Improving 1-Year Mortality Following Intensive Care Unit Admission in Adults with HIV: A 20-Year Observational Study.

BACKGROUND: Despite widespread use of combination antiretroviral therapy, people with HIV (PWH) continue to have an increased risk of admission to and mortality in the intensive care unit (ICU). Mortality risk after hospital discharge is not well described. Using retrospective data on adult PWH (≥18 years) admitted to ICU from 2000-2019 in an HIV-referral centre, we describe trends in 1-year mortality after ICU admission. METHODS: One-year mortality was calculated from index ICU admission to date of death; with follow-up right-censored at day 365 for people remaining alive at 1 year, or day 7 after ICU discharge if lost-to-follow-up after hospital discharge. Cox regression was used to describe the association with calendar year before and after adjustment for patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation II [APACHE II] score, CD4+ T-cell count, and recent HIV diagnosis) at ICU admission. Analyses were additionally restricted to those discharged alive from ICU using a left-truncated design, with further adjustment for respiratory failure at ICU admission in these analyses. RESULTS: Two hundred and twenty-one PWH were admitted to ICU (72% male, median [interquartile range] age 45 [38-53] years) of whom 108 died within 1-year (cumulative 1-year survival: 50%). Overall, the hazard of 1-year mortality was decreased by 10% per year (crude hazard ratio (HR): 0.90 (95% confidence interval: 0.87-0.93)); the association was reduced to 7% per year (adjusted HR: 0.93 (0.89-0.98)) after adjustment. Conclusions were similar among the subset of 136 patients discharged alive (unadjusted: 0.91 (0.84-0.98); adjusted 0.92 (0.84, 1.02)). CONCLUSIONS: Between 2000 and 2019, 1-year mortality after ICU admission declined at this ICU. Our findings highlight the need for multi-centre studies and the importance of continued engagement in care after hospital discharge among PWH.

Changes in short-term (in-ICU and in-hospital) mortality following intensive care unit admission in adults living with HIV: 2000-2019.

OBJECTIVE: Limited data suggest intensive care unit (ICU) outcomes have improved in people with HIV (PWH). We describe trends in in-ICU/in-hospital mortality among PWH following admission to ICU in a single UK-based HIV referral centre, from 1 January 2000 to 31 December 2019. METHODS: Modelling of associations between ICU admission and calendar year of admission was done using logistic regression with adjustment for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, CD4 + T-cell count and diagnosis of HIV at/within the past 3 months. RESULTS: Among 221 PWH (71% male, median [interquartile range (IQR)] age 45 years [38-53]) admitted to ICU, median [IQR] APACHE II score and CD4 + T-cell count were 19 [14-25] and 122 cells/µl [30-297], respectively; HIV-1 viral load was ≤50 copies/ml in 46%. The most common ICU admission diagnosis was lower respiratory tract infection (30%). In-ICU and in-hospital, mortality were 29 and 38.5%, respectively. The odds of in-ICU mortality decreased over the 20-year period by 11% per year [odds ratio (OR): 0.89 (95% confidence interval (CI): 0.84-0.94)] with in-hospital mortality decreasing by 14% per year [0.86 (0.82-0.91)]. After adjusting for patient demographics and clinical factors, both estimates were attenuated, however, the odds of in-hospital mortality continued to decline over time [in-ICU mortality: adjusted OR: 0.97 (0.90-1.05); in-hospital mortality: 0.90 (0.84-0.97)]. CONCLUSION: Short-term mortality of critically ill PWH admitted to ICU has continued to decline in the ART era. This may result from changing indications for ICU admission, advances in critical care and improvements in HIV-related immune status.

The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort.

OBJECTIVES: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in nonendemic countries. Our aim was to characterize diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification and to describe a virtual care model. METHODS: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV polymerase chain reaction testing, 70 were confirmed positive, and 70 were negative. Data were compared to generate odds ratios of demographic and clinical features. RESULTS: Patients who tested positive were predominantly cis-male (99%) and self-identified as gay, bisexual, and other men who have sex with men (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (odds ratio [OR] 7.69 [95% confidence interval (CI) 3.58, 16.51]). Patients who tested positive were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) than negative controls. A total of 79% of patients were engaged with a virtual ward follow-up. CONCLUSION: These data can inform a risk-based approach to the management of suspected monkeypox in gay, bisexual, and other men who have sex with men populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPHXV outbreak.

Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study.

OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/µL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/µL, and 95% had advanced HIV (CD4 count < 200 cells/µL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services.

Reducing the risk of tuberculosis transmission for HCWs in high incidence settings.

Globally, tuberculosis (TB) is a leading cause of death from a single infectious agent. Healthcare workers (HCWs) are at increased risk of hospital-acquired TB infection due to persistent exposure to Mycobacterium tuberculosis (Mtb) in healthcare settings. The World Health Organization (WHO) has developed an international system of infection prevention and control (IPC) interventions to interrupt the cycle of nosocomial TB transmission. The guidelines on TB IPC have proposed a comprehensive hierarchy of three core practices, comprising: administrative controls, environmental controls, and personal respiratory protection. However, the implementation of most recommendations goes beyond minimal physical and organisational requirements and thus cannot be appropriately introduced in resource-constrained settings and areas of high TB incidence. In many low- and middle-income countries (LMICs) the lack of knowledge, expertise and practice on TB IPC is a major barrier to the implementation of essential interventions. HCWs often underestimate the risk of airborne Mtb dissemination during tidal breathing. The lack of required expertise and funding to design, install and maintain the environmental control systems can lead to inadequate dilution of infectious particles in the air, and in turn, increase the risk of TB dissemination. Insufficient supply of particulate respirators and lack of direction on the re-use of respiratory protection is associated with unsafe working practices and increased risk of TB transmission between patients and HCWs. Delayed diagnosis and initiation of treatment are commonly influenced by the effectiveness of healthcare systems to identify TB patients, and the availability of rapid molecular diagnostic tools. Failure to recognise resistance to first-line drugs contributes to the emergence of drug-resistant Mtb strains, including multidrug-resistant and extensively drug-resistant Mtb. Future guideline development must consider the social, economic, cultural and climatic conditions to ensure that recommended control measures can be implemented in not only high-income countries, but more importantly low-income, high TB burden settings. Urgent action and more ambitious investments are needed at both regional and national levels to get back on track to reach the global TB targets, especially in the context of the COVID-19 pandemic.

A new era of cancer treatment: carbon nanotubes as drug delivery tools.

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.