Achieving optimal dose intensity with adjuvant chemotherapy in elderly breast cancer patients:A 10-year retrospective study in a UK institution

The study was to determine if breast cancer patients aged 65 and above could be given adjuvant chemotherapy safely while achieving an acceptable relative dose intensity of at least 85%. We identified all patients aged 65 and over who received adjuvant chemotherapy over the 10 year period, November 1999 to October 2009, and determined the proportion that achieved a relative dose intensity of at least 85% as well as the tolerability of their treatment. A total of 101 patients were identified, with a median age of 69 years (range 65-78).Of these, 25.7% of patients had at least one major comorbidity, 84.2% had a tumor size of 5 cm or less, 73.3% were node positive and 58.4% were hormone receptor positive. The chemotherapy regimens used were AC (Doxorubicin and Cyclophosphamide), FEC (Fluorouracil, Epirubicin, and Cyclophosphamide), CMF (Cyclophosphamide, Methotrexate, and Fluorouracil) and ECMF (Epirubicin followed by CMF). Seventy-nine patients (78.2%) achieved the relative dose intensity of at least 85%. With respect to toxicity, 11.9% of patients developed febrile neutropenia and 23.8% of patients required hospital admission during the treatment period, but there were no treatment-related deaths in the group. A significant proportion of patients aged 65 and above achieved the intended dose intensity of at least 85% over this 10-year period, with manageable toxicity levels. This supports the use of these regimens as adjuvant chemotherapy for breast cancer in this age group. © 2011 Wiley Periodicals, Inc.

Six-year follow-up of the SPHERE RCT: secondary prevention of heart disease in general practice.

Objective: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease.

Design: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction).

Setting: 48 general practices in the Republic of Ireland and Northern Ireland.

Participants: 903 patients with established coronary heart disease at baseline in the original trial.

Intervention: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased.

Outcome measures: Primary outcome: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control.

Results: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol.

Conclusions: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes.

Trial registration number: Current Controlled Trials ISRCTN24081411.

Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial.

METHODS: The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry, number ISRCTN97182923.

FINDINGS: 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4-64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (<1%), three (<1%) and three (<1%) men respectively (74 Gy vs 60 Gy, ptrend=0.64, 74 Gy vs 57 Gy, ptrend=0·59). We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months.

INTERPRETATION: The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Building professionalism and employability skills: embedding employer engagement within first-year computing modules

This paper outlines a means of improving the employability skills of first-year university students through a closely integrated model of employer engagement within computer science modules. The outlined approach illustrates how employability skills, including communication, teamwork and time management skills, can be contextualised in a manner that directly relates to student learning but can still be linked forward into employment. The paper tests the premise that developing employability skills early within the curriculum will result in improved student engagement and learning within later modules. The paper concludes that embedding employer participation within first-year models can help relate a distant notion of employability into something of more immediate relevance in terms of how students can best approach learning. Further, by enhancing employability skills early within the curriculum, it becomes possible to improve academic attainment within later modules.

Two-year changes in refractive error and related biometric factors in an adult Chinese population

Importance: This article provides, to our knowledge, the first longitudinal population-based data on refractive error (RE) in Chinese persons.

Objective: To study cohort effects and changes associated with aging in REs among Chinese adults.

Design, Setting, and Participants: A 2-year, longitudinal population-based cohort study was conducted in southern China. Participants, identified using cluster random sampling, included residents of Yuexiu District, Guangzhou, China, aged 35 years or older who had undergone no previous eye surgery.

Methods: Participants underwent noncycloplegic automated refraction and keratometry in December 2008 and December 2010; in a random 50% sample of the participants, anterior segment ocular coherence tomography measurement of lens thickness, as well as measurement of axial length and anterior chamber depth by partial coherence laser interferometry, were performed.

Main Outcomes and Measures: Two-year change in spherical equivalent refraction (RE), lens thickness, axial length, and anterior chamber depth in the right eye.

Results: A total of 745 individuals underwent biometric testing in both 2008 and 2010 (2008 mean [SD] age, 52.2 [11.5] years; 53.7% women). Mean RE showed a 2-year hyperopic shift from −0.44 (2.21) to −0.31 (2.26) diopters (D) (difference, +0.13; 95% CI, 0.11 to 0.16). A consistent 2-year hyperopic shift of 0.09 to 0.22 D was observed among participants aged 35 to 64 years when stratifying by decade, suggesting that a substantial change in RE with aging may occur during this 30-year period. Cross-sectionally, RE increased only in the cohort younger than 50 years (0.11 D/y; 95% CI, 0.06 to 0.16). In the cross-sectional data, axial length decreased at −0.06 mm/y (95% CI, −0.09 to −0.04), although the 2-year change in axial length was positive and thus could not explain the cross-sectional difference. These latter results suggest a cohort effect, with greater myopia developing among younger persons.

Conclusions and Relevance: This first Chinese population-based longitudinal study of RE provides evidence for both important longitudinal aging changes and cohort effects, most notably greater myopia prevalence among younger persons.

Causes and five-year incidence of blindness and visual impairment in urban southern China:The Liwan Eye Study

PURPOSE. We determined the causes and five-year incidence of blindness and visual impairment (VI) in an adult, urban Chinese population. METHODS. Participants underwent a comprehensive eye examination at baseline in 2003 and then five years later. The World Health Organization (WHO) and United States (US) definitions were used to define incident blindness (WHO visual acuity [VA] < 20/400 in the better-seeing eye, US VA ≤ 20/200) and incident VI (WHO VA < 20/60-20/400, US VA < 20/40->20/200). RESULTS. Among 1405 baseline participants, 924 (75%) of 1232 survivors (87.7%) participated in the 5-year follow-up. The incidences of VI and blindness were 5.38% (95% confidence interval [CI] 3.99% ~ 7.07%) and 0.33% (95% CI 0.07% ~ 0.95%), respectively, based on the WHO definition, and 9.85% (95% CI 7.96% ~ 12.0%) and 1.42% (95% CI 0.76% ~ 2.41%), respectively, based on the US definition. Incidence of blindness and VI (WHO definition) increased significantly with older age (P < 0.001) and poorer baseline presenting VA in the worse-seeing eye (P < 0.001). The leading cause of best-corrected VI (WHO definition) was cataract (64.6%), whereas the main causes of presenting VI were refractive error (40.4%) and cataract (38.4%). CONCLUSIONS. The incidence of VI in urban Southern China is high. The major causes are unoperated cataract and undercorrected refractive error, reflecting the need for better surgical and refractive care, even in this urban setting. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Five-year incidence and postoperative visual outcome of cataract surgery in urban southern China:The liwan eye study

Purpose. To determine the 5-year incidence and visual outcome of cataract surgery in an adult urban Chinese population. Methods. A comprehensive eye examination was performed at baseline and 5 years later on subjects participating in a population-based study. Incident cataract surgery was defined as having undergone surgery in either eye during the 5-year period. Postoperative visual impairment (PVI) was defined as visual acuity (VA) <6/18 based on both presenting VA (PVA) and best corrected VA (BCVA) in the operated eye. Results. Among the 1405 baseline participants, 75% (924) of survivors were seen at the 5-year follow-up visit. Forty-four returning participants (62 eyes) had undergone incident cataract surgery, an incidence of 4.84% (95% confidence interval [CI] - [3.53, 6.44]). Detailed medical and surgical records were available for 54/62 (87.1%) eyes, and of these, 5/ 54 (24.1%) had an immediate preoperative visual acuity <6/ 120. All recorded surgeries were performed at tertiary-level hospitals with phacoemulsification and foldable intraocular lens implantation. Those undergoing cataract surgery were more educated (P < 0.05) and had poorer baseline PVA in the worse-seeing eye (P < 0.001) than 54 persons with baseline PVA <6/18 due to cataract who had not had surgery. Among the 62 operated eyes, 22.6% (14/62) had PVI based on PVA and 9.6% (6/62) based on BCVA. Conclusions. Despite somewhat lower incidence, outcomes of cataract surgery in urban southern China are comparable with developed countries and better than for rural China. In urban China, emphasis should be on improving access to surgery. (Invest Ophthalmol Vis Sci. 2012;53:7936-7942) © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Determinants and two-year change in anterior chamber angle width in a Chinese population

Objective: To study the population distribution and longitudinal changes in anterior chamber angle width and its determinants among Chinese adults. Design: Prospective cohort, population-based study. Participants: Persons aged 35 years or more residing in Guangzhou, China, who had not previously undergone incisional or laser eye surgery. Methods: In December 2008 and December 2010, all subjects underwent automated keratometry, and a random 50% sample had anterior segment optical coherence tomography with measurement of angle-opening distance at 500 μm (AOD500), angle recess area (ARA), iris thickness at 750 μm (IT750), iris curvature, pupil diameter, corneal thickness, anterior chamber width (ACW), lens vault (LV), and lens thickness (LT) and measurement of axial length (AL) and anterior chamber depth (ACD) by partial coherence laser interferometry. Main Outcome Measures: Baseline and 2-year change in AOD500 and ARA in the right eye. Results: A total of 745 subjects were present for full biometric testing in both 2008 and 2010 (mean age at baseline, 52.2 years; standard deviation [SD], 11.5 years; 53.7% were female). Test completion rates in 2010 varied from 77.3% (AOD500: 576/745) to 100% (AL). Mean AOD500 decreased from 0.25 mm (SD, 0.13 mm) in 2008 to 0.21 mm (SD, 13 mm) in 2010 (difference, -0.04; 95% confidence interval [CI], -0.05 to -0.03). The ARA decreased from 21.5±3.73 10^-2 mm² to 21.0±3.64 10 ^-2 mm² (difference, -0.46; 95% CI, -0.52 to -0.41). The decrease in both was most pronounced among younger subjects and those with baseline AOD500 in the widest quartile at baseline. The following baseline variables were significantly associated with a greater 2-year decrease in both AOD500 and ARA: deeper ACD, steeper iris curvature, smaller LV, greater ARA, and greater AOD500. By using simple regression models, we could explain 52% to 58% and 93% of variation in baseline AOD500 and ARA, respectively, but only 27% and 16% of variation in 2-year change in AOD500 and ARA, respectively. Conclusions: Younger persons and those with the least crowded anterior chambers at baseline have the largest 2-year decreases in AOD500 and ARA. The ability to predict change in angle width based on demographic and biometric factors is relatively poor, which may have implications for screening. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

A 250-year periodicity in Southern Hemisphere westerly winds over the last 2600 years

Southern Hemisphere westerly airflow has a significant influence on the ocean–atmosphere system of the mid- to high latitudes with potentially global climate implications. Unfortunately, historic observations only extend back to the late 19th century, limiting our understanding of multi-decadal to centennial change. Here we present a highly resolved (30-year) record of past westerly wind strength from a Falkland Islands peat sequence spanning the last 2600 years. Situated within the core latitude of Southern Hemisphere westerly airflow (the so-called furious fifties), we identify highly variable changes in exotic pollen and charcoal derived from South America which can be used to inform on past westerly air strength. We find a period of high charcoal content between 2000 and 1000 cal. years BP, associated with increased burning in Patagonia, most probably as a result of higher temperatures and stronger westerly airflow. Spectral analysis of the charcoal record identifies a pervasive ca. 250-year periodicity that is coherent with radiocarbon production rates, suggesting that solar variability has a modulating influence on Southern Hemisphere westerly airflow. Our results have important implications for understanding global climate change through the late Holocene.