High frequency and mortality of head and neck malignancy in organ transplant recipients in Ireland - A national cohort study.

BACKGROUND: Solid organ transplant recipients are recognized to carry a high burden of malignancy and frequently this cancer develops in the head and neck region. Furthermore, cancer of the head and neck post-transplant carries a significantly increased mortality. In this study, we aim to conduct a national retrospective cohort study to investigate the impact of head and neck cancer in terms of frequency and mortality in a large group of solid organ transplant recipients over a 20 year time span and compare the mortality in transplant patients to non-transplant patients with head and neck cancer. METHODS: Patients in the Republic of Ireland who underwent solid organ transplantation between 1994 and 2014 who developed post-transplant head and neck malignancy were identified from the records of two prospective, national databases (National Cancer Registry of Ireland (NCRI) and The Irish Transplant Cancer Group database) working in conjunction with each other. Incidence of head and neck malignancy post-transplant was compared with the general population by means of standardised incidence ratios (SIR). Cumulative incidence of all cause and cancer related mortality from head and neck keratinocytic was undertaken by a competing risks analysis. RESULTS: A total of 3346 solid organ transplant recipients were identified, 2382 (71.2 %) kidney, 562 (16.8 %) liver, 214 (6.4 %) cardiac and 188 (5.6 %) lung. During the period of follow up of 428 patients developed head and neck cancer, representing (12.8 %) of the population. 97 % of these patients developed keratinocytic cancers, specifically, of head and neck. The frequency of post-transplant head and neck cancer was related to the duration of immunosuppression with 14 % of patients developing cancer at 10 years and 20 % having developed at least one cancer by 15 years. 12 (3 %) patients developed non-cutaneous head and neck malignancy. 10 (0.3 %) patients died due to head and neck keratinocytic malignancy post-transplant. Competing risk analysis demonstrated that organ transplantation conferred a strong independent effect of death, compared to non-transplant patients with head and neck keratinocytes. This applied specifically for kidney (HR 4.4, 95 % CI 2.5-7.8) and heart transplants (HR 6.5, 95 % CI 2.1-19.9), and overall, across the four transplant categories (P < 0.001). The SIR of developing keratinocyte cancer varied based on primary tumor site, gender, and type of transplant organ. CONCLUSION: Transplant patients demonstrate a particularly high rate of head and neck keratinocyte cancer with a very high rate of associated mortality. Physicians should be cognizant of the increased rate of malignancy in this population and monitor for red flag signs/symptoms.

Cancer survival in kidney transplant recipients in Ireland.

BACKGROUND: Transplantation is a well-known risk factor for malignancy. However, outcomes of cancer in transplant recipients compared with non-transplant recipients are less well studied. We aim to study the survival in kidney transplant recipients who develop cancer and compare this with cancer outcomes in the general population. METHODS: We linked data from the National Cancer Registry Ireland with the National Kidney Transplant Database. The period of observation was from 1 January 1994 until 31 December 2014. Transplant recipients were considered at risk from the time of diagnosing cancer. We administratively censored data at 10 years post-cancer diagnosis. Survival was compared with all patients in the general population that had a recorded diagnosis of cancer. RESULTS: There were 907 renal transplant recipients and 426679 individuals in the general population diagnosed with cancer between 1 January 1994 and 31 December 2014. In those with non-melanoma skin cancer, the hazard ratio (HR) for 10-year, all-cause mortality [HR = 3.06, 95% confidence interval (CI) 2.66-3.52] and cancer-specific mortality (HR = 3.91, 95% CI 2.57-5.96) was significantly higher among transplant recipients than the general population. Patients who developed non-Hodgkin lymphoma (HR = 2.89, 95% CI 1.96-4.25) and prostate cancer (HR = 4.32, 95% CI 2.39-7.82) had increased all-cause but not cancer-specific mortality. Colorectal, lung, breast and renal cell cancer did not show an increased risk of death in transplant recipients. CONCLUSION: Cancer-attributable mortality is higher in kidney transplant recipients with non-melanoma skin cancer compared with non-transplant patients. The American Joint Committee on Cancer staging should reflect the increased hazard of death in these immunosuppressed patients.

The impact of switching to mTOR inhibitor-based immunosuppression on long-term non-melanoma skin cancer incidence and renal function in kidney and liver transplant recipients.

Background: Solid organ transplantation is associated with increased risk of non-melanoma skin cancer. Studies with short follow up times have suggested a reduced occurrence of these cancers in recipients treated with mammalian target of rapamycin inhibitors as maintenance immunosuppression. We aimed to describe the occurrence of skin cancers in renal and liver transplant recipients switched from calcineurin inhibitor to sirolimus-based regimes.Methods: We performed a retrospective study of sirolimus conversion within the Irish national kidney and liver transplant programs. These data were linked with the National Cancer Registry Ireland to determine the incidence of NMSC among these recipients. The incidence rate ratio (IRR) for post versus pre-conversion NMSC rates are referred in this study as an effect size with [95% confidence interval].Results: Of 4,536 kidney transplants and 574 liver transplants functioning on the 1 January 1994 or transplanted between 1 January 1994 and 01 January 1994 and 01 January 2015, 85 kidney and 88 liver transplant recipients were transitioned to sirolimus-based immunosuppression. In renal transplants, the rate of NMSC was 131 per 1000 patient years pre-switch to sirolimus, and 68 per 1000 patient years post switch, with adjusted effect size of 0.48 [0.31 - 0.74] (p = .001) following the switch. For liver transplant recipients, the rate of NMSC was 64 per 1,000 patient years pre-switch and 30 per 1,000 patient years post switch, with an adjusted effect size of 0.49 [0.22 - 1.09] (p .081). Kidney transplant recipients were followed up for a median 3.4 years. Liver transplants were followed for a median 6.6 years.Conclusions: In this study, the conversion of maintenance immunosuppression from calcineurin inhibitors to mTOR inhibitors for clinical indications did appear to reduce the incidence of NMSC in kidney and liver transplant recipients.

Post-transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group.

OBJECTIVE: Solid organ transplant recipients are at increased risk of cancer compared to the general population. To date, this risk in Ireland has not been investigated. We conducted a national registry study of cancer incidence following solid organ transplantation. METHODS: National centers for solid organ transplantation supplied their respective registry databases to cross-reference with episodes of malignancy from the National Cancer Registry Ireland (NCRI) between 1994 and 2014. Standardized incidence of cancer post-transplant was compared to the general population by means of standardized incidence ratios (SIRs), and between solid organ transplant types by incidence rate ratios. RESULTS: A total of 3346 solid organ transplant recipients were included in this study. Kidney transplant recipients constituted the majority of participants (71.2%), followed by liver (16.8%), heart (6.4%), and lung (5.6%) transplants. The most common cancers within the composite of all transplant recipients included the following (SIR [95% CI]): squamous and basal cell carcinoma (20.05 [17.97, 22.31] and 7.16 [6.43, 7.96], respectively), non-Hodgkin lymphoma (6.23 [4.26, 8.59]), and renal cell carcinoma (3.36 [1.96, 5.38]). CONCLUSIONS: This study reports the incidence of cancer following solid organ transplantation in Ireland. These results have significant national policy implications for surveillance, and early diagnosis in this patient group.

Financial Impact of Colorectal Cancer and Its Consequences: Associations Between Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.

BACKGROUND: The financial impact and consequences of cancer on the lives of survivors remain poorly understood. This is especially true for colorectal cancer. OBJECTIVE: We investigated objective cancer-related financial stress, subjective cancer-related financial strain, and their association with health-related quality of life in colorectal cancer survivors. DESIGN: This was a cross-sectional postal survey. SETTINGS: The study was conducted in Ireland, which has a mixed public-private healthcare system. PATIENTS: Colorectal cancer survivors, diagnosed 6 to 37 months prior, were identified from the population-based National Cancer Registry. MAIN OUTCOME MEASURES: Cancer-related financial stress was assessed as impact of cancer on household ability to make ends meet and cancer-related financial strain by feelings about household financial situation since cancer diagnosis. Health-related quality of life was based on European Organisation for Research and Treatment of Cancer QLQ-C30 global health status. Logistic regression was used to identify associations between financial stress and strain and low health-related quality of life (lowest quartile, score ≤50). RESULTS: A total of 493 survivors participated. Overall, 41% reported cancer-related financial stress and 39% cancer-related financial strain; 32% reported both financial stress and financial strain. After adjustment for sociodemographic and clinical variables, the odds of low health-related quality of life were significantly higher in those who reported cancer-related financial stress postdiagnosis compared with those who reported no change in financial stress postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related quality of life were also significantly higher in those with worse financial strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59-4.22). LIMITATIONS: Survey responders were younger, on average, than nonresponders. Responders and nonresponders may have differed in cancer-related financial stress and strain or health-related quality of life. CONCLUSIONS: Four in 10 colorectal cancer survivors reported an adverse financial impact of cancer. Cancer-related financial stress and strain were significantly associated with low health-related quality of life. To inform support strategies, additional research is needed to better understand how both objective and subjective financial distress influence survivors' health-related quality of life. See Video Abstract http://links.lww.com/DCR/A447.

Socio-economic variations in anticipated adverse reactions to testing HPV positive: Implications for the introduction of primary HPV-based cervical screening.

Some cervical cancer screening programmes are replacing cytology with human papillomavirus (HPV) DNA testing as the primary screening test. Concerns have been previously raised around the potential psychosocial impact of testing positive for HPV. We analysed socio-economic variations in anticipated adverse reactions to testing positive for HPV in women of screening age in the general population. A questionnaire was mailed to a random sample of 5553 women aged 20-64 in 2010, selected through primary care in Ireland. This included questions on: socio-economics; HPV knowledge; and women's anticipated adverse psychosocial responses to testing HPV positive (shame, anxiety, stigma and worry). Multivariable linear regression was used to identify socio-economic factors significantly associated with each anticipated adverse reaction. The response rate was 62% (n = 3470). In multivariate analyses, having only attained primary level education were significantly associated with higher mean scores for all four adverse outcomes. Religion was significantly associated with all four adverse outcomes. Age was associated with anxiety and worry; younger women (<30 years) had the highest mean scores. Being married/cohabiting was significantly associated with significantly lower shame and worry scores. Not working was significantly associated with higher mean anxiety and worry scores. Our large population-based survey found significant socio-economic variations in anticipated adverse reactions to testing HPV positive. In order to minimise possible negative impacts on screening uptake and alleviate potential adverse psychological effects of HPV-based screening on women, screening programmes may need to develop specific messages around HPV infection and HPV screening that target certain subgroups of women.

Counting the cost of cancer: out-of-pocket payments made by colorectal cancer survivors.

PURPOSE: Cancer places a significant cost burden on health services. There is increasing recognition that cancer also imposes a financial and economic burden on patients but this has rarely been quantified outside North America. We investigate out-of-pocket costs (OOPCs) incurred by colorectal (CRC) survivors in Ireland. METHODS: CRC survivors (ICD10 C18-20) diagnosed 6-30 months previously were identified from the National Cancer Registry Ireland and invited to complete a postal questionnaire. Cancer-related OOPC for tests, procedures, drugs, allied medications and household management in approximately the year following diagnosis were calculated. Robust regression was used to identify predictors of OOPC; this was done for all survivors combined and stratified by age (<70 and ≥70 years) and employment status (working and not working) at diagnosis. RESULTS: Four hundred ninety-seven CRC survivors completed questionnaires (response rate = 39%). Almost all (90%) respondents reported some cancer-related OOPC. The average total OOPC was €1589. Stage III at diagnosis was associated with significantly higher OOPCs than other stages in the all-survivor model, in those not working in the employment model and in those under 70 years in the age-stratified model. In all-survivor model, those under 70 also had higher OOPCs, as did those in employment. Having one or more children was associated with significantly lower OOPCs in those under 70 years. CONCLUSIONS: Almost all CRC survivors incur cancer-related OOPCs; for some, these are not insignificant. Greater attention should be paid to the development of services to help survivors manage the financial and economic burden of cancer.

Cancer-related symptoms predict psychological wellbeing among prostate cancer survivors: results from the PiCTure study.

BACKGROUND: Prostate cancer treatments are associated with a range of symptoms and physical side-effects. Cancer can also adversely impact on psychological wellbeing. Because many prostate cancer-related symptoms and side-effects are potentially modifiable, we investigated associations between symptoms and psychological wellbeing among prostate cancer survivors. METHODS: Postal questionnaires were distributed to men diagnosed with prostate cancer 2-18 years previously identified through cancer registries. General and prostate cancer-specific symptoms were assessed using the EORTC QLQ-C30 and QLQ-PR25, with higher symptom scores indicating more/worse symptomatology. Psychological wellbeing was assessed by the DASS-21. Associations between symptoms and each outcome were investigated using multivariate logistic regression, controlling for socio-demographic and clinical factors. RESULTS: A total 3348 men participated (response rate = 54%). Seventeen percent (95%CI 15.2%-17.9%), 16% (95%CI 15.1%-17.8%) and 11% (95%CI 9.5%-11.8%) of survivors scored in the range for depression, anxiety and distress on the DASS scales, respectively. In multivariate models, risk of depression on the DASS scale was significantly higher in men with higher urinary and androgen deprivation therapy (ADT)-related symptoms, and higher scores for fatigue, insomnia and financial difficulties. Risk of anxiety on the DASS scale was higher in men with higher scores for urinary, bowel and ADT-related symptoms and fatigue, dyspnoea and financial difficulties. Risk of distress on the DASS scale was positively associated with urinary, bowel and ADT-related symptoms, fatigue, insomnia and financial difficulties. CONCLUSIONS: Cancer-related symptoms significantly predict psychological wellbeing among prostate cancer survivors. Greater use of interventions and medications and to alleviate symptoms might improve psychological wellbeing of prostate cancer survivors.

Trends in, and predictors of, anxiety and specific worries following colposcopy: a 12-month longitudinal study.

OBJECTIVE: Little is known about which women are at greatest risk of adverse psychological after-effects following colposcopy. This study examined time trends in, and identified predictors of, anxiety and specific worries over 12 months. METHODS: Women attending two hospital-based colposcopy clinics for abnormal cervical cytology were invited to complete psychosocial questionnaires at 4, 8 and 12 months following colposcopy. General anxiety and screening-specific worries (about cervical cancer, having sex and future fertility) were measured. Generalised estimating equations were used to assess associations between socio-demographic, lifestyle and clinical variables and risk of psychological outcomes. RESULTS: Of 584 women initially recruited, 429, 343 and 303 completed questionnaires at 4, 8 and 12 months, respectively. Screening-specific worries declined significantly over time but were still relatively high at 12 months: 23%, 39% and 18% for worries about cervical cancer, fertility and having sex, respectively. Anxiety remained stable (20%) over time. Risks of cervical cancer worry and anxiety were both almost double in women without private health insurance (cervical cancer worry: OR = 1.80, 95% CI 1.25-2.61; anxiety: OR = 1.84, 95% CI 1.20-2.84). Younger women (<40 years) had higher risk of fertility worries. Non-Irish women had higher risk of anxiety (OR = 2.13, 95% CI 1.13-4.01). CONCLUSIONS: Screening-specific worries declined over time but anxiety remained stable. Notable proportions of women still reported adverse outcomes 12 months following colposcopy, with predictors varying between outcomes. Women in socio-demographically vulnerable groups were at greatest risk of adverse psychological outcomes. This information could inform development of interventions to alleviate psychological distress post-colposcopy.

Mode of prostate cancer detection is associated with the psychological wellbeing of survivors: results from the PiCTure study.

PURPOSE: Many men with prostate cancer are asymptomatic, diagnosed following prostate specific antigen (PSA) testing. We investigate whether mode of detection, i.e. 'PSA detected' or 'clinically detected', was associated with psychological wellbeing among prostate cancer survivors. METHODS: A cross-sectional postal questionnaire was administered in 2012 to 6559 prostate cancer (ICD10 C61) survivors up to 18 years post-diagnosis, identified through population-based cancer registries in Ireland. Psychological wellbeing was assessed using the Depression Anxiety Stress Scale-21. Logistic regression was used to investigate associations between mode of detection and depression, anxiety and stress, adjusting for socio-demographic and clinical confounders. RESULTS: The response rate was 54 % (3348/6262). Fifty-nine percent of survivors were diagnosed with asymptomatic PSA-tested disease. Prevalence of depression (13.8 vs 20.7 %; p < 0.001), anxiety (13.6 vs 20.9 %; p < 0.001) and stress (8.7 vs 13.8 %; p < 0.001) were significantly lower among survivors diagnosed with PSA-detected, than clinically detected disease. After adjusting for clinical and socio-demographic factors, survivors with clinically detected disease had significantly higher risk of depression (odds ratio (OR) = 1.46 95 % CI 1.18, 1.80; p = 0.001), anxiety (OR = 1.36 95 % CI 1.09, 1.68; p = 0.006) and stress (OR = 1.43 95 % CI 1.11, 1.85; p = 0.006) than survivors with PSA-detected disease. CONCLUSIONS: These findings contribute to the ongoing debate on benefits and risks of PSA testing and may be considered by policy makers formulating population-based prostate cancer screening policies. The relatively high prevalence of negative psychological states among survivors means that a 'risk-adapted approach' should be implemented to screen survivors most at risk of psychological morbidity for psychological health, and mode of detection could be considered as a risk stratum.

Patient-reported 'ever had' and 'current' long-term physical symptoms after prostate cancer treatments.

OBJECTIVE: To investigate the prevalence of physical symptoms that were 'ever' and 'currently' experienced by survivors of prostate cancer at a population level, to assess burden and thus inform policy to support survivors. PATIENTS AND METHODS: The study included 3 348 men surviving prostate cancer for 2-18 years after diagnosis. A cross-sectional, postal survey of 6 559 survivors diagnosed 2-18 years ago with primary, invasive prostate cancer (ICD10-C61) identified via national, population-based cancer registries in Northern Ireland and Republic of Ireland. Questions included symptoms at diagnosis, primary treatments and physical symptoms (erectile dysfunction [ED]/urinary incontinence [UI]/bowel problems/breast changes/loss of libido/hot flashes/fatigue) experienced 'ever' and at questionnaire completion ('current'). Symptom proportions were weighted by age, country and time since diagnosis. Bonferroni corrections were applied for multiple comparisons. RESULTS: Adjusted response rate 54%; 75% reported at least one 'current' physical symptom ('ever' 90%), with 29% reporting at least three. Prevalence varied by treatment. Overall, 57% reported current ED and this was highest after radical prostatectomy (RP, 76%) followed by external beam radiotherapy with concurrent hormone therapy (HT, 64%). UI (overall 'current' 16%) was highest after RP ('current' 28%; 'ever' 70%). While 42% of brachytherapy patients reported no 'current' symptoms, 43% reported 'current' ED and 8% 'current' UI. 'Current' hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more often by patients on HT. CONCLUSION: Symptoms after prostate cancer treatment are common, often multiple, persist long-term and vary by treatment method. They represent a significant health burden. An estimated 1.6% of men aged >45 years are survivors of prostate cancer and currently experiencing an adverse physical symptom. Recognition and treatment of physical symptoms should be prioritised in patient follow-up. This information should facilitate men and clinicians when deciding about treatment as differences in survival between radical treatments is minimal.

Psychometric evaluation of the EORTC QLQ-PR25 questionnaire in assessing health-related quality of life in prostate cancer survivors: a curate's egg.

PURPOSE: The EORTC QLQ-PR25 was primarily developed to measure disease-specific health-related quality of life (HRQoL) of prostate cancer (PCa) patients undergoing active treatment. The growing number of cancer survivors has focussed interest on assessing survivors' HRQoL. We evaluated psychometric properties of the EORTC QLQ-PR25 questionnaire amongst PCa survivors. METHODS: A postal questionnaire, including the QLQ-PR25, was administered to 6559 PCa survivors 2-18 years post-diagnosis, identified through population-based cancer registries in Ireland; 3348 participated. The QLQ-PR25 has been suggested to have five multi-item subscales measuring urinary (US), bowel (BS) and hormone treatment-related symptoms (TS), sexual activity (SA) and sexual functioning (SF), and a single item measuring bother due to using incontinence aids (IA). Reliability analysis, divergent validity, discriminant validity (compared to EORTC QLQ-C30, DASS-21 and EuroQoL EQ-5D-5L), and exploratory and confirmatory factor analysis (EFA, CFA) were undertaken. RESULTS: The percentage of survivors completing QLQ-PR25 subscales was: US-79 %; IA-20 %; BS-83 %; TS-86 %; SA-87 %; and SF-26 %. Reliability was acceptable (Cronbach's α > 0.7) for three subscales (US, SA, SF). The instrument discriminated well between clinically distinct groups, especially those defined by primary treatment(s) and stage at diagnosis. The SA and SF subscales showed good discriminant validity compared to QLQ-C30, DASS-21 and EQ-5D-5L; other subscales did not. EFA reproduced a near fit to the proposed factor structure. CFA confirmed this. CONCLUSION: This is the largest ever QLQ-PR25 validation study. When used in PCa survivors, although the proposed factor structure was confirmed, some of the subscales (e.g. BS and TS) showed poor reliability, a lack of discriminant validity and moderate levels of item non-response.

How much does it cost to care for survivors of colorectal cancer? Caregiver's time, travel and out-of-pocket costs.

PURPOSE: Cancer treatment is increasingly delivered in an outpatient setting. This may entail a considerable economic burden for family members and friends who support patients/survivors. We estimated financial and time costs associated with informal care for colorectal cancer. METHODS: Two hundred twenty-eight carers of colorectal cancer survivors diagnosed on October 2007-September 2009 were sent a questionnaire. Informal care costs included hospital- and domestic-based foregone caregiver time, travel expenses and out-of-pocket (OOP) costs during two phases: diagnosis and treatment and ongoing care (previous 30 days). Multiple regression was used to determine cost predictors. RESULTS: One hundred fifty-four completed questionnaires were received (response rate = 68%). In the diagnosis and treatment phase, weekly informal care costs per person were: hospital-based costs, incurred by 99% of carers, mean = €393 (interquartile range (IQR), €131-€541); domestic-based time costs, incurred by 85%, mean = €609 (IQR, €170-€976); and domestic-based OOP costs, incurred by 68%, mean = €69 (IQR, €0-€110). Ongoing costs included domestic-based time costs incurred by 66% (mean = €66; IQR, €0-€594) and domestic-based OOP costs incurred by 52% (mean = €52; IQR, €0-€64). The approximate average first year informal care cost was €29,842, of which 85 % was time costs, 13% OOP costs and 2% travel costs. Significant cost predictors included carer age, disease stage, and survivor age. CONCLUSION: Informal caregiving associated with colorectal cancer entails considerable time and OOP costs. This burden is largely unrecognised by policymakers, service providers and society in general. These types of studies may facilitate health decision-makers in better assessing the consequences of changes in cancer care organisation and delivery.

The Uptake and Efficacy of Neoadjuvant Therapy in Older Adults with Locally Advanced Esophogastric Cancer.

BACKGROUND: Data on Neo+/- adjuvant treatment in older patients with cancer is sparse. The management of locally advanced esophagogastric cancer (LAEC) in older patients was evaluated to determine treatment modalities and identify factors associated with survival. METHODS: Patients diagnosed with LAEC (stage II or III) over 5 years were identified from the National Cancer Registry of Ireland. Treatment was classified as "best supportive care (BSC)," "surgery only," "neo/adjuvant treatment," and "chemo/radiation alone."Survival was assessed. Univariate and multivariate analysis (MVA) of clinicopathological factors and treatment was conducted. RESULTS: Forty-six percent (n = 580) of the 1251 patients were ≥ 70 years, 11% (n = 134) received BSC, 23% (n = 288) surgery only, 31% (n = 390) had chemo/radiation alone, and 35% (n = 439) had neo/adjuvant treatment. Forty-six percent, 10%, and 0% of patients < 75, ≥ 75, and ≥ 80 years of age, respectively, received neoadjuvant treatment. Age was associated with treatment received (p < 0.001). Older patients were less likely to receive neo/adjuvant treatment, surgery, and any treatment. Median survival (OS) decreased with age (< 70 years: 23 months; 70-74: 19 months; 75-79: 13 months; ≥ 80 years: 10 months). In MVA, older age, smoking, later stage, and higher grade were significantly associated with a higher risk of death. Patients receiving neo/adjuvant treatment had lower risk of death than any other treatment group regardless of age. CONCLUSION: Older patients were less likely to receive treatment for LAEC than younger patients. Patients aged ≥ 70 years benefit from neo/adjuvant treatment. Prospective clinical trials focusing on older patients and incorporating life expectancy, comorbidities, and geriatric assessment are needed to guide treatment.

Sleep Disturbance in Adjustment Disorder and Depressive Episode.

Background: In this paper, we aimed to examine the patterns of sleep disturbance in adjustment disorder (AD) and depressive episode (DE), to examine the variables associated with sleep disturbance in AD and DE and associated impairment in functioning. Methods: This is a multi-centre case-control study of 370 patients: 185 patients with AD and 185 patients with a diagnosis of DE, recruited from the liaison psychiatry services of three Dublin hospitals. We examined the participants' sleep pathology using the sleep disturbance items on the Schedule for Clinical Assessment in Neuropsychiatry, and the Inventory of Depressive Symptoms-Clinician-rated-30. Results: Patients with a diagnosis of AD were less likely to report disturbed sleep than those with a diagnosis of DE (p = 0.002). On multivariate analysis, sleep disturbance was significantly associated with greater severity of certain depressive symptoms: decreased appetite (p < 0.001) and psychomotor agitation (p = 0.009). Decreased appetite, younger age and single marital status were significantly associated with sleep disturbance in male patients, and decreased appetite and psychomotor agitation were significantly associated with sleep disturbance in female participants. Conclusions: This is the largest study to date which has examined sleep disturbance in adjustment disorder. Disturbance of sleep is a significant symptom in AD and may represent a potential target for treatment. With further research, patterns of sleep disturbance may be useful in differentiating AD from DE.

Variation in Nonmelanoma Skin Cancer Incidence by Treatment Modality Among Patients Receiving Multiple Kidney Transplants.

IMPORTANCE: Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described. OBJECTIVE: To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis. EXPOSURES: Kidney transplantation. MAIN OUTCOMES AND MEASURES: Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant. RESULTS: Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant. CONCLUSIONS AND RELEVANCE: In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.

Which primary care practitioners have poor human papillomavirus (HPV) knowledge? A step towards informing the development of professional education initiatives.

BACKGROUND: Primary care practitioners (PCP) play key roles in cervical cancer prevention. Human papillomavirus (HPV) knowledge is an important influence on PCPs' cervical cancer prevention-related behaviours. We investigated HPV knowledge, and associated factors, among general practitioners (GPs) and practice nurses. METHODS: A survey, including factual questions about HPV infection and vaccination, was mailed to GPs and practice nurses in Ireland. Multivariable logistic regression was used to determine which PCPs had low knowledge (questions correctly answered: infection ≤5/11; vaccination: ≤4/10). Questions least often answered correctly were identified. RESULTS: 697 PCPs participated. For HPV infection, GPs and practice nurses answered a median of nine and seven questions correctly, respectively (p<0.001). Significantly associated with low HPV infection knowledge were: being a practice nurse/male GP; working fewer hours/week; not having public patients; and having never taken a cervical smear. For HPV vaccination, both GPs and practice nurses answered a median of six questions correctly (p = 0.248). Significantly associated with low HPV vaccination knowledge were: being a practice nurse/male GP; working more years in general practice, fewer hours/week, in a smaller practice or in a practice not specialising in women's health; and having never taken a smear. Six HPV infection questions, and seven HPV vaccination questions, were not answered correctly by >⅓ of PCPs. CONCLUSIONS: There are important limitations in HPV infection and vaccination knowledge among PCPs. By identifying factors associated with poor knowledge, and areas of particular uncertainty, these results can inform development of professional education initiatives thereby ensuring women have access to uniformly high-quality HPV-related information and advice.

Lottery ticket was more effective than a prize draw in increasing questionnaire response among cancer survivors.

OBJECTIVES: Compare the effect of financial incentives on response to a cancer survivors' postal questionnaire. STUDY DESIGN AND SETTING: Prostate cancer survivors in Ireland, 1.5-18 years after diagnosis, were randomized to the (1) "lottery" arm [a € 1 lottery scratch card sent with the questionnaire (n = 2,413)] or (2) "prize" arm [entry into a draw on return of a completed questionnaire (n = 2,407)]. Impact of interventions on response overall and by survival period ("short term": < 5 years after diagnosis; "long term": ≥ 5 years after diagnosis) was compared as was cost-effectiveness. RESULTS: Adjusted response rate was 54.4%. Response was higher among younger men (P < 0.001) and those with earlier stage disease (P = 0.002). A modest 2.6% higher response rate was observed in the lottery compared with the prize arm [multivariate relative risk (RR) = 1.06; 95% confidence interval (CI): 1.00, 1.11]. When stratified by survival period, higher response in the lottery arm was only observed among long-term survivors (multivariate RR = 1.10; 95% CI: 1.02, 1.19; short-term survivors: RR = 1.01; 95% CI: 0.94, 1.09). Costs per completed questionnaire were € 4.54 and € 3.57 for the lottery and prize arms, respectively. Compared with the prize arm, cost per additional questionnaire returned in the lottery arm was € 25.65. CONCLUSION: Although more expensive, to optimize response to postal questionnaires among cancer survivors, researchers might consider inclusion of a lottery scratch card.

Suicidal behaviours in adjustment disorder and depressive episode.

BACKGROUND: Little is known about suicidal ideation and behaviours in adjustment disorder (AD). In this paper we sought to examine the variables independently associated with suicidal ideation and behaviour in patients diagnosed with AD or depressive (DE) episode among psychiatric outpatients and in liaison psychiatry. METHODS: 370 patients who were referred to the liaison psychiatry services (including those seen in the Emergency Department) at 3 Dublin hospitals, and were clinically diagnosed with either DE or AD, based on the ICD 10 diagnostic criteria, were recruited to the study. We examined their demographic and clinical characteristics, and the associations between these and suicidal ideation and behaviour on multivariate analysis. RESULTS: Younger age, single marital status, and greater severity of depressive symptoms were significantly associated with suicidality across both diagnoses. On multivariate analysis, greater severity of depressive symptoms was associated with suicidality in those with AD (p=0.012) and DE (p=0.009). Those with AD exhibited suicidality at lower symptom scores than did those with DE but in both groups it still occurred at the highest level of severity. There were differences in the objective circumstances measure of suicide intent. LIMITATIONS: We used clinical diagnosis rather as the main diagnostic classification. The generalisability of this paper may be limited to consultation-liaison psychiatry settings, where suicidal ideation and behaviours are common. CONCLUSIONS: Suicidality in AD and DE has broadly similar risk factors but differ in aspects of suicide intent. Different mechanisms may underpin suicidality in those with AD compared to DE.

Long-term health-related quality of life of prostate cancer survivors varies by primary treatment. Results from the PiCTure (Prostate Cancer Treatment, your experience) study.

PURPOSE: Men are living longer with prostate cancer. In a two-country study, we investigated the health-related quality of life (HRQoL) of prostate cancer survivors up to 18 years post-diagnosis. METHODS: Postal questionnaires were administered in 2012 to 6559 prostate cancer (ICD10 C61) survivors 2-18 years post-diagnosis, identified through population-based cancer registries in Ireland. HRQoL was measured using QLQ-C30 and QLQ-PR25. HRQoL, functional and symptom scores were compared by primary treatment(s) using multiple linear regression. RESULTS: Fifty-four percent responded (n = 3348). After controlling for socio-demographic and clinical factors, global HRQoL varied significantly by primary treatment (p < 0.001); compared to radical prostatectomy (RP), survivors who received androgen deprivation therapy alone (ADT; p < 0.001) or external beam radiotherapy (EBRT) without concurrent ADT (p = 0.001) had significantly lower global HRQoL. The global HRQoL of men who received brachytherapy (p = 0.157), EBRT with concurrent ADT (p = 0.940) or active surveillance/watchful waiting (p = 0.388) was not significantly different from men treated with RP. There were statistically and clinically significant differences in general (fatigue, pain, dyspnoea, appetite loss, constipation, diarrhoea, financial difficulties) and disease-specific symptoms (sexual, urinary, bowel, ADT) by primary treatment. Fatigue and insomnia scores were high for survivors in all treatment groups. CONCLUSIONS: Prostate cancer survivors' long-term HRQoL varied with primary treatment. IMPLICATIONS OF CANCER SURVIVORS: Population-based information regarding statistically and clinically significant treatment effects on long-term global HRQoL, symptom burden and functionality should be provided during treatment decision-making. Screening for symptoms and utilising interventions during long-term follow-up may improve survivors' HRQoL.