Systematic review and meta-analysis of anti-CD20 treatments in patients with COVID-19: an assessment of severe illness and mortality outcomes.

BACKGROUND: The use of anti-CD20 monoclonal antibodies, such as rituximab and ocrelizumab, has emerged as a matter of concern, in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: We aimed to summarize the overall evidence on the pre-admission/pre-diagnosis use of anti-CD20 among patients with COVID-19 with regards to mortality and severe illness outcomes. METHODS: A systematic literature search with no language restriction was performed in electronic databases, including PubMed, Google Scholar, Scopus, and preprint servers (medRxiv, Research Square, SSRN), to identify eligible studies published up to June 13, 2023. The outcomes of interest were the development of severe illness and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio for outcomes of interest using anti-CD20 monoclonal antibodies relative to non-use of anti-CD20 monoclonal antibodies, at 95% confidence intervals. RESULTS: Our systematic review and meta-analysis revealed significantly increased odds for development of severe illness (pooled odds ratio 2.95; 95% confidence interval 2.30, 3.78; n = 534,349) and significantly increased odds for mortality (pooled odds ratio 2.14; 95% confidence interval 1.37, 3.35; n = 333,462) with the use of anti-CD20 monoclonal antibodies, relative to non-use of anti-CD20 monoclonal antibodies, in patients with COVID-19. CONCLUSION: Healthcare practitioners should exercise caution when prescribing these anti-CD20 monoclonal antibodies during the COVID-19 pandemic to patients who are indicated for these agents, particularly those with underlying conditions like multiple sclerosis or rheumatoid arthritis.

Risk Factors Associated with Mortality in COVID-19 Hospitalized Patients: Data from the Middle East.

This study aimed to assess the risk factors for COVID-19 mortality among hospitalized patients in Jordan. All COVID-19 patients admitted to a tertiary hospital in Jordan from September 20, 2020, to August 8, 2021, were included in this study. Demographics, clinical characteristics, comorbidities, and laboratory results were extracted from the patients' electronic records. Multivariable logistic and machine learning (ML) methods were used to study variable importance. Out of 1,613 COVID-19 patients, 1,004 (62.2%) were discharged from the hospital (survived), while 609 (37.8%) died. Patients who were of elderly age (>65 years) (OR, 2.01; 95% CI, 1.28-3.16), current smokers (OR, 1.61; 95%CI, 1.17-2.23), and had severe or critical illness at admission ((OR, 1.56; 95%CI, 1.05-2.32) (OR, 2.94; 95%CI, 2.02-4.27); respectively), were at higher risk of mortality. Comorbidities including chronic kidney disease (OR, 2.90; 95% CI, 1.90-4.43), deep venous thrombosis (OR, 2.62; 95% CI, 1.08-6.35), malignancy (OR, 2.22; 95% CI, 1.46-3.38), diabetes (OR, 1.31; 95% CI, 1.04-1.65), and heart failure (OR, 1.51; 95% CI, 1.02-2.23) were significantly associated with increased risk of mortality. Laboratory abnormalities associated with mortality included hypernatremia (OR, 11.37; 95% CI, 4.33-29.81), elevated aspartate aminotransferase (OR, 1.81; 95% CI, 1.42-2.31), hypoalbuminemia (OR, 1.75; 95% CI, 1.37-2.25), and low platelets level (OR, 1.43; 95% CI, 1.05-1.95). Several demographic, clinical, and laboratory risk factors for COVID-19 mortality were identified. This study is the first to examine the risk factors associated with mortality using ML methods in the Middle East. This will contribute to a better understanding of the impact of the disease and improve the outcome of the pandemic worldwide.

Predictors of invasive mechanical ventilation in hospitalized COVID-19 patients: a retrospective study from Jordan.

OBJECTIVES: To identify early indicators for invasive mechanical ventilation utilization among COVID-19 patients. METHODS: This retrospective study evaluated COVID-19 patients who were admitted to hospital from 20 September 2020, to 8 August 2021. Multivariable logistic regression and machine learning (ML) methods were employed to assess variable significance. RESULTS: Among 1,613 confirmed COVID-19 patients, 365 patients (22.6%) received invasive mechanical ventilation (IMV). Factors associated with IMV included older age >65 years (OR,1.46; 95%CI, 1.13-1.89), current smoking status (OR, 1.71; 95%CI, 1.22-2.41), critical disease at admission (OR, 1.97; 95%CI, 1.28-3.03), and chronic kidney disease (OR, 2.07; 95%CI, 1.37-3.13). Laboratory abnormalities that were associated with increased risk for IMV included high leukocyte count (OR, 2.19; 95%CI, 1.68-2.87), low albumin (OR, 1.76; 95%CI, 1.33-2.34) and high AST (OR, 1.71; 95%CI, 1.31-2.22). CONCLUSION: Our study suggests that there are several factors associated with the increased need for IMV among COVID-19 patients. These findings will help in early identification of patients at high risk for IMV and reallocation of hospital resources toward patients who need them the most to improve their outcomes.

Potential applications and performance of machine learning techniques and algorithms in clinical practice: A systematic review.

PURPOSE: The advent of clinically adapted machine learning algorithms can solve numerous problems ranging from disease diagnosis and prognosis to therapy recommendations. This systematic review examines the performance of machine learning (ML) algorithms and evaluates the progress made to date towards their implementation in clinical practice. METHODS: Systematic searching of databases (PubMed, MEDLINE, Scopus, Google Scholar, Cochrane Library and WHO Covid-19 database) to identify original articles published between January 2011 and October 2021. Studies reporting ML techniques in clinical practice involving humans and ML algorithms with a performance metric were considered. RESULTS: Of 873 unique articles identified, 36 studies were eligible for inclusion. The XGBoost (extreme gradient boosting) algorithm showed the highest potential for clinical applications (n = 7 studies); this was followed jointly by random forest algorithm, logistic regression, and the support vector machine, respectively (n = 5 studies). Prediction of outcomes (n = 33), in particular Inflammatory diseases (n = 7) received the most attention followed by cancer and neuropsychiatric disorders (n = 5 for each) and Covid-19 (n = 4). Thirty-three out of the thirty-six included studies passed more than 50% of the selected quality assessment criteria in the TRIPOD checklist. In contrast, none of the studies could achieve an ideal overall bias rating of 'low' based on the PROBAST checklist. In contrast, only three studies showed evidence of the deployment of ML algorithm(s) in clinical practice. CONCLUSIONS: ML is potentially a reliable tool for clinical decision support. Although advocated widely in clinical practice, work is still in progress to validate clinically adapted ML algorithms. Improving quality standards, transparency, and interpretability of ML models will further lower the barriers to acceptability.

The use of remdesivir for the management of patients with moderate-to-severe COVID-19: a systematic review.

OBJECTIVE: We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a moderate-to-severe course of illness. METHODS: A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19. RESULTS: A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies. CONCLUSION: Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.

Home Medicines Review and frailty among community-dwelling older women.

OBJECTIVES: Home Medicines Reviews (HMRs) can optimize medications for frail older adults. This study aimed to determine the use of HMRs according to frailty status and the association between frailty and use of HMRs. METHODS: The study included 9139 female participants enrolled in the Australian Longitudinal Study on Women's Health from 2003 (aged 77-82 years) to 2017 (aged 91-96 years). Generalized estimating equations (GEEs) using log-binomial regressions were used to determine associations using repeated measures on individuals over time. KEY FINDINGS: The majority of participants in the study remained non-frail and did not receive HMRs from 2003 [7116 (77.86%)] to 2017 [1240 (71.31%)]. The use of HMRs was low in both groups with 33 (1.68%; 95% CI, 1.16 to 2.36) frail and 64 (0.89%; 95% CI, 0.69 to 1.14) non-frail participants receiving HMRs in 2003; by 2017, 19 (4.19%; 95% CI, 2.54 to 6.46) frail and 45 (3.50%; 95% CI, 2.57 to 4.66) non-frail participants received HMRs. Frailty was not associated with receiving a HMR (RR 1.06; 95% CI, 0.95 to 1.20), although for every 1-year increase, participants were 10% more likely to receive a HMR (RR 1.10; 95% CI, 1.09 to 1.11). Participants with continuous polypharmacy, ≥4 chronic diseases, >4 general practitioner visits and Department of Veterans Affairs coverage were more likely to receive a HMR. CONCLUSIONS: Despite the proven value of HMRs for frail older people, HMRs were not used for most frail and non-frail community-dwelling women in this study. Reasons for low use of the service should be explored, with interventions to raise awareness of the benefits of the service.

Residential Medication Management Reviews and continuous polypharmacy among older Australian women.

Background Polypharmacy is an important consideration for the provision of Residential Medication Management Reviews (RMMRs) among older women given their enhanced risk of medication-related problems and admission to residential aged care (RAC). Objectives To determine the prevalence of the use of RMMRs among older women in RAC, and the association between RMMRs and polypharmacy, medications, and costs. Setting Older Australian women aged 79-84 years in 2005 who had at least one Medicare Benefits Schedule and Pharmaceutical Benefits Scheme record, received a service in aged care, and consented to data linkage. Methods Generalised estimating equations were used to determine the association between polypharmacy and RMMRs, while adjusting for confounding variables. Main outcome measures Prevalence of the use of RMMRs among older women in RAC, association between RMMRs and polypharmacy, medications, and costs. Results Most participants did not have continuous polypharmacy and did not receive RMMRs from 2005 [451 (67.4%)] until 2017 [666 (66.6%)]. Participants with continuous polypharmacy were 17% more likely to receive a RMMR (risk ratio 1.17; 95% confidence interval 1.11, 1.25). Participants in their final year of life and residing in outer regional/remote/very remote Australia were less likely to receive RMMRs. Out-of-pocket medication costs increased over time, and alendronate and aspirin were common contributors to polypharmacy among participants who received RMMRs. Conclusion Polypharmacy was associated with receiving RMMRs and around two-thirds of women who are entitled to a RMMR never received one. There is potential to improve the use of medicines by increasing awareness of the service among eligible individuals, their carers and health care professionals.

Availability, Affordability, Access, and Pricing of Anti-cancer Medicines in Low- and Middle-Income Countries: A Systematic Review of Literature.

Background: Cancer is the second leading cause of death globally accounting for more than half of deaths in Low- and Middle-Income Countries (LMICs). Cancer treatment is expensive and the high prices of cancer medicines have a huge impact on access in LMICs. Scarcity of pricing or affordability data is one of the major barriers in the development of effective and transparent pricing policies in LMICs. This study aimed to conduct a systematic review of the literature regarding pricing, availability, affordability, and access to anti-cancer medicines in LMICs. Method: A systematic search was conducted across six electronic databases: PubMed, Medline/CINAHL (EBSCO), Web of Science, Springer Links, Scopus, and Google Scholar. The literature (from 2015 to 2020) was reviewed to identify original research articles published in English. Results: A total of 13 studies were included in the review with some having multiple outcomes: five studies on pricing, four studies addressed affordability, five studies reported on availability, and four studies on access to anti-cancer medicines. The studies showed that in LMICs, there are wide variations in cancer prices and availability amongst the medicine brands and across different countries, with less affordability by patients with low-income levels, sometimes leading to treatment abandonment. Conclusion: Given the importance of medicine availability and prices in patient access and medicine buying capacity of governments, multi-pronged policy and program approaches by multiple stakeholders are needed to ensure access to cancer medicines.

Prevalence and association of continuous polypharmacy and frailty among older women: A longitudinal analysis over 15 years.

OBJECTIVES: This study aimed to determine the prevalence of continuous polypharmacy and hyperpolypharmacy, determine medications that contribute to continuous polypharmacy, and examine the association between frailty and continuous polypharmacy. STUDY DESIGN: A prospective study using data from the Australian Longitudinal Study on Women's Health. Women aged 77-82 years in 2003, and 91-96 years in 2017 were analysed, linking the Pharmaceutical Benefits Scheme data to participants' survey data. MAIN OUTCOME MEASURES: The association between frailty and continuous polypharmacy was determined using generalised estimating equations for log binomial regressions, controlling for confounding variables. Descriptive statistics were used to determine the proportion of women with polypharmacy, and medications that contributed to polypharmacy. RESULTS: The proportion of women with continuous polypharmacy increased over time as they aged. Among participants who were frail (n = 833) in 2017, 35.9 % had continuous polypharmacy and 1.32 % had hyperpolypharmacy. Among those who were non-frail (n = 1966), 28.2 % had continuous polypharmacy, and 1.42 % had hyperpolypharmacy. Analgesics (e.g. paracetamol) and cardiovascular medications (e.g. furosemide and statins) commonly contributed to continuous polypharmacy among frail and non-frail women. Accounting for time and other characteristics, frail women had an 8% increased risk of continuous polypharmacy (RR 1.08; 95 % CI 1.05, 1.11) compared to non-frail women. CONCLUSIONS: Combined, polypharmacy and frailty are key clinical and public health challenges. Given that one-third of women had continuous polypharmacy, monitoring and review of medication use among older women are important, and particularly among women who are frail.