Exacerbation Rate Research Articles

Comparison of a Supervised Home-Based Tele-Rehabilitation with Center-Based Pulmonary Rehabilitation: Protocol for a Randomized Non-Inferiority Multicenter Study in Ningxia.

Pulmonary rehabilitation (PR) is an effective intervention for people with chronic obstructive pulmonary disease (COPD). However, fewer than 5% of eligible individuals receive pulmonary rehabilitation, largely due to limited by the accessibility of rehabilitation and difficulties associated with travel and transport. Supervised home-based tele-rehabilitation (SHTR) is an alternative model to center-based pulmonary rehabilitation. We will determine whether supervised home-based tele-rehabilitation is non-inferior to center-based pulmonary rehabilitation. The participants will undergo an 8-week rehabilitation program. Pulmonary rehabilitation comprises four main modules: exercise training, education, nutritional support, and psychological and behavioral interventions. We mainly focus on the module of exercise training and education. The education module includes information on exercise training, nutrition, and psychology, which are presented in an educational booklet provided to each participant. Blinded assessors will evaluate the outcomes at baseline, post-intervention, and 6 months after the intervention. The primary outcome is the change in the 6-minute walking distance. Secondary outcomes will assess changes in the patients' 1-minute sit-to-stand test, maximal inspiratory pressure (MIP), scales (CAT, mMRC, HAD), diaphragm ultrasound (TD, DE, DIF), changes in extrathoracic muscle volume and mass, completion rate of patient exercise prescriptions, occurrence of adverse events, as well as disease exacerbation and rehospitalization rates after rehabilitation and during the 6-month follow-up. In order to improve the accessibility of pulmonary rehabilitation and patient-related outcomes, it is necessary to propose an alternative model of pulmonary rehabilitation. This trial will establish whether a supervised home-based tele-rehabilitation is not inferior to traditional center-based pulmonary rehabilitation. Chinese Clinical Trial Registry ChiCTR2300076969. Registered on October 25, 2023.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Baseline patient demographics for TETRIS: a prospective, noninterventional study to characterize the use of triple therapy for COPD in Germany.

Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2-48 weeks. For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. https://clinicaltrials.gov/study/NCT04657211.

Efficacy, Safety, and Continuation of Biological Therapy in Older Patients with Asthma in a Real-World Setting: A Retrospective Observational Study.

Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma. In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated. Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group. Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.

Impact of lumacaftor/ivacaftor on the bacterial and fungal respiratory pathogens in cystic fibrosis: a prospective multicenter cohort study in Sweden.

A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden. The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden. The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor. Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed. Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive. The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Evidence Construction of Chuankezhi Injection Against Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Pharmacology.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology. Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure. This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.

Bronchial thermoplasty for severe asthma: potential mechanisms and response markers.

Severe asthma (SA) poses a significant challenge to management and treatment, leading to a reduced quality of life and a heavy burden on society and healthcare resources. Bronchial thermoplasty (BT) has emerged as a non-pharmacological intervention for SA, demonstrating its efficacy and safety in improving patients' quality of life and reducing exacerbation rates for over a decade. In particular, BT encounters various obstacles in its clinical application. Since asthma is characterized by high heterogeneity, not all patients derive effective outcomes from BT. Furthermore, current knowledge of markers that indicate response to BT remains limited. Recent research has shed light on the intricate mechanism of action of BT, which extends beyond simple smooth muscle ablation. Therefore, to enhance the clinical practice and implementation of BT, this paper aims to elucidate the mechanism of action and identify potential markers associated with BT response.

Do respiratory virus infections modify associations of asthma exacerbation with aeroallergens or fine particulate matter? A time series study in Philadelphia PA

ABSTRACT Respiratory virus infections are related to over 80% of childhood asthma exacerbations. They enhance pro-inflammatory mediator release, especially for sensitized individuals exposed to pollens/molds. Using a time-series study design, we investigated possible effect modification by respiratory virus infections of the associations between aeroallergens/PM2.5 and asthma exacerbation rates. Outpatient, emergency department (ED), and inpatient visits for asthma exacerbation among children with asthma (28,540/24,444 [warm/cold season]), as well as viral infection counts were obtained from electronic health records of the Children’s Hospital of Philadelphia from 2011 to 2016. Rate ratios (RRs, 90th percentile vs. 0) for late-season grass pollen were 1.00 (0.85–1.17), 1.04 (0.95–1.15), and 1.12 (0.96–1.32), respectively, for respiratory syncytial virus (RSV) counts within each tertile. However, similar trends were not observed for weed pollens/molds or PM2.5. Overall, our study provides little evidence supporting effect modification by respiratory viral infections.

Analysis of the clinical and economic effectiveness of using benralizumab in comparison with standard therapy in patients with severe bronchial asthma

Objective: to evaluate the clinical and economic effectiveness of benralizumab in comparison with standard therapy in patients with severe bronchial asthma (SBA) with an eosinophilic phenotype in the Russian Federation.Material and methods. A clinical and economic analysis of using benralizumab in addition to standard therapy was carried out in comparison with standard therapy for SBA with an eosinophilic phenotype by means of a modeling method. Cost calculations were performed in a mathematical model adapted to the Russian healthcare conditions with the help of cost indicators and patient population characteristics.Results. The use of benralizumab as a mandatory component of standard therapy compared with standard therapy alone for SBA with an eosinophilic phenotype will allow for an additional 0.65 life years gained (LYGs) and 1.12 quality-adjusted life years (QALYs) per 1 patient during lifelong therapy. It will provide avoiding 4.95 exacerbations, simultaneously with a reduction in total costs by 584,144 rubles by reducing gross domestic product (GDP) losses due to mortality and temporary disability over an assessment horizon equal to life expectancy. The costs of 1 LYG and 1 QALY in the case of benralizumab were 869,455 and 1,252,056 rubles, in the case of standard therapy they were 911,615 and 1,303,811 rubles, respectively.Conclusion. Intensification of SBA therapy with an eosinophilic phenotype with benralizumab is clinically justified (leads to an increase in life expectancy, a decrease in the rate of exacerbations and an increase in patients’ working life), and is also economically feasible, as it allows to reduce direct costs and GDP losses of the state.

The ADEM project: implementation of ‘Good medicines use conversation’ for COPD-patients, embedded in multidisciplinary context.

COPD is a chronic, progressive disease, for which a multidisciplinary approach is crucial. Appropriate follow-up is crucial to improve the quality of life of COPD-patients and reduce associated healthcare costs. &#x0D; A ‘Good medicines use conversation’ COPD is a pharmaceutical care intervention, conducted by the community pharmacist, consisting of a tailored-made education of the COPD-patient on the disease and its treatment. Scientific research (PHARMACOP-trial) has shown that this intervention significantly improves therapy adherence and inhalation technique and reduces exacerbation rates and associated hospitalizations. &#x0D; The aim of the ADEM implementation project was to investigate the needs for a sustainable implementation of this intervention.&#x0D; The ADEM project was conducted in Flemish-Brabant (Belgium), with the integrated care region ‘Leuven Cares’ as a separate entity. &#x0D; All participating pharmacies (9 in region Flemish-Brabant and 8 in region ‘Leuven Cares’) received a support package consisting of: 1) a three-part online training about COPD and a visual COPD-atlas; 2) a population management-tool (a query to identify COPD-patients in the pharmacy, resulting in a list of COPD-patients with a ‘score’ per patient as an initial proxy for patient prioritization); and 3) local interdisciplinary meetings (LIM) to discuss and promote the intervention. Pharmacist of the region Caring Leuven additionally received individual care plans, providing an overview of the healthcare status of each COPD-patient, and an individual coaching session.&#x0D; Semi-structured interviews were conducted with 8 participating pharmacists (4 region Flemish-Brabant, 4 region ‘Leuven Cares’). Thematic analysis was performed.&#x0D; &#x0D; All elements of the support package were positively evaluated by the participating pharmacists. The population management tool seemed to support pharmacists in planning, interpreting and prioritizing care for COPD-patients. A follow-up study is needed to further investigate the tool and to what extent population management contributes to a more qualitative and effective pharmaceutical care. &#x0D; COVID-19, lack of personnel, lack of reimbursement and lack of time were identified as limiting factors for the implementation of the protocol-based COPD-intervention. Cooperation with the GP was indicated by the majority as minimal and insufficient. Therefore, LIM’s were evaluated as very important to inform GP’s about the pharmaceutical intervention and make local agreements about the multidisciplinary approach of COPD.&#x0D; The findings of this study are in line with the available evidence on the implementation of new services in pharmacies. Many pharmacists have the intrinsic motivation to offer extended pharmaceutical care, but current practices often do not allow this. Population management appeared to be a major factor that can be used to facilitate the implementation. By considering the needs of the local population, pharmacists can work in a more targeted way and prioritize the pharmaceutical services they offer. Given the group of chronically ill people in Belgium is expected to grow in the coming years due to the increasing ageing of the population, there will be an increasing demand for specialized interventions and advice from the pharmacist. It is therefore necessary to provide a sufficient framework for these services, bearing in mind the needs of the local population and the requirement for a pragmatic approach in the pharmacy. &#x0D;

Tezepelumab in patients with allergic and eosinophilic asthma.

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma

BackgroundThere is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. ObjectiveTo investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. MethodsThis was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). ResultsPercentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti–IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. ConclusionOur results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. Trial RegistrationThe ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

Impact of COPD on mortality: An 8-year observational retrospective healthcare claims database cohort study

BackgroundChronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Here we present a large observational study on the association of COPD and exacerbations with mortality (AvoidEx Mortality). MethodsA real-world, observational cohort study with longitudinal analyses of German healthcare claims data in patients ≥40 years of age with a COPD diagnosis from 2011 to 2018 (n = 250,723) was conducted. Patients entered the cohort (index date) upon the first COPD diagnosis. To assess the impact of COPD on all-cause death, a propensity score-matched control group of non-COPD patients was constructed. The number and severity of exacerbations during a 12-month pre-index period were used to form subgroups. For each exacerbation subgroup the exacerbations during 12 months prior to death were analysed. ResultsCOPD increases the all-cause mortality risk by almost 60% (HR 1.57 (95% CI 1.55–1.59)) in comparison to matched non-COPD controls, when controlling for other baseline covariates. The cumulative risk of death after 8 years was highest in patients with a history of more than one moderate or severe exacerbation. Among all deceased COPD patients, 17.2% had experienced a severe, and 34.8% a moderate exacerbation, within 3 months preceding death. Despite increasing exacerbation rates towards death, more than the half of patients were not receiving any recommended pharmacological COPD therapy in the year before death. ConclusionOur study illustrates the impact of COPD on mortality risk and highlights the need for consequent COPD management comprising exacerbation assessment and treatment.

Public Health Expenditure and Infant Mortality Rate in Nigeria

This study investigated the effect of public health expenditure on infant mortality rate in Nigeria from 2002 to 2021. To achieve the above objective, this study utilized data on infant mortality rate, total government expenditure on health and migration of doctors and nurses trained in Nigeria - doctors and nurses trained in Nigeria but working in other countries from OECD Health Statistics, 2021, WHO, UNICEF, UNFPA, World Bank Group, the United Nations Population Division and Statistical Bulletin of Nigeria’s apex bank. The study employed an Autoregressive Distributed Lag (ARDL) Bounds testing procedure for data analyses. The results revealed that in the long run, total government expenditure on health, as well as migration of doctors and nurses trained in Nigeria - doctors and nurses trained in Nigeria but working in other countries have negative and insignificant relationship with infant mortality rate in Nigeria. However, in the short run, total government expenditure on health, as well as migration of doctors and nurses trained in Nigeria - doctors and nurses trained in Nigeria but working in other countries have positive and significant relationship with infant mortality rate in Nigeria. What this means is that though there has been expenditures on health sector in Nigeria by the government from 2002 to 2021, but the expenditures are low and couldn’t reduce infant mortality rate to a near-zero level in Nigeria. Also, in the short-term, the movement of doctors and nurses from Nigeria to others countries of the world, exacerbated infant mortality rate in Nigeria during the period of study. Based on the forgoing, it is recommended here that government should spend at least 15% of its annual budget on health sector as agreed by African leaders at Abuja in 2015. Government should also reduce the exodus of Nigerian doctors to other countries of the world. This, the government may be able to achieve by increasing budgetary allocation to healthcare sector, enhance doctors’ remuneration, ensure a better work environment with modern healthcare facilities together with general enhancements in basic life facilities including housing, health insurance, security, constant power supply and good roads.

Efficacy and safety of the Gam-COVID-Vac in patients with immunoinflammatory rheumatic diseases: preliminary data of prospective study

Objective: to study the efficacy and safety of the Gam-COVID-Vac vaccine in patients with immunoinflammatory rheumatic diseases (IRD) in a prospective study.Material and methods. The study included 42 patients with IRD and 57 individuals without IRD (control group) who received at least one component of Gam-COVID-Vac. Immunization with the first component of the vaccine was carried out from March 25th to August 1st, 2022, the second – 3 weeks after the first dose. On days 1, 3 and 7 after administration of the first and second components, the study participants provided information on adverse events (AEs) by telephone. All subjects were examined by a rheumatologist 1, 3 and 6 months after complete immunization. The observation period after immunization with the second dose was 6 months.Results and discussion. 42 patients received the first component of the vaccine, and 39 patients received two components. In the control group, 57 subjects were immunized with two components of the vaccine. 30–180 days after vaccination with two components of Gam-COVID-Vac, 3 (7.7%) patients were diagnosed with SARS-CoV-2 infection, which was confirmed by polymerase chain reaction. In all cases, a mild course of COVID-19 without signs of pneumonia was observed. There were no cases of COVID-19 in the control group. After immunization with the first component, a combination of at least one local and one systemic AE (SAE) was documented in 28.6% of patients with IRD and 33.3% of individuals in the control group (p&gt;0.05). No AEs were recorded in 42.9% and 36.8% of cases respectively (p&gt;0.05). After vaccination with the second component, a combination of ≥1 local AE and SAE was recorded in 15.4 % of patients with IRD and 22.8% of individuals in the control group (p&gt;0.05). No AEs occurred in 71.8% and 56.1% of cases respectively (p&gt;0.05). In 10.3% of patients with IRD and 12.3 % of those without IRD (p&gt;0.05), a combination of local and systemic AEs was recorded after the introduction of both first and second components. No AEs were observed in 35.9% and 28.1% of cases, respectively (p&gt;0.05). The overall rate of IRD exacerbations was 4.8%.Conclusion. Based on the available data, vaccination against COVID-19 appears to be effective and quite safe in patients with IRD.

Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma

BackgroundAsthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and...

Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein–protein interaction analyses

IntroductionBiomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab.MethodsAptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways.ResultsOver two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E−05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E−05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E−07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E−06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E−06, FDR-corrected: 0.0006) with worse response. Protein–protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab.ConclusionsThis study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection.

The Natural and Therapeutic Components of Tourism in Najaf Governorate

The current study is interested in studying the most critical natural potentials that characterize the province of Najaf and the possibility of investing them in the field of tourism due to the active and prominent role that it plays in the growth of the economies of most countries of the world, as it provides additional financial resources for the population and works to improve their social and cultural level, as it represents one of the effective invisible exports. It is an essential element of economic activity. It is closely related to development. And it works to solve several financial problems that these countries face, including, for example, the issue of unemployment. Tourism works to mitigate its exacerbation rates by its ability to create new job opportunities, as well as its role in developing Regions and cities that enjoy natural and human tourism potential by providing infrastructure facilities and necessary facilities to serve tourists and citizens alike, because tourism has a set of economic, social, cultural, environmental and political developmental influences on the tourist destination.

Discontinuation Schedule of Inhaled Corticosteroids in Patients With Chronic Obstructive Pulmonary Disease.

Long-term use of inhaled corticosteroids (ICSs) is associated with several potential adverse effects. While patients unlikely to benefit should stop ICS use, abrupt discontinuation may result in an increased risk of chronic obstructive pulmonary disease (COPD) exacerbation. Stepwise tapering may reduce this risk but data are limited, and there is no consensus on the likelihood of COPD exacerbations following ICS discontinuation. The North Texas Veterans Affairs Health Care System conducted a single center, retrospective cohort study to evaluate the rate of COPD exacerbations following the discontinuation of ICS therapy using different schedules of discontinuation. Data were collected from the electronic health records of patients aged ≥ 40 years with a diagnosis of COPD who were on a stable dose of an ICS for ≥ 1 year that was subsequently discontinued with a last documented fill date between January 10, 2021 and September 1, 2021. Eligible patients were followed for COPD exacerbations that resulted in hospitalization until November 1, 2022. Descriptive statistics were used to evaluate characteristics of patients who experienced an exacerbation. Seventy-five patients were included: 5 (7%) experienced an exacerbation following ICS discontinuation. Age, sex, race, and ethnicity were similar for those patients who did vs did not have an exacerbation. Unexpectedly, the mean baseline eosinophil count for patients with an exacerbation was 92 cells/μL compared with 227.4 cells/μL for those without an exacerbation. Nine patients had their ICS tapered gradually, and none of them experienced an exacerbation. Study findings suggest that there is a relatively low risk of COPD exacerbation following ICS discontinuation, regardless of whether a taper was performed. This result may indicate that it is reasonable to abruptly discontinue ICS in eligible patients.