Long-Term Functional Limitations on Cardiopulmonary Exercise Testing in Emotion-Triggered Takotsubo Syndrome.

Background: In patients with prior Takotsubo syndrome (TTS), long-lasting functional cardiac limitations were described as compared with normal subjects. Emotion-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable factors. The aim of the present study was to assess long-term cardiac functional limitations in a cohort of asymptomatic E-TTS patients. Methods: We enrolled n = 40 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 (12-40) months median follow-up from the acute event. A cohort of n = 40 individuals matched for age, sex, body mass index and comorbidities served as control. Results: Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs. 22.1 ± 6.5; p < 0.001 and 75.2 ± 14.1% vs. 100.6 ± 17.1%, p < 0.001), VO2 at anaerobic threshold (AT) (11.5 [10.1-12.9] vs. 14.4 [12.5-18.7]; p < 0.001), peak O2 pulse (9.8 ± 2.5 vs. 12.9 ± 3.5; p < 0.001) and higher VE/VCO2 slope (30.5 ± 3.7 vs. 27.3 ± 3.5; p < 0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Conclusions: Despite its favorable outcome, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

Impact of Parenteral Prostanoids in Pulmonary Arterial Hypertension: The Relevance of Timing.

Parenteral prostanoids are being recommended in pulmonary arterial hypertension (PAH) treatment, but the prognostic relevance of delayed treatment initiation is still debated. This study assessed the impact of the timing of prostacyclin treatment initiation on reducing PVR and achieving a low-risk profile in PAH patients. The study enrolled 151 patients who started on parenteral prostanoids with different treatment strategies. All patients underwent right heart catheterization, clinical evaluation, and risk assessments at baseline and after 1-year follow-up. Patients with an upfront strategy including parenteral prostanoid plus one oral drug had -5.3 ± 6.2 WU (-50 ± 19%) reduction in PVR, patients with an upfront strategy including parenteral prostanoid plus double oral drug had -12.8 ± 5.9 WU (-68 ± 17%) reduction in PVR, while patients with an add-on strategy including parenteral prostanoid after oral drugs had -3.9 ± 3.5 WU (-23 ± 19%) reduction in PVR. An upfront strategy including parenteral prostanoids was independently associated with an increased likelihood of achieving the greater reduction of PVR compared with an add-on strategy. Additionally, the greater the severity of PH at the time of diagnosis, in terms of PVR and RV reverse remodeling, the higher the probability of treatment failure. An upfront strategy including a parenteral prostanoid is associated with the highest likelihood of achieving a low-risk profile and a greater reduction of PVR compared with parenteral prostanoid as an add-on to oral treatment.

New Challenges in Heart Failure with Reduced Ejection Fraction: Managing Worsening Events.

Patients with an established diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Despite guideline-directed medical therapy, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF, and patients experiencing WHF carry a substantially higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as arrows in the quiver for clinicians to address the residual risk of HF hospitalization and cardiovascular deaths in patients with WHF. This question-and-answer-based review will discuss the emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC), the new therapeutic approaches to treat WHF and then move on to their timing and safety concerns (i.e., renal profile).

The evidence governance system in Oman.

Background: In addition to the general question about what works, policymakers consider whether health interventions will work in their context, and consider the social values such as affordability, acceptability, equity, equality, and human rights. Aims: To highlight the importance of having and using an evidence governance system to inform health policymaking in Oman. Methods: We reviewed the literature and analysed local documents on evidence governance systems in Oman. Results: The Government of Oman has shown increasing interest in research and innovation in the past few decades. This interest was reinforced through the announcement in November 2021 of the intention to establish a decision-making support unit. Oman's strategies for evidence-informed policymaking provide direct and well-integrated channels for expert advice, however, the capacity for implementation remains challenging, and there is a lack of clarity in the evidence use mandate. It is not clear how evidence was selected, synthesized and used to inform some of the government policies on health. This can limit the scope of operation and subsequent achievements. Conclusion: Efforts to strengthen evidence-informed policymaking should focus on building a system for good governance of evidence to ensure that rigorous, systematic, and technically valid evidence is used for policymaking.

Contact tracing in the context of COVID-19: a case study from Oman.

In April 2020, the Ministry of Health (MoH) in Oman, a high-income country in the Eastern Mediterranean Region (EMR), implemented a robust contact tracing (CT) system for COVID-19. To capitalise on Oman's experience, EMRO has developed a case study presenting the methodology used to conduct the CT activities, main functions of the system, challenges encountered, lessons learnt, and the way forward. To develop the case study, a key informant interview was conducted virtually with the CT focal point in the MoH, using a semistructured questionnaire adapted from the WHO questionnaire for the assessment of CT activities. The Oman MoH launched a CT system based on three complementary digital tools: Tarassud plus, Medical Scout and HMushrif applications. Oman's CT strategy classifies contacts into close and casual contacts. Only close contacts are listed using the Tarassud plus application, while casual contacts are requested to self-monitor for 14 days using the other two applications. With the evolution of the outbreak, Oman MoH implemented stricter policies and prioritised the follow-up of close contacts to keep the CT activity manageable. Community health workers and volunteers facilitated the CT activities through sensitisation of the local community to the follow-up process and reducing the COVID-19-associated stigma. Challenges encountered revolved around contact data management, given the offline in-operability of the applications, and lack of national risk communication guidelines to address community concerns and widespread rumours.

Nationwide hepatitis C virus screening and treatment of adolescents in Egyptian schools.

Until 2018, Egypt had the highest prevalence of hepatitis C virus (HCV) infection globally, affecting approximately 7% of the population. Despite efforts in diagnosis and treatment since 2006, nearly 2 million individuals with chronic HCV infection had yet to be diagnosed as of early 2018. In December, 2018, a mass HCV screening campaign for adolescents aged 15-18 years was initiated. Among 3 024 325 adolescents screened, the HCV antibody seroprevalence was 11 477 (0·38%), of whom 8187 (78·7%) were HCV RNA-positive. Sustained virological response 12 weeks after completion of treatment (SVR12) was attained by 7327 (99·6%) adolescents with a fixed-dose combination of generic ledipasvir 90 mg plus sofosbuvir 400 mg. Although mass screening in this age group might not be regularly adopted by many health systems and its cost-effectiveness might be lower than the screening of adults and high-risk groups (eg, patients on haemodialysis, people who inject drugs), breaking the chain of transmission in younger populations should lead to a reduction in HCV incidence and complications, and hasten the elimination of the disease.

Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients.

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21-71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-ß-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.

Utility of procalcitonin and C-reactive protein as predictors of Gram-negative bacteremia in febrile hematological outpatients.

This study was designed to determine the utility of procalcitonin (PCT) and C-reactive protein (CRP) as predictors of Gram-negative bloodstream infection (GN-BSI) in hematological febrile outpatients at the time of the emergency unit admission. Overall, 286 febrile episodes, which included 42 GN-BSI (16%), were considered. PCT levels at patient admission were statistically higher in GNB-BSI when compared to Gram-positive bacteria BSI (median 4.06 ng/ml (range 1.10-25.04) vs 0.88 ng/ml (0.42-10), p<0.03) and to all other fever etiologies. For CRP, differences within fever etiologies were less profound but statistically significant, except for GN-BSIs vs GP BSIs (p=0.4). ROC analysis of PCT showed that an AUC of 0.85 (95%CI 0.79-0.95) discriminated GN-BSI from all other fever etiologies, with a best cut-off of 0.5 ng/ml, a negative predictive value (NPV) of 98%, and a negative likelihood ratio (negLR) of 0.1. ROC analysis of CRP showed an AUC of 0.67 (95%CI 0.53-0.81) with a best cut-off of 6.64 mg/dl, a NPV of 94%, and a negLR of 0.33. This study confirms that 0.5 ng/ml represents the PCT best cut-off to differentiate the cause of fever and rule out a GN-BSI in febrile hematologic outpatients at the time of the emergency unit admission. Therefore, introducing PCT testing could be a valid measure in order to tailor a more precise prompt antimicrobial therapy to the febrile outpatient while waiting for blood culture results.

Purchasing health services under the Egypt's new Universal Health Insurance law: What are the implications for universal health coverage?

BACKGROUND: Egypt's Universal Health Insurance (UHI) Law of 2018 implies major transformation to the health financing system. This commentary provides an assessment of the purchasing arrangements as stipulated by the UHI Law and Bylaw, their implications and contribution to progress towards universal health coverage (UHC). The purpose of this assessment is to inform the multi-year implementation process of the Law and propose options for progress towards UHC. METHODS: Guided by an analytical framework on purchasing, the qualitative analysis was based on the review of the legal provisions and structured discussions with key stakeholders. RESULTS: The Law foresees important changes, such as a purchaser-provider split, stricter referral rules and regulated cost-sharing. However, several purchasing aspects were not sufficiently specified in the legal provisions, for example benefit design and provider payment methods. It remains unclear for decision-makers how to proceed, hindering the Law's effective implementation. There are also concerns about the mixed provider payment system creating incoherent provider incentives. CONCLUSION: In view of the remaining legal unclarities on purchasing, progress towards UHC is restrained. Benefits design and the provider payment system should be further specified with a clearer governance structure around the purchasing decision-making processes. Additional technical options for strategic purchasing are suggested.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years.

OBJECTIVES: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. METHODS: This was a retrospective chart review looking at bacterial BSI episodes between 2007-2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. RESULTS: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/µL (OR = 0.12, 95% CI 0.03-0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. CONCLUSION: The persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.

Predominance of Candida Glabrata among Non-albicans Candida Species in a 16-Year Study of Candidemia at a Tertiary Care Center in Lebanon.

BACKGROUND: Candidemia is associated with a high mortality rate, and its incidence is increasing worldwide with a rise in non-albicans candidemia (NAC). Epidemiologic data from Arab countries are scarce and there are no data from Lebanon; Methods: This is a single-center retrospective chart review of patients with candidemia in a tertiary care center in Lebanon from 2004 to 2019. We extracted data on patient characteristics, isolated Candida species antifungal susceptibility, management and outcomes; Results: We included 170 cases of candidemia. NAC was more common than albicans candidemia (64.7% vs. 35.3%). C. glabrata was the most common non-albicans species (37 isolates) followed by C. tropicalis (14). Recent use of antifungals was a risk factor for NAC (OR = 2.8, p = 0.01), while the presence of a central venous catheter was protective (OR = 0.41, p = 0.02). Fluconazole resistance was 12.5% in C. albicans and 21.5% in non-albicans spp. Mortality at 30 days was 55.5%, with no difference between NAC and albicans candidemia. It was higher in older and critically ill patients but lower in patients whose central venous catheter was removed after detecting fungemia; Conclusions: Candidemia is associated with high mortality in Lebanon, with a predominance of NAC and high prevalence of C. glabrata.

Gram-Negative Skin and Soft Tissue Infections.

Skin and soft tissue infections (SSTIs) frequently are encountered in clinical practice, and gram-negative bacilli (GNB) constitute an underrated portion of their etiology. The rate of GNB-causing SSTIs is increasing, especially with the rise in antimicrobial resistance. Although the diagnosis of SSTIs mostly is clinical, rapid diagnostic modalities can shorten the time to initiating proper therapy and improving outcomes. Novel antibiotics are active against GNB SSTIs and can be of great value in the management. This review provides an overview of the role of GNB in SSTIs and summarizes their epidemiology, risk factors, outcome, and clinical management.

Current choices of antibiotic treatment for Pseudomonas aeruginosa infections.

PURPOSE OF REVIEW: Pseudomonas aeruginosa is one of the most feared nosocomial pathogens. Treatment of P. aeruginosa infections is challenging because of the limited choices of antibiotics and the emergent resistance of the pathogen. The present review aims at addressing the management of P. aeruginosa infections and highlighting the novel antibiotics that show a future promising role. RECENT FINDINGS: Novel fluoroquinolones have been recently introduced and show favorable activity. New combinations of ß-lactams/ß-lactamase inhibitors have been studied in various indications of infections because of P. aeruginosa. Cefiderocol, a new cephalosporin, shows very promising results against P. aeruginosa. Currently, combination therapy is only recommended in limited scenarios. Extended-infusion of ß-lactams exhibit clinical benefit. Bacteriophage therapy is a growing field of interest and may have an impactful effect on the treatment of resistant P. aeruginosa. SUMMARY: Factors that guide clinical decisions for empiric and directed P. aeruginosa therapy include the epidemiology, the patient's risk factors, the site of infection, and the available treatment options. Conventional antipseudomonal antibiotics have been used successfully for a long time, but the increase in worldwide resistance necessitates the need for newer agents. Antimicrobial stewardship is essential to preserve the new drugs and prevent future development of resistance.

Treatment of multidrug-resistant Gram-negative skin and soft tissue infections.

PURPOSE OF REVIEW: The increase in skin and soft tissue infections (SSTI) because of multidrug-resistant (MDR) pathogens is a global concern. Although MDR Gram-negative bacteria (GNB) are often overlooked as a cause of SSTIs, their burden on the morbidity of many subgroups of patients is high. There is a paucity in the available treatment options and guidelines on how to treat these pathogens. This manuscript reviews the management of SSTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. We also highlight a few novel antibiotics that show promise in the future management of MDR-GNB SSTIs. RECENT FINDINGS: Studies on treatment options of MDR-GNB SSTIs are scarce. Most clinical trials investigating new antibiotics have addressed conditions such as complicated intraabdominal infections, complicated urinary infections, and respiratory infections. CREs are a heterogenous group of pathogens with various mechanisms of resistance dictating susceptibility to different antimicrobial agents. Ceftazidime--avibactam, and meropenem--vaborbactam have potent activity against some of the CREs, especially Klebsiella pneumoniae carbapenemase (KPC) producers. Several novel antibiotics have potent activity against CRPA SSTIs, such as ceftazidime--avibactam, ceftolozane--tazobactam, cefiderocol, delafloxacin, finafloxacin, and murepavadin. Cefiderocol may also play an important role in the management of CRAB SSTIs, along with plazomicin and eravacycline. SUMMARY: MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs.

Epidemiology and burden of invasive fungal infections in the countries of the Arab League.

The burden of invasive fungal infections is alarming worldwide. The aim of this paper is to review the published literature and evaluate the knowledge gap pertaining to studies on invasive fungal infections in the countries of the Arab League. Few countries from this region have published reports. The most commonly studied invasive fungal infections is invasive candidiasis. Candida albicans remains overall the most common causative pathogen (33.8-60%), however, non-albicans Candida species are increasing. Antifungal susceptibility testing is non-standardized across the published studies. Data on aspergillosis and other fungal infections is scarce. This sheds light on the need for standardized surveillance in the region encompassing more countries of the Arab League to guide diagnostic approach and empiric therapy.

Evaluating tools to define influenza baseline and threshold values using surveillance data, Egypt, season 2016/17.

BACKGROUND: Establishing influenza thresholds and transmission intensity can help evaluate seasonal changes in influenza severity and potential pandemics. We aimed to evaluate the moving epidemic method (MEM) for calculating influenza thresholds for season 2016/17 in Egypt using four parameters, to identify the most useful parameter. Also to measure the agreement between both the country-specific statistical empirical method and World Health Organization method to MEM for determining the length and intensity level of activity of the influenza season. METHODS: Routinely epidemiological and laboratory data from sentinel surveillance sites for Severe Acute Respiratory Infection (SARI) and influenza-like illness (ILI) were used for calculating thresholds for seasons between 2010/11 and 2015/16 to test 2016/17 season. The parameters calculated were: screened ILI consultation rate × 1000, screened ILI composite parameter, influenza positivity percentage among sampled SARI cases, and influenza positivity percentage among sampled ILI and SARI cases. These parameters assess seasonality and intensity of influenza activity using the three proposed methods (mentioned above). Agreement between the three methods was done using several approaches. RESULTS: The intensity of influenza activity by MEM was lower than the other two methods. Agreement between MEM and each of the other two techniques varied appreciably from good to very good for seasonal duration, and poor to fair for intensity level. In addition, parameters including laboratory data showed a pattern of bi-wave activity; the first wave occurred in winter mostly between epidemiological weeks 39 and 52 and the second occurred in spring mostly between weeks 12 and 17. CONCLUSION: Parameters including laboratory data were more useful in defining seasonality of influenza. Further exploration of the MEM model in future seasons may help to provide a more comprehensive understanding of its use and application.

Towards a hepatitis-free Egypt: is this achievable? (Editorial).

Over the past few years, we have seen remarkable developments in the global commitment to address viral hepatitis. In May 2006, 194 countries of the World Health Assembly unanimously adopted the first-ever Global Health Sector Strategy on viral hepatitis, 2016-2021. Through these high-level strategies, countries made a commitment to eliminate viral hepatitis as a public health threat by 2030. Unfortunately, Egypt has one of the highest global burdens of hepatitis C virus (HCV) infections; it is estimated that prevalence of HCV is around 4.5% to 6.7%.

Elimination of schistosomiasis haematobia as a public health problem in five governorates in Upper Egypt.

The prevalence and intensity of Schistosoma haematobium infection was determined among schoolchildren living in five governorates in Upper Egypt. Between November 2016 and March 2017, urine samples were collected from 30,083 schoolchildren (6-16 years of age) from the governorates of Assiut (n = 7496; 6 districts), Bani Sweif (n = 4493; 7 districts), Fayoum (n = 4597; 6 districts), Menia (n = 7500; 9 districts) and Sohag (n = 5997; 11 districts). All samples were processed using urine filtration to detect and quantify S. haematobium eggs. The overall prevalence was 1.3% (95% Confidence Interval (CI) = 1.1%, 1.4%), but the prevalence varied considerably across districts in the studied governorates (from 0%, Fayoum to 13.4%, Sohag). The prevalence of heavy-intensity infections (≥50 egg/10 ml) varied from 0.05% (95% CI = 0.01-0.1) in Sohag to 0.3% (95% CI = 0.1-0.4) in Menia. No subject with heavy intensity of infection was detected in Fayoum and Bani Sweif governorates. Of the 39 studied districts 97.4% had prevalence of heavy intensity infection of <1%, indicating elimination of schistosomiasis haematobia as a public health problem in these districts. Of those studied 72.0% were male. Males were 2.9 times as likely to be infected (1.5% [95% CI: 1.4-1.7]) as females (0.5% [95% CI: 0.3-0.7]); χ2 = 51.2, p < 0.0001. Heavy intensity of infection was detected only in males. The prevalence of S. haematobium infection increased steadily with age, and the age group >15 years was 7 times as likely to be infected as the younger age group (6-<9; 0.8%); χ2 = 44.9, p < 0.0001. The national schistosomiasis control programme (NSCP) adopted a new elimination strategy by readjusting thresholds for MDA using praziquantel and targeting all transmission areas. The NSCP, after this major achievement of elimination of schistosomiasis haematobia as a public health problem, is now moving to interruption of its transmission.