International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Traumatic retroclival hematoma complicated with hyponatremia and delayed traumatic intracranial hematoma in an adult: A case report.

Intracranial hematoma is a common variety of brain insults in trauma. However, posterior fossa hematoma in the retroclival location is quite unusual. There are limited numbers of case reports regarding traumatic retroclival hematoma. Some are managed with surgery in this condition. We present a traumatic retroclival hematoma in a 34-year-old gentleman who sustained brain trauma in a motor vehicle accident. His condition was further complicated by hyponatremia and delayed traumatic intracerebral hematoma in a distant location. The only symptom he had later was severe headache which could be attributed to delayed traumatic intracerebral hematoma and hyponatremia. He was managed conservatively and discharged on the 12th day from the hospital.

Individualised risk prediction model for exacerbations in patients with severe asthma: protocol for a multicentre real-world risk modelling study.

INTRODUCTION: Severe asthma is associated with a disproportionally high disease burden, including the risk of severe exacerbations. Accurate prediction of the risk of severe exacerbations may enable clinicians to tailor treatment plans to an individual patient. This study aims to develop and validate a novel risk prediction model for severe exacerbations in patients with severe asthma, and to examine the potential clinical utility of this tool. METHODS AND ANALYSIS: The target population is patients aged 18 years or older with severe asthma. Based on the data from the International Severe Asthma Registry (n=8925), a prediction model will be developed using a penalised, zero-inflated count model that predicts the rate or risk of exacerbation in the next 12 months. The risk prediction tool will be externally validated among patients with physician-assessed severe asthma in an international observational cohort, the NOVEL observational longiTudinal studY (n=1652). Validation will include examining model calibration (ie, the agreement between observed and predicted rates), model discrimination (ie, the extent to which the model can distinguish between high-risk and low-risk individuals) and the clinical utility at a range of risk thresholds. ETHICS AND DISSEMINATION: This study has obtained ethics approval from the Institutional Review Board of National University of Singapore (NUS-IRB-2021-877), the Anonymised Data Ethics and Protocol Transparency Committee (ADEPT1924) and the University of British Columbia (H22-01737). Results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies, EU PAS Register (EUPAS46088).

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India.

BACKGROUND: Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models. METHODS: We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3 months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for 'months of intervention'. RESULTS: The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities. CONCLUSION: A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India. TRIAL REGISTRATION NUMBER: CTRI/2016/05/006963.

Validity of Estimation of Haemoglobin Content in Dried Blood Spot Samples.

The ability to use indirect cyanmethemoglobin method using 20 µl of dried blood spots (DBSs) on filter paper for the analysis of haemoglobin (Hb) levels could be an important diagnostic tool for areas that have limited access to laboratory facilities. We assessed the validity of a method for Hb estimation in which a single drop of whole blood was directly taken on the filter paper. We collected 124 DBSs containing 20 µl of blood (filter paper A) and single drop of whole blood (filter paper B) from subjects living in Nainital, Uttrakhand. Estimation of Hb was done by indirect cyanmethemoglobin method in both the filter papers. A correction factor for predicting value of Hb from DBSs of single drop of whole blood was established. The Bland-Altman plot suggested that the difference in Hb values obtained by the single drop of blood and 20 µl of DBSs was within the 1.5 SD limits, suggesting high validity of the correction factor. The estimation of Hb using single drop of whole blood on filter paper after applying the correction factor provides results similar to indirect cyanmethemoglobin method using 20 µl of blood. Hence, single drop of whole blood on filter paper can be used as an alternate method for estimation of Hb in large scale community surveys.

Large and giant pituitary adenoma resection by microscopic trans-sphenoidal surgery: Surgical outcomes and complications in 123 consecutive patients.

To evaluate surgical outcomes and complications of patients who underwent microscopic trans-sphenoidal surgery (MTS) for large and giant pituitary adenomas (PAs). A retrospective study of electively operated cases of PA over a six year period was performed. Surgical outcomes and complications of 64 patients with large PAs (≥3cm) and 59 patients with giant PAs (>4cm), who underwent MTS at same period, were reviewed. Medical reports of all selected patients were assessed to collect demographic information such as age, sex, clinical symptoms, PA size, the extent of PA extension and resection, outcomes and complications. Patients with large PAs had improvement in visual improvement (78.1%; 50/64), gross total resection (84.4%; 54/64) compared to patients with giant PAs who had improvement in visual (71.2%; 42/59) and gross total resection (74.6%; 44/59). The rate of CSF leakage was 7.8% and 23.7% for large and giant PAs (p=0.0399). After a mean follow-up period of 40.8 (6-75) months, 10 (15.6%) patients with large PAs experienced tumor recurrence, while 2 giant PA patients (3.4%) experienced tumor recurrence after a mean follow-up period of 40.6 (3-70) months (p=0.0314). Resection of both large and giant pituitary adenomas by microscopic trans-sphenoidal surgery may be safe and effective surgical technique with low morbidity and mortality.

Relationship between venous drainage subtypes and sub-arachnoid hemorrhage subtypes: a meta-analysis.

BACKGROUND: To investigate whether associations exist between venous drainage subtypes (types I, II, and III) and the risk of subarachnoid hemorrhage subtypes. METHODS: Published case-control and case series from 2010 to 2014 which met all the inclusion criteria for the meta-analysis were selected and subjected to rigorous statistical analysis. RESULTS: A total of 11 studies with an overall patient population (case and controls) of 891 were involved in the study. Types I and II venous drainage had odds against peri-mesencephalic subarachnoid hemorrhage. The odds were in favor of type III venous drainage and peri-mesencephalic sub-arachnoid hemorrhage and idiopathic sub-arachnoid hemorrhage (ISAH). CONCLUSIONS: Type I deep venous drainage may not be associated with the risks of peri-mesencephalic subarachnoid hemorrhage and ISAH, however, types II and III may be associated with high risk of peri-mesencephalic subarachnoid hemorrhage and ISAH, respectively.