Continuous Levodopa Delivery with an Intraoral Micropump System: An Open-Label Pharmacokinetics and Clinical Study.

BACKGROUND: Double-blind studies have demonstrated that motor complications in Parkinson's disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth. OBJECTIVES: Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations. METHODS: This was a 2-week, open-label study (NCT04778176) in 16 PD patients treated with ≥4 levodopa doses/day and experiencing motor fluctuations. On Day 1 (clinic setting) patients received their usual dose of standard LD/CD; DopaFuse therapy was initiated on Day 2, and on Day 3 patients received DopaFuse plus a morning oral LD/CD dose. Patients returned home on Days 4-14 and returned for in-clinic assessment on Day 15. RESULTS: Continuous DopaFuse delivery of LD/CD was associated with reduced variability in plasma levodopa levels compared to oral LD/CD (mean ± SD levodopa Fluctuation Index reduced from 2.15 ± 0.59 on Day1 to 1.50 ± 0.55 on Day 2 (P = 0.0129) and to 1.03 ± 0.53 on Day 3 (P < 0.0001)). This pharmacokinetic improvement translated into significantly reduced OFF time with DopaFuse therapy (reduction of -1.72 ± 0.37 h at Day 15; P = 0.0004) and increased ON time without severe dyskinesias (increase of 1.72 ± 0.37 h at Day 15; P = 0.0004) versus oral LD/CD administration. DopaFuse therapy was not associated with any clinically significant adverse events. CONCLUSIONS: Continuous delivery of LD/CD using the DopaFuse system was associated with significantly less variability in plasma levodopa concentrations and reductions in OFF time compared to treatment with standard oral LD/CD therapy and was well tolerated. © 2024 International Parkinson and Movement Disorder Society.

Clinical judgment in new nurse graduates: identifying the gaps.

OBJECTIVES: Clinical judgment has been identified as a key component of clinical practice. We sought to measure the elements of clinical judgment in new nurse graduates to identify future educational interventions. METHODS: Lasater's clinical judgment rubric was adapted and distributed to nurse preceptors at two significant health care systems in central Illinois. RESULTS: One hundred and six surveys were returned and one hundred and five of those were included in the study. New nurse graduates were found to be the lowest ranking in ability to identify significant data and calm, confident responses. CONCLUSIONS: The findings can guide nurse educators to create innovative, targeted educational interventions to improve students' ability to identify important pieces of data and respond to challenging situations in a self-assured manner. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: Identifying and addressing the gaps to improve students' clinical judgment may facilitate NCLEX success and entry to practice.

Endosome maturation factors Rabenosyn-5/VPS45 and caveolin-1 regulate ciliary membrane and polycystin-2 homeostasis.

Primary cilium structure and function relies on control of ciliary membrane homeostasis, regulated by membrane trafficking processes that deliver and retrieve ciliary components at the periciliary membrane. However, the molecular mechanisms controlling ciliary membrane establishment and maintenance, especially in relation to endocytosis, remain poorly understood. Here, using Caenorhabditis elegans, we describe closely linked functions for early endosome (EE) maturation factors RABS-5 (Rabenosyn-5) and VPS-45 (VPS45) in regulating cilium length and morphology, ciliary and periciliary membrane volume, and ciliary signalling-related sensory behaviour. We demonstrate that RABS-5 and VPS-45 control periciliary vesicle number and levels of select EE/endocytic markers (WDFY-2, CAV-1) and the ciliopathy membrane receptor PKD-2 (polycystin-2). Moreover, we show that CAV-1 (caveolin-1) also controls PKD-2 ciliary levels and associated sensory behaviour. These data link RABS-5 and VPS-45 ciliary functions to the processing of periciliary-derived endocytic vesicles and regulation of ciliary membrane homeostasis. Our findings also provide insight into the regulation of PKD-2 ciliary levels via integrated endosomal sorting and CAV-1-mediated endocytosis.

New nurse graduates and rapidly changing clinical situations: the role of expert critical care nurse mentors.

OBJECTIVES: New nurse graduates may be prone to instances of failure to rescue. Mentoring programs may be an opportunity to assist them with clinical decision making in situations of patient decline. We explored the experiences of new nurse graduates and expert nurses after participation in a mentoring program. METHODS: In this exploratory-descriptive study, five seasoned nurses were paired with five new nurse graduates. After four months, the new nurse graduates were interviewed, and the expert nurses participated in a focus group. RESULTS: Themes emerged for the new nurse graduates: 1) importance of the charge nurse, 2) differences in practice areas, and 3) supportive healthcare teams. The focus group revealed three themes: 1) remembering what it was like, 2) desiring to help, and 3) having confidence in their preparation as mentors. CONCLUSIONS: New nurse graduates relied on charge nurses for assistance. Therefore, it is imperative that charge nurses receive adequate support.

MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.

Cilia have a unique diffusion barrier ("gate") within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins--including the previously uncharacterised mammalian Tmem80--and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.

Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base.

Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.

Mutations in genes encoding cilia proteins cause human ciliopathies, diverse disorders affecting many tissues. Individual genes can be linked to ciliopathies with dramatically different phenotypes, suggesting that genetic modifiers may participate in their pathogenesis. The ciliary transition zone contains two protein complexes affected in the ciliopathies Meckel syndrome (MKS) and nephronophthisis (NPHP). The BBSome is a third protein complex, affected in the ciliopathy Bardet-Biedl syndrome (BBS). We tested whether mutations in MKS, NPHP and BBS complex genes modify the phenotypic consequences of one another in both C. elegans and mice. To this end, we identified TCTN-1, the C. elegans ortholog of vertebrate MKS complex components called Tectonics, as an evolutionarily conserved transition zone protein. Neither disruption of TCTN-1 alone or together with MKS complex components abrogated ciliary structure in C. elegans. In contrast, disruption of TCTN-1 together with either of two NPHP complex components, NPHP-1 or NPHP-4, compromised ciliary structure. Similarly, disruption of an NPHP complex component and the BBS complex component BBS-5 individually did not compromise ciliary structure, but together did. As in nematodes, disrupting two components of the mouse MKS complex did not cause additive phenotypes compared to single mutants. However, disrupting both Tctn1 and either Nphp1 or Nphp4 exacerbated defects in ciliogenesis and cilia-associated developmental signaling, as did disrupting both Tctn1 and the BBSome component Bbs1. Thus, we demonstrate that ciliary complexes act in parallel to support ciliary function and suggest that human ciliopathy phenotypes are altered by genetic interactions between different ciliary biochemical complexes.

The Life Science Exchange: a case study of a sectoral and sub-sectoral knowledge exchange programme.

BACKGROUND: Local and national governments have implemented sector-specific policies to support economic development through innovation, entrepreneurship and knowledge exchange. Supported by the Welsh Government through the European Regional Development Fund, The Life Science Exchange® project was created with the aim to increase interaction between stakeholders, to develop more effective knowledge exchange mechanisms, and to stimulate the formation and maintenance of long-term collaborative relationships within the Welsh life sciences ecosystem. The Life Science Exchange allowed participants to interact with other stakeholder communities (clinical, academic, business, governmental), exchange perspectives and discover new opportunities. METHODS: Six sub-sector focus groups comprising over 200 senior stakeholders from academia, industry, the Welsh Government and National Health Service were established. Over 18 months, each focus group provided input to inform healthcare innovation policy and knowledge mapping exercises of their respective sub-sectors. Collaborative projects identified during the focus groups and stakeholder engagement were further developed through sandpit events and bespoke support. RESULTS: Each sub-sector focus group produced a report outlining the significant strengths and opportunities in their respective areas of focus, made recommendations to overcome any 'system failures', and identified the stakeholder groups which needed to take action. A second outcome was a stakeholder-driven knowledge mapping exercise for each area of focus. Finally, the sandpit events and bespoke support resulted in participants generating more than £1.66 million in grant funding and inward investment. This article outlines four separate outcomes from the Life Science Exchange programme. CONCLUSIONS: The Life Science Exchange process has resulted in a multitude of collaborations, projects, inward investment opportunities and special interest group formations, in addition to securing over ten times its own costs in funding for Wales. The Life Science Exchange model is a simple and straightforward mechanism for a regional or national government to adapt and implement in order to improve innovation, skills, networks and knowledge exchange.

Lessons learned from conducting qualitative research in a hospital.

AIM: To examine unexpected barriers to the conduct of hospital research during a study of nurses' activation of rapid response teams. BACKGROUND: We interviewed hospital nurses regarding their decisions to activate rapid response teams and encountered unexpected barriers to the conduct of this study in the hospital setting. DATA SOURCES: Experience of conducting qualitative research with bedside nurses in a community hospital. REVIEW METHODS: Review of the reports of others who have conducted hospital research. DISCUSSION: Barriers related to administrative support, environmental distractors, constraints on nurses' time, apparent lack of investment in research by staff and a cumbersome recruitment process are identified. Recommendations on study site selection, timing of research, gaining access to nurses, scheduling and conducting interviews, and transcribing recorded data are made. CONCLUSION: As evidence is necessary to deliver safe, quality care, it is important that nurses understand and participate in research. This participation involves not only conducting research, but also serving as subjects. Given the importance of bedside nurses' willingness to engage in research, it is crucial to understand factors that impede or assist their participation. IMPLICATIONS FOR RESEARCH/PRACTICE: We offer several recommendations to nurses conducting research in hospitals, including: ■ Seek hospitals that are supportive of research, yet not over-invested in the process. ■ Build extra time into data collection schedules to maximize flexibility and accommodate work-place demands. ■ Emphasise the relevance and benefits of the research to nurses.

Nursing department orientation: are we missing the mark?

Hospitals routinely provide orientation for the new nurses they hire. The evolution of nursing practice is not reflected in the current teaching methods of nursing orientation. The authors examine the past 60 years of nursing department orientation and assert the need to move toward more effective and innovative teaching strategies.

The effects of emergency department staff rounding on patient safety and satisfaction.

BACKGROUND: Two recent inpatient studies documented that regular nursing staff rounding increased patient safety and satisfaction. However, the effect of systematic emergency department (ED) staff rounding on patient safety and satisfaction has not been adequately tested. STUDY OBJECTIVE: The objective of this study was to test the effectiveness of three different rounding techniques. METHODS: An 8-week study using a quasi-experimental, non-equivalent group, time-sampling design was conducted in 28 EDs. The three rounding protocols were: 1) rounds every 30 min; 2) rounds every hour; 3) rounds every hour with an Individualized Patient Care tactic (IPC; patients were asked to name their most important expectation for the ED visit). Baseline data were collected the first 4 weeks; rounding was done the second 4 weeks. Outcome measures compared the baseline to the rounding period data for patients who left without being seen (LWBS), those leaving against medical advice (AMA), patient satisfaction, call light use, and nursing station encounters. RESULTS: The three rounding protocols combined reduced LWBS by 23.4%, leaving AMA by 22.6%, falls by 58.8%, call light use by 34.7%, and approaches to the nursing station by 39.5%. Patient satisfaction ratings for overall care and pain management increased significantly. The protocol using the IPC tactic produced the most significantly improved outcomes. CONCLUSIONS: Rounding in the ED reception and treatment areas is effective and improves outcomes. Further research should determine the optimal design for rounding considering the mixed shifts in EDs, seek ways to increase communicating delays to patients, and investigate how to integrate rounding with physician activities.

Lessons Learned in Implementation of an Expert Nurse Mentor Program.

Experienced critical care nurses have the expertise to respond quickly and appropriately in emergency situations. New graduate nurses, however, typically lack this expertise and may benefit from mentoring as they learn to manage rapidly deteriorating patients. The purpose of this article is to describe the lessons learned during implementation of an Expert Nurse Mentor Program. Nurse educators may benefit from this information as they strive to establish and maintain mentoring programs.

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction.

Background Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results A prespecified physiology substudy of the T-TIME trial. From 2016 to 2017, patients with ST-segment-elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double-blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2-4, and ≥4 hours) were prespecified. One hundred forty-four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0-55.0), coronary flow reserve(1.4 [1.1-2.0]), and resistive reserve ratio (1.7 [1.3-2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions In ST-segment-elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling.

Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, the roles of cilia in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME). We demonstrate that C. elegans EFHC-1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC-1 also localizes at the synapse, where it further modulates dopamine signaling in cooperation with the orthologue of an R-type voltage-gated calcium channel. Our findings unveil a previously undescribed dual-regulation of neuronal excitability at sites of neuronal sensory input (cilium) and neuronal output (synapse). Such a distributed regulatory mechanism may be essential for establishing neuronal activation thresholds under physiological conditions, and when impaired, may represent a novel pathomechanism for epilepsy.

CiliaCarta: An integrated and validated compendium of ciliary genes.

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the Atypical MAP Kinase MAPK15 in Caenorhabditis elegans and Human Cells.

Motile and immotile (or primary) cilia are microtubule-based structures that mediate multiple cellular functions, including the transduction of environmental cues, developmental signaling, cellular motility, and modulation of fluid flow. Although their core architectures are similar, motile and primary cilia exhibit marked structural differences that underlie distinct functional properties. However, the extent to which ciliogenesis mechanisms are shared between these different cilia types is not fully described. Here, we report that the atypical MAP kinase MAPK15 (ERK7/8), implicated in the formation of vertebrate motile cilia, also regulates the formation of primary cilia in Caenorhabditis elegans sensory neurons and human cells. We find that MAPK15 localizes to a basal body subdomain with the ciliopathy protein BBS7 and to cell-cell junctions. MAPK15 also regulates the localization of ciliary proteins involved in cilium structure, transport, and signaling. Our results describe a primary cilia-related role for this poorly studied member of the MAPK family in vivo, and indicate a broad requirement for MAPK15 in the formation of multiple ciliary classes across species.

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial.

Background: Children who recover from moderate acute malnutrition (MAM) have high rates of relapse in the year after nutritional recovery. Interventions to decrease these adverse outcomes are needed to maximize the overall effectiveness of supplemental feeding programs (SFPs).Objective: We evaluated the effectiveness of a package of health and nutrition interventions on improving the proportion of children who sustained recovery for 1 y after MAM treatment. We further explored factors related to sustained recovery.Design: We conducted a cluster-randomized clinical effectiveness trial involving rural Malawian children aged 6-62 mo who were enrolled on discharge from an SFP for MAM. We enrolled 718 children at 10 control sites and 769 children at 11 intervention sites. In addition to routine health and nutrition counseling, the intervention group received a package of health and nutrition interventions that consisted of a lipid nutrient supplement, deworming medication, zinc supplementation, a bed net, and malaria chemoprophylaxis. A survival analysis was used to determine the effectiveness of the intervention as well as to identify factors associated with sustained recovery.Results: Of 1383 children who returned for the full 12-mo follow-up period, 407 children (56%) and 347 children (53%) sustained recovery in the intervention and control groups, respectively. There was no significant difference in relapse-free survival curves between the treatment and control groups (P = 0.380; log-rank test). The risk factors for relapse or death after initial recovery were a smaller midupper arm circumference on SFP admission (P = 0.01) and discharge (P < 0.001), a lower weight-for-height z score on discharge (P < 0.01), and the receipt of ready-to-use supplementary food as opposed to ready-to-use therapeutic food during treatment (P < 0.05).Conclusion: The provision of a package of health and nutrition services in addition to traditional SFP treatment has no significant effect on improving sustained recovery in children after treatment of MAM. This trial was registered at clinicaltrials.gov as NCT02351687.

MRSA acquisition in an intensive care unit.

BACKGROUND: This paper describes a retrospective investigation of methicillin-resistant Staphylococcus aureus (MRSA) acquisition in an 8-bed intensive care unit (ICU) over a 5-month period. METHODS: Clinical and microbiologic data were collected from the ICU, including MRSA detection dates, patient dependency scores, standardized environmental screening data, weekly bed occupancies, number of admissions, and nurse staffing levels. MRSA acquisition weeks were defined as weeks during which initial delivery of MRSA occurred before sampling and laboratory confirmation. Weekly workloads were plotted against staffing levels and modelled against MRSA acquisition weeks and hygiene failures. RESULTS: Of 174 patients admitted into the ICU, 28 (16%) were found to have MRSA; 12 of these (7%) acquired MRSA on the ICU within 7 of the 23 weeks studied. Six of these 7 weeks were associated with a deficit of trained nurses during the day and 5 with hygiene failures (data unavailable for 2). Pulsed-field gel electrophoresis (PFGE) profiles demonstrated relationships between staphylococci from staff hands, hand-touch sites, and patients' blood. CONCLUSION: MRSA acquisition in the ICU was temporally associated with reduced numbers of trained nurses and hygiene failures predominantly involving hand-touch sites. Epidemiologic analysis suggested that patient acquisitions were 7 times more likely to occur during periods of nurse understaffing.