Próby leczenia chorych z zespołem złożonego bezdechu śródsennego aparatami wytwarzającymi dwupoziomowe ciśnienie w drogach oddechowych w trybie spontanicznym

Introduction: Patients with complex sleep apnoea (CompSAS) have obstructive sleep apnoea and experience persistent central apnoeas when exposed to positive airway pressure. Elevated loop gain is one of the postulated mechanisms of CompSAS. We speculated that bilevel positive airway pressure — spontaneous (BPAP-S), by producing relative hyperventilation, may more readily produce CompSAS activity than continuous positive airway pressure (CPAP). If found to do so, a trial of BPAP-S might be a simple way of identifying patients with elevated loop gain who are at risk for CompSAS. Materials and methods: Thirty-nine patients with complex sleep apnoea were included in the study. Segments of NREM sleep on CPAP and BPAP-S matched for body position and expiratory airway pressure (comparison pressure) were retrospectively analysed. Correlations between clinical and demographic variables and polysomnographic response to CPAP and BPAP-S were sought. Results: There was no difference in any of the polysomnographic indices on CPAP and BPAP-S. In 19 patients the use of CPAP was associated with lower AHI at the comparison pressure; in 20 patients the opposite was true. No clinical variables correlated to the differential response to CPAP vs. BPAP-S. Conclusions: BPAP-S was not more effective than CPAP in stimulating complex sleep apnoea activity.Wstęp: Zastosowanie terapii stałym dodatnim ciśnieniem dróg oddechowych (CPAP) u chorych na zespół złożonego bezdechu śródsennego (CompSAS) prowadzi do wystąpienia zaburzeń oddychania typu ośrodkowego. Jednym z podstawowych postulowanych mechanizmów powstawania CompSAS jest zwiększenie loop gain — wzmocnienia pętli sprzężenia — definiowanego jako całkowita odpowiedź układu oddechowego na zaburzenie jego stanu równowagi. Teoretycznie, zastosowanie terapii aparatem wytwarzającym dwupoziomowe ciśnienie w drogach oddechowych w trybie spontanicznym (BPAP-S), powinno nasilać hiperwentylację i prowadzić do łatwiejszego powstawania fenotypu CompSAS niż CPAP. Praktyczne potwierdzenie tej teorii pozwoliłoby na łatwiejszą identyfikację osób z wysokim wzmocnieniem pętli sprzężenia, narażonych na CompSAS. Materiał i metody: Badaniem objęto grupę 39 chorych na CompSAS. Przeprowadzono retrospektywną analizę porównawczą fragmentów snu NREM uzyskanych podczas polisomnografii terapeutycznej (PSG) uzyskanych podczas stosowania CPAP i BPAP-S, zgodnych co do pozycji ciała pacjenta i ciśnienia wydechowego (ciśnienie porównawcze). Poszukiwano korelacji pomiędzy parametrami klinicznymi, demograficznymi oraz odpowiedzią chorych na CPAP i BPAP-S. Wyniki: Nie stwierdzono różnic w żadnym parametrze polisomnograficznym pomiędzy segmentami snu podczas próby stosowania CPAP i BPAP-S. U 19 chorych, wskaźnik bezdechów i spłyceń oddechu (AHI) był niższy podczas leczenia aparatem CPAP na poziomie ciśnienia porównawczego niż podczas leczenia BPAP-S, zaś u 20 pacjentów obserwowano odwrotną zależność. Nie stwierdzono korelacji żadnego z badanych parametrów klinicznych ze skutecznością CPAP lub BPAP-S. Wnioski: Nie obserwowano zwiększenia częstości wywoływania CompSAS przez BPAP-S w porównaniu z CPAP

Improving access to pre-exposure prophylaxis for adolescent girls and young women: recommendations from healthcare providers in eastern Zimbabwe

Background: In sub-Saharan Africa, adolescent girls and young women (AGYW) are at high risk of acquiring HIV. A growing number of sub-Saharan African countries are beginning to avail pre-exposure prophylaxis, or PrEP, but with limited success. Unpacking strategies to overcome barriers to the uptake of PrEP is critical to prevent HIV amongst AGYW. This article explores health professionals’ views and recommendations on what is required to increase uptake of PrEP. Methods: The study draws on interview data from 12 providers of HIV prevention services in eastern Zimbabwe. The healthcare providers were purposefully recruited from a mix of rural and urban health facilities offering PrEP. The interviews were transcribed and imported into NVivo 12 for thematic coding and network analysis. Results: Our analysis revealed six broad strategies and 15 concrete recommendations which detail the range of elements healthcare providers consider central for facilitating engagement with PrEP. The healthcare providers called for: (1) PrEP marketing campaigns; (2) youth-friendly services or corners; (3) improved PrEP delivery mechanisms; (4) improvements in PrEP treatment; (5) greater engagement with key stakeholders, including with young people themselves; and (6) elimination of costs associated with PrEP use. These recommendations exemplify an awareness amongst healthcare providers that PrEP access is contingent on a range of factors both inside and outside of the clinical setting. Conclusions: Healthcare providers are at the frontline of the HIV epidemic response. Their community-embeddedness, coupled with their interactions and encounters with AGYW, make them well positioned to articulate context-specific measures for improving access to PrEP. Importantly, the breadth of their recommendations suggests recognition of PrEP use as a complex social practice that requires integration of a combination of interventions, spanning biomedical, structural, and behavioural domains

Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa.

Tuberculous pericarditis is one of the most severe forms of extrapulmonary tuberculosis, causing death or disability in a substantial proportion of affected people.1,2 In Africa, the incidence of tuberculous pericarditis is rising as a result of the HIV epidemic.3 The effect of HIV infection on survival in patients with tuberculous pericarditis is unknown.2,4 Whereas some investigators have suggested that HIV-infected patients with tuberculous pericarditis have a similar outcome to non-infected cases,5 others have shown that there may be an increase in mortality in HIV associated with tuberculous pericarditis.2,6,7 We established a prospective observational study, the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry, to obtain current information on the diagnosis, management and outcome of patients with presumed tuberculous pericarditis living in sub-Saharan Africa, where the burden of HIV infection is the greatest in the world.4,8-10 In this paper, we report the mortality rate and its predictors during the 6 months of antituberculosis treatment among patients enrolled in the regis

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease

Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18–65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain

Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa

Objective: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. Design: Between 1 March 2004 and 31 October 2004, we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon, Nigeria, and South Africa, and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study, with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression, we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. Results: We obtained the vital status of 174 (94%) patients (median age 33; range 14-87 years). The overall mortality rate was 26%. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40% versus 17%, P=0.001). Independent predictors of death during follow-up were: (1) a proven non-tuberculosis final diagnosis (hazard ratio [HR] 5.35, 95% confidence interval 1.76 to 16.25), (2) the presence of clinical signs of HIV infection (HR 2.28, 1.14-4.56), (3) co-existent pulmonary tuberculosis (HR 2.33, 1.20-4.54), and (4) older age (HR 1.02, 1.01-1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80, 0.90-3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34, 0.10-1.19). Conclusion: A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africans. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease