A roadmap toward implementing health technology assessment in Egypt.

Background: The Egyptian healthcare system is currently in the early phase of health technology assessment (HTA) implementation. The aim of this study is to propose an implementation roadmap based on the national healthcare system status. Methods: A survey was conducted among Egyptian healthcare sector decision-makers to assess the current and future (preferred) HTA implementation status in Egypt based on a widely used international scorecard methodology. Subsequently, interviews were conducted with experts representing middle- and top-tier management in the Egyptian healthcare system to interpret the survey results and recommend specific actions. Results: Experts recommended more capacity-building programs for HTA and health economics. Additionally, they proposed establishing HTA units in separate healthcare authorities and merging them into a single central HTA unit in the long term. Regarding the scope of implementation, experts recommended commencing with the assessment of innovative pharmaceuticals, and thereafter, expanding the scope to cover all health technologies in the long term. Additionally, they recommended using innovative tools such as "multi-criteria decision analysis (MCDA)" for tendering, and "managed entry agreements" for reimbursement decisions. Local burden of diseases and costing studies were also recommended to facilitate the implementation of HTA. Conclusion: Experts agreed that several actions are required for successful HTA implementation in Egypt, including coordination between HTA bodies, application of an explicit MCDA framework, and strengthening of local evidence generation. To implement these actions, investment in technical capacity-building is indispensable. Most experts favored using multiple and soft cost-effectiveness thresholds. Efforts should be made to publish HTA submission guidelines and timelines of the processes.

SARS-CoV-2 genome variations and evolution patterns in Egypt: a multi-center study.

A serious global public health emergency emerged late November 2019 in Wuhan City, China, by a new highly pathogenic virus, SARS-CoV-2. The virus evolution spread has been tracked by three developing databases: GISAID, Nextstrain and PANGO to understand its circulating variants. In this study, 110 diagnosed positive COVID-19 patient's samples, were collected from Kasr Al-Aini Hospital and the Children Cancer Hospital Egypt 57357 between May 2020 and January 2021, with clinical severity ranging from mild to severe. The viral genomes were sequenced by next generation sequencing, and phylogenetic analysis was performed to understand viral transmission dynamics. According to Nextstrain clades, most of our sequenced samples belonged to clades 20A and 20D, which in addition to clade 20B were present from the beginning of sample collection in May 2020. Clades 19A and 19B, on the other hand, appeared in the mid and late 2020 respectively, followed by the disappearance of clade 20B at the end of 2020. We identified a relatively high prevalence of the D614G spike protein variant and novel patterns of mutations associated together and with different clades. We also identified four mutations, spike H49Y, ORF3a H78Y, ORF8 E64stop and nucleocapsid E378V, associated with higher disease severity. Altogether, our study contributes genetic, phylogenetic, and clinical correlation data about the spread of the SARS-CoV-2 pandemic in Egypt.

Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality.

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 µM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

Unmet need in the management of chronic obstructive pulmonary disease in the Middle East and Africa region: An expert panel consensus.

Chronic obstructive pulmonary disease (COPD) has a significant impact on healthcare systems and health-related quality of life. Increased prevalence of smoking is an important factor contributing to high burden of COPD in the Middle East and Africa (MEA). Several other factors including sedentary lifestyle, urbanization, second-hand smoke, air pollution, and occupational exposure are also responsible for the upsurge of COPD in the MEA. Frequent COPD exacerbations accelerate disease progression, progressively deteriorate the lung function, and negatively affect quality of life. This consensus is based on review of the published evidence, international and regional guidelines, and insights provided by the expert committee members from the MEA region. Spirometry, though the gold standard for diagnosis, is often unavailable and/or underutilized leading to underdiagnosis of COPD in primary care settings. Low adherence to the treatment guidelines and delayed use of appropriate combination therapy including triple therapy are additional barriers in management of COPD in MEA. It is necessary to recognize COPD as a screenable condition and develop easy and simple screening tools to facilitate early diagnosis. Knowledge of the disease symptomatology at patient and physician level and adherence to the international or regional guidelines are important to create awareness about harmful effects of smoking and develop national guidelines to focus on prevention on COPD. Implementation of vaccination program and pulmonary rehabilitation are equally valuable to manage patients with COPD at local and regional level. We present recommendations made by the expert panel for improved screening, diagnosis, and management of COPD in MEA.

A budget impact analysis of budesonide/formoterol in patients with mild asthma in Egypt.

Background: The aim of this study is to estimate the budget impact of budesonide/formoterol fixed dose combination (FDC) vs salbutamol, both used as needed, in mild asthma patients, from the perspective of the Health Insurance Organization (HIO). Methods: A static budget impact model was developed to assess the impact of budesonide/formoterol FDC entry on HIO budget over a 3-year period in Egyptian settings. Direct medical costs, including the costs of asthma medications, exacerbations, and management of side-effects, were obtained from HIO cost data. Population data were obtained from the World Bank and supplemented with local studies, and the rates of exacerbations, adverse effects, and number of sick leave days were elicited from the SYGMA 1 trial. Scenario analyses from a societal perspective and deterministic sensitivity analyses were conducted. Results: The total costs (drug and non-drug costs) for managing mild asthma patients from the HIO perspective were estimated to be EGP8.563 billion before budesonide/formoterol entry compared to EGP5.525 billion post-entry, leading to a total budget savings of EGP3.038 billion after 3 years. This total budget saving included an increase in drug costs (EGP104 million) and a decrease in non-drug costs (EGP3.143 billion). Drug costs were higher in the budesonide/formoterol group than in the salbutamol group, but this cost was offset by reductions in non-drug costs, resulting in a reduction in the total costs of healthcare resources. At the societal level, the total budget savings after including the indirect costs was expected to be EGP5.976 billion after 3 years of budesonide/formoterol entry. Conclusion: Budesonide/formoterol in mild asthma instead of salbutamol produces better patient outcomes and decreases total costs, with increases in drug cost offset by reductions in non-drug costs due to fewer exacerbations. Budesonide/formoterol is a budget saving option for guideline-directed treatment, from the economic perspective of the payer and the health perspective of the patient.

Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010-2014.

BACKGROUND: Respiratory viral and atypical bacterial infections data in Egyptian patients are sparse. This study describes the clinical features and outcomes of patients with severe acute respiratory infections (SARI) in hospitalized patients in Egypt. METHODS: SARI surveillance was implemented at Cairo University Hospital (CUH) during the period 2010-2014. All hospitalized patients meeting the WHO case definition for SARI were enrolled. Nasopharyngeal/oropharyngeal (NP/OP) swabs were collected and samples were tested using RT-PCR for influenza A, B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza virus (PIV 1,2,3,4), adenovirus, bocavirus, coronavirus, enterovirus, rhinovirus, and atypical bacteria. Data were analyzed to calculate positivity rates for viral pathogens and determine which pathogens related to severe outcomes or resulted in death. RESULTS: Overall, 1,075/3,207 (33.5%) cases had a viral etiology, with a mean age of 5.74 (±13.87) years. The highest rates were reported for RSV (485 cases, 45.2%), PIV (125, 11.6%), and adenovirus (105, 9.8%). Children had a higher viral rate (981, 91.2%) compared to 94 (8.8%) cases in adults. Patients with identified viruses had significantly lower rates for ICU admission, hospital stay, mechanical ventilation, and overall mortality than those without identified viruses. No infections were independently associated with severe outcomes. CONCLUSIONS: Viral pathogens were encountered in one-third of hospitalized adult and pediatric Egyptian patients with SARI, while atypical bacteria had a minor role. Highest rates of viral infections were reported for RSV, PIV, and adenovirus. Viral infections had neither negative impacts on clinical features nor outcomes of patients with SARI in our locality.

Manubriotomy versus median sternotomy in thymectomy for myasthenia gravis. Evaluation of the pulmonary status.

OBJECTIVE: In a prospective study, the effect of thymectomy on the pulmonary status of 50 consecutive patients with myasthenia gravis was evaluated over a time range of 4 years in the Chest and Chest surgery departments in the Cairo University Clinics and Thoracic Surgery Department of the Evangelisches Krankenhaus Duisburg-Nord. METHODS: The patients were divided into two groups: Group I included 26 patients who underwent thymectomy through median sternotomy. The mean age of the patients in this group was 24.8+/-10.5 (5-41) years. They were 19 females and seven males. Thirteen of the patients were in Myasthenia Gravis Foundation of America (MGFA) class IIa, and 12 were in class IIb, and one was in class IIIa. Group II included 24 patients who underwent thymectomy through manubriotomy. The mean age of the patients in this group was 25.2+/-9.2 (12-41) years. They were 13 females and 11 males. Eight of the patients were in MGFA class 2a, 14 were in class IIb, and two were in class IIIa. RESULTS: When compared to group I in which postoperative ventilation was required in 15.4% of patients, postoperative ventilation was not necessary in patients of group II with a statistically significant difference (P=0.04). The mean duration of stay in the intensive care unit was 111.4h in group II, and 169.7h in group I (P=0.03). The peak inspiratory flow rate and the forced vital capacity were also statistically significantly better in group II. There was no mortality in both groups, and the morbidity was higher in the median sternotomy group. CONCLUSION: Thymectomy through a manubriotomy, which allows extensive removal of ectopic thymic tissue in addition to the thymus through a less invasive approach than a full median sternotomy, is associated with a significantly smoother postoperative course and less pulmonary complications, when compared with thymectomy through a full median sternotomy.