The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.

BACKGROUND: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. OBJECTIVES: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. METHODS: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. RESULTS: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. CONCLUSIONS: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.

Qualitative Study of Food Insecurity in Hospitalized Pediatric Patients during the COVID-19 Pandemic.

OBJECTIVES: Food insecurity (FI) is defined as limited or uncertain access to sufficient food for a healthy and active lifestyle. Our objective was to explore how the coronavirus disease 2019 (COVID-19) pandemic affected the FI status of pediatric patients and their families through interviewing caregivers who screen positive for FI. METHODS: Caregivers of all hospitalized patients at a tertiary children's hospital who screen positive for FI with a two-question screening tool were approached about enrolling in the study. Those who consented completed a presurvey and participated in a semistructured individual interview. Interviews were audio recorded, transcribed, and analyzed according to the guidelines of thematic analysis using NVivo 12. RESULTS: Interviews were conducted with 15 caregivers between July 2021 and January 2022. Caregivers were 100% female and 80% Black, 13% White, and 7% Hispanic/Latinx, with a mean age of 33 years. Seventy-three percent did not experience FI until the COVID-19 pandemic. Themes include lost wages, mothers forced out of the workforce due to childcare limitations, inflation and shortages of goods, increased stress/anxiety for caregivers and children, the centrality of extended family support, and the necessity/inadequacy of federal food programs. CONCLUSIONS: The COVID-19 pandemic impacted unemployment and poverty and consequently exacerbated FI. Our findings point to the need to focus on proximal societal solutions, such as federal policies aimed at food assistance and childcare. Understanding the challenges related to FI that caregivers and patients experience can improve screening, support, and treatment of patients presenting for care and inform the design of necessary interventions for individuals and communities beyond COVID-19.

Delivery of School-based Physical Therapy via Telehealth: Perceptions and Attitudes of School-based Physical Therapists.

AIMS: School-based physical therapists (SBPTs) rapidly transitioned to telehealth during the pandemic. This study explored the perceptions of, and strategies utilized by, SBPTs delivering therapy via telehealth. METHODS: Using a grounded theory qualitative design, semi-structured interviews were completed with 13 SBPTs. Interviews were transcribed and theme coded until saturation was achieved. RESULTS: The following themes emerged: supports and education, challenges, strategies promoting success, and the outcomes of telehealth. SBPTs overcame challenges including those associated with technology, communication, space, equipment, and examination. Coaching techniques, incorporation into the daily routine, and the sharing of demonstrations promoted success. Telehealth service delivery was perceived to improve communication with educational teams and families, improve efficiency and productivity, increase access to students, promote an appreciation of the family and home context, and enhance family engagement. SBPTs believe incorporating elements of telehealth in conjunction with in-person delivery is ideal. CONCLUSIONS: While the COVID-19 pandemic forced a rapid transition to telehealth for SBPTs, lessons learned could have a long-lasting positive impact on school-based services. The benefits of telehealth should be considered in the delivery of school-based physical therapy services.

Vascular perfusion differs in two distinct PDGFRß-positive zones within the ischemic core of male mice 2 weeks following photothrombotic stroke.

Stroke therapy has largely focused on preventing damage and encouraging repair outside the ischemic core, as the core is considered irreparable. Recently, several studies have suggested endogenous responses within the core are important for limiting the spread of damage and enhancing recovery, but the role of blood flow and capillary pericytes in this process is unknown. Using the Rose Bengal photothrombotic model of stroke, we illustrate blood vessels are present in the ischemic core and peri-lesional regions 2 weeks post stroke in male mice. A FITC-albumin gel cast of the vasculature revealed perfusion of these vessels, suggesting cerebral blood flow (CBF) may be partially present, without vascular leakage. The length of these vessels is significantly reduced compared to uninjured regions, but the average width is greater, suggesting they are either larger vessels that survived the initial injury, smaller vessels that have expanded in size (i.e., arteriogenesis), or that neovascularization begins with larger vessels. Concurrently, we observed an increase in platelet-derived growth factor receptor beta (PDGFRß, a marker of pericytes) expression within the ischemic core in two distinct patterns, one which resembles pericyte-derived fibrotic scarring at the edge of the core, and one which is vessel associated and may represent blood vessel recovery. We find little evidence for dividing cells on these intralesional blood vessels 2 weeks post stroke. Our study provides evidence flow is present in PDGFRß-positive vessels in the ischemic core 2 weeks post stroke. We hypothesize intralesional CBF is important for limiting injury and for encouraging endogenous repair following cerebral ischemia.

Brain pericytes in culture display diverse morphological and functional phenotypes.

Pericytes play several important functions in the neurovascular unit including contractile control of capillaries, maintenance of the BBB, regulation of angiogenesis, and neuroinflammation. There exists a continuum of pericyte subtypes along the vascular tree which exhibit both morphological and transcriptomic differences. While different functions have been associated with the pericyte subtypes in vivo, numerous recent publications have used a primary human brain vascular pericytes (HBVP) cell line where this pericyte heterogeneity has not been considered. Here, we used primary HBVP cultures, high-definition imaging, cell motility tracking, and immunocytochemistry to characterise morphology, protein expression, and contractile behaviour to determine whether heterogeneity of pericytes also exists in cultures. We identified five distinct morphological subtypes that were defined using both qualitative criteria and quantitative shape analysis. The proportion of each subtype present within the culture changed as passage number increased, but pericytes did not change morphological subtype over short time periods. The rate and extent of cellular and membrane motility differed across the subtypes. Immunocytochemistry revealed differential expression of alpha-smooth muscle actin (αSMA) across subtypes. αSMA is essential for cell contractility, and consequently, only subtypes with high αSMA expression contracted in response to physiological vasoconstrictors endothelin-1 (ET1) and noradrenaline (NA). We conclude that there are distinct morphological subtypes in HBVP culture, which display different behaviours. This has significance for the use of HBVP when modelling pericyte physiology in vitro where relevance to in vivo pericyte subtypes along the vascular tree must be considered.

A systematic review of the effect of therapeutic drug monitoring on patient health outcomes during treatment with penicillins.

BACKGROUND: Dosing regimens guided by therapeutic drug monitoring (TDM) may be able to improve penicillin exposure in patients, which could result in improved patient health outcomes. OBJECTIVES: This systematic review aims to describe the impact penicillin TDM has on health outcomes, including antimicrobial resistance (AMR). METHODS: Studies measuring penicillins in patient samples that adjusted regimens according to the result, and reported health outcomes were selected. Study bias was assessed according to study type. Included study characteristics were tabulated and described by narrative synthesis. RESULTS: Three randomized controlled trials (RCTs), 16 cohort studies, and 9 case studies were included. No RCTs showed statistically significant improvements in health outcomes. Five cohort studies showed improvement in at least one health outcome associated with target attainment. However, there was a high risk of bias in all studies for health outcomes. One study assessed the impact of penicillin TDM on AMR and found that improved target attainment was associated with suppression of resistance. No studies found a detrimental effect of penicillin TDM. CONCLUSIONS: There is little evidence to suggest that TDM improves health outcomes, however neither health outcomes nor impact on AMR were adequately addressed. Variations in TDM implementation meant that a meta-analysis was not suitable. Penicillin TDM needs standardization, however there is currently no clear evidence of optimal conditions. Suitably powered studies are required to resolve the ambiguity surrounding the impact of TDM on clinical outcomes, including AMR. Further, standardized protocols and concentration targets need to be identified for TDM to be implemented successfully.

Pharmacological PDGFRß inhibitors imatinib and sunitinib cause human brain pericyte death in vitro.

Capillary pericytes have numerous functions important for tissue maintenance. Changes in pericyte function are implicated in diseases such as cancer, where pericyte-mediated angiogenesis contributes to the blood supply that tumors use to survive. Some anti-cancer agents, like imatinib, target platelet-derived growth factor receptor-beta (PDGFRß). Healthy pericytes rely on PDGFRß phosphorylation for their survival. Therefore, we hypothesised that pharmacological agents that block PDGFRß phosphorylation could be used to kill pericytes. We treated human brain vascular pericytes, which express PDGFRß, with three receptor tyrosine kinase inhibitors: imatinib, sunitinib and orantinib. Imatinib and sunitinib, but not orantinib, inhibited PDGFRß phosphorylation in pericytes. Imatinib and sunitinib also reduced viability, prevented proliferation, and induced death, while orantinib only blocked pericyte proliferation. Overall, we found that receptor tyrosine kinase inhibitors that block PDGFRß phosphorylation cause healthy pericytes to die in vitro. While useful in cancer to limit tumor growth, these agents could impair healthy brain pericyte survival and impact brain function.

Aspirin use for cancer prevention: A systematic review of public, patient and healthcare provider attitudes and adherence behaviours.

We undertook a systematic review to synthesise the data on attitudes and behaviour towards the use of aspirin for cancer prevention, and healthcare providers' attitudes towards implementing aspirin in practice. Searches were carried out across 12 databases (e.g. MEDLINE, EMBASE). We used the Mixed Methods Appraisal Tool to evaluate study quality, and conducted a narrative synthesis of the data. The review was pre-registered (PROSPERO: CRD42018093453). Thirty-eight studies were identified. Uptake and adherence data were all from trials. Trials recruited healthy participants, those at higher risk of cancer, and those with cancer. Four studies reported moderate to high (40.9-77.7%) uptake to an aspirin trial among people who were eligible. Most trials (18/22) reported high day-to-day adherence (≥80%). Three trials observed no association between gender and adherence. One trial found no association between adherence and colorectal cancer risk. Three studies reported moderate to high (43.6-76.0%) hypothetical willingness to use aspirin. Two studies found that a high proportion of healthcare providers (72.0-76.0%) perceived aspirin to be a suitable cancer prevention option. No qualitative studies were identified. The likelihood that eligible users of aspirin would participate in a trial evaluating the use of aspirin for preventive therapy was moderate to high. Among participants in a trial, day-to-day adherence was high. Further research is needed to identify uptake and adherence rates in routine care, the factors affecting aspirin use, and the barriers to implementing aspirin into clinical care.

Trends in preservative allergy: Benzisothiazolinone emerges from the pack.

BACKGROUND: Preservatives are used widely in cosmetic, household, and industrial products to prevent microbial growth and spoiling of the products. There has been a recent epidemic of contact allergy to methylisothiazolinone (MI). OBJECTIVES: To establish emerging trends in preservative contact allergy as MI is replaced. METHODS: We performed a retrospective study on consecutively patch-tested patients at our center from January 2011 to December 2019. RESULTS: A total of 7846 consecutively patch-tested patients were included who were patch tested between January 2011 and December 2019. The prevalence of allergy to MI fell from a peak of 9.39% in 2013 to 1.98% in 2019. MI/methylchloroisothiazolinone (MCI) followed a similar trend, with a peak prevalence of 7.85% in 2014 and falling to 1.39% in 2018. The prevalence of contact allergy to benzisothiazolinone (BIT) has increased steadily increased in 2014 from 0.26% (confidence interval [CI] 0.03-0.93) to 3.42% (CI 2.43-4.66) in 2019. CONCLUSIONS: Our data show a significant increase in the prevalence of contact allergy to BIT over the last 6 years, probably as a consequence of increased use in household products. It is essential to continue to look for emerging trends in contact allergy to enable prompt preventative measures to be taken.

Drivers of antimicrobial resistance within the communities of Nepal from One Health perspective: a scoping review.

Background: A major driver of antimicrobial resistance (AMR) is the inappropriate use of antimicrobials. At the community level, people are often engaged in behaviors that drive AMR within human, animal, and environmental (One Health) impacts. This scoping review consolidates research to determine (a) the community's knowledge, attitudes, and practices around AMR; (b) existing community-based interventions; and (c) barriers and enablers to addressing AMR in Nepal. Methods: This scoping review follows the Joanna Briggs Institute scoping review methodology. Literature indexed in PubMed, Scopus, CINAHL, Global Index Medicus, HINARI-SUMMON, Embase (Ovid), Global Health (Ovid), CAB Abstracts (Ovid), Web of Science, and Google Scholar between January 2000 and January 2023 were reviewed for inclusion. Articles were included in the review if they considered the issues of AMR at the community level in Nepal; this excluded clinical and laboratory-based studies. A total of 47 studies met these criteria, were extracted, and analyzed to consolidate the key themes. Results: A total of 31 (66%) articles exclusively included human health; five (11%) concentrated only on animal health; no studies solely focused on environmental aspects of AMR; and the remaining studies jointly presented human, animal, and environmental aspects. Findings revealed inadequate knowledge accompanied by inappropriate practice in both the human and animal health sectors. Four community interventions improved knowledge and practices on the appropriate use of antimicrobials among community people. However, various social and economic factors were found as barriers to the appropriate use of antimicrobials in the community. Conclusion: Community engagement and One Health approaches could be key tools to improve awareness of AMR and promote behavioral change related to AM use in communities, as current studies have revealed inadequate knowledge alongside inappropriate practices shared in both human and animal health sectors. Systematic review registration: DOI: 10.17605/OSF.IO/FV326.

Evidence of quality of life for hospitalised patients with COVID-19: a scoping review.

Background: Information on the quality of life of people hospitalised with COVID-19 is important, both in assessing the burden of disease and the cost-effectiveness of treatments. However, there were potential barriers to collecting such evidence. Objective: To review the existing evidence on quality of life for people hospitalised with COVID-19, with a focus on the amount of evidence available and methods used. Design: A scoping review with systematic searches. Results: A total of 35 papers were selected for data extraction. The most common study type was economic evaluation (N = 13), followed by cross-sectional (N = 10). All economic evaluations used published utility values for other conditions to represent COVID-19 inpatients' quality of life. The most popular quality-of-life survey measure was the Pittsburgh Sleep Quality Index (N = 8). There were 12 studies that used a mental health-related survey and 12 that used a sleep-related survey. Five studies used EQ-5D, but only one collected responses from people in the acute phase of COVID-19. Studies reported a negative impact on quality of life for people hospitalised with COVID-19, although many studies did not include a formal comparison group. Limitations: Although it used systematic searches, this was not a full systematic review. Conclusion: Quality-of-life data were collected from people hospitalised with COVID-19 from relatively early in the pandemic. However, there was a lack of consensus as to what survey measures to use, and few studies used generic health measures. Economic evaluations for COVID-19 treatments did not use utilities collected from people with COVID-19. In future health crises, researchers should be vigilant for opportunities to collect quality-of-life data from hospitalised patients but should try to co-ordinate as well as ensuring generic health measures are used more. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132254.

Quality of life can be measured using short, simple surveys. It is important to assess quality of life in this way, as it can show how health conditions affect people. Quality-of-life surveys can also be used to measure how treatments benefit people and to judge whether it is cost-effective to fund them. COVID-19 is a new disease, with new treatments developed to treat it. COVID-19 also created possible barriers to collecting quality-of-life survey data, especially from people in hospital at the start of the pandemic. This paper reviews studies which report data on quality of life for people hospitalised with COVID-19, especially how much evidence is available and how the studies were carried out. There were 35 studies included in the review. Of these, 13 assessed how cost-effective treatments for COVID-19 were. None of them collected survey responses directly from patients. Instead, they used data previously collected from people with other conditions such as influenza to represent people with COVID-19's quality of life. The studies which did collect data from patients used a wide variety of different surveys, which made comparing their results difficult. Mental health-related surveys were used by 12 studies, and a further 12 used sleep-related surveys. Relatively few studies used general surveys which could assess the overall effect of COVID-19 on people's quality of life. In future health crises, we recommend using more general quality-of-life measures. We also recommend that researchers co-ordinate to reduce the number of different surveys they use, as this will make comparing results easier.

Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility.

BACKGROUND: Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood-brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). METHODS: We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. RESULTS: iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. CONCLUSIONS: iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.

Progression of frailty as measured by a cumulative deficit index: A systematic review.

BACKGROUND: Frailty is a risk factor for adverse health outcomes. There is a paucity of literature on frailty progression defined by a cumulative deficit model among community dwelling older people. The objective of this review was to synthesise evidence on these changes in health and mortality among community-dwelling older people. METHODS: Six databases (Medline, Embase, CINAHL, Cochrane, PsycInfo, Web of Science) and a clinical trials registry were searched in July 2021. The inclusion criteria were studies using a frailty index and providing information on transition between frailty states or to death in community-dwelling older people aged ≥ 50. Exclusion criteria were studies examining specific health conditions, conference abstracts and non-English studies. To standardise the follow-up period and facilitate comparison, we converted the transition probabilities to annual transition rates. RESULTS: Two reviewers independently screened 5078 studies and 61 studies were included for analysis. Of these, only three used the same frailty state cut-points to facilitate cross-cohort comparison. This review found that frailty tends to increase with time, people who are frail at baseline have greater likelihood to progress in frailty and die, and the main factor that accelerates frailty progression is age. Other risk factors for progression are having chronic disease, smoking, obesity, low-income or/and low-education levels. A frailty index is an accurate predictor of adverse outcomes and death. DISCUSSION: This systematic review demonstrated that worsening in frailty was a common frailty transition, and older people who are frail at baseline are more likely to die. A frailty index has significant power to predict adverse health outcomes. It is a useful tool for within-cohort comparison but there are challenges comparing different cohorts due to dependence of frailty progression on age and differences in how frailty index is defined and measured.

Smoking History and the Development of Incisional Umbilical Hernia After Laparoscopic and Laparoendoscopic Single-Site Cholecystectomy.

The aim of this study was to analyze umbilical hernia occurrences in patients who underwent laparoscopic or laparoendoscopic single-sight (LESS) cholecystectomy. Patients who underwent cholecystectomy by a single surgeon between 2015 and 2020 were surveyed. Data are presented as median (mean +/- standard deviation). Two hundred and fifty-three patients were sent the survey and 130 (51%) patients responded. The overall age was 57 (31 +/- 18) and the overall BMI was 30 (31 +/- 7). Twelve (9%) patients developed an umbilical hernia. Seventeen patients were active smokers and four (24%) developed an umbilical hernia. One hundred and thirteen patients were inactive smokers and eight (7%) developed an umbilical hernia. There was a statistical significance between umbilical hernia occurrence and smoking history (P < .05). Active smokers have a higher risk of developing an umbilical hernia following a minimally invasive cholecystectomy, regardless of operative approach. Elective cholecystectomy should be reconsidered for current smokers.

How effective is group intervention in the treatment for unaccompanied and accompanied refugee minors with mental health difficulties: A systematic review.

BACKGROUND: Unaccompanied refugee minors (URM) are at significantly higher risk of trauma exposure and mental illness. Research examining the most effective treatments for this population is limited. AIMS: To study the available research evidence on outcomes from various group interventions in this population. The objective is to investigate if these can be used clinically in future interventions. METHODS: Systematic review was carried out for patient outcomes where group therapy was used as treatment in URM. Studies with ARM (Accompanied refugee minors) were included because of similarities between these groups and because many studies were mixed population. RESULTS: Seventeen papers met eligibility criteria with a total of N = 1,119 participants. About 80% studies with a quantitative component reported improvements, and 69% of the studies that carried out statistical analyses reported statistically significant improvements in mental health symptoms. Every qualitative measure reported positive outcome for the participants. Studies with URM tended to show improved outcomes more often than studies exclusively with ARM. CONCLUSIONS: The evidence demonstrates the efficacy of group therapy in improving mental health outcomes, although the number of studies with robust methodology is small. Group intervention has potential to improve engagement and outcomes of URM with mental illness. Future direction for research is discussed.

The cost-effectiveness of using rapid diagnostic tests for the diagnosis of typhoid fever in patients with suspected typhoid fever: a systematic review.

INTRODUCTION: Despite the availability of several commercial rapid diagnostic tests (RDTs) developed to detect typhoid fever, the cost-effectiveness in resource-limited settings is unclear. This review aimed to explore the literature on typhoid economic evaluations in order to assess the cost-effectiveness of using typhoid RDTs in resource-limited settings. AREAS COVERED: A systematic review was conducted focusing on the identification of economic evaluations of typhoid RDTs to diagnose patients with suspected typhoid fever. Two studies were identified and included for narrative synthesis. Whilst highlighting a gap in the published literature, this review shows the use of typhoid RDTs to potentially be cost-effective in resource-limited settings. Factors that appeared as significant in determining cost-effectiveness related to test characteristics (such as sensitivity, specificity, and cost) and the prevalence of typhoid fever and should factor into any future evaluations. EXPERT OPINION: Concerted effort is needed in resource-limited settings with regard to medical device regulation to ensure that clinically effective and cost-effective typhoid RDTs are widely available and introduced into clinical practice. Typhoid modeling (with respect to typhoid testing and treatment strategies) represents an understudied area and further work is needed.

A Systematic Review of the Effect of Therapeutic Drug Monitoring on Patient Health Outcomes during Treatment with Carbapenems.

Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration. Bias in the studies was assessed with risk of bias analysis tools. Study characteristics and outcomes were tabulated and a narrative synthesis was performed. In total, 2 randomised controlled trials (RCTs), 17 non-randomised studies, and 19 clinical case studies were included. Significant variation in TDM practice was seen; consequently, a meta-analysis was unsuitable. Few studies assessed impacts on AMR. No significant improvement on health outcomes and no detrimental effects of carbapenem TDM were observed. Five cohort studies showed significant associations between achieving target concentrations and clinical success, including suppression of resistance. Studies in this review showed no obvious improvement in clinical outcomes when TDM is implemented. Optimisation and standardisation of carbapenem TDM practice are needed to improve intervention success and enable study synthesis. Further suitably powered studies of standardised TDM are required to assess the impact of TMD on clinical outcomes and AMR.