Selective laser trabeculoplasty (SLT) performed by optometrists—enablers and barriers to a shift in service delivery

Background/objectives: To explore the acceptability, training requirements, enablers and barriers of optometrist-delivered SLT. / Subjects/methods: Optometrists, fellowship and consultant grade ophthalmologists, hospital managers and patients were interviewed using pre-defined topic guides. Interviews were audio-recorded, transcribed, and subjected to thematic analysis. Overarching themes were defined by the study aims and the topic guides; subthemes were derived from the interview data. / Results: Sixty-six participants (three managers, eight glaucoma specialist consultant ophthalmologists, seven clinical glaucoma fellows, 12 optometrists (two of them performing SLT), two ophthalmic nurses and 34 patients) participated in the study. Overarching themes (and subthemes) were: necessity of non-medical SLT delivery, clinical practice and training, advantages, disadvantages, concerns, challenges, community delivery of SLT, patient values and other healthcare professionals that could also deliver SLT. / Conclusions: Certain clinical pre-requisites, such as gonioscopy and independent prescribing rights, were perceived as necessary for undertaking SLT training. An optometrist-delivered SLT service was expected to benefit the NHS, but there was an identified need of a standardised training scheme and robust governance. Patients were accepting of an optometrist-delivered SLT service in the hospital eye service

How can Multi-Professional Education Support Better Stewardship?

Antimicrobial stewardship is widely accepted as an efficient strategy to combat the growing threat of antimicrobial resistance. Education is one of the cornerstones of successful antimicrobial stewardship programs. There is also general agreement that antimicrobial stewardship is a team effort that must involve the whole continuum of healthcare workers. Providing adequate education for all different professionals although challenging is deemed crucial to achieve good results. This paper reviews the different strategies available to educate the multiple healthcare workers, discusses how education can improve antimicrobial stewardship programs and outlines some of the challenges faced and research gaps that need to be addressed in order to improve education in this field

Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated Intraocular Pressure

PURPOSE: We determined whether there is relative sparing of pupil function in glaucoma patients with normal pressures compared to those with high pressures. METHODS: A cross-sectional study was done of 68 patients with primary open angle glaucoma (POAG): 38 had normal IOPs on all-day phasing before treatment (never >21 mm Hg), with confirmed progression of glaucomatous optic neuropathy (NTG) and 30 had glaucomatous optic neuropathy associated with elevated intraocular pressures (>25 mm Hg; HP-POAG). The relative afferent pupillary defect (RAPD) was quantified with the RAPDx device, and mean deviation of visual field loss was obtained from reliable Humphrey visual fields. Outcomes measures evaluated were difference in slope between NTG and HP-POAG when plotting: (1) RAPD score against difference in mean deviation (MD) between eyes, and (2) RAPD score against difference in RNFL thickness between eyes. RESULTS: The slopes for magnitude of RAPD versus difference in MD were -0.06 (95% confidence interval [CI], -0.076, -0.044) for patients with NTG and -0.08 (95% CI, -0.109, -0.067) for those with HP-POAG. Fitting the interaction term showed a statistically significant difference between the slopes (0.023; 95% CI [0.0017, 0.0541]; P value = 0.037; HP-POAG reference group). Thus, for difference in MD, the slope for patients with NTG was flatter than the slope for those with HP-POAG. CONCLUSIONS: Glaucoma patients with NTG have a lesser RAPD for a given level of intereye difference of HVF MD, compared to patients with high IOPs. This suggests that damage to intrinsically photosensitive retinal ganglion cells (ipRGCs) differs between the normal and high-pressure forms of open-angle glaucoma (OAG), and supports the theory that mitochondrial optic neuropathies may have a role in the group of diagnoses currently termed normal tension glaucoma

Potential limits of AAV-based gene therapy with the use of new transgenes expressing factor IX fusion proteins

Introduction: The variety of treatment for haemophilia B (HB) has recently improved with the emergence of both AAV‐based gene therapy and bioengineered human factor IX (hFIX) molecules with prolonged half‐life due to fusion to either albumin (Alb) or immunoglobulin Fc fragment (Fc). / Aim: Adeno‐associated viral vectors (AAV) mediating expression of hFIX‐Alb and hFIX‐Fc fusion proteins was investigated for gene therapy of HB to explore if their extended half‐life translates to higher plasma levels of FIX. / Methods: Single‐stranded cross‐packaged AAV2/8 vectors expressing hFIX‐Alb, hFIX‐Fc and hFIX were evaluated in vitro, and in mice. / Results: Both hFIX‐Alb and hFIX‐Fc fusion proteins were synthesized and expressed as single chains of expected size following AAV‐mediated gene transfer in vitro and in vivo. The procoagulant properties of these hFIX‐fusion proteins were comparable to wild‐type hFIX. However, their expression levels were threefold lower than wild‐type hFIX in vivo most likely due to inefficient secretion. / Conclusion: This, the first, evaluation of hFIX‐fusion proteins in the context of AAV gene transfer suggests that the hFIX‐fusion proteins are secreted inefficiently from the liver, thus preventing their optimal use in gene therapy approaches

Polonium-210 poisoning: a first-hand account

Background: Polonium-210 (210Po) gained widespread notoriety after the poisoning and subsequent death of Mr Alexander Litvinenko in London, UK, in 2006. Exposure to 210Po resulted initially in a clinical course that was indistinguishable from infection or exposure to chemical toxins, such as thallium. Methods: A 43-year-old man presented to his local hospital with acute abdominal pain, diarrhoea, and vomiting, and was admitted to the hospital because of dehydration and persistent gastrointestinal symptoms. He was initially diagnosed with gastroenteritis and treated with antibiotics. Clostridium difficile toxin was subsequently detected in his stools, which is when he first raised the possibility of being poisoned and revealed his background and former identity, having been admitted under a new identity with which he had been provided on being granted asylum in the UK. Within 6 days, the patient had developed thrombocytopenia and neutropenia, which was initially thought to be drug induced. By 2 weeks, in addition to bone marrow failure, he had evidence of alopecia and mucositis. Thallium poisoning was suspected and investigated but ultimately dismissed because blood levels of thallium, although raised, were lower than toxic concentrations. The patient continued to deteriorate and within 3 weeks had developed multiple organ failure requiring ventilation, haemofiltration, and cardiac support, associated with a drop in consciousness. On the 23rd day after he first became ill, he suffered a pulseless electrical activity cardiorespiratory arrest from which he could not be resuscitated and was pronounced dead. Findings: Urine analysis using gamma-ray spectroscopy on day 22 showed a characteristic 803 keV photon emission, raising the possibility of 210Po poisoning. Results of confirmatory analysis that became available after the patient's death established the presence of 210Po at concentrations about 109-times higher than normal background levels. Post-mortem tissue analyses showed autolysis and retention of 210Po at lethal doses in several organs. On the basis of the measured amounts and tissue distribution of 210Po, it was estimated that the patient had ingested several 1000 million becquerels (a few GBq), probably as a soluble salt (eg, chloride), which delivered very high and fatal radiation doses over a period of a few days. Interpretation: Early symptoms of 210Po poisoning are indistinguishable from those of a wide range of chemical toxins. Hence, the diagnosis can be delayed and even missed without a high degree of suspicion. Although body surface scanning with a standard Geiger counter was unable to detect the radiation emitted by 210Po, an atypical clinical course prompted active consideration of poisoning with radioactive material, with the diagnosis ultimately being made with gamma-ray spectroscopy of a urine sample

Weight-based antibiotic dosing in a real-world European study of complicated skin and soft-tissue infections due to methicillin-resistant <i>Staphylococcus aureus</i>

AbstractWe aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs

Comparison of vancomycin and linezolid in patients with peripheral vascular disease and/or diabetes in an observational European study of complicated skin and soft-tissue infections due to methicillin-resistant <i>Staphylococcus aureus</i>

AbstractSuboptimal antibiotic penetration into soft tissues can occur in patients with poor circulation due to peripheral vascular disease (PVD) or diabetes. We conducted a real-world analysis of antibiotic treatment, hospital resource use and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or vancomycin for the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This subgroup analysis evaluated data obtained from a retrospective, observational medical chart review study that captured patient data from 12 European countries. Data were obtained from the medical records of patients ≥ 18 years of age, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Hospital length of stay and length of treatment were compared between the treatment groups using inverse probability of treatment weights to adjust for clinical and demographic differences. A total of 485 patients had PVD or diabetes and received treatment with either vancomycin (n = 258) or linezolid (n = 227). After adjustment, patients treated with linezolid compared with vancomycin respectively had significantly shorter hospital stays (17.9 ± 13.6 vs. 22.6 ± 13.6 days; p < 0.001) and treatment durations (12.9 ± 7.9 vs. 16.4 ± 8.3 days; p < 0.001). The proportions of patients prescribed oral, MRSA-active antibiotics at discharge were 43.2% and 12.4% of patients in the linezolid and vancomycin groups, respectively (p < 0.001). The reduction in resource use may result in lower hospital costs for patients with PVD and/or diabetes and MRSA cSSTIs if treated with linezolid compared with vancomycin

Efficacy of Repeat Selective Laser Trabeculoplasty in Medication-Naïve Open Angle Glaucoma and Ocular Hypertension during the LiGHT Trial

PURPOSE: To determine the efficacy of repeat selective laser trabeculoplasty (SLT) in medication-naïve open angle glaucoma (OAG) and ocular hypertensive (OHT) patients requiring repeat treatment for early to medium-term failure during the Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. // DESIGN: Post-hoc analysis of SLT treatment arm of a multicentre prospective randomised-controlled-trial. // PARTICIPANTS: Treatment-naïve OAG or OHT requiring repeat 360-degree SLT within 18 months. Re-treatment was triggered by pre-defined IOP and disease-progression criteria (using objective individualised target IOPs) // METHODS: After SLT at baseline, patients were followed for a minimum of 18 months after second (‘repeat’) SLT. A mixed model analysis was performed with the eye as the unit of analysis, with crossed random-effects to adjust for correlation between fellow eyes and repeated measures within eyes. Kaplan-Meier curves plot the duration of effect. // OUTCOME MEASURES: Initial (‘early’) IOP lowering at 2-months and duration of effect following initial and Repeat SLT. // RESULTS: 115 eyes of 90 patients received Repeat SLT during first 18 months of the trial. Pre-treatment IOP prior to Initial SLT was significantly higher than that prior to pre-retreatment IOP of Repeat SLT (mean difference: 3.4, 95% confidence interval (CI) 2.6 to 4.3, mmHg; p<0.001). Absolute IOP reduction at 2-months was greater following Initial, compared to Repeat, SLT (mean difference: 1.0, 95% CI 0.2 to 1.8, mmHg; p=0.02). Adjusted absolute IOP reduction at 2-months (adjusting for IOP prior to initial or repeat laser) was greater following Repeat SLT (adjusted mean difference: -1.1, 95% CI -1.7 to -0.5, mmHg; p=0.001). 34 eyes were ‘early failures’ (retreated 2-months after Initial SLT) vs 81 ‘later failures’ (retreatment beyond 2-months following Initial SLT). No significant difference in early absolute IOP reduction at 2-months following Repeat SLT was noted between ‘early’ vs ‘later’ failures’ (mean difference: 0.3, 95% CI, -1.1 to 1.8,mmHg; p=0.655). Repeat SLT maintained drop-free IOP control in 67% of 115 eyes at 18 months, with no clinically-relevant adverse events. // CONCLUSION: These exploratory analyses demonstrate Repeat SLT can maintain IOP at or below Target IOP in medication-naive OAG and OHT eyes requiring retreatment with atleast an equivalent duration of effect to initial laser

Implementing criteria-based early switch/early discharge programmes:a European perspective

AbstractEarly switch (ES) from intravenous (IV) to oral antibiotic therapy programmes is increasingly included as a component of hospital antimicrobial stewardship initiatives that aim to optimize antimicrobial therapy while limiting toxicity and resistance. In terms of prioritizing the most cost-effective stewardship interventions, ES has been seen as a ‘low-hanging fruit’, which refers to selecting the most obtainable targets rather than confronting more complicated issues. Administration of highly bioavailable oral antibiotics should be considered for nearly all non-critically ill patients and has been recommended as an effective and safe strategy for over two decades. However, to accrue the most benefit from ES, it should be combined with an early discharge (ED) plan, protocol, or care pathway. Benefits of this combined approach include improved patient comfort and mobility, reduced incidence of IV-line-related adverse effects, reduced IV antimicrobial preparation time, decreased hospital stays, reduced antimicrobial purchasing and administration costs, decreased patient deconditioning, and shortened recovery times. Results from published studies document decreases in healthcare resource use and costs following implementation of ES programmes, which in most studies facilitate the opportunity for ED and ED programmes. Barriers to the implementation of these programmes include clinician misconceptions, practical considerations, organizational factors, and a striking lack of awareness of IV to oral switch guidance. These and other barriers will need to be addressed to maximize the effectiveness of ES and ED programmes. As national antimicrobial stewardship programmes dictate the inclusion of ES and ED programmes within healthcare facilities, programmes must be developed and success must be documented