Research Articles (Critical Care)

Permanent URI for this collectionhttp://hdl.handle.net/2263/82683

Browse

Now showing 1 - 20 of 39

Rationale and methodological approach underlying the development of the sequential organ failure assessment (SOFA)–2 score
Moreno, Rui; Rhodes , Andrew; Ranzani , Otavio; Salluh, Jorge I.F.; Berger-Estilita, Joana; Coopersmith, Craig M.; Juffermans, Nicole P.; Laffey, John; Reinikainen , Matti; Neto, Ary Serpa; Tavares, Miguel; Timsit, Jean-François; Lopez, Maria Del Pilar Arias; Arulkumaran, Nish; Azoulay, Elie; Chaudhuri , Dipayan; De Lange, Dylan; De Waele, Jan; Dos Santos, Claudia C.; Du, Bin; Einav, Sharon; Ferrer, Ricard; Fujii, Tomoko; Gershengorn, Hayley B.; Haniffa, Rashan; Martin, Greg S.; Metnitz, Philipp; Myatra, Sheila N.; Paiva, José-Artur; Paruk, Fathima; Pekkarinen, Pirkka T.; Pilcher, David; Piquilloud, Lise; Pölkki , Anssi; Prescott , Hallie C.; Blaser, Annika Reintam; Rezende, Ederlon; Robba, Chiara; Rochwerg, Bram; Schenck, Edward J.; Sendagire, Cornelius; Siaw-Frimpong, Moses; Simpkin , Andrew J.; Soares, Márcio; Summers, Charlotte; Szczeklik, Wojciech; Takala , Jukka; Vincent , Jean-Louis; Wendon, Julia; Zampieri, Fernando G; Shankar-Hari, Manu; Singer, Mervyn (American Medical Association, 2026-10-29)
IMPORTANCE : The Sequential Organ Failure Assessment (SOFA) score was published in 1996 to describe organ dysfunction in critically ill adult patients in a readily quantifiable and sequential manner. Considerable changes have occurred over the last 3 decades in the use of organ support drugs and devices and in patient outcomes, necessitating revision of the score. OBJECTIVES : To develop definitions of organ dysfunction that reflect current understanding and to identify representative variables to generate a revised SOFA score (SOFA-2) of individual organ dysfunction. EVIDENCE REVIEW : A task force of experts in intensive care medicine and epidemiology generated definitions of organ dysfunction, identified relevant variables (physiological and laboratory data specific to the organ system, pharmacological and mechanical organ support), and proposed a 0 to 4–point grading of dysfunction severity through meetings, Delphi processes, and explicit rules, informed by data synthesis, including systematic reviews and meta-analysis. Variables were tested in 2 validation exercises using separate datasets totaling 3.34 million patients within 10 representative databases from diverse geographical and socioeconomic settings to assess distribution and predictive validity (mortality at intensive care unit discharge). FINDINGS : A total of 60 experts participated, with 18 (30%) female participants. Overall, 65 countries were represented, with 33 (51%) from Europe and Central Asia, 13 (20%) from North America; and 8 (12%) from Latin America and the Caribbean. The physiological variables within the 6 organ systems used in the original SOFA score were retained, although some categories were renamed (ie, central nervous system was changed to brain, renal to kidney, coagulation to hemostasis, and hepatic to liver). Revisions of organ support drug and device variables were made to reflect current practice. Alternative variables were added for instances when laboratory data and/or organ support interventions would be inaccessible (eg, in some low-resource settings) or not indicated (eg, ceiling of treatment). Some point cutoff thresholds were modified based on evidence from systematic reviews and data analyses. Scores could not be developed for 2 additional organ systems (gastrointestinal and immune) due to insufficient data, complexity, or lack of content and predictive validity for the variables assessed. Explicit rules were developed to facilitate scoring consistency. CONCLUSIONS AND RELEVANCE : Through a methodologically robust development process, the SOFA-2 score offers updated definitions to describe organ dysfunction in adult patients requiring critical care and readily quantifiable criteria to grade the degree of dysfunction in individual organ systems. This score considers contemporaneous changes in patient management and outcomes.
Development and validation of the sequential organ failure assessment (SOFA)-2 score
Ranzani, Otavio T.; Singer, Mervyn; Salluh, Jorge I.F.; Shankar-Hari, Manu; Pilcher, David; Berger-Estilita, Joana; Coopersmith, Craig M.; Juffermans, Nicole P.; Laffey, John; Reinikainen, Matti; Neto, Ary Serpa; Tavares, Miguel; Timsit, Jean-François; Lopez, Maria Del Pilar Arias; Arulkumaran, Nish; Aryal, Diptesh; Azoulay, Elie; Celi, Leo Anthony; Chaudhuri, Dipayan; De Lange, Dylan; De Waele, Jan; Dos Santos, Claudia C.; Einav, Sharon; Engelbrecht, Teresa; Fazla, Fathima; Ferrer, Ricard; Finazzi, Stefano; Fujii, Tomoko; Gershengorn, Hayley B.; Greene, John D.; Haniffa, Rashan; Hao, Sicheng; Hasan, Mohd Shahnaz; Hollenberg, Steve; Ippolito, Mariachiara; Jung, Christian; Kirov, Mikhail; Kobari, Shigetaka; Lakbar, Inès; Lipman, Jeffrey; Liu, Vincent; Liu, Xiaoli; Lobo, Suzana M.; Magatti, Demetrio; Martin, Greg S.; Metnitz, Barbara; Metnitz, Philipp; Myatra, Sheila N.; Oczkowski, Simon; Paiva, José-Artur; Paruk, Fathima; Pekkarinen, Pirkka T.; Piquilloud, Lise; Pölkki, Anssi; Prescott, Hallie C.; Blaser, Annika Reintam; Rezende, Ederlon; Robba, Chiara; Rochwerg, Bram; Ruckly, Stephane; Samei, Rasoul; Schenck, Edward J.; Secombe, Paul; Sendagire, Cornelius; Siaw-Frimpong, Moses; Simpkin, Andrew J.; Soares, Márcio; Summer, Charlotte; Szczeklik, Wojciech; Takala, Jukka; Tanaka, Shiro; Tricella, Giovanni; Vincent, Jean-Louis; Wendon, Julia; Zampieri, Fernando G.; Rhodes, Andrew; Moreno, Rui (American Medical Association, 2025-12)
IMPORTANCE : Acute dysfunction of vital organs is the hallmark of critical illness. The Sequential Organ Failure Assessment (SOFA) score, the most widely adopted approach to describe organ dysfunction, has not been updated in 30 years and therefore may not appropriately capture current clinical practice and outcomes. OBJECTIVES : To inform the data-driven component of an updated score (SOFA-2) in varied geographical and resource settings (stages 6-8) after expert input via a modified Delphi process (stages 1-5). DESIGN, SETTING AND PARTICIPANTS : A federated analysis was performed on data collected from adult patients admitted to 1319 intensive care units (ICUs) in 9 countries (Australia, Austria, Brazil, France, Italy, Japan, Nepal, New Zealand, United States) between 2014 and 2023. Four representative multicenter cohorts containing data from 2 098 356 patients were used for data-driven score development and internal validation. External validation was performed on 6 cohorts containing data from 1 241 114 patients. MAIN OUTCOMES AND MEASURES : Content validity for organ dysfunction identified through the modified Delphi process should be reflected by predictive validity using the area under the receiver operating characteristic (AUROC) curve of the score measured on the first ICU day (higher scores indicate worse organ dysfunction). RESULTS : Of 3.34 million patient encounters, 270 108 (8.1%) died in the ICU (range, 4.5% to 20.5% across the 10 cohorts). SOFA-2 modified the 6 organ systems of the original SOFA score (brain, respiratory, cardiovascular, liver, kidney, hemostasis), including new variables and revised thresholds that better describe the organ dysfunction distribution from 0 to 4 points and their associated mortality (SOFA-2 AUROC, 0.79; 95% CI, 0.76-0.81; SOFA-1 AUROC, 0.77; 95% CI, 0.74-0.81). Evaluation of sequential SOFA-2 data from ICU day 1 to day 7 maintained its predictive validity. Insufficient data and lack of content validity precluded incorporation of gastrointestinal and immune dysfunction scores into SOFA-2. CONCLUSIONS AND RELEVANCE : The SOFA-2 score, updated to include contemporary organ support treatments and new score thresholds, describes organ dysfunction in a large, geographically and socioeconomically diverse population of critically ill adults.
Survey to evaluate clinical benefits and acceptance in international tele-intensive care unit collaboration
Lezius, Franziska; Steinecke, Karin; Herholz, Anne; Schuurhuis, Stephen; Terentyuk, Vadym; Lisnyy, Ivan; Anvarov, Khkmat; Paruk, Fathima; Konig, Jens-Peter; Grosse, Joachim; Edel, Andreas; Hechler, Daniel; Spies, Claudia D.; Weiss, Bjorn (BioMed Central, 2026-05)
OBJECTIVES : Tele-intensive care unit (TICU) networks have evolved quickly in recent years and have proved their value in providing care for the critically ill. Objective measures to assess performance and quantify success e.g. clinical and economic outcome parameters are desirable but not easily accessible in international collaboration with very diverse clinical settings and legal prerequisites. Therefore, we initiated a study to evaluate the performance in our tele-intensive care unit network. METHODS : We conducted an online survey addressing clinical staff at ten spoke sites in four countries connected to one TICU hub to assess subjective clinical benefit, acceptance and potential for improvement. RESULTS : The majority of the 30 participants felt well supported clinically and personally, with a high acceptance and trust as well as a positive working relationship in tele-medical collaboration. Ethical principles and data protection were discovered to be persistently of utmost significance in tele-intensive care unit networks. CONCLUSION : International telemedicine in critical care is perceived positively without major differences between diverse health care systems when crossing borders, showing potential for improvement to guide future clinical and research approaches. CLINICAL TRIAL REGISTRY : The study was registered on August 11th, 2023 with the German Clinical Trials Register (DRKS-IDDRKS00032246; https://www.drks.de/search/de/trial/DRKS00032246/details).
Beyond survival : functionality and health-related quality of life among a cohort of ICU survivors 6 months after hospital discharge - a single-centre study in the Eastern Cape Province of South Africa
Van der Merwe, Elizabeth; Stroud, Louise; Sharp, Gary; Van Vuuren, Noline; Mosola, M.; Fodo, T.; Paruk, Fathima (South African Medical Association, 2025-09)
BACKGROUND : New or worsened impairments in physical, cognitive and/or psychological health may persist after critical care discharge and impact negatively on survivors' health-related quality of life (HRQOL), functionality and life roles. OBJECTIVES : To describe functionality, changes in life roles and HRQOL among an Eastern Cape single-centre cohort of ICU survivors, 6 months after hospital discharge. METHODS : The study was conducted in a multidisciplinary tertiary ICU in the Eastern Cape and enrolled critically ill patients who required organ support and had an ICU stay for at least 48 hours. Patients were assessed at 6 weeks and 6 months post hospital discharge. The Lawton's Instrumental Activities of Daily Living (IADL) score and employment/educational status were determined. The Rand Short Form 36 HRQOL questionnaire's physical and mental component scores (PCS and MCS) were used to determine quality of life at baseline and study visits. RESULTS : A total of 107 patients with a median age of 42, half of whom had COVID-19, completed the 6-month follow-up. At the 6-month follow-up, 17.5% of previously non-frail patients were still unable to complete at least two IADLs, and 24.3% one IADL. Overall, 34% had not returned to their life roles of home making, studying or remunerative work due to ill-health. At 6 months, 58.9% and 62.6% had significantly lower mean PCS and MCS scores, respectively. Overall, 62.6 % of survivors had either a significantly lower PCS and/or MCS at 6 months. CONCLUSION : This relatively young cohort of ICU survivors, with minimal previous comorbidities, demonstrated a high incidence of significantly lower HRQOL scores at the 6-month follow-up, affecting 6 out of every 10 patients. The proportion of patients who were unable to complete all IADLs at follow-up, explains the reported changes in relation to life roles, including remunerative employment. These findings have implications for the introduction or reengineering of rehabilitation resources and ICU follow-up services.
Six-month trajectory of physical function in ICU survivors: Experience from an Eastern Cape centre
Van der Merwe, Elizabeth; Stroud, Louise; Sharp, Gary; Van Vuuren, Noline; Paruk, Fathima (AOSIS, 2025-08-12)
BACKGROUND : Physical impairment affects up to 60% of intensive care unit (ICU) survivors due to factors such as ICU-acquired neuromuscular weakness (ICU-AW), chronic pain, deconditioning and reduced organ and metabolic function. This impairment is linked to lower health-related quality of life (HRQOL). OBJECTIVES : Our study aimed to assess physical impairment and HRQOL among critically ill patients post hospital discharge. METHOD : Intensive care unit survivors were assessed six weeks and six months post hospital discharge. Physical performance was evaluated using the six-minute walk test (6MWT) and muscle strength with the Medical Research Council (MRC) score. Patients’ HRQOL was determined using the Rand Short Form-36 questionnaire. RESULTS : A total of 107 patients (median age 42 years), including 50% with COVID-19, completed the 6-month follow-up. Although significant improvements were observed, 53.5% walked less than 80% of the predicted 6MWT distance at six months, with females disproportionately affected. Poor physical performance was associated with lower physical and mental HRQOL. Pain interfering with activities was reported by 26.2% at six months. Only 2% met full criteria for ICU-AW at six months. By six weeks, only 15% had attended physiotherapy. CONCLUSION : Intensive care unit survivors exhibited a high incidence of physical impairment and pain at six months, impacting HRQOL. Very few patients met full ICU-AW criteria. CLINICAL IMPLICATIONS : Physical impairment after critical illness is multifactorial and is not only attributable to muscle weakness. The recovery process of young, previously non-frail ICU survivors in the public healthcare setting may be improved by introducing rehabilitation pathways.
Symptoms of anxiety, depression, and post‑traumatic stress disorder 6 weeks and 6 months after ICU : six out of 10 survivors affected
Van der Merwe, E.; Stroud, L.; Sharp, G.; Van Vuuren, N.; Mosola, M.; Fodo, T.; Paruk, Fathima; Mosola, M.B. (South African Medical Association, 2024-07)
BACKGROUND : Mental health conditions such as depression, anxiety and post-traumatic stress disorder (PTSD) are being increasingly recognised as common adverse outcomes for critical illness survivors. These conditions can have lasting consequences on their wellbeing, ability to return to their pre-illness level of functioning and health-related quality of life. There is a paucity of South African data in terms of the psychological aspects of the post-intensive care unit (ICU) syndrome. OBJECTIVE : To identify and characterise patients who suffered from significant symptoms of mental health disease and poor mental health-related quality of life after ICU admission and who may benefit from appropriate referral, further investigation and medical intervention. METHODS : Critically ill patients in a multidisciplinary tertiary ICU were prospectively enrolled upon ICU discharge. Survivors were screened for anxiety, depression and post-traumatic stress syndrome at 6 weeks and 6 months after hospital discharge. The Hospital Anxiety and Depression Score (HADS) and the Impact Of Events Scale – Revised (IES-R) were used as screening tools. The mental component summary score (MCS) of the RAND short form-36 was used to determine the effect of psychological symptoms on health-related quality of life (HRQOL). RESULTS : The median age of the 107 ICU survivors was 42 years, and half of them were admitted for complications of COVID‑19. Six out of every 10 ICU survivors experienced significant symptoms of anxiety, depression and/or PTSD at follow-up. At the 6-month study visit, 4 out of every 10 patients were experiencing significant psychological symptoms. Those affected had a significantly lower mental HRQOL when compared with those who were unaffected. More than half of those affected had co-occurrence of psychological symptoms. Significant symptoms of anxiety were common, with 5 out of every 10 participants experiencing significant symptoms at either, or both, of the study visits. More than 3 out of 10 of affected patients’ symptoms only occurred after the 6-week visit. Associations for significant psychological symptoms comprised female sex, younger age, a diagnosis of trauma and frightening memories of the ICU admission. CONCLUSION : The burden of mental health disease in ICU survivors is substantial, affecting their HRQOL. Six out of 10 patients experienced symptoms of anxiety, depression and PTSD, and more than half of those affected experienced co-occurrence of the conditions. A third of those affected developed these symptoms only beyond 6 weeks after hospital discharge. A potentially modifiable association with psychological symptoms was frightening memories of the ICU stay.
Upper limb muscle strength and exercise endurance as predictors of successful extubation in mechanically ventilated patients
De Beer‑Brandon, Caroline R.; Van Rooijen, Agatha Johanna; Becker, Piet J.; Paruk, Fathima (SpringerOpen, 2024-05-22)
BACKGROUND : Failed extubation increases the intensive care unit (ICU) length of stay, hospital length of stay, and financial costs and it reduces the patient’s functional ability. Avoiding failed extubation is of utmost importance, therefore predictors for successful extubation are paramount. OBJECTIVE : To determine if successful extubation in mechanically ventilated patients can be predicted by physiotherapists using upper limb muscle strength and exercise endurance. METHODS : Fifty-seven patients from the medical and trauma ICUs of a large academic hospital were eligible for testing. Muscle strength was evaluated using the Oxford grading scale, Medical Research Council score (MRC score), handgrip dynamometer, and maximum inspiratory pressure (MIP). Exercise endurance was tested while the patient was actively riding the MOTOmed ® letto2 cycle ergometer for six minutes with the upper limbs. RESULTS : Exercise endurance (time the patient rode actively) (P = 0.005), MRC-score (P = 0.007), and number of days ventilated (P = 0.005) were associated with successful extubation. The handgrip strength (P = 0.061), MIP (P = 0.095), and muscle strength of the sternocleidomastoid (P = 0.053) and trapezius muscles (P = 0.075) were marginally associated with successful extubation. Due to multicollinearity when developing the prediction equation, the final multivariable logistic regression prediction model included only exercise endurance and the number of days ventilated. The newly developed prediction equation conferred a sensitivity of 81.82% and a specificity of 77.14% to predict successful extubation. CONCLUSION : Successful extubation of mechanically ventilated patients can be predicted by physiotherapists using the newly developed prediction equation consisting of exercise endurance and number of days ventilated.
Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
Alli, Ahmad; Paruk, Fathima; Roger, Claire; Lipman, Jeffrey; Calleemalay, Daren; Wallis, Steven C.; Scribante, Juan; Richards, Guy A.; Roberts, Jason A. (Public Library of Science, 2023-09-20)
OBJECTIVE :There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens. METHODS : Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics® to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT>MIC). RESULTS : From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT>MIC for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations 50 μmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli. CONCLUSIONS : We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency.
Maternal high-care and intensive care units in low- and middle-income countries
Rojas-Suarez, Jose; Paruk, Fathima (Elsevier, 2024-03)
Despite notable advancements in minimizing maternal mortality during recent decades, a pronounced disparity persists between high-income nations and low-to middle-income countries (LMICs), particularly in intensive and high-care for pregnant and postpartum individuals. This divergence is multifactorial and influenced by factors such as the availability and accessibility of community-based maternity healthcare services, the quality of preventive care, timeliness in accessing hospital or critical care, resource availability, and facilities equipped for advanced interventions. Complications from various conditions, including human immunodeficiency virus (HIV), unsafe abortions, puerperal sepsis, and, notably, the COVID-19 pandemic, intensify the complexity of these challenges. In confronting these challenges and deliberating on potential solutions, we hope to contribute to the ongoing discourse around maternal healthcare in LMICs, ultimately striving toward an equitable health landscape where every mother, regardless of geographic location or socioeconomic status, has access to the care they require and deserve. The use of traditional and innovative methods to achieve adequate knowledge, appropriate skills, location of applicable resources, and strong leadership is essential. By implementing and enhancing these strategies, limited-resource settings can optimize the available resources to promptly recognize the severity of illness in obstetric individuals, ensuring timely and appropriate interventions for mothers and children. Additionally, strategies that could significantly improve the situation include increased investment in healthcare infrastructure, effective resource management, enhanced supply chain efficiency, and the development and use of low-cost, high-quality equipment. Through targeted investments, innovations, efficient resource management, and international cooperation, it is possible to ensure that every maternal high-care and ICU unit, regardless of geographical location or socioeconomic status, has access to high-quality critical care to provide life-saving care.
Core competencies in critical care for general medical practitioners in South Africa : a Delphi study
Maasdorp, S.D.; Paruk, Fathima; De Vasconcellos, K.; Grion, C.; Joubert, I.; Joynt, G.M.; Kalafatis, N.; Lapinsky, S.E.; Lipman, J.; Malbrain, M.L.N.G.; Mrara, B.; Richards, Guy A.; Spruyt, M.; Van der Merwe, E.; Vincent, J.L.; Van der Merwe, L.J. (Health and Medical Publishing Group, 2023-12)
BACKGROUND : Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. OBJECTIVES : To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. METHODS : A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. RESULTS : A final list of 153 core competencies in critical care was identified. CONCLUSION: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA.
Clinical efficacy and safety of a novel antifungal, Fosmanogepix, in patients with candidemia caused by Candida auris : results from a Phase 2 trial
Vazquez, Jose A.; Pappas, Peter G.; Boffard, Kenneth D.; Paruk, Fathima; Bien, Paul A.; Tawadrous, Margaret; Ople, Eric; Wedel, Pamela; Oborska, Iwona; Hodges, Michael R. (American Society for Microbiology, 2023-04)
Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates (MIC range: 0.008 to 0.015 μg/mL [CLSI]; 0.004–0.03 μg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.
Decreased severity of disease during the first global Omicron variant COVID-19 outbreak in a large hospital in Tshwane, South Africa
Abdullah, Fareed; Myers, J.; Basu, Debashis; Tintinger, Gregory Ronald; Ueckermann, Veronica; Mathebula, M.; Ramlall, R.; Spoor, S.; De Villiers, T.; Van der Walt, Z.; Cloete, Jeane; Soma-Pillay, Priya; Rheeder, Paul; Paruk, Fathima; Engelbrecht, Adel; Lalloo, Vidya; Myburg, M.; Kistan, J.; Van Hougenhouck-Tulleken, Wesley G.; Boswell, Michael T.; Gray, G.; Welch, R.; Blumberg, Lucille Hellen; Jassat, W. (Elsevier, 2022-03)
INTRODUCTION : The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponen- tial increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS : 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admis- sions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occu- pancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS : For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p < 0.0 0 0 01), and 1% vs 4.3% (p < 0.0 0 0 01) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION : There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.
'Acute kidney injury predictive models : advanced yet far from application in resource-constrained settings.'
Mrara, Busisiwe; Paruk, Fathima; Oladimeji, Olanrewaju (F1000 Research Ltd, 2022)
Acute kidney injury (AKI) remains a significant cause of morbidity and mortality in hospitalized patients, particularly critically ill patients. It poses a public health challenge in resource-constrained settings due to high administrative costs. AKI is commonly misdiagnosed due to its painless onset and late disruption of serum creatinine, which is the gold standard biomarker for AKI diagnosis. There is increasing research into the use of early biomarkers and the development of predictive models for early AKI diagnosis using clinical, laboratory, and imaging data. This field note provides insight into the challenges of using available AKI prediction models in resource-constrained environments, as well as perspectives that practitioners in these settings may find useful.
Development and validation of a clinical prediction model of acute kidney injury in intensive care unit patients at a rural tertiary teaching hospital in South Africa : a study protocol
Mrara, Busisiwe; Paruk, Fathima; Sewani-Rusike, Constance; Oladimeji, Olanrewaju (BMJ Publishing Group, 2022-07)
INTRODUCTION : Acute kidney injury (AKI) is a decline in renal function lasting hours to days. The rising global incidence of AKI, and associated costs of renal replacement therapy, is a public health priority. With the only therapeutic option being supportive therapy, prevention and early diagnosis will facilitate timely interventions to prevent progression to chronic kidney disease. While many factors have been identified as predictive of AKI, none have shown adequate sensitivity or specificity on their own. Many tools have been developed in developed-country cohorts with higher rates of non-communicable disease, and few have been validated and practically implemented. The development and validation of a predictive tool incorporating clinical, biochemical and imaging parameters, as well as quantification of their impact on the development of AKI, should make timely and improved prediction of AKI possible. This study is positioned to develop and validate an AKI prediction tool in critically ill patients at a rural tertiary hospital in South Africa. METHOD AND ANALYSIS : Critically ill patients will be followed from admission until discharge or death. Risk factors for AKI will be identified and their impact quantified using statistical modelling. Internal validation of the developed model will be done on separate patients admitted at a different time. Furthermore, patients developing AKI will be monitored for 3 months to assess renal recovery and quality of life. The study will also explore the utility of endothelial monitoring using the biomarker Syndecan-1 and capillary leak measurements in predicting persistent AKI. ETHICS AND DISSEMINATION : The study has been approved by the Walter Sisulu University Faculty of Health Science Research Ethics and Biosafety Committee (WSU No. 005/2021), and the Eastern Cape Department of Health Research Ethics (approval number: EC 202103006). The findings will be shared with facility management, and presented at relevant conferences and seminars.
Quantifying the burden of the post-ICU syndrome in South Africa : a scoping review of evidence from the public health sector
Van der Merwe, E.; Paruk, Fathima (South African Medical Association, 2022-07)
BACKGROUND. The post-ICU syndrome (PICS) comprises unexpected impairments in physical, cognitive, and mental health after intensive care unit (ICU) discharge, and is associated with a diminished health-related quality of life (HRQOL). A Cochrane review recommended more research in this field from low- and middle-income countries. OBJECTIVE. This review aims to examine the extent and nature of publications in the field of PICS in the South African (SA) public health sector. Findings of available local research are contextualised through comparison with international data. METHODS. A comprehensive literature search strategy was employed. Inclusion criteria comprised publications enrolling adult patients following admission to SA public hospital ICUs, with the aim to study the main elements of PICS (ICU-acquired neuromuscular weakness, neurocognitive impairment, psychopathology and HRQOL). RESULTS. Three studies investigated physical impairment, 1 study psychopathology, and 2 studies HRQOL. Recommended assessment tools were utilised. High rates of attrition were reported. Neuromuscular weakness in shorter-stay patients had recovered at 3 months. Patients who were ventilated for ≥5 days were more likely to be impaired at 6 months. The study on psychopathology reported high morbidity. The HRQOL of survivors was diminished, particularly in patients ventilated for ≥5 days. CONCLUSION. This review found a paucity of literature evaluating PICS in the SA public health sector. The findings mirror those from international studies. Knowledge gaps pertaining to PICS in medical, surgical and HIV-positive patients in SA are evident. No publications on neurocognitive impairment or the co-occurrence of PICS elements were identified. There is considerable scope for further research in this field in SA.
Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients
Mitton, Barend; Paruk, Fathima; Gous, A.; Chausse, J.; Milne, M.; Becker, Piet J.; Said, Mohamed (South African Medical Association, 2022-09)
BACKGROUND. Antibiotic dosing in critically ill patients is complicated by variations in the pharmacokinetics of antibiotics in this group. The dosing of imipenem/cilastatin is usually determined by severity of illness and renal function. OBJECTIVES. To determine the correlation between estimated glomerular filtration rates (eGFRs) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and imipenem trough levels in critically ill patients. METHODS. This prospective observational study was done in the surgical intensive care unit (ICU) at Steve Biko Academic Hospital, Pretoria, South Africa. Imipenem trough levels were measured by high-performance liquid chromatography and compared with eGFRs calculated with the CKD-EPI equation. Correlation was evaluated by the Pearson product-moment correlation coefficient. RESULTS. The study population consisted of 68 critically ill patients aged between 18 and 81 years; 43 (63%) were male, and the mean weight was 78 kg (range 40 - 140). On admission, 30 patients (44%) had sepsis, 16 (24%) were admitted for trauma, and 22 (32%) were admitted for miscellaneous surgical conditions. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ranged from 4 to 39 (mean 18). The 28-day mortality rate was 29%. The mean albumin level was 16 g/L (range 7 - 25), the mean creatinine level 142 μmol/L (range 33 - 840), and the mean eGFR 91 mL/min/1.73 m2 (range 6 - 180). Imipenem trough levels ranged between 3.6 and 92.2 mg/L (mean 11.5). The unadjusted Pearson product-moment correlation coefficient between eGFR and imipenem trough level was –0.04 (p=0.761). CONCLUSION. Considering the high mortality rate of sepsis in ICUs and the rapid global increase in antimicrobial resistance, it is crucial to dose antibiotics appropriately. Owing to the variability of antibiotic pharmacokinetics in critically ill patients, this task becomes almost impossible when relying on conventional dosing guidelines. This study found that eGFRs do not correlate with imipenem blood levels in critically ill patients and should not be used to determine the dose of imipenem/cilastatin. Instead, the dose should be individualised for patients through routine therapeutic drug monitoring.
Long-stay medical-surgical intensive care unit patients in South Africa : quality of life and mortality 1 year after discharge
Van der Merwe, E.; Baker, D.; Sharp, G.; Van Niekerk, M. (Health and Medical Publishing Group, 2022-03)
BACKGROUND. Although mortality is the primary measure of critical care outcome, the health-related quality of life (HRQOL) of survivors is often diminished. There is a paucity of South African research on HRQOL in intensive care unit (ICU) survivors. OBJECTIVES. To evaluate the 1-year post-discharge data of long-stay ICU patients, a group known to consume 20 - 40% of ICU resources. METHODS. A 1-year prospective observational study was conducted in a multidisciplinary medical-surgical ICU. Adult patients who were mechanically ventilated beyond 6 days were included. Clinical and mortality data were collected. Pre-admission and 6- and 12-month HRQOL were measured with the Short Form-36 questionnaire. Physical and mental component summary scores (PCS and MCS) were calculated. Associations between 12-month mortality and poor HRQOL scores were determined. RESULTS. Of 119 patients enrolled, 40.3% had sustained trauma, 19.3% were post-surgical and 40.3% had medical conditions; 29.2% were HIV-positive (HIV status was known for 74.8% of the cohort). The hospital and 12-month mortality rates were 42.9% and 57.4% (n=66/115), respectively. Age, longer ICU stay, higher disease severity scores and vasopressor use were associated with 12-month mortality. The survivors’ median PCS and MCS at 6 and 12 months were significantly lower compared with pre-admission scores (both p<0.001). At 12 months, 53.1% of survivors demonstrated a poor PCS and 42.9% a poor MCS. Associations with poor 12-month PCS included longer ICU stay, male gender and trauma, while trauma and sepsis were associated with a poor 12-month MCS. Among the 19 trauma survivors, 78.9% had a poor MCS and/or PCS. Of previously employed patients, 54.8% were unemployed at 12 months. CONCLUSIONS. Patients ventilated beyond 6 days in a multidisciplinary ICU had a high mortality. Poor HRQOL at 12 months post discharge was frequently observed among survivors. Trauma was associated with poor 12-month outcomes. These findings highlight the need to further explore the outcomes of long-stay ICU patients in Africa.
Predictors of in-hospital mortality among HIV-positive patients presenting with an acute illness to the emergency department
Laher, Abdullah E.; Paruk, Fathima; Venter, Willem Daniel Francois; Ayeni, Oluwatosin A.; Richards, Guy A. (Wiley, 2021-08)
OBJECTIVES : Despite better access to antiretroviral therapy (ART) over recent years, HIV remains a major global cause of mortality. The present study aimed to identify predictors of in-hospital mortality among HIV-positive patients presenting to an emergency department (ED). METHODS : In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 07 July 2017 and 18 October 2018 were prospectively enrolled. Data were compared between participants who survived to hospital discharge and those who died. The data were further subjected to univariate and multivariate logistic regression analyses to determine variables that were associated with in-hospital mortality. RESULTS : Of a total of 1224 participants, the in-hospital mortality was 13.6% (n = 166). On multivariate analysis, respiratory rate > 20 breaths/min [odds ratio (OR) = 1.90, P = 0.012], creatinine > 120 μmol/L (OR = 1.97, P = 0.006), oxygen saturation < 90% (OR = 2.09, P = 0.011), white cell count < 4.0 × 109/L (OR = 2.09, P = 0.008), ART non-adherence or not yet on ART (OR = 2.39, P = 0.012), Glasgow Coma Scale < 15 (OR = 2.53, P = 0.000), albumin < 35 g/L (OR = 2.61, P = 0.002), lactate > 2 mmol/L (OR = 4.83, P = 0.000) and cryptococcal meningitis (OR = 6.78, P = 0.000) were significantly associated with in-hospital mortality. CONCLUSIONS : Routine clinical and laboratory parameters are useful predictors of in-hospital mortality in HIV-positive patients presenting to the ED with an acute illness. These parameters may be of value in guiding clinical decision-making, directing the appropriate use of resources and influencing patient disposition, and may also be useful in developing an outcome prediction tool.
Development and internal validation of the HIV In-hospital mortality prediction (HIV-IMP) risk score
Laher, Abdullah E.; Paruk, Fathima; Venter, Willem Daniel Francois; Ayeni, Oluwatosin A.; Motara, Feroza; Moolla, Muhammed; Richards, Guy A. (Wiley, 2022-01)
BACKGROUND : Despite advances in availability and access to antiretroviral therapy (ART), HIV still ranks as a major cause of global mortality. Hence, the aim of this study was to develop and internally validate a risk score capable of accurately predicting in-hospital mortality in HIV-positive patients requiring hospital admission. METHODS : Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult emergency department between 7 July 2017 and 18 October 2018 were prospectively enrolled. Multivariate logistic regression was used to determine parameters for inclusion in the final risk score. Discrimination and calibration were assessed by means of the area under the receiver operating curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test, respectively. Internal validation was conducted using the regular bootstrap technique. RESULTS : The overall in-hospital mortality rate was 13.6% (n = 166). Eight predictors were included in the final risk score: ART non-adherence or not yet on ART, Glasgow Coma Scale < 15, respiratory rate > 20 breaths/min, oxygen saturation < 90%, white cell count < 4 × 109/L, creatinine > 120 μmol/L, lactate > 2 mmol/L and albumin < 35 g/L. After internal validation, the risk score maintained good discrimination [AUROC 0.83, 95% confidence interval (CI): 0.78–0.88] and calibration (Hosmer–Lemeshow χ2 = 2.26, p = 0.895). CONCLUSION : The HIV In-hospital Mortality Prediction (HIV-IMP) risk score has overall good discrimination and calibration and is relatively easy to use. Further studies should be aimed at externally validating the score in varying clinical settings.
Antiretroviral therapy non-adherence among HIV- positive patients presenting to an emergency department in Johannesburg, South Africa: associations and reasons
Laher, Abdullah E.; Richards, Guy A. ; Paruk, Fathima; Venter, Willem Daniel Francois (Health and Medical Publishing Group, 2021-08)
BACKGROUND. Suboptimal antiretroviral therapy (ART) adherence is associated with viral resistance, opportunistic infections and increased mortality. OBJECTIVES. To determine the rates of ART non-adherence and its associations, and also the reasons for ART non-adherence, among HIV-positive patients presenting to a major central hospital emergency department (ED). METHODS. Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 7 July 2017 and 18 October 2018 were prospectively enrolled. Self-reported adherence was assessed using the AIDS Clinical Trials Group Adherence Questionnaire (ACTG-AQ). RESULTS. Of the 1 224 consecutive HIV-positive participants enrolled, 761 (75.2%) were on ART at the time of ED presentation. Of these, 245 (32.2%) were non-adherent as per the ACTG-AQ. Participants not yet on ART prior to ED presentation had significantly higher in-hospital mortality than participants on ART (odds ratio 1.69; 95% confidence interval 1.21 - 2.34; p=0.002). Younger age, male sex, CD4 count <100 cells/µL, lack of viral suppression, a high National Early Warning Score 2 (≥7 points) and length of hospital stay ≥7 days were significantly associated with ART non-adherence (p<0.05). Forgetfulness (13.9%) and lack of social support, depression/stress/mental illness, and lack of money for transport to collect medications (9.9% each) were the most common reasons given for ART non-adherence. CONCLUSIONS. Of HIV-positive patients presenting to the ED, a high proportion were either not yet initiated on ART or ART non-adherent. HIV programmes should focus on HIV-positive ED attendees with the aim of identifying high-risk patients and providing adequate ART adherence support

Browse

Recent Submissions