A population-based study of adverse physical effects following prostate cancer treatments: Results from the PiCTure (Prostate cancer treatment – your experience) study

Background:

Men and clinicians need reliable population based information when making decisions about investigation and treatment of prostate cancer. In the absence of clearly preferred treatments, differences in outcomes become more important.

Aim:

To investigate rates of adverse physical effects among prostate cancer survivors 2-15 years post diagnosis by treatment, and estimate population burden.

Methods:

A cross sectional, postal survey to 6,559 survivors (all ages) diagnosed with primary, invasive prostate cancer (ICD10-C61), identified in Northern Ireland and the Republic of Ireland via cancer registries. Questions included symptoms at diagnosis, treatments received and adverse physical effects (impotence, urinary incontinence, bowel problems, breast changes, libido loss, hot flashes, fatigue) experienced ‘ever’ and ‘current’ i.e. at questionnaire completion. Physical effect levels were weighted by age, country and time since diagnosis for all prostate cancer survivors. Bonferroni corrections were applied to account for multiple comparisons.

Results:

Adjusted response rate 54%, (n=3,348). 75% reported at least one current physical effect (90% ever), with 29% reporting at least three. These varied by treatment. Current impotence was reported by 76% post-prostatectomy, 64% post-external beam radiotherapy with hormone therapy, with average for all survivors of 57%. Urinary incontinence (overall current level: 16%) was highest post-prostatectomy (current 28%, ever 70%). 42% of brachytherapy patients reported no current adverse physical effects; however 43% reported current impotence and 8% current incontinence. Current hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more commonly by patients on hormone therapy.

Conclusions:

This study provides evidence that adverse physical effects following prostate cancer represent a significant public health burden; an estimated 1.6% of men over 45 is a prostate cancer survivor with a current adverse physical effect. This information should facilitate investigation and treatment decision-making and follow-up care of patients.

Treatment of retinopathy of prematurity in Northern Ireland, 2000-2011: a population-based study

Purpose To evaluate the incidence of treatment-requiring retinopathy of prematurity (ROP) over a 12-year-period in Northern Ireland. Methods The medical records of all infants treated for ROP from January 2000 to December 2011were retrospectively reviewed and cross-referenced with the Neonatal Intensive Care Outcomes Research and Evaluation (NICORE) database. Results The Northern Ireland population data showed an increase in the number of live births from 2000 to 2011. The proportion of babies born with a birth weight <1501 g and/or <32 weeks’ gestational age remained constant (χ2 trend = 3.220, P = 0.0727), although the proportion of these babies who died prior to 42 weeks’ gestation decreased from 2000 to 2011 (P = 0.0196 using χ2 for trend = 5.445; P = 0.0354 using χ2 = 20.809). The prevalence of treatment-requiring ROP in these infants increased from 1.05% in 2000 to 5.78% in 2011 (P < 0.001 using χ2 trend = 16.309; P < 0.001 using χ2 = 31.378). Conclusions The present population-based study highlights that the incidence of treatment- requiring ROP is increasing in Northern Ireland. The increasing number of infants requiring treatment will need to be taken into consideration in the commissioning process for ROP services in Northern Ireland.

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 a population-based study.

BACKGROUND: Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time.
METHODS: We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999-2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site.
RESULTS: Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx).
CONCLUSIONS: This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche^® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n=684) and 5.1% for HPV-18 (n=93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n=283), 34.1% CIN II (n=145), 18.7% of CIN III (n=146), 7.8% of SCC (n=5), and 35.7% of AC (n=5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines.

A two-site, population-based study of barriers to cataract surgery in rural china.

PURPOSE: China has among the lowest cataract surgical rates in Asia. This study was conducted to identify barriers to cataract surgery in rural China. METHODS: All subjects having undergone cataract surgery and persons with presenting visual acuity <or=6/60 (in Yangjiang) or <or=6/18 (in Handan) in >or=1 eye due to nonsurgically treated cataract were identified in two population-based studies in southern (Yangjiang) and northern (Handan) China. The subjects were administered a questionnaire assessing attitudes in four areas constituting potential barriers to surgery: knowledge about cataract, perceptions of local surgical quality, transportation and cost, and available resources. RESULTS: Interviews were completed on 71% to 86% of eligible subjects in both sites. Interviewed subjects did not differ significantly from nonrespondents with regard to age, sex, and presenting acuity in the better-seeing eye. A total of 214 (80.4%) nonsurgical and 131 (76.6%) surgical participants were interviewed, with a mean age of 71.8 +/- 8.0 and 73.7 +/- 7.4 years, respectively (P > 0.1). Among the nonsurgical subjects, 67.8% were blind (presenting vision, <or=6/60) in >or=1 eye due to cataract, whereas among the surgical participants, 25.2% remained blind in the eye that had undergone surgical removal of the cataract. In a multivariate analysis adjusted for age, sex, and site, increased knowledge and higher estimates of the quality of surgery were associated with having had surgery, whereas cost and transportation scores were not. CONCLUSIONS: Lack of knowledge about cataract and concerns about the quality of local services appear to be the principal barriers to cataract surgery in rural China.

A population-based study of visual impairment among pre-school children in Beijing: the Beijing study of visual impairment in children.

PURPOSE: To evaluate the prevalence and causes of visual impairment among Chinese children aged 3 to 6 years in Beijing. DESIGN: Population-based prevalence survey. METHODS: Presenting and pinhole visual acuity were tested using picture optotypes or, in children with pinhole vision < 6/18, a Snellen tumbling E chart. Comprehensive eye examinations and cycloplegic refraction were carried out for children with pinhole vision < 6/18 in the better-seeing eye. RESULTS: All examinations were completed on 17,699 children aged 3 to 6 years (95.3% of sample). Subjects with bilateral correctable low vision (presenting vision < 6/18 correctable to >or= 6/18) numbered 57 (0.322%; 95% confidence interval [CI], 0.237% to 0.403%), while 14 (0.079%; 95% CI, 0.038% to 0.120%) had bilateral uncorrectable low vision (best-corrected vision of < 6/18 and >or= 3/60), and 5 subjects (0.028%; 95% CI, 0.004% to 0.054%) were bilaterally blind (best-corrected acuity < 3/60). The etiology of 76 cases of visual impairment included: refractive error in 57 children (75%), hereditary factors (microphthalmos, congenital cataract, congenital motor nystagmus, albinism, and optic nerve disease) in 13 children (17.1 %), amblyopia in 3 children (3.95%), and cortical blindness in 1 child (1.3%). The cause of visual impairment could not be established in 2 (2.63%) children. The prevalence of visual impairment did not differ by gender, but correctable low vision was significantly (P < .0001) more common among urban as compared with rural children. CONCLUSION: The leading causes of visual impairment among Chinese preschool-aged children are refractive error and hereditary eye diseases. A higher prevalence of refractive error is already present among urban as compared with rural children in this preschool population.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study

Aim To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. Methods A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n = 135), including a viewed-DVD subgroup (n = 58), were compared with an historical cohort (pre-DVD, n = 114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. Results Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8 mmol/mol]; p = 0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8 mmol/mol], P < 0.001; planned pregnancy (88% vs. 59%, P < 0.001); taken folic acid preconception (81% vs. 43%, P = 0.001); and had HbA1c recorded preconception (88% vs. 53%, P < 0.001) than the pre-DVD cohort. Conclusions Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study

Background: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers.

Objectives: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma.

Methods: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case–control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing.

Results: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68–1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56–1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality.

Conclusions: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

Socio-economic inequalities in cerebral palsy prevalence in the United Kingdom: a register-based study

Evidence is unclear as to whether there is a socio-economic gradient in cerebral palsy (CP) prevalence beyond what would be expected from the socio-economic gradient for low birthweight, a strong risk factor for CP. We conducted a population-based study in five regions of the UK with CP registers, to investigate the relationship between CP prevalence and socio-economic deprivation, and how it varies by region, by birthweight and by severity and type of CP. The total study population was 1 657 569 livebirths, born between 1984 and 1997. Wards of residence were classified into five quintiles according to a census-based deprivation index, from Q1 (least deprived) to Q5 (most deprived). Socio-economic gradients were modelled by Poisson regression, and region-specific estimates combined by meta-analysis.

The prevalence of postneonatally acquired CP was 0.14 per 1000 livebirths overall. The mean deprivation gradient, expressed as the relative risk in the most deprived vs. the least deprived quintile, was 1.86 (95% confidence interval [95% CI 1.19, 2.88]). The prevalence of non-acquired CP was 2.22 per 1000 livebirths. For non-acquired CP the gradient was 1.16 [95% CI 1.00, 1.35]. Evidence for a socio-economic gradient was strongest for spastic bilateral cases (1.32 [95% CI 1.09, 1.59]) and cases with severe intellectual impairment (1.59 [95% CI 1.06, 2.39]). There was evidence for differences in gradient between regions. The gradient of risk of CP among normal birthweight births was not statistically significant overall (1.21 [95% CI 0.95, 1.54]), but was significant in two regions. There was non-significant evidence of a reduction in gradients over time.

The reduction of the higher rates of postneonatally acquired CP in the more socioeconomically deprived areas is a clear goal for prevention. While we found evidence for a socio-economic gradient for non-acquired CP of antenatal or perinatal origin, the picture was not consistent across regions, and there was some evidence of a decline in inequalities over time. The steeper gradients in some regions for normal birthweight cases and cases with severe intellectual impairment require further investigation.