Multidisciplinary, multicomponent interventions to reduce frailty among older persons in residents of residential care facilities: a scoping review.

BACKGROUND: Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. METHODS: A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. RESULTS: The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. CONCLUSION: This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.

The game changer: UCH-L1 and GFAP-based blood test as the first marketed in vitro diagnostic test for mild traumatic brain injury.

INTRODUCTION: Major organ-based in vitro diagnostic (IVD) tests like ALT/AST for the liver and cardiac troponins for the heart are established, but an approved IVD blood test for the brain has been missing, highlighting a gap in medical diagnostics. AREAS COVERED: In response to this need, Abbott Diagnostics secured FDA clearance in 2021 for the i-STAT Alinity™, a point-of-care plasma blood test for mild traumatic brain injury (TBI). BioMerieux VIDAS, also approved in Europe, utilizes two brain-derived protein biomarkers: neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). These biomarkers, which are typically present in minimal amounts in healthy individuals, are instrumental in diagnosing mild TBI with potential brain lesions. The study explores how UCH-L1 and GFAP levels increase significantly in the bloodstream following traumatic brain injury, aiding in early and accurate diagnosis. EXPERT OPINION: The introduction of the i-STAT Alinity™ and the Biomerieux VIDAS TBI blood tests mark a groundbreaking development in TBI diagnosis. It paves the way for the integration of TBI biomarker tools into clinical practice and therapeutic trials, enhancing the precision medicine approach by generating valuable data. This advancement is a critical step in addressing the long-standing gap in brain-related diagnostics and promises to revolutionize the management and treatment of mild TBI.

Blood-based traumatic brain injury biomarkers - Clinical utilities and regulatory pathways in the United States, Europe and Canada.

INTRODUCTION: Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. AREAS COVERED: This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada. EXPERT OPINION: TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.

Thorough overview of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity affecting all ages. It remains to be a diagnostic and therapeutic challenge, in which, to date, there is no Food and Drug Administration-approved drug for treating patients suffering from TBI. The heterogeneity of the disease and the associated complex pathophysiology make it difficult to assess the level of the trauma and to predict the clinical outcome. Current injury severity assessment relies primarily on the Glasgow Coma Scale score or through neuroimaging, including magnetic resonance imaging and computed tomography scans. Nevertheless, such approaches have certain limitations when it comes to accuracy and cost efficiency, as well as exposing patients to unnecessary radiation. Consequently, extensive research work has been carried out to improve the diagnostic accuracy of TBI, especially in mild injuries, because they are often difficult to diagnose. The need for accurate and objective diagnostic measures led to the discovery of biomarkers significantly associated with TBI. Among the most well-characterized biomarkers are ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. The current review presents an overview regarding the structure and function of these distinctive protein biomarkers, along with their clinical significance that led to their approval by the US Food and Drug Administration to evaluate mild TBI in patients.

Innovation in resuscitation: A novel clinical decision display system for advanced cardiac life support.

INTRODUCTION: The Advanced Cardiac Life Support (ACLS) Clinical Decision Display System (CDDS) is a novel application designed to optimize team organization and facilitate decision-making during ACLS resuscitations. We hypothesized that resuscitation teams would more consistently adhere to ACLS guideline time intervals in simulated resuscitation scenarios with the CDDS compared to without. METHODS: We conducted a simulation-based, non-blinded, randomized, crossover-design study with resuscitation teams comprised of Emergency Medicine physicians, registered nurses, critical care technicians, and paramedics. Each team performed 4 ACLS scenarios in randomized sequences, half with the CDDS and half without. We analyzed the resuscitations and recorded the times of interventions that have defined intervals by ACLS: rhythm checks, epinephrine administration, and shock delivery. In addition, we surveyed each resuscitation team regarding their experience using the CDDS. RESULTS: On average, teams performed rhythm checks 4.9 s closer to ACLS guidelines with the CDDS (p = 0.0358). Teams were also more consistent; on average, teams reduced the variation of time between consecutive doses of epinephrine by 45% (p = 0.0001) and defibrillation by 47% (p < 0.0001). Ninety-eight percent of participants indicated they would use the CDDS if available in real cardiac arrests. CONCLUSIONS: This study demonstrates that the CDDS improves the accuracy and precision of timed ACLS interventions in a simulated setting. Resuscitation teams were strongly in favor of utilizing the CDDS in clinical practice. Further investigations of the introduction of the platform into real time clinical environments will be needed to assess true efficacy and patient outcomes.

The Association between Emergency Department Super-Utilizer Status and Willingness to Participate in Research.

BACKGROUND: Research based on emergency departments (EDs) primarily focuses on medical conditions. There is limited research that investigates patients who willingly participate in research. This current study explored ED super-utilizers' (SUs') and nonsuper-utilizers' (NSUs') attitudes toward research. OBJECTIVE: The study assesses the willingness of SUs to participate in research. We hypothesize that the SU population will be as interested as nonutilizers in participating in medical research. METHODS: This prospective observational study stratified participants into SU and NSU cohorts based on their self-reported number of ED visits within 6 months. Surveys were captured in a secured database and analyzed using SAS 9.4. RESULTS: 7,481 completed questionnaires. SUs were more interested in participating in all types of research compared to NSUs. Both groups were most willing to participate in surveys. Neither group was particularly interested in studies that required medications. SUs were not more willing to participate in studies without payment than NSUs. Both groups trusted researchers at the same rates. CONCLUSION: Although rarely included in medical research, SUs were more willing to participate in nearly all types of research and expressed a similar trust in medical research when compared to nonsuper-utilizers.

Health Impact of Hurricanes Irma and Maria on St Thomas and St John, US Virgin Islands, 2017-2018.

Objectives. To assess the health impact of Hurricane Irma and Hurricane Maria on St Thomas, US Virgin Islands.Methods. We collected data from interviews conducted 6 and 9 months after the hurricanes, a review of 597 randomly selected emergency department (ED) encounters, and administrative records from 10 716 ED visits 3 months before, between, and 3 months after the hurricanes.Results. Informants described damaged hospital infrastructure, including flooding, structural damage, and lost staff. The greatest public health impact was on the elderly and persons with chronic diseases. In the setting of loss of the electronic medical record system, ED chart reviews were limited by problems with missing data. ED administrative data demonstrated that posthurricane patients, compared with prehurricane patients, were older and had less severe complaints. There was a significant increase in patients being seen for diabetes-related and respiratory complaints, especially asthma. Suboptimal recordkeeping for medical evacuees limited the ability to assess outcomes for patients with severe illnesses.Conclusions. Hurricanes Irma and Maria caused major disruptions to health care on St Thomas. Emphasis should be given to building a resilient health care system that will optimally respond to future hurricanes.

An update on diagnostic and prognostic biomarkers for traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.

Prognostic utility of neuroinjury biomarkers in post out-of-hospital cardiac arrest (OHCA) patient management.

Despite aggressive intervention, patients who survive an out-of-hospital cardiac arrest (OHCA) generally have very poor prognoses, with nationwide survival rates of approximately 10-20%. Approximately 90% of survivors will have moderate to severe neurological injury ranging from moderate cognitive impairment to brain death. Currently, few early prognostic indicators are considered reliable enough to support patients' families and clinicians' in their decisions regarding medical futility. Blood biomarkers of neurological injury after OHCA may be of prognostic value in these cases. When most bodily tissues are oxygen-deprived, cellular metabolism switches from aerobic to anaerobic respiration. Neurons are a notable exception, however, being dependent solely upon aerobic respiration. Thus, after several minutes without circulating oxygen, neurons sustain irreversible damage, and certain measurable biomarkers are released into the circulation. Prior studies have demonstrated value in blood biomarkers in prediction of survival and neurologic impairment after OHCA. We hypothesize that understanding peptide biomarker kinetics in the early return of spontaneous circulation (ROSC) period, especially in the setting of refractory cardiac arrest, may assist clinicians in determining prognosis earlier in acute resuscitation. Specifically, during and after immediate resuscitation and return of ROSC, clinicians and families face a series of important questions regarding patient prognosis, futility of care and allocation of scarce resources such as the early initiation of extracorporeal cardiopulmonary resuscitation (ECPR). The ability to provide early prognostic information in this setting is highly valuable. Currently available, as well as potential biomarkers that could be good candidates in prognostication of neurological outcomes after OHCA or in the setting of refractory cardiac arrest will be reviewed and discussed.

Expanding prevertebral soft tissue swelling subsequent to a motor vehicle collision.

Cervical acceleration/deceleration or whiplash injuries are a common cause of cervical spine trauma. Cervical acceleration/deceleration can result in vertebral fractures, subluxations, and ligamentous and other soft tissue injuries. Severe injuries are often evidenced by increased prevertebral swelling on lateral X-ray. Assessment of the prevertebral space on lateral cervical spine films is an essential component for identifying potential traumatic neck injuries. We describe a case in which an 84-year-old man on coumadin presented to the emergency department after a low-impact motor vehicle crash. The patient initially complained of neck and shoulder pain which subsequently progressed to hoarseness, dysphagia, and dyspnea. Imaging studies revealed significant prevertebral tissue swelling with anterior compression of his airway that required airway stabilization via awake fiber-optic intubation and reversal of his anticoagulation therapy.

Impact of helmet use in traumatic brain injuries associated with recreational vehicles.

Objective. To study the impact of helmet use on outcomes after recreational vehicle accidents. Methods. This is an observational cohort of adult and pediatric patients who sustained a TBI while riding a recreational vehicle. Recreational vehicles included bicycles, motorcycles, and all-terrain vehicles (ATVs), as well as a category for other vehicles such as skateboards and scooters. Results. Lack of helmet use was significantly associated with having a more severe traumatic brain injury and being admitted to the hospital. Similarly, 25% of those who did wearing a helmet were admitted to the ICU versus 36% of those who did not (P = 0.0489). The hospital length of stay was significantly greater for patients who did not use helmets. Conclusion. Lack of helmet use is significantly correlated with abnormal neuroimaging and admission to the hospital and ICU; these data support a call for action to implement more widespread injury prevention and helmet safety education and advocacy.

Emergency department crowding and time to antibiotic administration in febrile infants.

INTRODUCTION: Early antibiotic administration is recommended in newborns presenting with febrile illness to emergency departments (ED) to avert the sequelae of serious bacterial infection. Although ED crowding has been associated with delays in antibiotic administration in a dedicated pediatric ED, the majority of children that receive emergency medical care in the United States present to EDs that treat both adult and pediatric emergencies. The purpose of this study was to examine the relationship between time to antibiotic administration in febrile newborns and crowding in a general ED serving both an adult and pediatric population. METHODS: We conducted a retrospective chart review of 159 newborns presenting to a general ED between 2005 and 2011 and analyzed the association between time to antibiotic administration and ED occupancy rate at the time of, prior to, and following infant presentation to the ED. RESULTS: We observed delayed and variable time to antibiotic administration and found no association between time to antibiotic administration and occupancy rate prior to, at the time of, or following infant presentation (p>0.05). ED time to antibiotic administration was not associated with hospital length of stay, and there was no inpatient mortality. CONCLUSION: Delayed and highly variable time to antibiotic treatment in febrile newborns was common but unrelated to ED crowding in the general ED study site. Guidelines for time to antibiotic administration in this population may reduce variability in ED practice patterns.

TBI surveillance using the common data elements for traumatic brain injury: a population study.

BACKGROUND: To characterize the patterns of presentation of adults with head injury to the Emergency Department. METHODS: This is a cohort study that sought to collect injury and outcome variables with the goal of characterizing the very early natural history of traumatic brain injury in adults. This IRB-approved project was conducted in collaboration with our Institution's Center for Translational Science Institute. Data were entered in REDCap, a secure database. Statistical analyses were performed using JMP 10.0 pro for Windows. RESULTS: The cohort consisted of 2,394 adults, with 40% being women and 79% Caucasian. The most common mechanism was fall (47%) followed by motor vehicle collision (MVC) (36%). Patients sustaining an MVC were significantly younger than those whose head injury was secondary to a fall (P < 0.0001). Ninety-one percent had CT imaging; hemorrhage was significantly more likely with worse severity as measured by the Glasgow Coma Score (chi-square, P < 0.0001). Forty-four percent were admitted to the hospital, with half requiring ICU admission. In-hospital death was observed in 5.4%, while neurosurgical intervention was required in 8%. For all outcomes, worse TBI severity per GCS was significantly associated with worse outcomes (logistic regression, P < 0.0001, adjusted for age). CONCLUSION: These cohort data highlight the burden of TBI in the Emergency Department and provide important demographic trends for further research.

In vivo seizure induction and affinity studies of domoic acid and isodomoic acids-D, -E and -F.

Domoic acid and its isomers are produced via algal blooms and are found in high concentrations in shellfish. Here, we assessed the acute seizurogenic potencies of isomers-D, -E and -F and their binding affinities at heterogeneous populations of KA receptors from rat cerebrum. In addition, binding affinities of all six isomers (Iso-A through -F) were assessed at AMPA receptors. Radioligand displacement studies indicated that the seizurogenic potency of Iso-F (E-configuration) closely correlates with its affinities at both KA and AMPA receptors, whereas isomers-D (Z) and -E (E), which exhibit distinctly lower seizurogenic potencies, are quite weak displacers. Previously observed functional potencies for isomers-A, -B and -C (Sawant et al., 2008) correlated with AMPA receptor affinities observed here. Taken together, these findings call into question previous structure-activity rules. Significantly, in our hands, Iso-D was ten-fold less potent than Iso-F. To further explain observed links between structural conformation and functional potency, molecular modeling was employed. Modeling results closely matched the rank order of potency and binding data observed. We further assessed the efficacy of isomers-D, -E and -F as pharmacological preconditioning agents. Acute preconditioning with low-dose Iso-D, -E or -F, before high-dose DA failed to impart behavioural tolerance. This study has shed new light on structural conformations affecting non-NMDA ionotropic glutamate receptor binding and functional potency, and provides a foundation for future work in areas of AMPA and KA receptor modeling.

Written and verbal information versus verbal information only for patients being discharged from acute hospital settings to home.

BACKGROUND: It is becoming commonplace for patients to be discharged earlier from acute hospital settings to their own homes and be required to manage various aspects of their own care. This has increased the need for detailed information to be given to patients and/or significant others to enable them to effectively manage care at home. It has been suggested that providing written health information can assist in this self management. OBJECTIVES: To determine the effectiveness of providing written health information in addition to verbal information for patients and/or significant others being discharged from acute hospital settings to home. SEARCH STRATEGY: Computerised searches from 1990 to June 2002 of the Cochrane Consumers and Communication Review Group Specialised Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE, CINAHL, PsycINFO, ERIC, OVID (including Ageline, EBM Reviews, DARE, Best Evidence, Pre-MEDLINE and PsycARTICLES), Sociological abstracts, Austhealth and bibliographies in articles that met inclusion criteria. SELECTION CRITERIA: Articles were selected if they were randomised control trials or controlled clinical trials; included patients discharged from acute hospital settings to home; the patient and/or significant others received written health information and verbal information in the intervention group, and verbal information only in the control group; and the intervention (written health information and verbal information) was provided at discharge. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened abstracts to determine relevance. Relevant full paper copies were then reviewed against the inclusion criteria. The findings were extracted by one reviewer and confirmed by the other reviewer. The two trials that met the inclusion criteria were too disparate to warrant meta-analysis. MAIN RESULTS: The participants in the two trials were parents of children who were discharged from children's hospitals, one in the United States (n=197) the other in Canada (n=123). Provision of verbal and written health information significantly increased knowledge and satisfaction scores. REVIEWER'S CONCLUSIONS: This review recommends the use of both verbal and written health information when communicating about care issues with patients and/or significant others on discharge from hospital to home. The combination of verbal and written health information enables the provision of standardised care information to patients and/or significant others, which appears to improve knowledge and satisfaction. Many of our objectives could not be addressed in this review due to lack of trials which met the review's inclusion criteria. There is therefore scope for future research to investigate the effects of providing verbal and written health information on readmission rates, recovery time, complication rates, costs of health care, consumers' confidence level, stress and anxiety and adherence to recommended treatment and staff training in the delivery of verbal and written information. In addition there are other factors which impact on the effectiveness of information provided that were not considered in this review but are worthy of a separate systematic review, such as the impact of the patient and/or significant others being involved in the development of the written information, and cultural issues around development and provision of information. Due to concerns about literacy levels for some population groups, other systematic reviews should also focus on other modes of delivery of information besides the written format.

Designing supramolecular structures from models of cyclic peptide scaffolds with heterocyclic constraints.

Cyclic peptides containing oxazole and thiazole heterocycles have been examined for their capacity to be used as scaffolds in larger, more complex, protein-like structures. Both the macrocyclic scaffolds and the supramolecular structures derived therefrom have been visualised by molecular modelling techniques. These molecules are too symmetrical to examine structurally by NMR spectroscopy. The cyclic hexapeptide ([Aaa-Thz](3), [Aaa-Oxz](3)) and cyclic octapeptide ([Aaa-Thz](4), [Aaa-Oxz](4)) analogues are composed of dipeptide surrogates (Aaa: amino acid, Thz: thiazole, Oxz: oxazole) derived from intramolecular condensation of cysteine or serine/threonine side chains in dipeptides like Aaa-Cys, Aaa-Ser and Aaa-Thr. The five-membered heterocyclic rings, like thiazole, oxazole and reduced analogues like thiazoline, thiazolidine and oxazoline have profound influences on the structures and bioactivities of cyclic peptides derived therefrom. This work suggests that such constrained cyclic peptides can be used as scaffolds to create a range of novel protein-like supramolecular structures (e.g. cylinders, troughs, cones, multi-loop structures, helix bundles) that are comparable in size, shape and composition to bioactive surfaces of proteins. They may therefore represent interesting starting points for the design of novel artificial proteins and artificial enzymes.

Macrocycles mimic the extended peptide conformation recognized by aspartic, serine, cysteine and metallo proteases.

It has been previously demonstrated that aspartic, serine, metallo and cysteine proteases bind to their inhibitors and substrate analogues in a single conformation, the saw-tooth or extended beta-strand. Consequently a generic approach to the development of protease inhibitors is the use of constraints that conformationally restrict putative inhibitor molecules to an extended form. In this way the inhibitor is pre-organized for binding to a protease and does not need to rearrange its structure. One constraining device that has proven to be effective for such pre-organization is macrocyclization. This article illustrates the general principle that macrocycles, especially those composed of 3-4 amino acids and usually 13-17 ring atoms, can effectively mimic the extended conformation of short peptide sequences. Such structure-stabilising macrocycles are stable to degradation by proteases, valuable components of potent protease inhibitors, and in many cases they are also bioavailable.

Analyzing pacemaker leads: application of a form of energy.

In the province of Ontario, analyzing of pacemaker leads is a delegated controlled act. This article describes the certification/recertification process for analyzing of pacemaker leads at the Hamilton Health Sciences Corporation.

Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease.

Three new peptidomimetics (1-3) have been developed with highly stable and conformationally constrained macrocyclic components that replace tripeptide segments of protease substrates. Each compound inhibits both HIV-1 protease and viral replication (HIV-1, HIV-2) at nanomolar concentrations without cytotoxicity to uninfected cells below 10 microM. Their activities against HIV-1 protease (K(i) 1.7 nM (1), 0.6 nM (2), 0.3 nM (3)) are 1-2 orders of magnitude greater than their antiviral potencies against HIV-1-infected primary peripheral blood mononuclear cells (IC(50) 45 nM (1), 56 nM (2), 95 nM (3)) or HIV-1-infected MT2 cells (IC(50) 90 nM (1), 60 nM (2)), suggesting suboptimal cellular uptake. However their antiviral potencies are similar to those of indinavir and amprenavir under identical conditions. There were significant differences in their capacities to inhibit the replication of HIV-1 and HIV-2 in infected MT2 cells, 1 being ineffective against HIV-2 while 2 was equally effective against both virus types. Evidence is presented that 1 and 2 inhibit cleavage of the HIV-1 structural protein precursor Pr55(gag) to p24 in virions derived from chronically infected cells, consistent with inhibition of the viral protease in cells. Crystal structures refined to 1.75 A (1) and 1.85 A (2) for two of the macrocyclic inhibitors bound to HIV-1 protease establish structural mimicry of the tripeptides that the cycles were designed to imitate. Structural comparisons between protease-bound macrocyclic inhibitors, VX478 (amprenavir), and L-735,524 (indinavir) show that their common acyclic components share the same space in the active site of the enzyme and make identical interactions with enzyme residues. This substrate-mimicking minimalist approach to drug design could have benefits in the context of viral resistance, since mutations which induce inhibitor resistance may also be those which prevent substrate processing.