Factors associated with current and severe physical side-effects after prostate cancer treatment: What men report.

We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion). Men were grouped by "early" (localised) and "late" (locally advanced/advanced) disease at diagnosis. Multivariable logistic regression analysis identified patient and disease-related factors associated with post-treatment side-effects. Complications post-biopsy were associated with higher risk of "current" libido loss and impotence. Radical prostatectomy was associated with higher risk of "current" and "severe" incontinence, libido loss and impotence in both early and late disease. In early disease, brachytherapy was associated with lower risk of "current" fatigue and "severe" impotence. Comorbidities were associated with higher risk of "current" experience of four side-effects (incontinence, libido loss, bowel problems, fatigue). Men on active surveillance/watchful-waiting reported lower risk of sexual dysfunction. These findings could inform development of tailored information on side-effects, which, in turn, could inform treatment decision-making and post-treatment monitoring.

Economics of Early Warning Scores for identifying clinical deterioration-a systematic review.

AIM: In 2013, a National Early Warning System (EWS) was implemented in Ireland. Whilst evidence exists to support the clinical effectiveness of EWS in the acute health care setting, there is a paucity of information on their cost and cost effectiveness. The objective of this systematic literature review was to critically evaluate the economic literature on the use of EWS in adult patients in acute health care settings for the timely detection of physiological deterioration. METHODS: A systematic literature review was conducted to accumulate the economic evidence on the use of EWS in adult patients in acute health care settings. RESULTS: The search yielded one health technology assessment, two budget impact analyses and two cost descriptions. Three of the studies were Irish, and considered the national EWS system. A Dutch study reported financial consequences of a single parameter EWS, as part of a rapid response system, in a surgical ward. The fifth study examined an advanced triage system in a medical emergency admission unit in Wales. CONCLUSIONS: The economic evidence on the use of EWS amongst adult patients in acute health care settings for the timely detection of physiological deterioration is limited. Further research is required to investigate the cost effectiveness of EWS, and the appropriateness of using standard methods to do so. The recent implementation of a national EWS in Ireland offers a unique opportunity to bridge this gap in the literature to examine the costs and cost effectiveness of a nationally implemented EWS system.

Establishing a population-based patient-reported outcomes study (PROMs) using national cancer registries across two jurisdictions: the Prostate Cancer Treatment, your experience (PiCTure) study.

OBJECTIVE: To establish an international patient-reported outcomes (PROMs) study among prostate cancer survivors, up to 18 years postdiagnosis, in two countries with different healthcare systems and ethical frameworks. DESIGN: A cross-sectional, postal survey of prostate cancer survivors sampled and recruited via two population-based cancer registries. Healthcare professionals (HCPs) evaluated patients for eligibility to participate. Questionnaires contained validated instruments to assess health-related quality of life and psychological well-being, including QLQ-C30, QLQ-PR25, EQ-5D-5L, 21-question Depression, Anxiety and Stress Scale (DASS-21) and the Decisional Regret Scale. SETTING: Republic of Ireland (RoI) and Northern Ireland (NI). PRIMARY OUTCOME MEASURES: Registration completeness, predictors of eligibility and response, data missingness, unweighted and weighted PROMs. RESULTS: Prostate cancer registration was 80% (95% CI 75% to 84%) and 91% (95% CI 89% to 93%) complete 2 years postdiagnosis in NI and RoI, respectively. Of 12,322 survivors sampled from registries, 53% (n=6559) were classified as eligible following HCP screening. In the multivariate analysis, significant predictors of eligibility were: being ≤59 years of age at diagnosis (p<0.001), short-term survivor (<5 years postdiagnosis; p<0.001) and from RoI (p<0.001). 3348 completed the questionnaire, yielding a 54% adjusted response rate. 13% of men or their families called the study freephone with queries for assistance with questionnaire completion or to talk about their experience. Significant predictors of response in multivariate analysis were: being ≤59 years at diagnosis (p<0.001) and from RoI (p=0.016). Mean number of missing questions in validated instruments ranged from 0.12 (SD 0.71; EQ-5D-5L) to 3.72 (SD 6.30; QLQ-PR25). Weighted and unweighted mean EQ-5D-5L, QLQ-C30 and QLQ-PR25 scores were similar, as were the weighted and unweighted prevalences of depression, anxiety and distress. CONCLUSIONS: It was feasible to perform PROMs studies across jurisdictions, using cancer registries as sampling frames; we amassed one of the largest, international, population-based data set of prostate cancer survivors. We highlight improvements which could inform future PROMs studies, including utilising general practitioners to assess eligibility and providing a freephone service.

The number of tPSA tests continues to rise and variation in testing practices persists: a survey of laboratory services in Ireland 2008-2010.

BACKGROUND: Ireland had the highest incidence of prostate cancer in Europe in 2008, due to widespread prostate specific antigen (PSA) testing. AIMS: To investigate practices and costs of PSA testing in Ireland, 2008-2010. METHODS: Postal laboratory questionnaire. Results were compared with 2006 and 2007 surveys. RESULTS: Response rate was 95 % (42/44). In 2010, 37 laboratories measured total PSA (tPSA); 10 measured free PSA (fPSA). Eight assays were used and cut-offs to define 'normal' tPSA varied widely. There was a 9.9 % annual increase in the number of tPSA tests and a -31 % annual decrease in the number of fPSA, 2006-2010. A 100-fold difference in tPSA workload was observed across laboratories. In 2010, the estimated cost of PSA testing was 3,649,984 (95 % CI 2,532,745-4,767,222). CONCLUSIONS: Health service costs of PSA testing are significant. The number of tPSA tests continues to rise; fPSA use fell by almost one-third. Inter-laboratory variation in testing practices persists. These have potentially important clinical consequences for men and need to be addressed.

Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland.

OBJECTIVES: To investigate the impact of different PSA testing policies and health-care systems on prostate cancer incidence and mortality in two countries with similar populations, the Republic of Ireland (RoI) and Northern Ireland (NI). METHODS: Population-level data on PSA tests, prostate biopsies and prostate cancer cases 1993-2005 and prostate cancer deaths 1979-2006 were compiled. Annual percentage change (APC) was estimated by joinpoint regression. RESULTS: Prostate cancer rates were similar in both areas in 1994 but increased rapidly in RoI compared to NI. The PSA testing rate increased sharply in RoI (APC = +23.3%), and to a lesser degree in NI (APC = +9.7%) to reach 412 and 177 tests per 1,000 men in 2004, respectively. Prostatic biopsy rates rose in both countries, but were twofold higher in RoI. Cancer incidence rates rose significantly, mirroring biopsy trends, in both countries reaching 440 per 100,000 men in RoI in 2004 compared to 294 in NI. Median age at diagnosis was lower in RoI (71 years) compared to NI (73 years) (p < 0.01) and decreased significantly over time in both countries. Mortality rates declined from 1995 in both countries (APC = -1.5% in RoI, -1.3% in NI) at a time when PSA testing was not widespread. CONCLUSIONS: Prostatic biopsy rates, rather than PSA testing per se, were the main driver of prostate cancer incidence. Because mortality decreases started before screening became widespread in RoI, and mortality remained low in NI, PSA testing is unlikely to be the explanation for declining mortality.

Trends in prostate specific antigen testing in Ireland: lessons from a country without guidelines.

BACKGROUND: Prostate specific antigen (PSA) testing is associated with increased prostate cancer (PCa) incidence. Ireland has no national guidelines on PCa screening and had the highest PCa incidence in Europe, 2006. AIMS: To investigate trends in PSA testing in Ireland. METHODS: Data on PSA tests, 1994-2005, was collated. RESULTS: Age-standardised rates of PSA testing increased 39 and 25% annually in men <50 and >or=50 years, respectively. Most tests were performed in men 50-69 years; 26 and 22% were performed in men <50 and >or=70 years, respectively. Baseline PSA tests peaked in 2004, at 16% of men. 83% of baseline tests were <4.0 ng/ml. Repeat testing increased with age and PSA level (P < 0.001); men <50 years and with levels <4.0 ng/ml had >1 tests in <21 months. PCa incidence increased 9% annually, 1994-2005. CONCLUSIONS: Uptake of PSA testing was rapid: increased use was simultaneous with increased PCa incidence. National guidelines are needed to manage this important public health issue.

Major inter-laboratory variations in PSA testing practices: results from national surveys in Ireland in 2006 and 2007.

BACKGROUND: Ireland had the highest prostate cancer incidence in Europe in 2006. In that year, the National Cancer Forum (NCF) recommended against prostate specific antigen (PSA) testing for population-based screening. AIMS: To investigate (1) PSA services and (2) impact of the NCF recommendation. METHODS: Questionnaires were dispatched to biochemistry laboratories nationwide in 2006 and 2007. RESULTS: All 55 laboratories responded in 2006; 33/36 (89%) responded in 2007. 36 laboratories measured total PSA (tPSA); 14 measured free PSA (fPSA). Laboratories with higher tPSA workload were more likely to measure fPSA (P = 0.024). A total of 15 laboratories used age-specific PSA ranges. In 2006, there were [382,000 tPSA and [48,000 fPSA tests costing an estimated euro 4,900,000. During 2006-2007 tPSA tests increased by 11%; fPSA tests decreased by 36%. CONCLUSIONS: There is considerable inter-laboratory variation in PSA testing practices. Because of the potential clinical consequences, standardisation should be considered. Testing practice was unaffected by the NCF recommendation.

Screening for asymptomatic celiac disease among patients referred for bone densitometry measurement.

Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. An increased prevalence of subclinical CD has been reported in many populations. Even among asymptomatic patients a reduction in bone mineral density (BMD) has been observed. The aim of this study was to evaluate the prevalence of silent CD in a cohort of consecutive individuals referred for bone densitometry measurement. Serum samples were taken from 454 women attending for bone densitometry (mean age: 56 +/- 11 years). Of the individuals evaluated, 89 had normal BMD and 365 had low BMD (T score < -1.0). Subjects were screened for the presence of serum IgA anti-endomysial antibodies (EMA) and IgA tissue transglutaminase (tTG) antibodies by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA), respectively. BMD was measured by dual X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Eight EMA tTG-positive individuals were identified in this population (1.8% or 1:57). Serologically positive women had a lower mean Z score at both the lumbar spine and femoral neck than EMA tTG-negative women. But this did not approach significance. There was no significant difference in the incidence of CD between the normal- and low-BMD groups in this dataset (P = 0.365). In conclusion, our study indicates that the prevalence of CD in our dataset is high. However, the frequency of asymptomatic CD among low-BMD individuals is similar to that among normal-BMD individuals in our population. These observations do not support the hypothesis that serological testing for CD may be a good accompaniment to DEXA scanning.

Suggestive linkage of 2p22-25 and 11q12-13 with low bone mineral density at the lumbar spine in the Irish population.

Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1alpha) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score < or = -1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores >1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.

Colon carbonic anhydrase 1: transactivation of gene expression by the homeodomain protein Cdx2.

The homeodomain protein, Cdx2, has been implicated in the transcriptional regulation of genes expressed in the small intestine. In vitro studies of the carbonic anhydrase 1 (CA1) colon promoter implied that Cdx2 may also play a role in the regulation of colon-specific gene expression. The current work follows up this proposal by examining the ability of Cdx2 to transactivate gene expression in cultured cells mediated by CA1 promoter sequences. The results show that Cdx2 exerts a positive regulatory effect by binding to a motif 87 bp upstream of the CA1 TATA box; this motif appears to act as an enhancer since gene activation is independent of its orientation.