Analgesia for emergency laparotomy: a systematic review.

Aims/Background Poorly controlled pain is common after emergency laparotomy. It causes distress, hinders rehabilitation, and predisposes to complications: prolonged hospitalisation, persistent pain, and reduced quality of life. The aim of this systematic review was to compare the relative efficacies of pre-emptive analgesia for emergency laparotomy to inform practice. Methods We performed a search of MEDLINE, MEDLINE In-Process, Embase, PubMed, Web of Science and SCOPUS for comparator studies of preoperative/intraoperative interventions to control/reduce postoperative pain in adults undergoing emergency laparotomy (EL) for general surgical pathologies. Exclusion criteria: surgery including non-abdominal sites; postoperative sedation and/or intubation; non-formal assessment of pain; non-English manuscripts. All manuscripts were screened by two investigators. Results We identified 2389 papers. Following handsearching and removal of duplicates, 1147 were screened. None were eligible for inclusion, with many looking at elective and/or laparoscopic surgeries. Conclusion Our findings indicate there is no evidence base for pre-emptive analgesic strategies in emergency laparotomy. This contrasts substantially with elective cohorts. Potential reasons include variation in practice, management of physiological derangement taking priority, and perceived contraindications to neuraxial techniques. We urge a review of contemporary practice, with analysis of clinical data, to generate expert consensus.

Evaluation of Changes in Oral Microflora in Children with Early Childhood Caries after Full Mouth Rehabilitation.

Aim: To evaluate the change in microflora in children suffering from severe early childhood caries (ECC) after full mouth rehabilitation. Materials and methods: A total of 60 children, aged 3-5 years suffering from severe ECC who fulfilled the inclusion and exclusion criteria were included in the study. Pooled plaque samples were taken and subjected to quantitative reverse transcriptase polymerase chain reaction (PCR) to obtain baseline mean values of Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Candida albicans (C. albicans), and Candida dubliniensis (C. dubliniensis) before full mouth rehabilitation was done under general anesthesia. Posttreatment samples were collected at 6, 12, and 18 months. Wilcoxon signed-rank test was used to compare the mean values of S. mutans, S. sobrinus, C. albicans, and C. dubliniensis before and after full mouth rehabilitation. Results: A total of 60 patients recruited for the study were present at the follow-up at 6 and 12 months. At 18 months, 55 patients returned, and five were lost due to follow-up. A statistically significant reduction was seen in all microorganisms at 6, 12, and 18 months compared to baseline values. At 18 months a slight increase in S. mutans, S. sobrinus, and C. albicans was seen. C. dubliniensis was not detected in any cases after full mouth rehabilitation. Caries recurrence was seen in four patients at 18 months. Conclusion: Significant reduction of S. mutans, S. sobrinus, C. albicans, and C. dubliniensis was seen at 6, 12, and 18 months. A complete reduction of only C. dubliniensis was seen. A significant but not permanent reduction of S. mutans, S. sobrinus, and C. albicans. Caries recurrence was seen in 7.27% of patients at 18 months. How to cite this article: Mathew MG, Jeevanandan G, Rathod NN. Evaluation of Changes in Oral Microflora in Children with Early Childhood Caries after Full Mouth Rehabilitation. Int J Clin Pediatr Dent 2024;17(1):21-25.

Screening and Phasewise Management of Burn Injuries.

Thermal, electrical, chemical, or electromagnetic radiation can cause painful wounds or burns. Spilling hot liquids onto the skin can also cause these kinds of injuries. The two biggest factors contributing to burn injuries in the elderly are smoking and exposure to open flames, while scalding is the primary cause of burn damage in children. Newborns and the elderly make up the majority of burn casualties. In India, there are estimated to be 6-7 million burn cases per year. The high incidence is attributed to the population's illiteracy, poverty, and lack of awareness of safety. The problem is made much worse by the fact that basic and secondary healthcare levels do not provide systematic burn care. Coagulation necrosis is caused by denaturing proteins due to heat from burns. Platelets clump together, arteries narrow, and partly perfused tissue (called the stasis zone) may spread out around the wound. In the stasis zone, tissue is hyperemic and inflammatory. When the skin's natural barrier is breached, microorganisms can enter the body and cause poor temperature regulation, fluid loss, and invasion. Intravascular volume loss is typically worsened by injured or edematous tissues. Significant heat loss may occur from the wounded dermis' lack of thermoregulation, particularly in exposed wounds. The severity determines the different treatments. Serious burns require considerable care, while lesser burns just require cleaning and painkillers. Just-partially thickened burns must be cleansed with soap and water before being clothed. For full-thickness burns, surgery, including skin grafting, is frequently required. Extensive intravenous fluid doses are often required to treat serious burns resulting from tissue edema and capillary fluid leakage.

Kenya's experience implementing event-based surveillance during the COVID-19 pandemic.

Event-based surveillance (EBS) can be implemented in most settings for the detection of potential health threats by recognition and immediate reporting of predefined signals. Such a system complements existing case-based and sentinel surveillance systems. With the emergence of the COVID-19 pandemic in early 2020, the Kenya Ministry of Health (MOH) modified and expanded an EBS system in both community and health facility settings for the reporting of COVID-19-related signals. Using an electronic reporting tool, m-Dharura, MOH recorded 8790 signals reported, with 3002 (34.2%) verified as events, across both community and health facility sites from March 2020 to June 2021. A subsequent evaluation found that the EBS system was flexible enough to incorporate the addition of COVID-19-related signals during a pandemic and maintain high rates of reporting from participants. Inadequate resources for follow-up investigations to reported events, lack of supportive supervision for some community health volunteers and lack of data system interoperability were identified as challenges to be addressed as the EBS system in Kenya continues to expand to additional jurisdictions.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study.

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

How general practitioners and patients discuss type 2 diabetes mellitus and cardiovascular diseases concerns during consultations: Implications for digital health.

Objective: To analyse general practitioner-patient consultations about type 2 diabetes mellitus or cardiovascular diseases and describe (i) the nature of self-management discussions; (ii) actions required from patients during and after consultation regarding self-management; and (iii) implications for digital health to support patients during (and after) consultation. Method: This study screened 281 general practitioner consultations conducted in 2017 within the UK general practice setting from an existing dataset containing videos and transcripts of consultations between GPs and patients. Secondary analysis was conducted using a multi-method approach, including descriptive, content, and visualisation analysis, to inform the nature of self-management discussions, what actions are required from patients, and whether digital technology was mentioned during the consultation to support self-management. Results: Analysis of eligible 19 consultations revealed a discord between what self-management actions are required of patients during and after consultations. Lifestyle discussions are often discussed in depth, but these discussions rely heavily on subjective inquiry and recall. Some patients in these cohorts are overwhelmed by self-management, to the detriment of their personal health. Digital support for self-management was not a major topic of discussion, however, we identified a number of emergent gaps where digital technology can support self-management concerns. Conclusion: There is potential for digital technology to reconcile what actions are required of patients during and after consultations. Furthermore, a number of emergent themes around self-management have implications for digitalisation.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

A Versatile Prison Psychiatric Pharmacy Program.

BACKGROUND: Before the coronavirus disease 2019 (COVID-19) pandemic, 20% of the adult population in the United States experienced mental illness annually. Since the COVID-19 pandemic, 93% of countries have reported disruptions to mental health services. The demand for services is high whereas infrastructure and qualified professionals are appallingly low. Health care in the correctional setting is unique, where mental illness prevalence is double than that in the community. The intersection of policies and procedures and the beneficence plus nonmaleficence responsibility of health care professionals is exceptionally complex. Studies have shown the potential benefits of pharmacists following patients in chronic care psychiatry visits. OBJECTIVES: An inpatient psychiatric pharmacy clinic was launched to fill gaps to provide safe and up-to-date patient-centric services for more than 240 extremely psychiatrically ill inmate patients at the Federal Correctional Center Butner (FCC Butner), a Federal Bureau of Prisons medical center. METHODS: The inpatient psychiatric pharmacist practiced independently under a collaborative practice agreement and completed mental health clinical visits for a revolving portion of 240 inpatient mental health inmate patients at FCC Butner. The pharmacist provided ancillary services including completing movement disorder testing, monitoring narrow therapeutic index medication laboratory test results, and executing an antipsychotic psychoeducation meeting with other health care departments and inmate patients. RESULTS: Notably, 74% of patients monitored in the specialty program experienced stable or improved symptoms of depression, schizophrenia, and bipolar disorder. Adverse effects, particularly psychiatric-related movement disorders, were also more closely managed. Finally, 43% of the total inmate patient population who previously declined psychiatric medication treatment consented to begin treatment after participation in a pilot antipsychotic psychoeducation meeting. CONCLUSION: The inpatient psychiatric pharmacy program at FCC Butner is a dynamic program that has bolstered the facility's health care mission. The services detailed in this article can be applied to other correctional environments that have a medical outpatient or inpatient presence.

Botulinum Toxin Injection for Masseteric Hypertrophy Using 6 Point Injection Technique - A Case Report. Proposal of a Clinical Technique to Quantify Prognosis.

Introduction: Masseter hypertrophy presents as unilateral or bilateral swellings over the ramus and angle of the mandible. It is caused by malocclusion, clenching, TMJ disorders, etc and alters facial symmetry, leading to discomfort and negative cosmetic impact in many patients, making this a popular request for aesthetic and functional correction. Materials and Methods: This case report involves injecting Botulinum toxin into 6 equidistant bulging points on the masseter. Standardized photography and clinical parameters were used to assess facial contour and masseter muscle thickness at baseline and successive follow ups. Results and Discussion: Significant masseteric bulk reduction was observed in subsequent follow ups. Conclusion: The 6-point technique was found to be an effective treatment modality for Botox injection in masseteric hypertrophy. The clinical method to quantify prognosis was easy and economical.

Factors Associated With Receiving Longer Than Recommended Therapy Among Culture-Negative Pulmonary Tuberculosis Patients.

Background: US tuberculosis (TB) guidelines recommend treatment ≥6 months with a regimen composed of multiple effective anti-TB drugs. Since 2003, a 4-month regimen for a specific subset of TB patients has also been recommended. Methods: We used 2011-2018 US National Tuberculosis Surveillance System data to characterize factors associated with 4-month (111-140 days) therapy among adult patients who had completed treatment and were potentially eligible at that time for 4-month therapy (culture-negative pulmonary-only TB, absence of certain risk factors, and initial treatment that included pyrazinamide). We used modified Poisson regression with backward elimination of main effect variables to calculate adjusted relative risks (aRRs). Results: During 2011-2018, 63 393 adults completed TB treatment: 5560 (8.8%) were potentially eligible for 4-month therapy; of these, 5560 patients (79%) received >4-month therapy (median, 193 days or ∼6 months). Patients with cavitary disease were more likely to receive >4-month therapy (aRR, 1.10; 95% CI, 1.07-1.14) vs patients without cavitary disease. Patients more likely to receive 4-month therapy included patients treated by health departments vs private providers only (aRR, 0.94; 95% CI, 0.91-0.98), those in the South and West vs the Midwest, non-US-born persons (aRR, 0.95; 95% CI, 0.91-0.99) vs US-born persons, and aged 25-64 years vs 15-24 years. Conclusions: Most patients potentially eligible for 4-month therapy were treated with standard 6-month courses. Beyond clinical eligibility criteria, other patient- and program-related factors might be more critical determinants of treatment duration.

Nucleic acid therapies for CNS diseases: Pathophysiology, targets, barriers, and delivery strategies.

Nucleic acid therapeutics have emerged as one of the very advanced and efficacious treatment approaches for debilitating health conditions, including those diseases affecting the central nervous system (CNS). Precise targeting with an optimal control over gene regulation confers long-lasting benefits through the administration of nucleic acid payloads via viral, non-viral, and engineered vectors. The current review majorly focuses on the development and clinical translational potential of non-viral vectors for treating CNS diseases with a focus on their specific design and targeting approaches. These carriers must be able to surmount the various intracellular and extracellular barriers, to ensure successful neuronal transfection and ultimately attain higher therapeutic efficacies. Additionally, the specific challenges associated with CNS administration also include the presence of blood-brain barrier (BBB), the complex pathophysiological and biochemical changes associated with different disease conditions and the existence of non-dividing cells. The advantages offered by lipid-based or polymeric systems, engineered proteins, particle-based systems coupled with various approaches of neuronal targeting have been discussed in the context of a variety of CNS diseases. The possibilities of rapid yet highly efficient gene modifications rendered by the breakthrough methodologies for gene editing and gene manipulation have also opened vast avenues of research in neuroscience and CNS disease therapy. The current review also underscores the extensive scientific efforts to optimize specialized, efficacious yet non-invasive and safer administration approaches to overcome the therapeutic delivery challenges specifically posed by the CNS transport barriers and the overall obstacles to clinical translation.

Tumor-targeted miRNA nanomedicine for overcoming challenges in immunity and therapeutic resistance.

miRNA are critical messengers in the tumor microenvironment (TME) that influence various processes leading to immune suppression, tumor progression, metastasis and resistance. Strategies to modulate miRNAs in the TME have important implications in overcoming these challenges. However, miR delivery to specific cells in the TME has been challenging. This review discusses nanomedicine strategies to achieve cell-specific delivery of miRNAs. The key goal of delivery is to activate the tumor immune landscape as well as to prevent chemotherapy resistance. Specifically, the use of hyaluronic acid-based nanoparticle miRNA delivery to the TME is discussed. The discussion is focused on miRNA-125b for reprogramming tumor-associated macrophages to overcome immunosuppression and miRNA-let-7b to overcome resistance to anticancer chemotherapeutics because both these miRNAs have been extensively evaluated for delivery with hyaluronic acid-based delivery systems.

miRNAs are the messenger molecules with the tumor that have significant influence on the cancer growth and progression. Many strategies have been evaluated to modulate these messengers artificially to obstruct cancer growth and destroy cancer cells. This review discusses one such strategy to deliver these messenger miRNAs using hyaluronic acid-based nanoparticles that harness the body's own immune system to fight cancer. The two miRNAs that this review discusses are miRNA-125b and miRNA-let7b.

Recent advances in the use of high flow nasal oxygen therapies.

High flow nasal oxygen is a relatively new option for treating patients with respiratory failure, which decreases work of breathing, improves tidal volume, and modestly increases positive end expiratory pressure. Despite well-described physiologic benefits, the clinical impact of high flow nasal oxygen is still under investigation. In this article, we review the most recent findings on the clinical efficacy of high flow nasal oxygen in Type I, II, III, and IV respiratory failure within adult and pediatric patients. Additionally, we discuss studies across clinical settings, including emergency departments, intensive care units, outpatient, and procedural settings.

Predictors of Respiratory Support Use in Emergency Department Patients With COVID-19-Related Respiratory Failure.

BACKGROUND: Given the known downstream implications of choice of respiratory support on patient outcomes, all factors influencing these decisions, even those not limited to the patient, warrant close consideration. We examined the effect of emergency department (ED)-specific system factors, such as work load and census, on the use of noninvasive versus invasive respiratory support. METHODS: We conducted a multi-center retrospective cohort study of all adult subjects with severe COVID-19 requiring an ICU admission from 5 EDs within a single urban health care system. Subject demographics, severity of illness, and the type of respiratory support used were obtained. Using continuous measures of ED census, boarding, and active management, we estimated ED work load for each subjects' ED stay. The subjects were categorized by type(s) of respiratory support used: low-flow oxygen, noninvasive respiratory support (eg, noninvasive ventilation [NIV] and/or high-flow nasal cannula [HFNC]), invasive mechanical ventilation, or invasive mechanical ventilation after trial of NIV/HFNC. We used multivariable logistic regression to examine system factors associated with the type of respiratory support used in the ED. RESULTS: A total of 634 subjects were included. Of these, 431 (70.0%) were managed on low-flow oxygen alone, 108 (17.0%) on NIV/HFNC, 54 (8.5%) on invasive mechanical ventilation directly, and 41 (6.5%) on NIV/HFNC prior to invasive mechanical ventilation in the ED. Higher severity of illness and underlying lung disease increased the odds of requiring invasive mechanical ventilation compared to low-flow oxygen (odds ratio 1.05 [95% CI 1.03-1.07] and odds ratio 3.47 [95% CI 1.37-8.78], respectively). Older age decreased odds of being on invasive mechanical ventilation compared to low-flow oxygen (odds ratio 0.96 [95% CI 0.94-0.99]). As ED work load increased, the odds for subjects to be managed initially with NIV/HFNC prior to invasive mechanical ventilation increased 6-8-fold. CONCLUSIONS: High ED work load was associated with higher odds on HFNC/NIV prior to invasive mechanical ventilation.

Estimating COVID-19 Hospitalizations in the United States With Surveillance Data Using a Bayesian Hierarchical Model: Modeling Study.

BACKGROUND: In the United States, COVID-19 is a nationally notifiable disease, meaning cases and hospitalizations are reported by states to the Centers for Disease Control and Prevention (CDC). Identifying and reporting every case from every facility in the United States may not be feasible in the long term. Creating sustainable methods for estimating the burden of COVID-19 from established sentinel surveillance systems is becoming more important. OBJECTIVE: We aimed to provide a method leveraging surveillance data to create a long-term solution to estimate monthly rates of hospitalizations for COVID-19. METHODS: We estimated monthly hospitalization rates for COVID-19 from May 2020 through April 2021 for the 50 states using surveillance data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) and a Bayesian hierarchical model for extrapolation. Hospitalization rates were calculated from patients hospitalized with a lab-confirmed SARS-CoV-2 test during or within 14 days before admission. We created a model for 6 age groups (0-17, 18-49, 50-64, 65-74, 75-84, and ≥85 years) separately. We identified covariates from multiple data sources that varied by age, state, and month and performed covariate selection for each age group based on 2 methods, Least Absolute Shrinkage and Selection Operator (LASSO) and spike and slab selection methods. We validated our method by checking the sensitivity of model estimates to covariate selection and model extrapolation as well as comparing our results to external data. RESULTS: We estimated 3,583,100 (90% credible interval [CrI] 3,250,500-3,945,400) hospitalizations for a cumulative incidence of 1093.9 (992.4-1204.6) hospitalizations per 100,000 population with COVID-19 in the United States from May 2020 through April 2021. Cumulative incidence varied from 359 to 1856 per 100,000 between states. The age group with the highest cumulative incidence was those aged ≥85 years (5575.6; 90% CrI 5066.4-6133.7). The monthly hospitalization rate was highest in December (183.7; 90% CrI 154.3-217.4). Our monthly estimates by state showed variations in magnitudes of peak rates, number of peaks, and timing of peaks between states. CONCLUSIONS: Our novel approach to estimate hospitalizations for COVID-19 has potential to provide sustainable estimates for monitoring COVID-19 burden as well as a flexible framework leveraging surveillance data.