Safety and efficacy of Sinopharm vaccine (BBIBP-CorV) in elderly population of Faisalabad district of Pakistan.

INTRODUCTION: The first case of novel SARS-COV-2 (COVID-19) in Pakistan was detected on 26 February 2020. Pharmacological and non-pharmacological strategies have been tried to lessen the mortality and morbidity burden. Various vaccines have been approved. The Drug Regulatory Authority of Pakistan gave emergency approval for Sinopharm (BBIBP-CorV) COVID-19 vaccine in December 2021. The phase 3 trial of BBIBP-CorV included only 612 participants aged 60 years and above. The primary aim of this study was to assess the safety and efficacy of BBIBPP-CorV (Sinopharm) vaccine within the Pakistani adult population aged 60 or above. The study was carried out in the Faisalabad district of Pakistan. METHODS: A test negative case-control study design was used to assess safety and efficacy of BBIBP-CorV in individuals aged 60 and above against symptomatic infection, hospitalisations and mortality due to SARS-CoV-2 among vaccinated and unvaccinated individuals. ORs were calculated using logistic regression model at 95% CI. ORs were used to calculate the vaccine efficacy (VE) by using the following formula.VE= (1-OR) ×100. RESULTS: 3426 individuals with symptoms of COVID-19 were PCR tested between 5 May 2021 and 31 July 2021. The results showed that Sinopharm vaccine 14 days after the second dose was efficient in reducing the risk of symptomatic COVID-19 infection, hospitalisations and mortality by 94.3%, 60.5% and 98.6%, respectively, among vaccinated individuals with a significant p value of 0.001. CONCLUSION: Our study showed that BBIBP-CorV vaccine is highly effective in preventing infection, hospitalisations and mortality due to COVID-19.

The role of impulse oscillometry in the management of asthma when forced expiratory maneuvers are contraindicated: case series and literature review.

Objectives: The impulse oscillometry system (IOS) provides an alternative method of lung function testing for patients in whom forced expiratory manoeuvres are contraindicated, such as those with inherited vascular connective tissue disorders. Here we examine the role of IOS in the diagnosis and monitoring of asthma in such patients through a clinical case series and literature review.Methods: The clinical case series comprised of data from 12 patients with inherited connective tissue disorders representing 32 clinical encounters. Of these, 11 encounters were for asthma diagnosis and 21 were for asthma monitoring. Symptoms, exhaled nitric oxide (FeNO) and IOS were assessed at each encounter.Results: In the clinical case series, 5 of 6 patients with likely asthma (as determined by physician review and exhaled nitric oxide testing) had abnormal IOS parameters compared with 0 of 5 of those with unlikely asthma. In the monitoring group, 11 encounters resulted in treatment escalation (demonstrating suboptimal control), and 8 resulted in no change to treatment (good control). Six of 11 of those with suboptimal control had abnormalities in ≥3 IOS parameters, with R5 and R5-20 most frequently affected. Only 1 of 8 of those with good control had abnormalities in ≥3 IOS parameters.Conclusions: IOS can be used as an alternative to conventional lung function testing to support the diagnosis and monitoring of asthma when forced expiratory manoeuvres are contraindicated. Larger studies are required to establish severity and treatment escalation thresholds and provide clearer comparisons with spirometry values.

Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting.

BACKGROUND: 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of normal lung parenchyma and interstitial lung disease (ILD). OBJECTIVES: In this study, we investigated whether FDG-PET/CT parameters were associated with a change in the quality of life (QoL) in patients with ILD over 4 years of follow-up. METHODS: Patients underwent PET-CT imaging at diagnosis and were followed up with annual QoL assessment using the St George's Respiratory Questionnaire (SGRQ) until death or 4 years of follow-up. Maximum standard uptake value (SUVmax) and Tissue-to-Background Ratio (TBR) were assessed against SGRQ overall and subscale scores. RESULTS: 193 patients (94 patients in the idiopathic pulmonary fibrosis (IPF) subgroup and 99 patients in the non-IPF subgroup) underwent baseline FDG-PET/CT imaging and QoL assessment. Weak-to-moderate correlation was observed between baseline SUVmax and SGRQ scores in both ILD subgroups. No relationship was observed between baseline SUVmax or TBR and change in SGRQ scores over 4 years of follow-up. In the IPF subgroup, surviving patients reported a decline in QoL at 4 years post diagnosis whereas an improvement in QoL was seen in surviving patients with non-IPF ILD. CONCLUSIONS: Weak-to-moderate positive correlation between baseline SUVmax and SGRQ scores was observed in both ILD subgroups (IPF:rs=0.187, p=0.047, non-IPF: rs=0.320, p=0.001). However, baseline SUVmax and TBR were not associated with change in QoL in patients with IPF and non-IPF ILD over 4 years of follow-up. At 4 years post diagnosis, surviving patients with IPF reported declining QoL whereas improvement was seen in patients with ILD who did not have IPF.

Role of advanced respiratory support in acute respiratory failure in clinically frail patients with COVID-19.

Background: The main aim of this study was to assess the efficacy of advanced respiratory support (ARS) for acute respiratory failure in do-not-attempt cardiopulmonary resuscitation order (DNACPR) COVID-19 patients. Methods: In this single-center study, the impact of different types of ARS modality, PaO2/FiO2 (PF) ratio, clinical frailty score (CFS) and 4C score on mortality was evaluated. Results: There was no significant difference in age, type of ARS modality, PF ratio and 4C scores between those who died and those who survived. Overall survival rates/hospital discharge of patients still requiring ARS at 5 and 7 days post admission were 20 and 17%, respectively. Conclusion: Our study showed that ARS can be a useful tool in frail, elderly and high-risk COVID-19 patients irrespective of high 4C mortality score.

Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge.

BACKGROUND: Prone positioning has a beneficial role in coronavirus disease 2019 (COVID-19) patients receiving ventilation but lacks evidence in awake non-ventilated patients, with most studies being retrospective, lacking control populations and information on subjective tolerability. METHODS: We conducted a prospective, single-centre study of prone positioning in awake non-ventilated patients with COVID-19 and non-COVID-19 pneumonia. The primary outcome was change in peripheral oxygenation in prone versus supine position. Secondary outcomes assessed effects on end-tidal CO2, respiratory rate, heart rate and subjective symptoms. We also recruited healthy volunteers to undergo proning during hypoxic challenge. RESULTS: 238 hospitalised patients with pneumonia were screened; 55 were eligible with 25 COVID-19 patients and three non-COVID-19 patients agreeing to undergo proning - the latter insufficient for further analysis. 10 healthy control volunteers underwent hypoxic challenge. Patients with COVID-19 had a median age of 64 years (interquartile range 53-75). Proning led to an increase in oxygen saturation measured by pulse oximetry (SpO2) compared to supine position (difference +1.62%; p=0.003) and occurred within 10 min of proning. There were no effects on end-tidal CO2, respiratory rate or heart rate. There was an increase in subjective discomfort (p=0.003), with no difference in breathlessness. Among healthy controls undergoing hypoxic challenge, proning did not lead to a change in SpO2 or subjective symptom scores. CONCLUSION: Identification of suitable patients with COVID-19 requiring oxygen supplementation from general ward environments for awake proning is challenging. Prone positioning leads to a small increase in SpO2 within 10 min of proning though is associated with increased discomfort.

Relationship of D-dimer and prediction of pulmonary embolism in hospitalized COVID-19 patients: a multicenter study.

Aim: COVID-19 is a known risk factor for pulmonary embolism (PE). In this retrospective, multicenter study, we aimed to determine an optimal D-dimer cutoff to predict PE in hospitalized patients with COVID-19. Materials & methods: A total of 193 patients underwent computerized tomographic pulmonary angiography imaging and were classified into PE positive and negative groups. Physiological, radiological and biochemical parameters were compared and receiver operator curve analysis was conducted to determine a predictive D-dimer threshold. Results: An optimal D-dimer cutoff of 2494 ng/ml was selected (Youden index: 0.906), giving a sensitivity of 100% (95% CI: 100-100) and specificity of 90.62% (95% CI: 90.5-90.8) for predicting PE. Conclusion: We propose that in the absence of other clinical signs, a D-dimer threshold of 2495 ng/ml could be used with high sensitivity and specificity to predict PE in hospitalized patients with COVID-19.

The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.

Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts. Mechanistically, we show that SET1B accumulates on chromatin in hypoxia, and is recruited to HIF target genes by the HIF complex. The selective induction of H3K4 trimethylation at HIF target loci is both HIF- and SET1B-dependent and, when impaired, correlates with decreased promoter acetylation and gene expression. Together, these findings show SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.