Budget impact and cost-utility analysis of prophylactic emicizumab versus on-demand bypassing agents for adolescent severe haemophilia A patients with inhibitors in India.

Introduction: Severe Haemophilia A patients with inhibitors are currently being treated with bypassing agents like activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa. Emicizumab is a recombinant humanized monoclonal antibody, introduced to reduce the bleeding events, improve treatment adherence, and quality of life. However, cost-effectiveness and long-term sustainability of the intervention is not studied in a low middle income setting like India. Aim: The primary objective of this study was to evaluate the cost-utility of Emicizumab compared to traditional bypassing agents in the treatment of severe haemophilia A patients with inhibitors in India. Secondary objective was to analyze the budgetary impact of introducing Emicizumab for this patient population from the perspective of public health system in India. Methods: Markov model was created to compare the prophylactic emicizumab therapy against bypassing agents for a hypothetical cohort of 10-year-old adolescents in India. The time horizon was 10 years and model built based on health system perspective. Cost utility was expressed as costs per quality-adjusted life-years (QALYs) gained. All costs were expressed as 2021 US dollars. Probabilistic sensitivity analysis was performed to check the robustness of the estimates. Results: Prophylactic emicizumab was a cost saving intervention with negative Incremental Cost Utility Ratio (ICUR) against recombinant factor VIIa of -853,573 USD (INR -63,109,773), and negative ICUR of -211,675 USD (INR -15,650,403) against APCC. The estimated total budget for treating all the severe Haemophilia A patients with inhibitors in India was USD 59,042,000 (INR 4,365,329,312) for 10 years' time horizon (per patient cost of USD 295,210 [INR 21,826,646.56]). Conclusion: Prophylactic emicizumab therapy is a cost saving intervention when compared to both the bypassing agents as it is less costly and more effective for severe Haemophilia A patients with inhibitors in India.

Association between acute liver injury & severity and mortality of COVID-19 patients: A systematic review and meta-analysis.

Background: Acute liver injury (ALI), a complication often seen in COVID-19 patients, can lead to severe liver damage, multi-organ failure, acute vascular events, and can potentially escalate to patient mortality. Given this, we initiated a meta-analysis to investigate the correlation between ALI and adverse outcomes in COVID-19 patients. Methods: We conducted an exhaustive search of databases, including Medline, Embase, PubMed Central, ScienceDirect, Google Scholar, and the Cochrane Library, from the November 2019 until January 2022. The quality of the included studies was evaluated using the Newcastle Ottawa (NO) scale. Our meta-analysis was carried out using a random-effects model and results were presented as pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs). Results: Our analysis incorporated 20 studies involving a total of 13,850 participants, predominantly from China and the United States. According to the NO scale, the majority of these studies were categorized as low-quality. Patients with ALI faced approximately 7 times higher odds of severe COVID-19 symptoms (pooled OR = 7.09; 95%CI: 4.97 to 10.12) and over 5 times higher odds of mortality (pooled OR = 5.50; 95%CI: 3.37 to 8.99) when compared to those without ALI. Conclusion: Our findings affirm that ALI is a potent predictor of adverse outcomes, including severity and mortality, among COVID-19 patients. Recognizing and promptly addressing ALI in COVID-19 patients could be pivotal in improving prognosis and tailoring individualized patient management strategies. This underscores the need for clinicians to be vigilant about liver complications in the COVID-19 patients and integrate appropriate interventions in the treatment paradigm.

phoP maintains the environmental persistence and virulence of pathogenic bacteria in mechanically stressed desiccated droplets.

Despite extensive studies on kinematic features of impacting drops, the effect of mechanical stress on desiccated bacteria-laden droplets remains unexplored. In the present study, we unveiled the consequences of the impaction of bacteria-laden droplets on solid surfaces and their subsequent desiccation on the virulence of an enteropathogen Salmonella typhimurium (STM). The methodology elucidated the deformation, cell-cell interactions, adhesion energy, and roughness in bacteria induced by impact velocity and low moisture because of evaporation. Salmonella retrieved from the dried droplets were used to understand fomite-mediated pathogenesis. The impact velocity-induced mechanical stress deteriorated the in vitro viability of Salmonella. Of interest, an uninterrupted bacterial proliferation was observed in macrophages at higher mechanical stress. Wild-type Salmonella under mechanical stress induced the expression of phoP whereas infecting macrophages. The inability of STM ΔphoP to grow in nutrient-rich dried droplets signifies the role of phoP in sensing the mechanical stress and maintaining the virulence of Salmonella.

Effectiveness of nursing interventions for management of children with bronchial asthma: A systematic review and meta-analysis.

AIM: Nursing interventions include the preventive care that can support and guide the nurse's effort to provide asthma interventions for children. Hence, this review was done to assess the effectiveness of nursing interventions for management of childhood asthma. METHODS: We conducted a search in Medline, the Cochrane library, EMBASE, ScienceDirect and Google Scholar from 1964 until April 2022. Meta-analysis was done using a random-effects model and pooled weighted mean difference (WMD) or standardized mean difference (SMD) and/or risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Fourteen studies were analysed. The pooled RR was 0.49 for emergency visits (95% CI: 0.32 to 0.77) and 0.46 for hospitalizations (95% CI: 0.27 to 0.79). The pooled WMD was -1.20 for number of days with symptoms (95% CI: -3.50 to 1.11), -0.98 for number of nights with symptoms (95% CI: -2.94 to 0.98) and -0.69 for frequency of asthma attacks (95% CI: -1.19 to -0.20). The pooled SMD was 0.39 for quality of life (95% CI: 0.11 to 0.66) and 0.58 for asthma control (95% CI: -0.29 to 1.46). CONCLUSION: Nursing interventions were relatively effective in improving the quality of life and reducing asthma related emergencies, acute attacks and hospitalization amongst childhood asthma patients.

Diagnostic accuracy of ultrasonography for the confirmation of endotracheal tube intubation: a systematic review and meta-analysis.

AIM: Despite several studies and reviews reporting data accuracy of ultrasonography for confirmation of endotracheal intubation, there has been limited pooled evidence summarizing the diagnostic accuracy of this imaging modality, especially based on recent evidence. Hence, the current study reviews the recent literature and conducts a meta-analysis to compare the accuracy of ultrasonography for the confirmation of endotracheal tube placement. MATERIAL AND METHODS: We conducted a systematic search for all studies reporting the diagnostic accuracy of ultrasonography in the databases of Medline, EMBASE,PubMed Central, ScienceDirect, Google Scholar & Cochrane library from inception till December 2021. Meta-analysis was performed using STATA software "midas" package. RESULTS: Thirty-eight studies with 3,268 participants were included. Thepooled sensitivity was 98% (95% CI, 97%-99%) and specificity was 95% (95% CI, 90%-98%), respectively. The AUC was 0.98 (95%CI: 0.96-1.00). The pooled DOR was 1090 (95% CI, 408-2910). Pooled LRP was 19 (95% CI, 9-39) and pooled LRN was 0.02 (0.01-0.03). There was significant heterogeneity found in the outcome with significant chi-square tests and I2 statistics > 75%. CONCLUSION: Findings from our review demonstrate promise in the applicability of ultrasonography as a major diagnostic tool for confirming the endotracheal tube intubation.

COVID-19 Severity and Mortality Among Chronic Liver Disease Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Pre-existing comorbid conditions in COVID-19 patients are risk factors for developing severe disease and death. We aimed to determine the association of chronic liver disease (CLD), a comorbid condition, with severity of disease and death among COVID-19 patients. METHODS: We searched for studies reporting COVID-19 outcomes among CLD and non-CLD patients in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception of the pandemic until February 2022. Risk of bias assessment was conducted by using the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. We conducted a meta-analysis with a random-effects model and reported pooled odds ratios (ORs) with 95% CIs. RESULTS: We included 40 studies with 908,032 participants. Most studies were conducted in China and the US. COVID-19 patients with CLD had significantly higher odds of having a severe form of COVID-19 (pooled OR = 2.44; 95% CI, 1.89-3.16) and death (pooled OR = 2.35; 95% CI, 1.85-3.00) when compared with COVID-19 patients without CLD. CONCLUSION: The presence of CLD is significantly related to adverse clinical outcomes among COVID-19 patients in terms of severity and mortality. Clinicians should develop a comprehensive intervention plan to manage these high-risk patients and reduce COVID-19-related deaths.

Diagnostic accuracy of fine-needle aspiration cytology for lymphoma: A systematic review and meta-analysis.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has become one of the most useful modalities for diagnosis and staging of lymphoma. However, diagnostic accuracy of this technique has been reported with varying results across several studies around the world. Hence, this meta-analysis was done to assess the accuracy of FNAC for lymphoma diagnosis. METHODS: We conducted a systematic search for all studies reporting the diagnostic accuracy of FNAC for lymphoma in the databases of PubMed Central, MEDLINE, EMBASE, MEDLINE, SCOPUS and Cochrane library from inception till January 2021. Meta-analysis was performed using STATA software "midas" package. RESULTS: Forty-seven studies with 7268 patients were included. The pooled sensitivity and specificity of FNAC for diagnosing lymphoma were 93% (95% CI, 90%-95%) and 97% (95% CI, 95%-98%), respectively. Likelihood ratio positive was 33.5 (95% CI, 18.5-60.7) and likelihood ratio negative was 0.07 (0.05-0.11) making the technique to occupy the left upper quadrant in LR scattergram indicating that FNAC can be used for confirmation and exclusion. There was significant heterogeneity with significant chi-square test and I2 statistic >75%. There was significant publication bias as per Deek's test and funnel plot. CONCLUSION: To summarize, our study found that FNAC has a vital role as a diagnostic tool for lymphoma with higher sensitivity and specificity. Further studies assessing the accuracy of FNAC on specific types of lymphoma is required.