Estimating utilities/disutilities for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and treatment-related adverse events.

PURPOSE: To capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost-utility analyses. METHODS: A literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]. Six additional health states described treatment-related AEs. The health states were validated with experts and piloted with general public participants. Health state utilities were obtained using the time trade-off (TTO) method with 200 members of the UK general population. A generalised estimating equation (GEE) model was used to estimate disutility weights. RESULTS: Mean TTO scores for Base State 1 to 3 were 0.71 (SD = 0.26), 0.64 (SD = 0.27), and 0.68 (SD = 0.26), respectively, indicating that receiving docetaxel plus ADT was most impactful on HRQL. The GEE model indicated when compared to Base State 2 that the nausea and vomiting AE had the most impact on HRQL (- 0.21), while alopecia was least burdensome (- 0.04). CONCLUSIONS: The study highlights the differences in utility between base health states and the significant impact of treatment-related AEs on the HRQL of patients with mHSPC. These findings underline the importance of accounting for impaired HRQL when assessing treatments for mHSPC.

Combined Phacoemulsification-Endoscopic Cyclophotocoagulation versus Phacoemulsification Alone in Primary Angle-Closure Glaucoma: A Pilot Randomized Controlled Trial.

PURPOSE: To compare combined phacoemulsification plus endoscopic cyclophotocoagulation (ECP) versus phacoemulsification alone in primary angle-closure glaucoma (PACG) with coexisting cataract. DESIGN: Prospective randomized controlled clinical trial-a pilot study. PARTICIPANTS: Forty-eight PACG eyes of 48 patients with coexisting cataract. INTERVENTION: Recruited patients were randomized into undergoing phacoemulsification plus ECP or phacoemulsification alone. After surgery, patients were followed up every 3 months for 2 years. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS: Twenty-seven PACG eyes were randomized to receive combined phacoemulsification plus ECP, and 21 PACG eyes underwent phacoemulsification alone. There was no statistically significant difference in mean preoperative IOP between combined phacoemulsification plus ECP and phacoemulsification groups (20.0 mmHg vs. 20.7 mmHg; P = 0.71). Phacoemulsification plus ECP resulted in lower mean postoperative IOP than phacoemulsification alone at all follow-up visits, but the differences only reached statistical significance at 1 month (P = 0.01), 12 months (P = 0.01), and 24 months (P = 0.04) postoperatively. There was no statistically significant difference in mean preoperative number of topical glaucoma drugs between combined phacoemulsification plus ECP and phacoemulsification groups (3.3 vs 3.1, P = 0.71). Combined phacoemulsification plus ECP resulted in lower glaucoma drug requirement than phacoemulsification alone at all follow-up visits, but the differences did not reach statistical significance at any time points postoperatively (P ≥ 0.05). Both groups were comparable in visual improvement, complication rate, need for additional surgical intervention, and visual field changes. CONCLUSIONS: Combined phacoemulsification plus ECP is noninferior to phacoemulsification alone in controlling IOP in PACG eyes with cataract. Combined phacoemulsification plus ECP resulted in lower mean IOP and glaucoma drug requirement than phacoemulsification alone at all follow-up visits in this pilot study, but the differences did not reach statistical significance at the majority of time points. A large-scale randomized controlled trial is in progress to evaluate these differences.

Health utility values associated with diabetic retinopathy.

AIMS: Different estimates exist regarding the impact of diabetic retinopathy (DR) on health utility. A previously reported prospective observational study has reported much larger decrements in self-reported utility than generic utility data from the UK Prospective Diabetes Study and the Lipids in Diabetes Study. The present study was designed to estimate utility loss using multiple methods. METHODS: Detailed health state descriptions reflecting declining DR (five different visual acuity levels), neuropathy and nephropathy were validated with patients and used to elicit utility values from people with DR, people with diabetes and members of the UK general public using standard gamble. In addition, a larger sample of people with retinopathy completed different health-related quality of life measures in an interview [EuroQoL (EQ-5D), Health State Utilities Index (HUI)-3, and National Eye Institute Visual Functioning Questionnaire-25]. RESULTS: The utility scores from the standard gamble interviews were not significantly different between the three groups. There was a decline in utility from 6/6 vision to counting fingers of -0.244. The utility data derived from the generic measures revealed an equivalent decline of -0.41 on both the EQ-5D single index and the HUI-3. CONCLUSIONS: This study has re-examined the utility decrements associated with DR and has identified much larger declines in utility than previously reported. The study has also reported the utility values of patients with retinopathy as assessed by standard gamble. We believe that this may be the first study to report utility values for health states associated with vision loss which have been elicited from patients with vision loss.

Ultrasound evaluation of glaucoma drainage devices in children.

This study evaluated B-scan ultrasound as a technique for assessing glaucoma drainage device (GDD) patency/function in refractory pediatric glaucoma. We retrospectively evaluated 70 eyes of 52 patients after Ahmed (n = 40 eyes), Baerveldt (n = 27 eyes) and Molteno (n = 5 eyes) GDD implantation; 2 eyes each had 2 GDDs. Median age was 6.5 years. Glaucoma diagnoses included primary congenital glaucoma (n = 19) and secondary glaucoma associated with aphakia (n = 16), aniridia (n = 5), Peters anomaly (n = 3), uveitis (n = 2), and other conditions (n = 7). B-scan ultrasound evaluation proved helpful to clinical assessment when the GDD tube was not seen because of opaque corneas (n = 20 eyes), the bleb was not visualized (n = 21 eyes), or IOP was elevated (n = 28 eyes). Ultrasound findings suggesting a nonpatent or malfunctioning GDD were further confirmed by subsequent intraoperative bleb needling (n = 2 eyes) and GDD revision (n = 7 eyes). B-scan ultrasound evaluation can serve as a useful adjunct in evaluating GDD patency/function in selected eyes with refractory pediatric glaucoma and may aid in clinical management.

In vitro characteristics of Tenon's fibroblast lines derived from pediatric and adult eyes do not fully explain pediatric glaucoma surgery failure: a preliminary report.

PURPOSE: To compare the in vitro characteristics of Tenon's capsule fibroblasts from children and adults that may be relevant to filtration surgery success. METHODS: Fibroblast cell lines derived from 5 young (median patient age, 2.4 years) and 7 old (median patient age, 71 years) discarded Tenon's capsule surgical specimens were used at early passage (P2-P3). Fibroblasts were plated at "high" (10(4)cells/cm(2)) or "low" density (10(3)cells/cm(2)) and harvested at days 0-14, for growth curve and doubling time comparisons. Migration was measured using a wound model (confluent monolayers ± 5-fluorouracil [5-FU] over 1-96 hours). Collagen synthesis was measured as secreted hydroxyproline/24 hours from confluent monolayers. RESULTS: At low density, "young" fibroblasts achieved higher cell numbers at confluence (day 14) compared with "old": 158 ± 35 versus 105 ± 12 × 10(3)cells/cm(2) (P = 0.0034). Mean doubling time for young versus old was similar at low density plating: 20.95 ± 1.55 versus 22.37 ± 2.09 hours (P = 0.26). It was shorter, however, for young versus old at high-density plating: 42.11 ± 6.01 versus 54.26 ± 4.24 hours (P = 0.0051). Wound closure rates were similar for young versus old cells (4 lines for each group) with and without 5-FU. Collagen synthesis was similar for young and old (4 lines for each group). CONCLUSIONS: Although young fibroblasts reached higher density than old at confluence and had shorter doubling times at high-density plating, wound closure/migration and collagen synthesis rates were similar. Despite the preliminary nature of this study (few specimens, limited cell features explored), factors besides those intrinsic to the fibroblasts themselves likely mediate the more rapid healing/scarring after glaucoma filtration surgery in children.

Intraocular pressure profiles during femtosecond laser-assisted cataract surgery.

PURPOSE: To document the intraocular pressure (IOP) profiles during femtosecond laser-assisted cataract surgery. SETTING: Refractive cataract surgery center. DESIGN: Prospective case series. METHODS: Intraocular pressure was measured using a handheld portable applanation tonometer (Tono-Pen Avia) during femtosecond laser-assisted cataract surgery using the Victus platform. RESULTS: Forty-one eyes of 35 patients were recruited. The mean age of the patients was 70.5 years ± 8.2 (SD) (range 51 to 85 years). The mean IOP before, during, and after suction was 17.2 ± 3.2 mm Hg (range 10 to 23 mm Hg), 42.1 ± 10.8 mm Hg (range 20 to 55 mm Hg), and 13.8 ± 3.4 mm Hg (range 9 to 25 mm Hg), respectively. The mean difference between IOP before and during suction was 25.0 ± 11.3 mm Hg (range 5 to 43 mm Hg) (P<.01, Wilcoxon signed-rank test). The mean difference between IOP during and after suction was -28.7 ± 10.8 mm Hg (range -45 to -10 mm Hg) (P<.01, Wilcoxon signed-rank test). The mean suction duration was 216 ± 15 seconds (range 180 to 245 seconds). CONCLUSIONS: The increase in IOP during the suction phase of femtosecond laser-assisted cataract surgery was statistically significant compared with the baseline IOP. Caution should be taken in patients with ocular conditions that are vulnerable to IOP fluctuation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Health state utilities for metastatic breast cancer.

The aim of the study was to obtain United Kingdom-based societal preferences for distinct stages of metastatic breast cancer (MBC) and six common toxicities. Health states were developed based on literature review, iterative cycles of interviews and a focus group with clinical experts. They described the burden of progressive, responding and stable disease on treatment; and also febrile neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade 3/4 toxicities) and hair loss. One hundred members of the general public rated them using standard gamble to determine health state utility. Data were analysed with a mixed model analysis. The study sample was a good match to the general public of England and Wales by demographics and current quality of life. Stable disease on treatment had a utility value of 0.72, with a corresponding gain of +0.07 following a treatment response and a decline by 0.27 for disease progression. Toxicities lead to declines in utility between 0.10 (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the value that society place on the avoidance of disease progression and severe side effects in MBC. This may be the largest preference study in breast cancer designed to survey a representative general public sample.

'I was running away from death'- the pre-flight experiences of unaccompanied asylum seeking children in the UK.

OBJECTIVE: To collect information about the pre-flight experiences of unaccompanied asylum seeking children (UASC) in the UK to increase the understanding of support needed on arrival in the UK. METHODS: Retrospective social services case file and legal statement review and semi-structured in-depth interviews with 100 UASC. RESULTS: Nearly half of all UASC have experienced separation from or loss of parents and/or family members (47%), and a further 41% had personally experienced or witnessed violence. Sexual violence (such as rape) was reported by 24% of African girls. Many children reported complex journeys to the UK. CONCLUSIONS: UASC arrive in the UK with a variety of potentially traumatic experiences. Whilst research is starting to identify some of the experiences of UASC, further culturally appropriate research is needed to identify their health and social needs after arrival. Further research will help to identify the specific experiences of UASC, indicating where services should be improved to deal with their complex and diverse needs.