Impacts of anterior-posterior jaw disproportions on speech of dentofacial disharmony patients.

BACKGROUND/OBJECTIVES: Articulation problems impact communication, development, and quality of life, and are diagnosed in 73-87% of patients with Class II Dentofacial Disharmony (DFD). We evaluated whether differences exist in stop (/t/ or/k/), fricative (/s/ or/ʃ/), and affricate (/tʃ/) consonant sounds of Class II DFD subjects, and whether extent of malocclusion correlates with severity of speech distortion. We hypothesized that Class II patients display milder distortions than Class III and anterior open bite (AOB), as Class II patients can posture into a Class I occlusion. MATERIALS/METHODS: Audio and orthodontic records were collected from DFD patients (N = 53-Class II, 102-Class III, 72-Controls) who were pursuing orthodontics and orthognathic surgery. A speech pathologist perceptually scored speech. Acoustic differences in recordings were measured using Spectral Moment Analysis. RESULTS: When Class II subjects were compared to controls, significant differences were found for the centroid frequency (M1) of the /s/ sound and the spectral spread (M2) of /t/, /tʃ/, and /s/ sounds, with pairwise significance for controls relative to Class II AOB and all Class II subjects. Class II AOB subjects had higher M1 and M2 values than patients with Class II closed bites and Class I controls for most sounds. When comparing across anterior-posterior (AP) groups, differences exist between controls, Class II and III DFD subjects for M1 of /t/, /tʃ/, and/ʃ/ and M2 for /t/, /tʃ/, /s/, and /ʃ/ sounds. Using linear regression, correlations between Class II and III severity and spectral measures were found for /t/ and /tʃ/ sounds. CONCLUSIONS/IMPLICATIONS: Class II and III patients have a higher prevalence of qualitative distortions and spectral changes in consonants compared to controls, but Class II spectral shifts are smaller and affect fewer sounds than in Class III and AOB cohorts. Linear correlations between AP discrepancy and spectral change suggest causation and that treatment may improve articulation problems.

Impacts of Skeletal Anterior Open Bite Malocclusion on Speech.

Introduction: Articulation problems are seen in 80-90% of dentofacial deformity (DFD) subjects compared with 5% of the general population, impacting communication and quality of life, but the causal link is unclear. We hypothesize there are both qualitative (perceptual) and quantitative (spectral) differences in properties of stop (/t/ or /k/), fricative (/s/ or /∫/), and affricate (/t∫/) consonant sounds and that severity of anterior open bite (AOB) jaw disharmonies correlates with degree of speech abnormality. Methods: To test our hypotheses, surgical orthodontic records and audio recordings were collected from DFD patients (n=39 AOB, 62 controls). A speech pathologist evaluated subjects and recordings were analyzed using spectral moment analysis (SMA) to measure sound frequency distortions. Results: Perceptually, there is a higher prevalence of auditory and visual speech distortions in AOB DFD patients when compared to controls. Quantitatively, a significant (p<0.01) increase in the centroid frequency (M1) was seen in the /k/, /t/, /t∫/, and /s/ sounds of AOB subjects compared to the controls. Using linear regression, correlations between AOB skeletal severity and spectral distortion were found for /k/ and /t/ sounds. Conclusions: A higher prevalence of qualitative distortion and significant quantitative spectral distortions in consonant sounds were seen in AOB patients compared to controls. Additionally, severity of skeletal AOB is correlated with degree of distortion for consonant sounds. These findings provide insight into how the surgical and/or orthodontic treatment of AOB may impact speech.

Palliative care for non-cancer conditions in primary care: a time trend analysis in the UK (2009-2014).

OBJECTIVES: While guidelines recommend palliative care in non-cancer conditions, this has not been widely implemented. We examined whether the recording of a palliative care approach and the numbers of hospital deaths for deceased patients with heart failure, dementia, chronic obstructive pulmonary disease (COPD) and cancer have changed since the UK End-of-Life Care Strategy was introduced. METHODS: We conducted sequential cross-sectional studies of decedents within the UK's Clinical Practice Research Datalink and Hospital Episode Statistics. All adults with a primary care record of COPD (n=5426), dementia (n=7339), heart failure (n=6409) or cancer (n=18 668) who died during three 1 year periods (April 2009 to March 2014) were included. Evidence of a palliative care approach was identified from primary care records, and death in hospital from secondary care data. RESULTS: From 2009 to 2014, proportions with a primary care record of palliative care increased for COPD from 13.6% to 21.2%; dementia from 20.9% to 40.7%; and heart failure from 12.6% to 21.2%; but remained substantially lower than for cancer (57.6% to 61.9%). Median days before death of recording improved for COPD (145 to 224) and dementia (44 to 209); but not for heart failure (168.5 to 153) and cancer (123 to 114). Trends in hospital deaths were not consistently downward, although the proportions of patients dying in hospital were lower in the last period compared with the first. CONCLUSIONS: Recording of a palliative care approach for non-cancer conditions has increased since the introduction of the UK End-of-Life Care Strategy, but remains inadequate.

Risk of mature B-cell neoplasms and precursor conditions after joint replacement: A report from the Haematological Malignancy Research Network.

Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.

Non-attendance at urgent referral appointments for suspected cancer: a qualitative study to gain understanding from patients and GPs.

BACKGROUND: The 2-week-wait urgent referral policy in the UK has sought to improve cancer outcomes by accelerating diagnosis and treatment. However, around 5-7% of symptomatic referred patients cancel or do not attend their hospital appointment. While subsequent cancer diagnosis was less likely in non-attenders, those with a diagnosis had worse early mortality outcomes. AIM: To examine how interpersonal, communication, social, and organisational factors influence a patient's non-attendance. DESIGN AND SETTING: Qualitative study in GP practices in one Northern English city. METHOD: In-depth, individual interviews were undertaken face-to-face or by telephone between December 2016 and May 2018, followed by thematic framework analysis. RESULTS: In this study 21 GPs, and 24 patients who did not attend or had cancelled their appointment were interviewed, deriving a range of potential explanations for non-attendance, including: system flaws; GP difficulties with booking appointments; patient difficulties with navigating the appointment system, particularly older patients and those from more deprived areas; patients leading 'difficult lives'; and patients' expectations of the referral, informed by their beliefs, circumstances, priorities, and the perceived prognosis. GPs recognised the importance of communication with the patient, particularly the need to tailor communication to perceived patient understanding and anxiety. GPs and practices varied in their responses to patient non-attendance, influenced by time pressures and perceptions of patient responsibility. CONCLUSION: Failure to be seen within 2 weeks of urgent referral resulted from a number of patient and provider factors. The urgent referral process in general practice and cancer services should accommodate patient perceptions and responses, facilitate referral and attendance, and enable responses to patient non-attendance.

Non-attendance at urgent referral appointments for suspected cancer: a qualitative study to gain understanding from patients and GPs.

BACKGROUND: The 2-week-wait urgent referral policy in the UK has sought to improve cancer outcomes by accelerating diagnosis and treatment. However, around 5-7% of symptomatic referred patients cancel or do not attend their hospital appointment. While subsequent cancer diagnosis was less likely in non-attenders, those with a diagnosis had worse early mortality outcomes. AIM: To examine how interpersonal, communication, social, and organisational factors influence a patient's non-attendance. DESIGN AND SETTING: Qualitative study in GP practices in one Northern English city. METHOD: In-depth, individual interviews were undertaken face-to-face or by telephone between December 2016 and May 2018, followed by thematic framework analysis. RESULTS: In this study 21 GPs, and 24 patients who did not attend or had cancelled their appointment were interviewed, deriving a range of potential explanations for non-attendance, including: system flaws; GP difficulties with booking appointments; patient difficulties with navigating the appointment system, particularly older patients and those from more deprived areas; patients leading 'difficult lives'; and patients' expectations of the referral, informed by their beliefs, circumstances, priorities, and the perceived prognosis. GPs recognised the importance of communication with the patient, particularly the need to tailor communication to perceived patient understanding and anxiety. GPs and practices varied in their responses to patient non-attendance, influenced by time pressures and perceptions of patient responsibility. CONCLUSION: Failure to be seen within 2 weeks of urgent referral resulted from a number of patient and provider factors. The urgent referral process in general practice and cancer services should accommodate patient perceptions and responses, facilitate referral and attendance, and enable responses to patient non-attendance.

Patient non-attendance at urgent referral appointments for suspected cancer and its links to cancer diagnosis and one year mortality: A cohort study of patients referred on the Two Week Wait pathway.

BACKGROUND: The 'Two Week Wait' policy aims to ensure patients with suspected cancer are seen within two weeks of referral. However, patient non-attendance can result in this target being missed. This study aimed to identify predictors of non-attendance; and analyse the relationship between attendance and outcomes including cancer diagnosis and early mortality. METHODS: A cohort study of 109,433 adults registered at 105 general practices, referred to a cancer centre within a large NHS hospital trust (April 2009 to December 2016) on the 'Two Week Wait' pathway. RESULTS: 5673 (5.2%) patients did not attend. Non-attendance was largely predicted by patient factors (younger and older age, male gender, greater deprivation, suspected cancer site, earlier year of referral, greater distance to the hospital) over practice factors (greater deprivation, lower Quality and Outcomes Framework score, lower cancer conversion rate, lower cancer detection rate). 10,360 (9.6%) patients were diagnosed with cancer within six months of referral (9.8% attending patients, 5.6% non-attending patients). Among these patients, 2029 (19.6%) died within 12 months of diagnosis: early mortality risk was 31.3% in non-attenders and 19.2% in attending patients. CONCLUSIONS: Non-attendance at urgent referral appointments for suspected cancer involves a minority of patients but happens in predictable groups. Cancer diagnosis was less likely in non-attending patients but these patients had worse early mortality outcomes than attending patients. The study findings have implications for cancer services and policy.

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

The impact of rheumatological disorders on lymphomas and myeloma: a report on risk and survival from the UK's population-based Haematological Malignancy Research Network.

BACKGROUND: Autoimmune inflammatory disease increases the risk of diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), but findings for other mature B-cell malignancies are equivocal. Furthermore, it has been suggested that the increase in DLBCL is due to the activated B-cell (ABC) subtype; but data on this, and the impact of inflammatory co-morbidities on survival, are sparse and contradictory. METHODS: Data are from an established UK population-based cohort. Patients (n = 6834) diagnosed between 01/2009 and 08/2015 are included; DLBCL (n = 1771), myeloma (n = 1760), chronic lymphocytic leukaemia (CLL, n = 1580), MZL (n = 936), and follicular lymphoma (FL, n = 787). Information on rheumatological disorders and deaths was obtained by record-linkage to nationally compiled Hospital Episode Statistics, with age-and sex-matched individuals (n = 68,340) from the same catchment population (˜4 million people) providing the comparator. RESULTS: Significantly increased risks for DLBCL (OR = 2.3, 95% CI 1.8-2.8) and MZL (OR = 2.0, 95% CI 1.5-2.7) were found for those with rheumatological disorders; the site distribution of those with/without rheumatological conditions differing for DLBCL (p = 0.007) and MZL (p = 0.002). No increases in risk were observed for the remaining mature B-cell malignancies, and no associations with survival were detected for DLBCL (age-adjusted HR = 1.2, 95% CI 0.9-1.6) or MZL (age-adjusted HR = 1.0, 95% CI 0.6-1.9). Furthermore, whilst our findings provide evidence for an association with rheumatological disease severity for DLBCL, they offer little support for the notion that the association is driven by an increase in the incidence of the ABC subtype. CONCLUSION: Our findings support the hypothesis that the chronic activation and proliferation of specific B-cell populations which characterize autoimmune disease increase the potential for the lymphomagenic events that lead to DLBCL and MZL in both males and females; but have no impact on the development of CLL, FL or MM, or on survival.

Time intervals from first symptom to diagnosis for head and neck cancers: An analysis of linked patient reports and medical records from the UK.

BACKGROUND: England has significantly higher mortality risks due to Head and Neck Cancer (HNC) compared with other European countries. Early diagnosis is important as it is likely to increase early-stage diagnosis and improve survival and better quality of life. This study sought to improve understanding of the intervals from first symptom recognition to diagnosis for HNC and investigate associations between patient-reported symptoms and socio-demographic factors. METHODS: People within 3 months of diagnosis, completed a researcher-administered questionnaire and data were extracted from primary and secondary care clinical records. RESULTS: Eighty (mean age 62.9 [SD 11.7] years; 66% men) were interviewed. The appraisal interval was longer than a month for 39% of participants and the help-seeking interval was longer than a week for 44%. The median diagnostic interval was 92 (IQR; 34-172) days. Appraisal intervals of > 1 month were associated with male gender, ulceration and persistent throat pain. The only symptom that associated with a help-seeking interval of > 1 week was ulceration. Participants who reported red/white patches in the mouth and ulceration were associated with a reduced likelihood of a diagnostic interval of > 3 months. A higher proportion of participants with a diagnostic interval of > 3 months were diagnosed with advanced disease (78%) than those with an interval < 3 months (68%). CONCLUSION: These data improve understanding of the intervals from first symptom recognition to HNC diagnosis and provide preliminary evidence to identify targets to reduce overall time to diagnosis.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

Importance: Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. Objective: To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. Design, Setting, and Participants: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. Intervention: An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Main Outcomes and Measures: Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Results: Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Conclusions and Relevance: Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. Trial Registration: ISRCTN Identifier: ISRCTN92187251.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

OBJECTIVES: Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). SETTING, PARTICIPANTS AND OUTCOME MEASURES: Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. RESULTS: The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). CONCLUSION: A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. TRIAL REGISTRATION NUMBER: ISRCTN20141297,NCT02044172.

Acridinium-Based Photocatalysts: A Sustainable Option in Photoredox Catalysis.

The emergence of visible light photoredox catalysis has enabled the productive use of lower energy radiation, leading to highly selective reaction platforms. Polypyridyl complexes of iridium and ruthenium have served as popular photocatalysts in recent years due to their long excited state lifetimes and useful redox windows, leading to the development of diverse photoredox-catalyzed transformations. The low abundances of Ir and Ru in the earth's crust and, hence, cost make these catalysts nonsustainable and have limited their application in industrial-scale manufacturing. Herein, we report a series of novel acridinium salts as alternatives to iridium photoredox catalysts and show their comparability to the ubiquitous [Ir(dF-CF3-ppy)2(dtbpy)](PF6).

Estimating the prevalence of hematological malignancies and precursor conditions using data from Haematological Malignancy Research Network (HMRN).

OBJECTIVE: Well-established cancer registries that routinely link to death registrations can estimate prevalence directly by counting patients alive at a particular point in time (observed prevalence). Such direct methods can only provide prevalence for the years over which the registry has been operational. Time-defined estimates, including 5- and 10-year prevalence, may however underestimate the total cancer burden, and compared with other cancers, there is a lack of accurate information on the total prevalence of hematological malignancy subtypes. Accordingly, we aimed to estimate prevalence (observed and total prevalence) of hematological malignancies and precursor conditions by clinically meaningful subtypes using data from the UK's specialist population-based register, the Haematological Malignancy Research Network ( www.hmrn.org ). METHODS: Observed and total prevalences were estimated from 15,810 new diagnoses of hematological malignancies from 2004 to 2011 and followed up to the 31 August 2011 (index data). Observed prevalence was calculated by the counting method, and a method based on modelling incidence and survival was used to estimate total prevalence. Estimates were made according to current disease classification for the HMRN region and for the UK. RESULTS: The overall observed and total prevalence rates were 281.9 and 548.8 per 100,000, respectively; the total number of observed and total prevalent cases in the UK was estimated as 165,841 and 327,818 cases, as expected variation existed by disease subtype reflecting the heterogeneity in underlying disease incidence, survival and age distribution of hematological cancers. CONCLUSIONS: This study demonstrates the importance of estimating 'total' prevalence rather than 'observed' prevalence by current disease classification (ICD-O-3), particularly for subtypes that have a more indolent nature and for those that are curable. Importantly, these analyses demonstrate that relying on observed prevalence alone would result in a significant underestimation of the relative burden of some subtypes. While many of these cases may be considered cured and no longer being actively treated, people in this survivorship phase may have long-term medical needs and accordingly, it is important to provide accurate counts to allow for healthcare planning.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee.

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.

Family Caregivers Who Would Be Unwilling to Provide Care at the End of Life Again: Findings from the Health Survey for England Population Survey.

BACKGROUND: Family caregivers provide significant care at the end of life. We aimed to describe caregiver characteristics, and of those unwilling to repeat this role under the same circumstances. METHODS: Observational study of adults in private households (Health Survey for England [HSE]). Caregiving questions included: whether someone close to them died within past 5 years; relationship to the deceased; provision, intensity and duration of care; supportive/palliative care services used; willingness to care again; able to carry on with life. Comparison between those willing to care again or not used univariable analyses and an exploratory multiple logistic regression. A descriptive comparison with Health Omnibus Survey (Australia) data was conducted. FINDINGS: HSE response was 64%. 2167/8861 (25%) respondents had someone close to them die in the previous 5 years. Some level of personal care was provided by 645/8861 (7.3%). 57/632 (9%) former caregivers would be unwilling to provide care again irrespective of time since the death, duration of care, education and income. Younger age (≤65; odds ratio [OR] 2.79; 95% CI 136, 5.74) and use of palliative care services (odds ratio: 1.95, 95% CI: 1.09, 3.48) showed greater willingness to provide care again. Apart from use of palliative care services, findings were remarkably similar to the Australian data. CONCLUSIONS: A significant group of caregivers would be unwilling to provide care again. Older people and those who had not used palliative care services were more likely to be unwilling to care again. Barriers preventing access for disadvantaged groups need to be overcome.

Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C-N Coupling with Chiral Bisphosphine Mono-oxides.

A novel approach to hemiaminal synthesis via palladium-catalyzed C-N coupling with chiral bisphosphine mono-oxides is described. This efficient new method exhibits a broad scope, provides a highly efficient synthesis of HCV drug candidate elbasvir, and has been applied to the synthesis of chiral N,N-acetals.

Variation in incidence and survival by ethnicity for patients with myeloma in England (2002-2008).

Incidence and relative survival of myeloma by ethnic group was estimated using data from cancer registries in England (2002-2008). Multiple imputation was used to address missing ethnicity data. In total 24 361 cases of myeloma were identified. Age-standardized incidence rate (ASIR) (per 100 000) was higher in the Black ethnic category at 15.00 (95% confidence interval [CI] 13.50-16.40), than amongst South Asians (ASIR = 5.45, 95% CI 4.76-6.14) or the White group (ASIR = 6.11, 95% CI 6.00-6.22). There was a lower risk of death in the Black group for both 1- and 3-year survival (hazard ratio [HR]1 year = 0.66, 95% CI 0.55-0.79; HR3 year = 0.69, 95% CI 0.58-0.83) and South Asians at 1, 3 and 5 years (HR1 year = 0.65, 95% CI 0.51-0.82; HR3 year = 0.72, 95% CI I 0.57-0.90; HR5 year = 0.68, 95% CI 0.50-0.92) when compared to the White population. Further study of differences in myeloma and precursor biology between population groups is important.

Palliative care among heart failure patients in primary care: a comparison to cancer patients using English family practice data.

INTRODUCTION: Patients with heart failure have a significant symptom burden and other palliative care needs often over a longer period than patients with cancer. It is acknowledged that this need may be unmet but by how much has not been quantified in primary care data at the population level. METHODS: This was the first use of Clinical Practice Research Datalink, the world's largest primary care database to explore recognition of the need for palliative care. Heart failure and cancer patients who had died in 2009 aged 18 or over and had at least one year of primary care records were identified. A palliative approach to care among patients with heart failure was compared to that among patients with cancer using entry onto a palliative care register as a marker for a palliative approach to care. RESULTS: Among patients with heart failure, 7% (234/3 122) were entered on the palliative care register compared to 48% (3 669/7 608) of cancer patients. Of heart failure patients on the palliative care register, 29% (69/234) were entered onto the register within a week of their death. CONCLUSIONS: This confirms that the stark inequity in recognition of palliative care needs for people with heart failure in a large primary care dataset. We recommend a move away from prognosis based criteria for palliative care towards a patient centred approach, with assessment of and attention to palliative needs including advance care planning throughout the disease trajectory.