Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients.

Introduction: One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients. Methods: The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices. Discussion: While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

Protective effects of ethnic enclaves: Testing pathways to alcohol use and use disorders in Mexican American young adults.

Ethnic enclave residence is associated with decreased risk for drinking and related problems, but less is known about the mechanisms that explain this association. Informed by theories of social control, we used a multilevel framework to examine whether negative attitudes toward drinking mediated associations between ethnic enclave residence (i.e., neighborhood linguistic isolation) and alcohol outcomes among Mexican American young adults (N = 628) in Southern California. Model 1 assessed mediation effects in the pathways from linguistic isolation to current drinking and alcohol use disorder (AUD). Model 2 adjusted for parental drinking attitudes and neighborhood alcohol availability. There were differential associations by gender in direct effects of linguistic isolation and negative drinking attitudes on both drinking and AUD. Among women only, linguistic isolation was related to greater abstinence and decreased AUD after accounting for social control proxies of parent attitudes and alcohol availability. Young adults' own drinking attitudes did not mediate relationships between linguistic isolation and alcohol outcomes. This study offers evidence on the importance of disaggregating Hispanic national groups by gender to uncover social mechanisms within ethnic enclave settings for tailored supports in reducing risk of drinking and alcohol-related harms.

Real-time PCR primers and probes for the detection of Shiga toxin genes, including novel subtypes.

Shiga toxin-producing Escherichia coli (STEC) are foodborne enteric pathogens. STEC are differentiated from other E. coli by detection of Shiga toxin (Stx) or its gene (stx). The established nomenclature of Stx identifies ten subtypes (Stx1a, Stx1c, Stxd, Stx2a to Stx2g). An additional nine subtypes have been reported and described (Stx1e, Stx2h to Stx2o). Many PCR protocols only detect a subset of Stx subtypes which limits their inclusivity. Here we describe a real-time PCR assay inclusive of the DNA sequences of representatives of all currently described Stx subtypes. A multiplex real-time PCR assay for detection of stx was developed using nine primers and four probes. Since the identification of STEC does not require differentiation of stx subtypes, the probes use the same fluorescent reporter to enable detection of multiple possible targets in a single reaction. The PCR mixture includes an internal positive control to detect inhibition of the reaction. Thus, the protocol can be performed on a two-channel real-time PCR platform. To reduce the biosafety risk inherent in the use of STEC cultures as process controls, the protocol also includes the option of a non-pathogenic E. coli transformant carrying a plasmid encoding the targeted fragment of the stx2a sequence. The inclusivity of the PCR was assessed against colonies of 137 STEC strains and one strain of Shigella dysenteriae, including strains carrying single copies of stx representing fourteen subtypes (stx1 a, c, d; stx2 a-j and o). Five additional subtypes (stx1e, 2k, 2l, 2m and 2n) were represented by E. coli transformed with plasmids encoding toxoid (enzymatically inactive A subunit) sequences. The exclusivity panel consisted of 70 bacteria, including 21 stx-negative E. coli. Suitability for food analysis was assessed with artificially inoculated ground beef, spinach, cheese, and apple cider. The real-time PCR generated positive results for all 19 stx subtypes, represented by colonies of STEC, S. dysenteriae and E. coli transformants carrying stx toxoid plasmids. Tests of exclusivity panel colonies were all negative. The real-time PCR detected the presence of stx in all inoculated food enrichments tested, and the presence of STEC was confirmed by isolation.

Novel therapies in juvenile idiopathic arthritis.

PURPOSE OF REVIEW: This review summarises the major novel treatment options for children with juvenile idiopathic arthritis (JIA) since the pandemic, reflecting not only on advancements in therapeutics but also approach to management and research. RECENT FINDINGS: Several recent international paediatric trials have been important in advancing understanding of JIA and furthering available treatment options. Biologic and small molecule agents were demonstrated to be effective and safe in recalcitrant or severe JIA (including extra-articular complications), mirroring the adult equivalent diseases. SUMMARY: Although joint and overall health have vastly improved for young people with JIA, ongoing international collaboration, critical review of treatment strategies and high quality research are essential to optimize outcomes.

Nexplanonectomy-the surgical removal of an embolized implanted contraceptive device: a case report and review of the literature.

BACKGROUND: Nexplanon implants are a common hormonal contraceptive modality. Though rare, these devices can embolize into the injured wall of the basilic vein, through the right heart, and finally wedge itself into a pulmonary artery. With adherence to the arterial wall over time, it becomes less amenable to endovascular retrieval. Patients may present with symptoms mimicking a pulmonary embolism, or without any symptoms at all. In asymptomatic cases, endovascular retrieval and/or surgery is required when patients wish to begin having children prior to biological inactivity. The current literature showed as little as nine case reports detailing lung tissue removal in the aim of reversing a patient's implanted contraceptive device. CASE PRESENTATION: A 22-year-old asymptomatic active-duty Caucasian female presented for elective outpatient Nexplanon removal. The suspicion of possible implant migration arose when it was discovered to be non-palpable in her left arm. After plain film x-rays failed to localize the implant, a chest x-ray and follow-up Computed Tomography (CT) scan revealed that the Nexplanon had migrated to a distal branch of the left pulmonary artery. Due to the patient's strong desires to begin having children, the decision was made for removal. Initial endovascular retrieval failed due to Nexplanon encapsulation within the arterial wall. Ultimately, the patient underwent a left video-assisted thoracoscopic surgery (VATS) for exploration and left lower lobe basilar S7-9 segmentectomy, which successfully removed the Nexplanon. CONCLUSIONS: Implanted contraceptive devices can rarely result in migration to the pulmonary vasculature. These radiopaque devices are detectable on imaging studies if patients and clinicians are unable to palpate them. An endovascular approach should be considered first to spare lung tissue and avoid chest-wall incisions, but can be complicated by encapsulation and adherence to adjacent tissue. A VATS procedure with single-lung ventilation via a double-lumen endotracheal tube allows surgeons to safely operate on an immobilized lung while anesthesiologists facilitate single-lung ventilation. This patient's case details the uncommon phenomenon of Nexplanon migration, and the exceedingly rare treatment resolution of lung resection to remove an embolized device.

Prevalence of Cardiovascular Disease and Risk Factors Among Former National Football League Players.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, but prevalence estimates in former professional athletes are limited. OBJECTIVES: HUDDLE (Heart Health: Understanding and Diagnosing Disease by Leveraging Echocardiograms) aimed to raise awareness and estimate the prevalence of CVD and associated risk factors among members of the National Football League (NFL) Alumni Association and their families through education and screening events. METHODS: HUDDLE was a multicity, cross-sectional study of NFL alumni and family members aged 50 years and older. Subjects reported their health history and participated in CVD education and screening (blood pressure, electrocardiogram, and transthoracic echocardiogram [TTE] assessments). Phone follow-up by investigators occurred 30 days postscreening to review results and recommendations. This analysis focuses on former NFL athletes. RESULTS: Of 498 participants screened, 57.2% (N = 285) were former NFL players, the majority of whom were African American (67.6%). The prevalence of hypertension among NFL alumni was estimated to be 89.8%, though only 37.5% reported a history of hypertension. Of 285 evaluable participants, 61.8% had structural cardiac abnormalities by TTE. Multivariable analysis showed that hypertension was a significant predictor of clinically relevant structural abnormalities on TTE. CONCLUSIONS: HUDDLE identified a large discrepancy between participant self-awareness and actual prevalence of CVD and risk factors, highlighting a significant opportunity for population health interventions. Structural cardiac abnormalities were observed in most participants and were independently predicted by hypertension, affirming the role of TTE for CVD screening in this population aged older than 50 years. (Heart Health: Understanding and Diagnosing Disease by Leveraging Echocardiograms [HUDDLE]; NCT05009589).

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland.

OBJECTIVES: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. METHODS: Data were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. RESULTS: Between September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. CONCLUSIONS: This study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Cannabis donation as a harm reduction strategy: a case study.

BACKGROUND: The United States (US) continues to experience unprecedented rates of overdose mortality and there is increased need to identify effective harm reduction practices. Research from Canada describes cannabis donation through harm reduction agencies as an adjunctive strategy to mitigate the negative consequences of more harmful drugs. This case study describes the operational logistics, feasibility, and potential benefits of a cannabis donation program that was operated through a harm reduction program in rural Michigan. CASE PRESENTATION: We applied a community driven research approach to gather information from harm reduction program staff about the implementation and evolution of cannabis donation efforts in Michigan. We also examined 20-months (September 2021 through May 2023) of administrative data from a cannabis company to compare the sale and donation of cannabis products. Ten cannabis-experienced harm reduction clients received cannabis donations, with clinical staff determining client interest and appropriateness, and providing weekly pick-up or delivery. To expand product availability and sustainability, we examined administrative data from a commercialcannabis company that volunteered to provide donations. This administrative data suggests that while flower products constitute most of the adult and medical sales, edible, oil, and topical products predominated donations. Further, cost analysis suggests that donations represent only 1% of total gross sales and account for much less than the expected yearly donation amount. CONCLUSIONS: Research suggests there is potential to reduce alcohol and drug use related harms of more dangerous substances through substitution with cannabis. This case study is the first to document cannabis donation as a harm reduction practice in the US and suggests potential for sustainability dependent on state laws. Findings from this case study provide a starting point for inquiry into cannabis donation as a harm reduction strategy in the US; future research is needed to fully understand the individual-level outcomes, public health impacts, necessary legal regulations, and best practices for cannabis donation programs through harm reduction organizations.

Attitudes and perceptions of Irish health care professionals regarding functional neurological disorder: A national survey.

BACKGROUND: Functional neurological disorder (FND) is a common and often disabling condition. Limited access to services for FND poses challenges both for patients and their health care providers. This survey explored the attitudes, experiences, support needs and training needs of health care professionals (HCPs) who provide care to individuals with FND in Ireland. METHODS: A broad range of HCPs working with patients with FND in Ireland partook in an anonymous online 12-item survey. Participants were recruited via professional bodies and snowball convenience sampling utilising social media and email invitation. Descriptive and inferential statistics were employed to analyze data. RESULTS: A total of 314 HCPs working in Ireland completed the survey. 80% were female and over half worked in their current role for more than 10 years.   75% of the sample encountered three or less individuals with FND per month. Identified service-related challenges to effective patient care included insufficient clinic time, lack of confidence explaining the diagnosis, and the need for greater access to specialist support.  Data revealed persisting negative attitudes toward FND patients among a proportion of respondents. The majority of respondents did not feel they received adequate education on FND, with the exception of neurologists, of whom 65% felt adequately trained.  The majority of respondents (85%) also felt that people with FND did not have access to appropriate FND services in Ireland. CONCLUSION: This study indicates that there is a significant need to improve FND education among HCPs in Ireland, in addition to developing appropriately resourced, integrated, multidisciplinary care pathways for the FND patient group.

Imaging flow cytometric detection of del(17p) in bone marrow and circulating plasma cells in multiple myeloma.

BACKGROUND: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno-flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. METHODS: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno-flowFISH. Plasma cells were identified by CD38/CD138-immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. RESULTS: Chromosome 17 abnormalities were identified in CD38/CD138-positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%-100% of plasma cells. CONCLUSIONS: The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.

Chromosomal defects in multiple myeloma.

Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification. Other molecular methods are increasingly being utilised to provide a genome-wide view at high resolution (e.g. single nucleotide polymorphism (SNP) microarray analysis) and these can detect abnormalities in most cases. Despite their wide application at diagnostic assessment, both FISH and SNP-array have relatively low sensitivity, limiting their use for identification of prognostically significant low-level sub-clones or for disease monitoring. Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.

Fentanyl Exposure and Detection Strategies Utilized by Clinical Trial Participants Seeking Linkage to Opioid Use Disorder Treatment at a Syringe Service Program.

INTRODUCTION: The USA continues to face a fentanyl-driven overdose epidemic. Prior research has demonstrated users of illicit opioids are concerned about fentanyl exposure and overdose, but the strategies they report using to detect fentanyl's presence lack empirical support. This study compares self-report and biologically detected fentanyl use and investigates overdose risk and risk reduction behaviors among a sample of high-risk people who use opioids. METHODS: Structured enrollment interviews conducted as part of a larger clinical trial assessed self-reported fentanyl exposure as well as strategies used to determine believed fentanyl exposure and prevent overdose among 240 participants enrolled at a Chicago, IL syringe service program. Urinalysis measured actual fentanyl exposure. RESULTS: Most participants identified as African American (66.7%) and had considerable overdose experience (76.7% lifetime and 48% in the past year). Most also tested positive for fentanyl (93.75%) despite reporting no past year use of fentanyl or fentanyl-adulterated drugs (64.17%). The most utilized approaches reported for identifying fentanyl exposure were stronger effects of the drug (60.7%), sight or taste (46.9%), and being told by someone using the same drugs (34.2%). Few participants (14%) reported using fentanyl test strips. No significant associations were identified between self-report and urinalysis measures or urinalysis results and risk reduction strategies. CONCLUSION: This study adds to prior fentanyl exposure risk research. The disconnect between participants' fentanyl detection methods and reported overdose experiences supports the need for more research to identify and understand factors driving access and use of overdose prevention resources and strategies.

Associations between opioid overdose deaths and drugs confiscated by law enforcement and submitted to crime laboratories for analysis, United States, 2014-2019: an observational study.

Background: The overdose epidemic in the United States (US) continues to generate unprecedented levels of mortality. There is urgent need for a national data system capable of yielding high-quality, timely, and actionable information on existing and emerging drugs. Public health researchers have started using law enforcement forensic laboratory data to obtain surveillance information on illicit drugs. This study is the first to use drug reports from the entire US to examine correlations between a changing drug supply and increasing opioid-involved overdose deaths (OOD) on a national scale. Methods: This study is observational and investigates associations between law enforcement drug reports and OOD for the US from 2014 to 2019. OOD data are from the Centers for Disease Control and Prevention's National Vital Statistics System restricted-use multiple cause of death files. The US Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) contains forensic laboratory-tested drug exhibit information for the entire US (NFLIS-Drug). Counts of forensic laboratory reports and OOD were aggregated for each state by month, quarter, and year. A difference-in-differences framework was used to estimate contemporaneous and lagged associations. Findings: Between 2014 and 2019 in the US, 249,522 OOD were reported, with the annual number nearly doubling from 28,723 to 50,179. OOD involving illicitly manufactured fentanyls (IMF) also increased substantially during this period, from 19.4% to 72.9%. In addition, 3,817,438 forensic laboratory reports in the US that were reported to NFLIS-Drug contained an opioid, stimulant, or benzodiazepine. Reports of fentanyl and fentanyl-related compounds (FFRC) had the strongest association with OOD. Each additional FFRC exhibit was associated with a 2.97% (95% CI: 1.7%, 4.1%) increase in OOD per 100,000 persons per quarter. Interpretation: Adding to the emerging consensus, protracted growth in IMF supply was more strongly associated with OOD than all other illicit drugs reported to NFLIS-Drug over the study time period. Findings demonstrate NFLIS-Drug data usefulness for research that require proxy indicators for the illicit drugs supply. A concerted effort between public health and public safety to make NFLIS-Drug more timely could strengthen its utility as a national, public health, drug surveillance system. Funding: Sangeetha Arctic Slope Mission Services, LLC, ASMS Contract No. ASM5-00017.

Impact of personalized alcohol intake and cognitive feedback on alcohol use behavior in hazardous drinkers: A quasi-randomized trial.

BACKGROUND: Worldwide, alcohol use is a major contributor to the burden of disease and mortality. A sizeable literature suggests that brief web-based interventions that incorporate personalized normative and/or health consequences feedback are effective at reducing alcohol intake. The relative efficacy of an intervention that also includes individualized feedback about brain health has not been examined, nor has the utility of integrating a smartphone app component. METHOD: Participants (N = 436, Mage = 21.27) completed baseline protocols (n = 178 recorded alcohol use via an app for 14 days) and were then assigned to one of three feedback conditions using randomized block allocation with stratification based on the total number of standard drinks consumed. Control participants received no feedback; Alcohol Intake Feedback (Alc) participants received personalized information about their alcohol use; Alcohol Intake plus Cognitive Feedback (AlcCog) participants received personalized details about alcohol use plus individualized brain-health information related to impulsivity. The impact of feedback on alcohol consumption behavior was examined as a function of feedback condition and hazardous/non-harmful drinking status (as defined by the World Health Organization) at an 8-week follow-up. RESULTS: Hazardous drinkers in both the Alc and AlcCog conditions reduced their alcohol intake by 31% to 50% more than those in the Control condition. Reductions were not related to whether participants completed web- plus app-based components or web-only components of the intervention. There was no change in the alcohol intake of non-harmful drinkers. CONCLUSIONS: This proof-of-concept study showed that hazardous drinkers respond well to brief electronic interventions that incorporate personalized normative and/or health consequences feedback. Further research is required to determine how best to make impulsivity-related brain-health consequences of drinking manifest and how to maximize the potential of smartphones apps.

Innovative Approaches to Improve COVID-19 Case Investigation and Contact Tracing Among Refugees, Immigrants, and Migrants: Lessons Learned from a Newly Established National Resource Center.

Effective COVID-19 case investigation and contact tracing (CICT) among refugee, immigrant, and migrant (RIM) communities requires innovative approaches to address linguistic, cultural and community specific preferences. The National Resource Center for Refugees, Immigrants, and Migrants (NRC-RIM) is a CDC-funded initiative to support state and local health departments with COVID-19 response among RIM communities, including CICT. This note from the field will describe NRC-RIM and initial outcomes and lessons learned, including the use of human-centered design to develop health messaging around COVID-19 CICT; training developed for case investigators, contact tracers, and other public health professionals working with RIM community members; and promising practices and other resources related to COVID-19 CICT among RIM communities that have been implemented by health departments, health systems, or community-based organizations.

Characteristics of conventional high-risk coronary plaques and a novel CT defined thin-cap fibroatheroma in patients undergoing CCTA with stable chest pain.

BACKGROUND: Coronary computed tomography angiography (CCTA) can identify high-risk coronary plaque types. However, the inter-observer variability for high-risk plaque features, including low attenuation plaque (LAP), positive remodelling (PR), and the Napkin-Ring sign (NRS), may reduce their utility, especially amongst less experienced readers. METHODOLOGY: In a prospective study, we compared the prevalence, location and inter-observer variability of both conventional CT-defined high-risk plaques with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using individualised X-ray attenuation cut-offs (the CT-defined thin-cap fibroatheroma - CT-TCFA) in 100 patients followed-up for 7 years. RESULTS: In total, 346 plaques were identified in all patients. Seventy-two (21%) of all plaques were classified by conventional CT parameters as high-risk (either NRS or PR and LAP combined), and 43 (12%) of plaques were considered high-risk using the novel CT-TCFA definition of (Necrotic Core/fibrous plaque ratio of >0.9). The majority (80%) of the high-risk plaques (LAP&PR, NRS and CT-TCFA) were located in the proximal and mid-LAD and RCA. The kappa co-efficient of inter-observer variability (k) for NRS was 0.4 and for PR and LAP combined 0.4. While the kappa co-efficient of inter-observer variability (k) for the new CT-TCFA definition was 0.7. During follow-up, patients with either conventional high-risk plaques or CT-TCFAs were significantly more likely to have MACE (Major adverse cardiovascular events) compared to patients without coronary plaques (p value 0.03 & 0.03, respectively). CONCLUSION: The novel CT-TCFA is associated with MACE and has improved inter-observer variability compared with current CT-defined high-risk plaques.

Systematic Review and Meta-Analysis of the Effect of Loop Diuretics on Antibiotic Pharmacokinetics.

Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several potential drug interactions. A systematic review of the literature was performed to investigate the impact of loop diuretics on antibiotic PK. The primary outcome metric was the ratio of means (ROM) of antibiotic PK parameters such as area under the curve (AUC) and volume of distribution (Vd) on and off loop diuretics. Twelve crossover studies were amenable for metanalysis. Coadministration of diuretics was associated with a mean 17% increase in plasma antibiotic AUC (ROM 1.17, 95% CI 1.09-1.25, I2 = 0%) and a mean decrease in antibiotic Vd by 11% (ROM 0.89, 95% CI 0.81-0.97, I2 = 0%). However, the half-life was not significantly different (ROM 1.06, 95% CI 0.99-1.13, I2 = 26%). The remaining 13 observational and population PK studies were heterogeneous in design and population, as well as prone to bias. No large trends were collectively observed in these studies. There is currently not enough evidence to support antibiotic dosing changes based on the presence or absence of loop diuretics alone. Further studies designed and powered to detect the effect of loop diuretics on antibiotic PK are warranted in applicable patient populations.