Correlation of Quality Metrics of Acute Stroke Care with Clinical Outcomes in an Indian Tertiary-care University Hospital: A Prospective Evidence-based Study.

Aim: To characterize the impact of adherence to quality metrics of stroke care on the clinical outcomes of ischemic stroke (IS) and intracerebral hemorrhage (ICH) admissions. Methods: Consecutive patients with acute stroke were prospectively followed up for their demographic and clinical characteristics, acute stroke management, and associated clinical outcomes at discharge. Stroke quality metrics [adopted from the American Heart Association (AHA)/American Stroke Association's Get with The Guidelines (GWTG)] with a specific interest in an association between acute reperfusion therapies and functional recovery in stroke patients are analyzed and presented. A composite measure of care was considered "0 (non-adherence) to 1 (adherence)." An all-or-none measure of care was calculated to check whether eligible patients received all the quality-of-care interventions. Multivariate Cox regression models were used to study an association between optimal adherence and clinical outcomes. Results: During the study period, of the total 256 stroke admissions, 200 (78.1%) patients had IS, and the remaining 56 (21.9%) patients had ICH. The median [interquartile range (IQR)] age of total stroke admissions was 57 (36-78) years. Male preponderance was observed (IS: 80% and ICH: 67.9%). The conformity of performance metrics in IS patients was from 69.1% [95% confidence interval (CI), 68.5-69.6] for the use of deep vein thrombosis prophylaxis (DVTp) to 97.8% (95% CI, 96.2-98.6) for the use of statins. In ICH patients, it ranged from 61.7% (95% CI, 60.4-62.5) for the use of DVTp to 89.9% (95% CI, 88.6-89.7) for stroke rehabilitation. The unadjusted odds ratio (OR) of mortality (in-hospital plus the 28th-day postdischarge) was higher in ICH patients vs IS patients (4.42, p = 0.005). Optimal adherence with intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy [hazards ratio (HR) = 0.23], in-hospital acute measures [IS (HR = 0.41) and ICH (HR = 0.63)], and discharge measures [IS (HR = 0.35) and ICH (HR = 0.45)] were associated with reduced hazards of the 28th-day mortality in both cohorts. Compared to ICH, IS patients had significantly improved neurofunctional recovery [modified Rankin score (mRS) ≤ 2, p < 0.01]. Conclusion: Adherence to quality metrics and performance measures was associated with low mortality and favorable clinical outcomes. Also, DVTp as an in-hospital (acute) measure of stroke care needs attention in both cerebrovascular events. How to cite this article: Panda BK, Suryawanshi VR, Attarde G, Borkar N, Iyer S, Shah J. Correlation of Quality Metrics of Acute Stroke Care with Clinical Outcomes in an Indian Tertiary-care University Hospital: A Prospective Evidence-based Study. Indian J Crit Care Med 2023;27(11):806-815.

Antitubercular therapy causing drug reaction with eosinophilia and systemic symptoms manifesting multi-organ dysfunction syndrome and death in an elderly patient: A case report with review of literature.

We present the case of a drug reaction with eosinophilia and systemic symptoms (DRESS) manifesting multi-organ dysfunction syndrome (MODS) that led to death in an elderly patient during the intensive phase of antitubercular therapy (ATT). A 74-year-old male developed skin rash (morbilliform), patchy erythematous macules, pustular-purpuric nonblanching spots, fever, lymphadenopathy, liver dysfunction, leukocytosis, and eosinophilia during intensive phase of ATT (ATT: day 45). Laboratory tests revealed hypereosinophilia (eosinophils; 10500/µL), hyperacute fulminant hepatic failure (aspartate transaminase/alanine transaminase; 1444/1375 IU/L, total bilirubin; 11.3 mg/dL), hepatic encephalopathy (Child-Pugh score: 15), coagulopathy (international normalized ratio; 3.0 and activated partial thromboplastin time; 52 s), and acute renal failure (serum creatinine; 2.6 mg/dL). The patient was diagnosed with DRESS with a RegiSCAR score of 7 (definite). ATT was discontinued. Despite immediate treatment with pulse methylprednisolone, N-acetylcysteine and sustained low-efficiency dialysis, the patient's clinical condition evolved to shock due to MODS (sequential organ failure Assessment: 15 points), and on day 51, he succumbed. Concluding, an elderly patient with high-dose antitubercular drugs needs a clinical management review. Clinical symptoms pertaining to DRESS may paradoxically worsen after 3-4 days of discontinuation of the offending drug.

Adverse events associated with Pegaspargase biosimilar in pediatric patients with acute lymphoblastic leukemia: A prospective single-center study.

BACKGROUND: While Pegaspargase is an essential component of the treatment of acute lymphoid leukemia (ALL) in children, it causes adverse events (AEs) that sometimes make full use impossible. OBJECTIVE: The objective was to investigate the safety of Pegaspargase biosimilar in pediatric ALL patients undergoing treatment according to ICiCLe ALL-14 protocol. METHOD AND MATERIALS: A prospective study was carried out in a university teaching hospital located in the state of Maharashtra, India. Data on clinical factors and adverse reaction characteristics were gathered from hospital medical records. Suspected AEs were classified according to causality and severity. RESULTS: During the study period, 72 children had 52 suspicions of AEs during treatment with biosimilar Pegaspargase. The odds ratio of 1.11 (95%CI, 0.41-2.98) suggested that males and females were both equally likely to experience adverse drug events, despite the fact that the frequency of suspected AEs was higher in boys (66%) than in girls (33%). None of the patients experienced allergic reactions. The high-risk category had the highest number of suspected AEs (56%), followed by intermediate risk (20%) and standard risk (20%). These patients showed a high frequency of suspected AEs during the induction phase (43%) followed by the consolidation phase (26%). Sixty percent of the reactions were classified as grade 1 or 2. ALL cell type (p = 0.02), risk category (p = 0.04) and length of hospitalization (p = 0.003) were significantly correlated with suspected AEs. CONCLUSION: Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe.

Compliance with status epilepticus management protocol and effect on clinical outcomes in children with status epilepticus.

BACKGROUND: Guidelines for the management of status epilepticus (SE) aid in rationalising the treatment for a better clinical outcome; however, published literature regarding the use of antiepileptics and compliance is limited, even after the availability of a consensus guideline. OBJECTIVES: To evaluate the use of antiepileptics in children with SE and to analyse the effect of compliance with the Status Epilepticus Management Protocol on clinical outcomes. METHODS: An open-label non-randomised prospective observational study was conducted in children with SE aged 1 month to 14 years for 8 months in a tertiary care teaching hospital. The recommended antiepileptics, sequence of drug administration and time frames of management offered to paediatric patients were assessed for compliance with the Status Epilepticus Management Protocol adopted in our hospital. Comparison of clinical outcomes (hospital stay, intubation, refractory and super-refractory SE, duration of SE cessation, functional motor deficits and cognitive decline) between compliant and non-compliant patients was assessed. RESULTS: A total of 40 patients were included in the study, of which 28 (70%) were boys. All the patients received midazolam nasal spray in the triage area. Only 18% of the patients received rescue benzodiazepine (BZD) antiepileptic drug (AED) therapy in pre-hospital settings. Median time (p25-p75) of administration of first-line AED (BZD) and second-line AED (non-BZD) was 11 (8-15) min and 30 (22-35) min, respectively. Administration of continuous infusion (IV midazolam) was delayed at 57 (45-69) min. Compliance with the Status Epilepticus Management Protocol was seen in 24 (60%) patients. Non-compliance with the treatment protocol in relation to the time frame significantly prolonged the length of hospital stay (9 vs 4 days, p=0.0008) and SE duration from first assessment (115 vs 50 min; p=0.005). At discharge, the proportion of patients returning to their functional baseline was significantly different in the compliant and non-compliant patient groups (79% vs 44%). There were no deaths. CONCLUSION: Rescue therapy in the pre-hospital setting needs attention. There was full compliance with the Status Epilepticus Management Protocol for choice of AED and sequence of AED therapy. Non-compliance in treatment management within time frames significantly affected the length of hospital stay, duration of SE and clinical outcome.

A Case of Cerebral Toxoplasmosis and Cryptococcosis Preferred Therapy Associated Adverse Drug Reactions in a Patient Newly Co-diagnosed with Acquired Immune Deficiency Syndrome.

PURPOSE: The simultaneous occurrence of cerebral toxoplasmosis and cryptococcosis is rare. The infections continue to be treated with sulfadiazine and amphotericin-B-based regimens (preferred therapy), respectively. Both these drugs are linked to some serious adverse drug reactions (ADRs). We report such a unique instance of both; the CNS co-infections and adverse drug reactions to the preferred therapy. CASE PRESENTATION: A 44-year-old Asian-Indian female was diagnosed with cerebral toxoplasmosis, impending cryptococcal meningoencephalitis, and acquired immune deficiency syndrome (AIDS). The preferred therapy of opportunistic CNS co-infections commenced. Within a week, she had an occurrence of fall in hemoglobin concentrations (11.3 g/dL to 5.6 g/dL; grade IV), reticulocytosis (1% to 3.2%), and indirect hyperbilirubinemia (0.5 mg/dL to 2.8 mg/dL; grade IV) after sulfadiazine administration. The drug was discontinued and the patient was treated with hematocrit transfusions. After amphotericin-B deoxycholate (AmBd) administration, the patient developed hypokalemia (serum potassium; 4.5 mmol/L to 2.7 mmol/L) and increased serum creatinine (1.0 to 2.2 mg/dL; stage-I) levels. Hence, AmBd was discontinued and potassium correction was given. The patient got diagnosed with sulfadiazine induced hemolytic anemia and AmBd induced acute renal failure. He was switched to alternative therapy regimens for the treatment of cerebral toxoplasmosis and cryptococcosis. Radiological investigations were followed up to confirm the clinical outcomes of alternative therapy. Complete recovery from the ADRs and opportunistic infections was observed. CONCLUSION: The preferred therapy regimens for toxoplasmosis and cryptococcosis are accompanied by potential adverse drug reactions, thus continuous monitoring is vital, especially in the initial phases of therapy. Discontinuation of the treatment should be the preliminary intervention in the management. Having said that, alternative therapy regimens had an optimal clinical response in the present case.

Melatonin and Triclofos Sodium to Execute Sleep Electroencephalography in Pediatric Patients: A Cost-Effectiveness Analysis Alongside a Randomized Controlled Trial.

OBJECTIVES: To evaluate cost-effectiveness between oral sedatives melatonin and triclofos sodium used to perform sleep electroencephalography (EEG) in pediatric patients and develop a criterion for resource allocation by the institution. METHODS: This prospective study was conducted alongside the randomized controlled trial conducted at a tertiary care hospital, wherein pediatric patients arriving for sleep EEG were randomized to receive melatonin dosed at 0.3 mg/kg (< 10 kg), 3 mg (10-15 kg), and 6 mg (> 15 kg) and triclofos at 50 mg/kg (maximum dose 1 g, 6 mo to 11 y; 2 g, 11 to 18 y) after due consent. The cost-effectiveness analysis was performed from the healthcare institution's perspective. Successful EEG and abnormal EEG were the effectiveness parameters. RESULTS: Two hundred twenty-eight patients were divided equally between two groups. Melatonin (N = 114) and triclofos (N = 114) recorded successful EEG in 89.4% and 91.2% patients and abnormal EEG in 49% and 42.3% patients, respectively (p > 0.05). The total direct cost incurred was INR 1881.75 (USD 26.6) and INR 2772.5 (USD 39.2) for melatonin and triclofos, respectively (p < 0.05). The cost-effectiveness ratio-1 (CER-1) for melatonin and triclofos per successful EEG recorded was INR 18.45 (USD 0.39) and INR 26.66 (USD 0.58), respectively. The CER-2 for melatonin and triclofos per abnormal EEG detected was INR 37.64 (USD 0.53) and INR 63.01 (USD 0.89), respectively. CONCLUSIONS: Melatonin is more cost-effective than triclofos when charged based on individual dose requirements. Hospitals, diagnostic centers, healthcare institutions may consider resource-utilization-based costing system for cost-effective allocation of resources.

Plasma drug concentrations of 4-drug fixed-dose combination regimen and its efficacy for treatment of pulmonary tuberculosis under National Tuberculosis Elimination Programme: A prospective pilot study.

BACKGROUND: The thrice weekly dosing regimen of DOTS has shown low rifampicin plasma concentrations as an independent risk factor for unfavourable tuberculosis (TB) outcome. With introduction of daily regimen using fixed dose combinations (FDC) under National Tuberculosis Elimination Programme (NTEP) the existence of suboptimal plasma levels of first-line antitubercular drugs and its clinical significance remain poorly understood. METHOD: We included a prospective cohort of newly diagnosed pulmonary tuberculosis (PTB) patients receiving 4-FDC daily regimen under NTEP. Plasma concentration at 2 hours (C2h) of each drug was determined after two weeks of treatment using liquid chromatography (LCMS/MS) developed by us. TB card and laboratory reports were reviewed for baseline characteristics and clinical status at 2, 4 and 6 months after the initiation of treatment. At a 1 year follow-up, therapy failure was defined as death or a relapse of tuberculosis. RESULTS: Among 40 PTB patients, the C2h post dose plasma concentrations of H, R and E were suboptimal in 25%, 60% and 10% respectively. The C2h of H, R, Z and E were respectively 4.2 ± 2.0, 7.3 ± 2.8, 39.2 ± 8.8 and 3.5 ± 1.2 µg/ml; 60% of the patients had suboptimal plasma concentrations and commonly it was observed with H and R. C2h were lower than expected for at least two drugs i.e. H and R in 25% (10/40) of the patients. Plasma concentration of isoniazid and rifampicin has always been considered important for microbiological response and treatment outcome and low concentrations has been associated with poor treatment response. These patients may require a two year follow up and critical evaluation for prevention of MDR-TB. However, all the TB patients were cured and none of them had recurrence within one year follow up. CONCLUSIONS: All the pulmonary TB patients administering 4-FDC daily regimen under programmatic settings were cured despite the suboptimal levels of isoniaizd and rifampicin. All the patients achieved pyrazinamide plasma levels and probably this could be the reason behind favourable outcome. Further study is required on large sample size with various subset of population to understand the need of therapeutic drug monitoring.

Time Elapsed from Onset of Pediatric Convulsive Status Epilepticus to Antiepileptic Administration-An Experience of Single Institute.

Data regarding time elapsed from the onset of pediatric convulsive status epilepticus (CSE) to antiepileptic (AED) administration remains scarce after the adoption of standard treatment-guidelines in Indian healthcare settings. A prospective observational analysis was performed on 52 children presenting to an urban, academic tertiary care teaching hospital diagnosed with CSE and evolving to refractory CSE (RCSE). Time frames of AED administration were compared to the adopted 'Status Epilepticus Management Protocol'. Fifty-two patients [36 (69.2%) male] were enrolled, with a median age of 4.1 y. After CSE onset, the median (p25-p75) time until the administration of the first-line, second-line, and third-line therapy phases of AED doses were 30 (25-37) min, 68 (48-79) min, and 105 (100-135) min, respectively. The second dose of non-BZD AED was administered at a median (p25-p75) of 90 (71-95) min. Twenty-six (50%) patients received at least one continuous infusion. The time elapsed from CSE onset to AED administration and escalation from one class to another was delayed.

Efficacy and tolerability of Melatonin vs Triclofos to achieve sleep for pediatric electroencephalography: A single blinded randomized controlled trial.

PURPOSE: To compare Melatonin with Triclofos for efficacy (proportion of successful EEG, need of augmentation, sleep onset latency (SOL), yield of discharges, duration of sleep, presence and grade of artifacts) and tolerability (adverse effect profile). METHODS: A randomized trial was performed (block randomization). All children were advised regarding sleep deprivation, EEG technician administered the drug. EEG was labelled successful if at least 30 min of record could be obtained (sleep with or without awake state). Pediatric neurologist reported the EEG findings-sleep onset latency, epileptiform abnormalities and graded the artifacts (excess beta activity and movement artifacts if present). The parents were interviewed telephonically next day by a pediatric resident for any adverse effects. The parents, pediatric neurologist and pediatric resident were blinded for the drug given. RESULTS: 228 children were randomized (114 each received Melatonin and Triclofos). Both the groups were comparable at baseline for age group and demographic data. The proportion of successful EEG was 89.4% in Melatonin and 91.2% in Triclofos. First dose was effective in 64% in Melatonin and 63.15% in Triclofos group. Augmentation dose was needed in 25.4% in Melatonin and 28% in Triclofos group. Mean total sleep duration was 80 min after Melatonin and 82.39 after Triclofos administration. Adverse effects were observed in 6.14% of Melatonin and 8.65% of Triclofos group. None of the results were statistically significant. CONCLUSION: There was no significant difference between efficacy and tolerability of Melatonin and Triclofos. Melatonin can be safely used to achieve sleep for EEG in children.

A simple and reliable analytical method for simultaneous quantification of first line antitubercular drugs in human plasma by LCMS/MS.

The present study describes the optimization of a simple and reliable method for the determination of four first line antitubercular drugs in human plasma. The studied analytes were isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) in fixed dose combination recommended to patients under the Revised National Tuberculosis Control Programme (RNTCP, India). The analytes were extracted from the human plasma (150 µL) using the single step liquid-liquid extraction approach and were analyzed by liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS). The method was fully validated, according to USFDA guidelines. A linear range of 0.05-10 µg mL-1, 0.1-20 µg mL-1, 0.5-100 µg mL-1 and 0.05-10 µg mL-1 for H, R, Z and E respectively was established, presenting determination coefficients above 0.99. Concerning imprecision, the CV was lower than 15% for all analytes. All tested analytes were found to be stable in the samples. Although the values obtained for recovery were above 85%, the method proved to be sensitive, since low detection limits of 0.05 µg mL-1 for H and E, 0.1 µg mL-1 for R and 0.5 µg mL-1 for Z were obtained. The intra-day and inter-day accuracy and imprecision were within CV ±15%. The use of the conventional silica column in the extraction of these compounds through a single step protein precipitation method simplifies the analytical process. In addition due to its simplicity and sensitivity, it can be applied to carry out therapeutic drug monitoring and drug level assessment in human plasma samples. The results of analyte levels are comparable to other reported methods. The method had been successfully applied for simultaneous determination of first line anti-tubercular drugs in pulmonary tubercular patients. The method requires 150 µL of patient plasma and offers low volume for injection (10 µL) and blood sample collection (3 mL) which will be an added advantage for pediatric anti-TB drug level assessment and monitoring.