management strategies The review also attempts to contextualize the efficacy of therapeutics to the emerging variants. Vaccines, which remain the most effective prevention against hospitalization and deaths is not included in this review.

Progression of untreated gastric and pulmonary metastasis in a patient with resected acral melanoma.

We report a man in his 80s who presents with epigastric abdominal pain and fatigue for 2 weeks. His medical history was significant for left toe acral melanoma (excised 6 years prior) and a lung mass, further workup for which was declined at the time by the patient. On presentation, he had iron deficiency anaemia and esophagogastroduodenoscopy revealed a gastric mass. Histopathological analysis of gastric and subsequently, pulmonary, lesions were consistent with metastatic melanoma. This case demonstrates the unique slow progression of untreated pulmonary metastasis in metastatic melanoma.

Online Registry of COVID-19-Associated Mucormycosis Cases, India, 2021.

We established an online registry of coronavirus disease-associated mucormycosis cases in India. We analyzed data from 65 cases diagnosed during April-June 2021, when the Delta variant predominated, and found that patients frequently received antibacterial drugs and zinc supplementation. Online registries rapidly provide relevant data for emerging infections.

A Search for Secondary Hypertension: "Where's Waldo?"

Hypertension is an important modifiable risk factor for cardiovascular disease and stroke. Most cases are diagnosed as essential hypertension however, in some patients, a secondary (and potentially curable) cause is identified. Selecting the right patient to screen for a secondary cause can be challenging and certain clinical and laboratory characteristics can guide work-up. We report a case of a 67-year-old man who presented with intracranial hemorrhage. He had a history of resistant hypertension for three decades and chronic hypokalemia while on a non-diuretic antihypertensive regimen. We discuss our approach to a hypertensive hypokalemic phenotype that led to the diagnosis of Liddle's syndrome with complete amelioration of hypokalemia with directed therapy. This case highlights the importance of accurate and early screening for causes of secondary hypertension in the outpatient community, and in doing so, preventing downstream catastrophic outcomes. It is imperative to develop a clear, concise approach to secondary hypertension, and raising awareness for the importance of early diagnosis as it can potentially avoid downstream sequela.

Early and Significant Reduction in C-Reactive Protein Levels After Corticosteroid Therapy Is Associated With Reduced Mortality in Patients With COVID-19.

BACKGROUND: Corticosteroids may be beneficial in a subset of patients with coronavirus disease 2019 (COVID-19), but predictors of therapeutic response remain unknown. C-reactive protein (CRP) is a routinely measured biomarker, and reduction in its levels after initiation of therapy may predict inpatient mortality. METHODS: In this retrospective cohort study, the charts of patients who were admitted to Montefiore Medical Center between March 10, 2020, and May 2, 2020 for the management of COVID-19 were examined. Of all patients who met inclusion criteria, patients who received corticosteroid treatment were categorized as CRP responders (≥50% CRP level reduction) and CRP nonresponders (<50% CRP level reduction) based on change in CRP within 72 hours of corticosteroid treatment initiation. The outcomes of interest were two-fold: (1) CRP response after treatment with corticosteroid, and (2) differences in mortality among patients with CRP response compared those without. RESULTS: Of 2,707 patients admitted during the study period, 324 received corticosteroid treatment. Of patients who received corticosteroid treatment, CRP responders had reduced risk of death compared with risk among CRP nonresponders (25.2% vs 47.8%; unadjusted odds ratio [OR], 0.37; 95% CI, 0.21-0.65; P <.001). This effect remained strong and significant after adjustment for potential confounders (adjusted OR, 0.27; 95% CI, 0.14-0.54; P <.001). CONCLUSION: Reduction in CRP by 50% or more within 72 hours of initiating corticosteroid therapy potentially predicts inpatient mortality. This may serve as an early biomarker of response to corticosteroid therapy in patients with COVID-19.

Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19.

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York.

BACKGROUND & AIMS: New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes independently from age, gender and other comorbidities. METHODS: This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. RESULTS: 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m2. The median age was 64 years. Hypertension (76%), hyperlipidemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI < 25 kg/m2: 31.6%, BMI 25-34 kg/m2: 17.2%, BMI ≥ 35 kg/m2: 34.8%, p = 0.03). Increasing age (analyzed in quartiles), male sex, BMI ≥ 35 kg/m2 (reference: BMI 25-34 kg/m2), heart failure, CAD, and CKD or ESRD were found to have a significant univariate association with mortality. The multivariate analysis demonstrated that BMI ≥ 35 kg/m2 (reference: BMI 25-34 kg/m2, OR: 3.78; 95% CI: 1.45-9.83; p = 0.006), male sex (OR: 2.74; 95% CI: 1.25-5.98; p = 0.011) and increasing age (analyzed in quartiles, OR: 1.73; 95% CI: 1.13-2.63; p = 0.011) were independently associated with higher in-hospital mortality. Similarly, age, male sex, BMI ≥ 35 kg/m2 and current or prior smoking were significant predictors for increasing oxygenation requirements in the multivariate analysis, while male sex, age and BMI ≥ 35 kg/m2 were significant predictors in the multivariate analysis for the outcome of intubation. CONCLUSIONS: In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were independently associated with higher in-hospital mortality and in general worse in-hospital outcomes.

Agranulocytosis from Outpatient Antimicrobial Treatment with Ceftriaxone: A Case Report.

INTRODUCTION: Agranulocytosis from antimicrobial therapy with ceftriaxone is rare. We report a case of agranulocytosis resulting from ceftriaxone noted more than 3 weeks into therapy. CASE PRESENTATION: A 72-year-old woman who was started on ceftriaxone for septic arthritis of the left knee 3 weeks before presentation was admitted to the hospital after being found to be neutropenic on outpatient laboratory analysis. Her absolute neutrophil count on admission was 0/µL. The cause of the agranulocytosis was suspected to be ceftriaxone. The drug was stopped, and she was started on granulocyte colony-stimulating factor with gradual resolution of the neutropenia. DISCUSSION: Serious adverse effects of ceftriaxone therapy, such as agranulocytosis, must be monitored for, especially in patients who are receiving prolonged therapy or high doses. Once this cause of agranulocytosis is identified, ceftriaxone therapy should be stopped; if the patient is febrile, an infectious disease workup should be performed and antibiotics should be started; and granulocyte colony-stimulating factor should be administered with daily monitoring of the absolute neutrophil count.