Prediction of Weaning Outcome from Mechanical Ventilation Using Ultrasound Assessment of Parasternal Intercostal Muscle Thickness.

Background: Monitoring the function of parasternal intercostal muscles provides information on respiratory load and capacity and thus can be a weaning monitoring tool. Objective: The goal was to study the diagnostic accuracy of parasternal intercostal muscle thickness fraction (PICTF%) as a predictor of weaning. Materials and methods: A prospective observational study on consecutively admitted patients who were intubated and mechanically ventilated for a duration of at least 48 hours was carried out. When an SBT was planned by the treating physician, the study examiner performed the ultrasound measurements of parasternal intercostal muscle thickness (inspiration and expiration) and thickening fraction using M-mode ultrasonography (USG). The PICTF% was calculated as "(peak inspiratory thickness - end-expiratory thickness)/end-expiratory thickness) × 100." Weaning failure was defined if the patient had a failed spontaneous breathing trial (SBT) or the need for a reintubation within 48 hours following extubation. The SBT failure was defined as the need to connect the patient back to the ventilator prior to its completion due to any reason as decided by the clinician. Results: Of 81 screened patients, 60 patients met the inclusion criteria, of whom 49 patients had successful SBT, and 48 patients could be successfully extubated. The PMTF% cut-off value more than or equal to 15.38% was associated with the best sensitivity (75%) and specificity (87.8%) in predicting extubation failure. Conclusion: The PICTF% has a good diagnostic accuracy in predicting weaning failure. How to cite this article: Ramaswamy A, Kumar R, Arul M, Ish P, Madan M, Gupta NK, et al. Prediction of Weaning Outcome from Mechanical Ventilation Using Ultrasound Assessment of Parasternal Intercostal Muscle Thickness. Indian J Crit Care Med 2023;27(10):704-708.

Assessment of Effects of Investigational TAK-931, an Oral Cell Division Cycle 7 Kinase Inhibitor on the QTc Intervals in Patients With Advanced Solid Tumors.

TAK-931, a novel, selective, small-molecule inhibitor of cell division cycle 7 has been investigated in multiple clinical trials in patients with advanced solid tumors. An integrated analysis using data from 2 clinical studies assessed effects of TAK-931 on electrocardiogram QT intervals and heart rate (HR). Pharmacokinetic samples and matched triplicate electrocardiogram data were collected in 48 patients with cancer receiving oral administration of TAK-931 50 or 80 mg once daily. The relationships between TAK-931 plasma concentrations and the HR-corrected QT interval via Fridericia (QTcF) or population (QTcP) and HR were analyzed using linear mixed-effects models with fixed effects for day and time. At the geometric mean maximum TAK-931 plasma concentrations after administration of 50 mg, an HR change of 3.40 beats per minute (90%CI, 1.86-4.80) was predicted. Change in QTcF of -3.41 milliseconds (90%CI, -5.77 to -1.17) and QTcP of -2.02 milliseconds (90%CI, -4.15 to 0.0679) were estimated, indicating there was no effect of TAK-931 on the QT intervals at a recommended phase 2 dose of 50 mg once daily for 14 days in a 21-day cycle.

Assessment of airway reversibility in asthmatic children using forced oscillation technique - A single-center experience from North India.

BACKGROUND: Lung function testing is recommended for the management of asthma. Due to certain limitations of conventional spirometry in vulnerable patients, forced oscillation technique (FOT) has been studied with promising results. As there is a paucity of data from developing world, we planned to conduct this study in children using FOT. To assess airway reversibility after inhaled salbutamol in asymptomatic children with suspected asthma. SETTINGS: This study was conducted at pediatric asthma clinic of a tertiary care referral hospital in North India. DESIGN: This was a prospective interventional study over 1-year period. SUBJECTS AND METHODS: Asymptomatic children between 2 and 18 years of age, with history suggestive of asthma, were eligible for participation. Baseline and postbronchodilator pulmonary functions were assessed using FOT. Airway resistance and reactance were monitored at various frequencies. SPSS version 17 was used for statistical analysis. RESULTS: Among the 345 enrolled children, baseline mean ± standard deviation total airway resistance (R5), central airway resistance (R19), peripheral airway resistance (R5-R19), reactance (X5), and resonant frequency (Fres) were 6.85 ± 2.60, 5.23 ± 1.93, 1.6 ± 1.16, and - 2.54 ± 1.36 cmH2O/L/s and 17.28 ± 3.06 Hz. The median (interquartile range) percentage change after inhaled salbutamol was 19.9 (11.40, 29.12), 22.86 (6.88, 38.76), 14.08 (3.40, 22.62), 39.20 (8.20, 62.39), and 15.79 (8.33, 27.27) in respective parameters. All changes were statistically significant. The studied respiratory variables were in maximum negative correlation with height, followed by body mass index. CONCLUSIONS: FOT is a simple technique for monitoring lung functions in children during asthma management.

Early trends of socio-economic and health indicators influencing case fatality rate of COVID-19 pandemic.

Coronavirus disease 2019, i.e. COVID-19, started as an outbreak in a district of China and has engulfed the world in a matter of 3 months. It is posing a serious health and economic challenge worldwide. However, case fatality rates (CFRs) have varied amongst various countries ranging from 0 to 8.91%. We have evaluated the effect of selected socio-economic and health indicators to explain this variation in CFR. Countries reporting a minimum of 50 cases as on 14th March 2020, were selected for this analysis. Data about the socio-economic indicators of each country was accessed from the World bank database and data about the health indicators were accessed from the World Health Organisation (WHO) database. Various socioeconomic indicators and health indicators were selected for this analysis. After selecting from univariate analysis, the indicators with the maximum correlation were used to build a model using multiple variable linear regression with a forward selection of variables and using adjusted R-squared score as the metric. We found univariate regression results were significant for GDP (Gross Domestic Product) per capita, POD 30/70 (Probability Of Dying Between Age 30 And Exact Age 70 From Any of Cardiovascular Disease, Cancer, Diabetes or Chronic Respiratory Disease), HCI (Human Capital Index), GNI(Gross National Income) per capita, life expectancy, medical doctors per 10000 population, as these parameters negatively corelated with CFR (rho = -0.48 to -0.38 , p<0.05). Case fatality rate was regressed using ordinary least squares (OLS) against the socio-economic and health indicators. The indicators in the final model were GDP per capita, POD 30/70, HCI, life expectancy, medical doctors per 10,000, median age, current health expenditure per capita, number of confirmed cases and population in millions. The adjusted R-squared score was 0.306. Developing countries with a poor economy are especially vulnerable in terms of COVID-19 mortality and underscore the need to have a global policy to deal with this on-going pandemic. These trends largely confirm that the toll from COVID-19 will be worse in countries ill-equipped to deal with it. These analyses of epidemiological data are need of time as apart from increasing situational awareness, it guides us in taking informed interventions and helps policy-making to tackle this pandemic.

Recent Developments in Heterogeneous Catalytic Routes for the Sustainable Production of Succinic Acid from Biomass Resources.

Succinic acid is a "hot molecule" identified by United States Department of Energy as a substitute for petrochemicals with great scope for its production from biomass. It is used as an intermediate for the production of a huge variety of everyday consumer products with an addressable market share of billions of dollars. Succinic acid and its derivatives are mainly used as pharmaceuticals, adhesives, solvents, intermediates for polymer synthesis, and food additives. Succinic acid is commercially produced from petrochemicals and there is a deficiency of economically viable catalytic processes for its large-scale production from biomass. Recently, a lot of biochemical routes have been devised to enhance its production from biomass resources, but such processes are time-consuming and involve tedious separation procedures. Therefore, this Review focuses on metal-based and metal-free heterogeneous catalytic routes for the synthesis of succinic acid from biomass derived products. The presence of uniform channels, cavities, active sites of various strengths, and the unique surface structure of the heterogeneous catalysts are a few of the interesting features that promote their use in industrial processes.

Allergy Testing - An Overview.

Childhood allergies pose huge economic burden and adverse effects on quality of life. Serum IgE has been considered a surrogate allergy marker for decades. Availability of several over-the-counter allergy tests add to confusion of partially trained caregivers. The present review focuses on current status of allergy testing in Indian scenario. Various in-vitro and in-vivo diagnostic modalities are available for allergy detection. Skin prick tests are useful for aero-allergies whereas oral challenge tests are best for identifying suspected food allergies. An allergy test should be individualized based on clinical features, diagnostic efficacy, and cost-benefit analysis.

A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.

Obstructive Sleep Apnea in Bronchial Asthma Patients: Assessment of Prevalence and Risk Factors.

BACKGROUND: Sleep-related breathing disorders are group of respiratory disease among them obstructive sleep apnea (OSA) is highly prevalent and seen among those having recognized risk factors. Recent studies have shown that asthma and OSA contribute bi directional relationship where each disorder adversely influences the other one. This study was planned to assess OSA among bronchial sthma patients. METHODOLOGY: This study was conducted at Sleep lab of our department among adult patients of bronchial asthma after institutional ethical committee approval. Eligible and willing to participate patients were subjected to clinical assessment protocol that included history, clinical examination, measurement of Sleep Score, BMI, neck circumference etc followed by overnight Level 1 polysomnography. RESULTS: 50 patients with age range 30 to 68 years constituted the study population with mean age of 48.16 years. 70% patients were female with male female ratio of 1:2.3. The prevalence of OSA in asthma patients was 46%. 12% patients had mild OSA, 14% had moderate while 20% were having severe OSA. Mean BMI in our study was 27.87 Kg/m2 . OSA patients were associated with more BMI compared to patients without OSA (42% vs. 30%) (p value 0.04). Asthma patients who were smokers had more OSA symptoms compared to non-smokers (p value 0.002). Asthma patients with OSA were also associated with higher neck circumference and more snoring at night time as compared to non OSA population. Uncontrolled asthma was seen in 18 patients and 16 of them were having OSA (p=0.001). Most common co morbid illness in patients with OSA was GERD (78.26%) followed by allergic rhinitis (56%). Most of these patients (82%) were not having associated major local anatomical defect. CONCLUSION: :OSA is not uncommon in asthma patients. Careful assessment of sleep related symptoms and demographic parameters of asthma patients are essential to suspect diagnosis of OSA. Additional factors like smoking, obesity, GERD and allergic rhinitis are important contributing factor for higher risk of OSA among asthma patients. Early diagnosis of OSA in asthma patients by polysomnography may have a clinical benefit in the management of both diseases.

Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients.

BACKGROUND: Ixazomib is the first oral, proteasome inhibitor to reach phase III trials. Here, we present an integrated nonclinical and clinical assessment of ixazomib's effect on QTc intervals. METHODS: Nonclinical studies assessed (1) the in vitro binding of ixazomib to the hERG channel and (2) its effect on QT/QTc in dogs (N = 4) via telemetry. Pharmacokinetic-matched triplicate electrocardiograms were collected in four clinical phase I studies of intravenous (0.125-3.11 mg/m(2), N = 125, solid tumors/lymphoma) or oral (0.24-3.95 mg/m(2), N = 120, multiple myeloma) ixazomib. The relationship between ixazomib plasma concentration and heart rate (HR)-corrected QT using Fridericia (QTcF) or population (QTcP) methods was analyzed using linear mixed-effects models with fixed effects for day and time. RESULTS: In vitro binding potency for ixazomib to the hERG channel was weak (K i 24.9 µM; IC50 59.6 µM), and nonclinical telemetry studies showed no QT/QTc prolongation at doses up to 4.2 mg/m(2). In cancer patients, ixazomib, when evaluated at doses yielding various plasma concentrations (with 26 % of data greater than mean C max for the 4 mg phase 3 dose), had no meaningful effect on QTc based on model-predicted mean change in QTcF/QTcP from baseline. There was no relationship between ixazomib concentration and RR, suggesting no effect on HR. CONCLUSIONS: Ixazomib has no clinically meaningful effects on QTc or HR. Integrating preclinical data and concentration-QTc modeling of phase 1 data may obviate the need for a dedicated QTc study in oncology. A framework for QT assessment in oncology drug development is proposed.

Comparative assessment of sagittal skeletal discrepancy: a cephalometric study.

BACKGROUND AND OBJECTIVES: Evaluating the sagittal apical base relationship during orthodontic diagnosis and treatment planning is an important step. This study was aimed at comparison of Beta angle, ANB angle and Wit's appraisal for assessment of sagittal skeletal discrepancy. MATERIALS AND METHODS: Eighty six young adults (43 female and 43 male) were selected from the patient's reporting to Department of Orthodontics, College of Dental Sciences, Davangere, India. Family lineage was studied to know the nativity of Davangere. The standardized pre-treatment lateral cephalogram of the chosen sample was traced. The sample was divided into three skeletal pattern groups: Class I, Class II and Class III, based on the ANB angle and profile, Beta angle was assessed in each group. STATISTICAL ANALYSIS: The data was subjected to statistical analysis student's t-test, ANOVA test and correlation and regression analysis, using the software namely SPSS Software version 13. Microsoft word and Excel were used to generate graphs and tables. RESULTS: In the local Davangere population, Class I skeletal pattern group exhibited Beta angle between 26°-34°, Beta angle less than 27° was found in Class II skeletal pattern, and Beta angle greater than 32° was seen Class III skeletal pattern. The coefficient of variation of Beta angle in all the three groups was significantly homogenous compared to ANB angle and Wits appraisal. The correlation and regression analysis of the total sample indicated a highly significant correlation between Beta angle and ANB angle (p<.001), and between Beta angle and Wits appraisal (p<.01). CONCLUSION: Beta angle can be used to classify subjects into different skeletal patterns. The Correlation and regression analysis for the total sample suggests a highly significant relation between Beta angle and ANB angle and, between Beta angle and Wits appraisal. It can be more reliably used to assess sagittal jaw discrepancies than ANB angle and Wits appraisal.

Hering's Law Assessment Tool revisited: introducing a modified novel version--Patients' Response Assessment Tool after Homeopathic Treatment (PRATHoT) in chronic cases.

Hering's Law Assessment Tool emerged as a systematic outcome assessment tool following homeopathic intervention. The authors intend to modify it and develop a new tool-Patient Response Assessment Tool after Homeopathic Treatment (PRATHoT)-in chronic cases through Delphi technique for systematic categorization of probable outcomes following individualized homeopathic treatment in chronic cases. The PRATHoT was drafted after literature review and iterative Delphi rounds with multidisciplinary expert panel, setting Fleiss κ of 0.41 to 1.00 a priori as the desired level of multirater agreement. Following pilot testing, the tool was implemented on 37 patients suffering from knee osteoarthritis over 6 months. Logistic regression analysis confirmed that higher PRATHoT score was significantly associated with achieving pain visual analogue scale responses from the second follow-up visit onwards (B = 0.037-0.066; SE = 0.021-0.036; P = .003-.048). The tool appeared to have acceptable psychometric properties; hence, it may be considered as a promising tool, amendable for further development.

The timing of drug funding announcements relative to elections: a case study involving dementia medications.

BACKGROUND: Following initial regulatory approval of prescription drugs, many factors may influence insurers and health systems when they decide whether to add these drugs to their formularies. The role of political pressures on drug funding announcements has received relatively little attention, and elections represent an especially powerful form of political pressure. We examined the temporal relationship between decisions to add one class of drugs to publicly funded formularies in Canada's ten provinces and elections in these jurisdictions. METHODS: Dates of provincial formulary listings for cholinesterase inhibitors, which are drugs used to treat Alzheimer's disease and related dementias, were compared to the dates of provincial elections. Medical journal articles, media reports, and proceedings from provincial legislatures were reviewed to assemble information on the chronology of events. We tested whether there was a statistically significant increase in the probability of drug funding announcements within the 60-day intervals preceding provincial elections. RESULTS: Decisions to fund the cholinesterase inhibitors were made over a nine-year span from 1999 to 2007 in the ten provinces. In four of ten provinces, the drugs were added to formularies in a time period closely preceding a provincial election (P = 0.032); funding announcements in these provinces were made between 2 and 47 days prior to elections. Statements made in provincial legislatures highlight the key role of political pressures in these funding announcements. CONCLUSIONS: Impending elections appeared to affect the timing of drug funding announcements in this case study. Despite an established structure for evidence-based decision-making, drug funding remains a complex process open to influence from many sources. Awareness of such influences is critical to maintain effective drug policy and public health decision-making.

Occupational health crossing borders part 2: Comparison of 18 occupational health systems across the globe.

BACKGROUND: Occupational health and safety (OHS) is considered one of the most important factors for a sustainable development; however, it is often considered a luxury by decision-makers. This article compares OHS systems of 18 countries at different stages of development. METHODS: In an international summer school, structure of the national OHS system, definition of occupational accidents and diseases, procedures for compensation claims, outcome (expressed as incidence of occupational accidents) and training opportunities were presented. RESULTS: National OHS systems ranged from non-existent to systems implemented almost 200 years ago. Priorities, incidence of occupational accidents and training opportunities varied. Common problems included the lack of OHS service for small enterprises and in rural areas. CONCLUSIONS: International training programs like this summer school might enhance the exchange about OHS opportunities around the globe and contribute to improved workers health.