Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states.

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness, suprathreshold stimuli evoke perceptions; under anesthesia, perceptions are abolished; and during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perceptions. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia as well as during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely, in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is reliably elicited by external visual stimuli.

Alternative end-joining results in smaller deletions in heterochromatin relative to euchromatin.

Pericentromeric heterochromatin is highly enriched for repetitive sequences prone to aberrant recombination. Previous studies showed that homologous recombination (HR) repair is uniquely regulated in this domain to enable 'safe' repair while preventing aberrant recombination. In Drosophila cells, DNA double-strand breaks (DSBs) relocalize to the nuclear periphery through nuclear actin-driven directed motions before recruiting the strand invasion protein Rad51 and completing HR repair. End-joining (EJ) repair also occurs with high frequency in heterochromatin of fly tissues, but how alternative EJ (alt-EJ) pathways operate in heterochromatin remains largely uncharacterized. Here, we induce DSBs in single euchromatic and heterochromatic sites using a new system that combines the DR- white reporter and I-SceI expression in spermatogonia of flies. Using this approach, we detect higher frequency of HR repair in heterochromatin, relative to euchromatin. Further, sequencing of mutagenic repair junctions reveals the preferential use of different EJ pathways across distinct euchromatic and heterochromatic sites. Interestingly, synthesis-dependent microhomology-mediated end joining (SD-MMEJ) appears differentially regulated in the two domains, with a preferential use of motifs close to the cut site in heterochromatin relative to euchromatin, resulting in smaller deletions. Together, these studies establish a new approach to study repair outcomes in fly tissues, and support the conclusion that heterochromatin uses more HR and less mutagenic EJ repair relative to euchromatin.

Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states.

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness stimuli evoke perceptions; under anesthesia perceptions are abolished; during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perception. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia and during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is elicited by specifically by external visual stimuli.

Visual evoked feedforward-feedback traveling waves organize neural activity across the cortical hierarchy in mice.

Sensory processing is distributed among many brain regions that interact via feedforward and feedback signaling. Neuronal oscillations have been shown to mediate intercortical feedforward and feedback interactions. Yet, the macroscopic structure of the multitude of such oscillations remains unclear. Here, we show that simple visual stimuli reliably evoke two traveling waves with spatial wavelengths that cover much of the cerebral hemisphere in awake mice. 30-50 Hz feedforward waves arise in primary visual cortex (V1) and propagate rostrally, while 3-6 Hz feedback waves originate in the association cortex and flow caudally. The phase of the feedback wave modulates the amplitude of the feedforward wave and synchronizes firing between V1 and parietal cortex. Altogether, these results provide direct experimental evidence that visual evoked traveling waves percolate through the cerebral cortex and coordinate neuronal activity across broadly distributed networks mediating visual processing.

Novel open-source 3D-printed eye mount (TEMPO) for the ophthalmology wet lab.

OBJECTIVE: Procuring an affordable eye mount that can stabilise a cadaveric eye and simulate a patient's normal facial contours represents an ongoing challenge in the ophthalmology simulation wet lab, with notable limitations to all currently available commercial options. This project uses computer-assisted design and three-dimensional (3D)-printing techniques to tackle these challenges for ophthalmologic surgical training. METHODS AND ANALYSIS: Proof-of-concept study. Using Autodesk Fusion 360, we designed and 3D-printed a modular device that consists of 11 pieces forming a head structure. Standard OR tubing and syringes were adapted to create an adjustable-suction system to affix cadaveric eyes. Further modular inserts were customised to house non-cadaveric simulation eyes. RESULTS: Three-dimensional eye mount for procedures in ophthalmology (TEMPO) reliably fixed a cadaveric eye in stable position throughout surgical manipulation. Trainees were able to drape and practice appropriate hand positioning while corneal suturing. Overall, this model was affordable, at a cost of approximately $C200 to print. The modular nature renders individual pieces convenient for replacement and customisable to simulate regional anatomical variation and accommodate non-cadaveric eyes. CONCLUSIONS: TEMPO represents an affordable, high-fidelity alternative to existing commercially available eye mounts. It reliably fixates cadaveric and simulation eyes and provides an enhanced surgical training experience by way of its realistic facial contours. It is released as an open-source computer-aided design file, customisable to interested trainees with appropriate software and 3D-printing capacity.

Face and content validity of an artificial eye model for Ab-Interno Goniotomy.

PURPOSE: To determine the face and content validity of an artificial eye model for ab-interno goniotomy (SimulEYE KDB model, InsEYEt, Westlake Village, CA) by surveying ophthalmologists with varying experience using a Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) following a 90-min wet-lab course using the model. PARTICIPANTS: Overall 13 ophthalmologists participated following a surgical simulation session on goniotomy using the goniotomy blade at the 2019 Canadian Ophthalmological Society annual meeting. METHODS: A 17-question survey to assess the face and content validity of the model was given immediately following the surgical simulation session on goniotomy using the goniotomy blade. Responses to each survey question were recorded on a 5-point Likert scale ranging from (1) strongly agree to (5) strongly disagree. RESULTS: Respondents rated statements regarding the model with a median response of 1 (Strongly Agree) to 3 (Neither agree or disagree). Mann-Whitney U nonparametric analysis revealed no significant difference in responses between instructor vs. non-instructor or between prior experience vs. no prior experience for any of the survey statements. The model received highest survey ratings for utility in training residents, acquisition of surgical skills, accessibility, and higher likelihood of success with the procedure than theory and observation alone. Lowest ratings were for realism of the model compared to a human cadaveric eye. CONCLUSION: Our results suggest the SimulEYE KDB model is a reasonably cost-effective solution for simulating angle-based surgeries. Additionally, our project shows that experienced ophthalmologists found the artificial eye models useful and helpful for angle-based surgery training.

Rethinking the need for a platelet transfusion threshold of 50 × 109 /L for lumbar puncture in cancer patients.

BACKGROUND: Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic procedure in oncology patients. Transfusing to a minimum preprocedural platelet threshold of 50 × 109 /L is widely upheld without good quality evidence. The objective was to compare the outcomes of LPs performed with platelets above and below this threshold. An increased risk of adverse events in patients with lower platelet counts was not expected. As a corollary, transfusion reaction rates incurred by transfusing to this recommended threshold are also reported. METHODS: A total of 2259 LPs performed on 1137 oncology patients (adult, n = 871, and pediatric, n = 266) were retrospectively analyzed between February 2011 and December 2017. The incidence of LP-related complications for groups above and below the minimum platelet threshold was compared. Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebral spinal fluid. Groups were compared using the 2-Proportion Z-test and Fisher exact test. RESULTS: At time of LP, the total number of events with platelets less than 50 × 109 /L and 50 × 109 /L or greater were 110 and 2149, respectively. There were no significant differences in LP-associated complications between patients with platelet counts above or below 50 × 109 /L (P = .29). Patients with a pre-LP platelet count of less than 50 × 109 /L had a higher proportion of traumatic taps (P < .001). Three patients developed transfusion-related adverse events. CONCLUSION: Patients with platelet counts less than 50 × 109 /L did not have a higher incidence of clinically significant post-lumbar puncture complications (P = .29).

Canadian Opinions on Refractive Surgery and Approaches to Presbyopia Correction.

PURPOSE: To explore the opinions of Canadian ophthalmologists on refractive and presbyopia-correcting surgeries. METHODS: We distributed an online survey to the Canadian Ophthalmological Society members, covering laser refractive surgery (LRS), femtosecond laser-assisted cataract surgery (FLACS), lenticular refractive surgery (lenRS) that includes cataract refractive surgery (CRS) with premium intraocular lens (IOL) implantation, and presbyopia correction. RESULTS: There were 68 (7.6%) total respondents. Most respondents would not consider LRS (62.5%) nor FLACS (73.9%) for themselves. Male sex and performance of LRS or FLACS was significantly associated with consideration of these procedures for self. Most respondents (59.3%) would consider lenRS for themselves. The top method of personal presbyopia correction was spectacles, chosen by 52.5%. CONCLUSIONS: When surveying the wide body of Canadian ophthalmologists, most respondents preferred spectacle correction of presbyopia and would consider lenRS, but not LRS or FLACS for themselves. Surgeons performing these procedures were more likely to consider them for self.

Competency-based medical education in ophthalmology residency training: a review.

Competency-based medical education (CBME) is an outcomes-based training model that has become the new standard of medical education internationally. Regulatory and accrediting bodies have responded by establishing key competencies that residency programs may use to reshape their curricula. Available literature on the implementation of CBME in ophthalmology residency training programs across North America was examined. Ophthalmology-specific residency training objectives and milestones have been proposed within North America in the last 4 years. Curriculum guidelines and implementation blueprints and principles have also been proffered from various sources internationally but have met with some barriers. Assessment tools within ophthalmology have seen the most innovative development within the domain of surgical skills objectives. Competencies outside of the medical expert and patient care roles have proven more challenging to teach and assess. One ophthalmology program in Canada has undergone early implementation of a novel CBME curriculum. There is still considerable work to be done to successfully implement CBME curricula within ophthalmology residency programs in North America. Collaborative efforts to develop customizable curricula, tackle implementation barriers, and create specific assessment modalities will assist programs in meeting the competency mandates of CBME.

Competency-Based Education Assessment Tools for Laser Capsulotomy, Peripheral Iridotomy, and Selective Laser Trabeculoplasty.

PURPOSE: To produce Competency-Based Education Assessment Tools (C-BEAT) for performance of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy, laser peripheral iridotomy (LPI), and selective laser trabeculoplasty (SLT) on an artificial eye model that can be used in competency-based medical education (CBME) of ophthalmology residents. DESIGN: Survey. PARTICIPANTS: Eight content experts (residency program director and faculty members involved in ophthalmology resident training). METHODS: Task-specific checklists were created to assess the performance of Nd:YAG capsulotomy, LPI, and SLT on artificial eye models designed for each of these procedures, as well as a global rating scale (GRS). A modified Delphi process was used to establish face and content validity of the C-BEAT for lasers. Eight content experts participated in the Delphi process, and the consensus was achieved after 4 rounds. MAIN OUTCOME MEASURE: Survey responses. RESULTS: Final versions of checklists for Nd:YAG capsulotomy, LPI, and SLT, and a GRS for these laser procedures were produced with face and content validity. Modifications to the energy settings and the number of applications in the capsulotomy and peripheral iridotomy were implemented into the checklist and instructions, because the artificial models were not identical in their responses to the laser applications compared with real tissue. CONCLUSIONS: The C-BEAT for lasers can be used in an examination setting within ophthalmology residency training programs to establish competency in these procedures before performing them on real patients. These tools help to meet the demand for assessment modalities within a CBME model that is being implemented into residency training worldwide. To establish interrater and construct validities, further studies are required.

Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular disease: a systematic review and meta-analysis.

OBJECTIVE: Pseudoexfoliation syndrome (PEX) is a systemic disease, but evidence of its association with cardiovascular disease (CVD) and cerebrovascular disease (CVA) is controversial. A quantitative systematic review will provide an accurate summary of the current body of the literature. DESIGN: Meta-analysis. PARTICIPANTS: Not applicable. METHODS: A comprehensive literature search of published and unpublished English-language studies was performed. Summary statistics were calculated using inverse variance weighting and are presented in forest plots. Sources of variance were evaluated statistically. RESULTS: After screening 4547 studies, 47 articles were reviewed, and 25 eligible studies were selected that reported patients from around the world. Twenty studies enrolling 9583 individuals with PEX evaluated CVD, providing a summary odds ratio (OR) of 1.61 (95% CI 1.37-1.90). Eleven studies, enrolling 1308 PEX patients, evaluated CVA and generated a summary OR of 1.76 (1.40-2.22). For any vascular event (AVE) using all 25 studies, there were 9716 PEX patients and 363,312 control patients, yielding a summary OR of 1.64 (95% CI 1.39-1.92). Analysis for publication bias with the Egger's test was not significant for studies reporting CVD and AVE (p = 0.92 and 0.64, respectively) but was significant for CVA (p = 0.03). Asymmetry of Begg's funnel plot was noted for the CVA and AVE analyses. Multiple sensitivity analyses were performed, including assessment of study quality; the OR for all 3 outcomes varied minimally and remained significant in all analyses. CONCLUSION: There is strong evidence that PEX is significantly associated with both CVD and CVA.

Opinions on corrective refractive surgery.

OBJECTIVE: To investigate public perception that ophthalmologists are hesitant to undergo refractive surgery by determining the personal opinions of ophthalmologists on different surgical options. DESIGN: Prospective cross-sectional survey. PARTICIPANTS: Members of the American Society of Cataract and Refractive Surgery electronic mailing list. METHODS: An online survey administered from July to August 2014. RESULTS: There were 396 (5.7%) respondents: 204 (51.5%) would undergo laser refractive surgery (LRS) and 192 (48.5%) would not. Of the 228 (57.6%) with refractive error, 121 (53.1%) would have LRS, with 83 (36.4%) already having had the procedure done. Top reasons against LRS include existing contraindications, worry about intolerable side effects, and worry about complications. 179 (45.3%) would undergo lenticular refractive surgery (lenRS), with 22 (12.3%) having already had this done. Among those who said yes, most preferred a monofocal intraocular lens (IOL; 59 [33.0%]), whereas those who said no thought Toric IOLs to be superior (82 [38.0%]). 184 (46.6%) would undergo femtosecond laser-assisted cataract surgery (FLACS); the main reason against FLACS was concern regarding efficacy, followed by safety. Pearson χ2 analysis found that younger age and higher number of LRS procedures performed were associated with increased willingness to undergo LRS. Furthermore, willingness to undergo LRS was positively correlated with willingness to undergo lenRS. CONCLUSIONS: Ophthalmologists indeed are willing to undergo corrective refractive procedures. There is an approximately 50-50 divide on whether or not they would undergo LRS. Slightly less than half of ophthalmologists would personally undergo lenticular surgery, which includes cataract refractive surgery and FLACS.

Distinctive Infectious Complications in Patients with Central Nervous System Lymphoma Undergoing Thiotepa, Busulfan, and Cyclophosphamide-conditioned Autologous Stem Cell Transplantation.

We investigated the incidence of viral, fungal, bacterial, and parasitic infections observed in 57 patients with central nervous system lymphoma after thiotepa, busulfan, and cyclophosphamide-conditioned autologous stem cell transplantation (TBC-ASCT) and 79 patients with systemic non-Hodgkin lymphoma after traditional carmustine, etoposide, cytarabine, and melphalan-conditioned ASCT (BEAM-ASCT). Twenty of 57 (35%) TBC-ASCT patients had detectable viremia with human herpesvirus 6, cytomegalovirus, adenovirus, or BK virus, versus 9 of 79 (11%) BEAM-ASCT patients. Eight TBC-ASCT patients had clinically relevant viral infections (4 human herpesvirus 6, 2 cytomegalovirus, 1 adenovirus, 2 BK virus), versus 0 in the BEAM-ASCT group. Four TBC-ASCT patients suffered infections from either a fungal or parasitic pathogen versus 1 BEAM-ASCT patient. TBC was associated with greater risk of viral reactivation compared with BEAM, independent of other factors (hazard ratio, 4.42; 95% confidence interval, 1.9 to 11.3; P < .001). Prolonged lymphopenia and steroid use in the peri- and post-ASCT period did not explain these observed differences. The pathogenesis of these unusual infections in TBC-ASCT patients remains incompletely understood, and may involve more potent immune suppression with TBC conditioning. Clinicians should be aware of these differences in infection risk in TBC-ASCT patients, which more closely parallel those seen in allogenic hematopoietic cell transplantation recipients. New prophylactic approaches to help minimize these infections should be considered in this population.

Evaluation of occupational ocular trauma: are we doing enough to promote eye safety in the workplace?

OBJECTIVE: The aim of this study was to document the use of eye personal protective equipment (PPE) by patients who had sustained an eye injury in the workplace and to evaluate the characteristics and outcomes of these patients. DESIGN: Case-control study. PARTICIPANTS: All adult patients who had sustained an eye injury in the workplace and presented to the urgent ophthalmology clinic of a tertiary care hospital from October 1, 2013, to November 30, 2014, were eligible for inclusion. METHODS: Medical records were reviewed to obtain occupational eye injury data, including etiology, type, and severity of injury as per the Ocular Trauma Score. Use of eye PPE at the time of injury was recorded. Outcome data, including disposition, duration of follow-up, and return to baseline best-corrected visual acuity, were also recorded. RESULTS: One hundred sixty-nine patients were included in this study. The median age of the cohort was 31 years (range, 17-68 years), and 92.9% were male. Chemical exposure (31.4%), grinding (17.9%), and injuries sustained by a sharp-object, metal, or nail (13.1%) were overall the most common etiologies of injury. Eye PPE was not worn by 66.9% of the cohort, with 33.1% of the cohort sustaining an occupational eye injury despite the use of eye PPE. CONCLUSIONS: Use of eye PPE among workers who sustain an eye injury in the workplace remains low; yet, its use does not preclude a significant proportion of such workers from injury. Increasingly advocating for both the use and appropriate selection of eye PPE in the workplace is an important public health initiative that should therefore be encouraged.

Hospitalists on an inpatient tertiary care oncology teaching service.

PURPOSE: Hospitalists provide quality care in various inpatient settings, but the ability of hospitalists to provide quality inpatient care for patients with complex cancer has not been studied. This study explores outcomes with a hospitalist-led versus medical oncologist-led house staff team on an inpatient medical GI oncology teaching service. METHODS: This observational retrospective cohort study examined 829 patient discharges from August 2012 to January 2013 on the GI oncology inpatient teaching service at Memorial Sloan Kettering Cancer Center, a tertiary cancer center in New York, New York. We compared average length of stay (ALOS), 30-day readmission rates, establishment of new do not resuscitate (DNR) orders, nosocomial pneumonia and urinary tract infection (UTI) rates, radiographic and laboratory tests per patient, and disposition on discharge between hospitalist-led and oncologist-led teams. RESULTS: Median years of clinical experience was 6 (range, 4 to 9 years) for hospitalists and 7 (range, 0.5 to 36 years) for oncologists. ALOS (hospitalist led, 5.6 v oncologist led, 5.2 days; P = .30), readmission within 30 days (hospitalist led, 14% v oncologist led, 16%; P = .44), new DNR orders (hospitalist led, 18% v oncologist led, 19%; P = .90), nosocomial pneumonia (hospitalist led, 0.5% v oncologist led, 0.7%; P = .63) and UTI rates (hospitalist led, 0.5% v oncologist led, 0.7%; P = .63), number of radiographic studies and laboratory tests, and disposition on discharge were not significantly different between groups. CONCLUSION: A hospitalist-led inpatient service with house staff represents a novel approach for caring for hospitalized GI oncology patients with cancer.

Longitudinal fluorescent observation of retinal degeneration and regeneration in zebrafish using fundus lens imaging.

PURPOSE: Longitudinal observation of retinal degeneration and regeneration in animal models is time-consuming and expensive. To address this challenge, we used a custom fundus lens and zebrafish transgenic lines with cell-specific fluorescent reporters to document the state of individual retinal neurons in vivo. METHODS: We empirically tested several versions of a custom fundus lens and assessed its capabilities under a stereomicroscope to image retinal neurons in transgenic zebrafish lines expressing fluorescent reporters. Vascular branch points provided spatial references enabling determination of whether changes induced by ablating photoreceptors were repaired over the course of several days. RESULTS: Individual ultraviolet- and blue-sensitive cone photoreceptors were readily visualized in vivo, and green fluorescent protein-labeled blood vessels were used as landmarks to facilitate orientation. Sequential imaging of the same retinal areas over several weeks permitted documentation of photoreceptor reappearance in individual animals. Photoreceptor regeneration in these regions was evidenced by the reappearance of individual fluorescent cells. CONCLUSIONS: This technique permits real-time in vivo serial examination of individual fish, permitting temporal analysis of changes to the retinal mosaic. The key benefits this technique offers include that the same retinal locations can be recovered and viewed at multiple time points, that in vivo observations are comparable to those made ex vivo, and that fewer animals need to be euthanized over the course of an experiment. Our results promise the ability to detect individual cells, including reappearing cone photoreceptors, and to monitor disease progression during screening of therapies in an adult animal model of late onset disease.

Disparities in healthcare utilisation rates for Aboriginal and non-Aboriginal Albertan residents, 1997-2006: a population database study.

BACKGROUND: It is widely recognised that significant discrepancies exist between the health of indigenous and non-indigenous populations. Whilst the reasons are incompletely defined, one potential cause is that indigenous communities do not access healthcare to the same extent. We investigated healthcare utilisation rates in the Canadian Aboriginal population to elucidate the contribution of this fundamental social determinant for health to such disparities. METHODS: Healthcare utilisation data over a nine-year period were analysed for a cohort of nearly two million individuals to determine the rates at which Aboriginal and non-Aboriginal populations utilised two specialties (Cardiology and Ophthalmology) in Alberta, Canada. Unadjusted and adjusted healthcare utilisation rates obtained by mixed linear and Poisson regressions, respectively, were compared amongst three population groups - federally registered Aboriginals, individuals receiving welfare, and other Albertans. RESULTS: Healthcare utilisation rates for Aboriginals were substantially lower than those of non-Aboriginals and welfare recipients at each time point and subspecialty studied [e.g. During 2005/06, unadjusted Cardiology utilisation rates were 0.28% (Aboriginal, n = 97,080), 0.93% (non-Aboriginal, n = 1,720,041) and 1.37% (Welfare, n = 52,514), p = <0.001]. The age distribution of the Aboriginal population was markedly different [2.7%≥65 years of age, non-Aboriginal 10.7%], and comparable utilisation rates were obtained after adjustment for fiscal year and estimated life expectancy [Cardiology: Incidence Rate Ratio 0.66, Ophthalmology: IRR 0.85]. DISCUSSION: The analysis revealed that Aboriginal people utilised subspecialty healthcare at a consistently lower rate than either comparatively economically disadvantaged groups or the general population. Notably, the differences were relatively invariant between the major provincial centres and over a nine year period. Addressing the causes of these discrepancies is essential for reducing marked health disparities, and so improving the health of Aboriginal people.

The National Institute for Health and Clinical Excellence and its role in assessing the value of new cancer treatments in England and Wales.

The boundaries of medical science in the treatment of cancer are constantly extending. Developments of existing treatments, innovative approaches, new discoveries, and more targeted therapeutic options are translating into practice. With advances come increasing costs, often of a magnitude that stretches finite financial resources. When decisions about funding are made on behalf of a population, standardized processes and methods are needed in order to produce robust guidance in a fair, consistent, and transparent way. The challenges of making these difficult decisions are brought into particularly stark relief when potentially life-extending treatments for patients with a short life expectancy are appraised. The National Institute for Health and Clinical Excellence (NICE) produces guidance on the clinical- and cost-effectiveness of medicines compared with current standard practice. Approximately 40% of the technologies appraised by NICE are indicated for cancer, and the majority of these are pharmaceuticals, mostly biological agents. This article provides an overview of the current role of NICE in making new technologies for cancer available in England and Wales. This includes a summary of experiences with end-of-life treatments and the supplementary advice regarding such treatments that was issued by NICE to its decision-making committees in 2009.