Project description:Breast cancer is uncommon in men and knowledge about its causation limited. Obesity is a risk factor but there has been no investigation of whether weight change is an independent risk factor, as it is in women. In a national case-control study, 1998 men with breast cancer incident in England and Wales during 2005 to 2017 and 1597 male controls were interviewed about risk factors for breast cancer including anthropometric factors at several ages. Relative risks of breast cancer in relation to changes in body mass index (BMI) and waist/height ratios at these ages were obtained by logistic regression modelling. There were significant trends of increasing breast cancer risk with increase in BMI from age 20 to 40 (odds ratio [OR] 1.11 [95% confidence interval (CI) 1.05-1.17] per 2 kg/m2 increase in BMI; P < .001), and from age 40 to 60 (OR 1.12 [1.04-1.20]; P = .003), and with increase in self-reported adiposity compared to peers at age 11 to BMI compared with peers at age 20 (OR 1.19 [1.09-1.30]; P < .001). Increase in waist/height ratio from age 20 to 5 years before diagnosis was also highly significantly associated with risk (OR 1.13 [1.08-1.19]; P < .001). The associations with increases in BMI and waist/height ratio were significant independently of each other and of BMI or waist/height ratio at the start of the period of change analysed, and effects were similar for invasive and in situ tumours separately. Increases in BMI and abdominal obesity are each risk factors for breast cancer in men, independently of obesity per se. These associations might relate to increasing oestrogen levels with weight gain, but this needs investigation.
Project description:BackgroundPeople with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID.MethodsA retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups.Results190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12 months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services.ConclusionsPolypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach.
Project description:BackgroundHomelessness in England and Wales is on the rise together with the mortality rate among homeless people. Many homeless people have a mental illness, which is a risk factor for suicide.AimsThis study used data from the National Confidential Inquiry into Suicide and Safety in Mental Health to examine demographic and clinical characteristics of homeless people who died by suicide and were in recent contact with mental health services.MethodWe have compared 514 patients (2% of the total sample) who died by suicide and who were reported as being homeless or having no fixed abode by their clinicians with patients in stable accommodation between 2000 and 2016 to identify differences in sociodemographic characteristics and clinical care.ResultsOur analysis suggests that homeless patients who died by suicide had more acute (alcohol: 47% v. 25%, P < 0.01, drug: 39% v. 15%, P < 0.01) and chronic (alcohol: 72% v. 44%, P > 0.01, drug: 64% v. 31%) substance misuse issues than patients in stable accommodation. Homeless patients were also more likely to die as in-patients (21% v. 10%, P < 0.01) or within 3 months of discharge (32% v. 19%, P < 0.01).ConclusionsHomeless patients who died by suicide more often had known risk factors for suicide than patients in stable accommodation. As a result of the higher percentages of post-discharge and in-patient suicides in homeless patients as well as the high prevalence of substance misuse, this study recommends closer integration of services as well as awareness of risks during in-patient admission and in the weeks immediately after discharge.
Project description:BackgroundSome people diagnosed with schizophrenia are more prone to committing acts of serious violence, especially in the presence of drug or alcohol misuse. The rarity of homicide has meant that no large controlled study has previously examined clinical risk factors.AimsTo determine the risk factors for homicide by males diagnosed with schizophrenia.MethodA national nested case-control study of all previously admitted males diagnosed with schizophrenia, convicted of homicide between 1 January 1997 and 31 December 2012. Univariate and multivariable conditional logistic regression models were fitted to identify predictors of homicide in this population.ResultsDuring the observation period 160 male patients with schizophrenia and a history of psychiatric admission were convicted of homicide, and they were matched with 542 male control patients who had not been convicted of homicide. Patients who committed homicide were more likely to have a history of violence and comorbid personality disorder or drug misuse. They were more likely to have missed their last contact with services prior to the offence and to have been non-adherent with their treatment plan. Almost all (94%) of homicides were committed by patients who had a history of alcohol or drug misuse and/or who were not in receipt of planned treatment.ConclusionsIn England and Wales, homicides by patients with schizophrenia without substance misuse and in receipt of planned care are exceptionally rare. To prevent serious violence, mental health services should focus on drug and alcohol misuse, treatment adherence and maintaining contact with services.
Project description:BackgroundThere is uncertainty about overdiagnosis in mammography screening.MethodsWe aimed to estimate the effect of screening on breast cancer incidence and overdiagnosis in the NHS Breast Screening Programme in England. The study included 57,493 cases and 105,653 controls, with cases defined as women diagnosed at ages 47-89 with primary breast cancer, invasive or ductal carcinoma in situ, in 2010 or 2011. Where possible, two controls were selected per case, matched on date of birth and screening area. Conditional logistic regression was used to estimate the effect of screening on breast cancer risk, with adjustment for potential self-selection bias. Results were combined with national incidence data to estimate absolute rates of overdiagnosis. Overdiagnosis was calculated as the cumulative excess of cancers diagnosed in the age group 50-77 in a woman attending three-yearly screening between ages 50 and 70 compared with a woman attending no screens.ResultsThe estimated number of cases overdiagnosed in women attending all screens in the programme was 679.3 per 100,000 without adjustment for self-selection bias and 261.2 per 100,000 with adjustment. These corresponded to an estimated 9.5% of screen-detected cancers overdiagnosed without adjustment and 3.7% with adjustment for self-selection.ConclusionsThe NHS Breast Screening Programme in England confers at worst modest levels of overdiagnosis.
Project description:The United Kingdom NHS Breast Screening Programme was established in 1988, and women aged between 50 and 70 are routinely invited at three yearly intervals. Expected United Kingdom interval cancer rates have been calculated previously, but this is the first publication from an exercise to collate individual-based interval cancer data at a national level.Interval cancer case ascertainment is achieved by the regular exchange of data between Regional Breast Screening Quality Assurance Reference Centres and Cancer Registries. The present analysis includes interval cancers identified in women screened between 1st April 1997 and 31st March 2003, who were aged between 50 and 64 at the time of their last routine screen.In the periods >0-<12 months, 12-<24 months and 24-<36 months after a negative screen, we found overall interval cancer rates and regional ranges of 0.55 (0.43-0.76), 1.13 (0.92-1.47) and 1.22 (0.93-1.57) per 1000 women screened, respectively. Rates in the period 33-<36 months showed a decline, possibly associated with early re-screening or delayed presentation.Interval cancer rates were higher than the expected rates in the 24-month period after a negative screen, but were similar to published results from other countries. Increases in background incidence may mean that the expected rates are underestimated. It is also possible that, as a result of incomplete case ascertainment, interval cancers rates were underestimated in some regions in which rates were less than the expected.
Project description:PurposeTo describe drug utilisation patterns in neonatal units.MethodsRetrospective observational cohort study using data held in the National Neonatal Research Database (NNRD) for neonatal units in England and Wales including infants born at 23 to 44 weeks' gestational age (GA) from 01 January 2010 to 31 December 2017.ResultsThe cohort included 17,501 (3%) extremely preterm infants; 40,607 (7%) very preterm infants; 193,536 (31%) moderate-to-late preterm infants; and 371,606 (59%) term infants. The number of unique drugs received by an infant (median (IQR)) increased with decreasing GA: 17 (11-24) in extremely preterm, 7 (5-11) in very preterm, 3 (0-4) in moderate-to-late preterm, and 3 (0-3) in term infants. The two most frequently prescribed drugs were benzylpenicillin and gentamicin in all GA groups, and caffeine in extremely preterm. Other frequently used drugs among preterm infants were electrolytes, diuretics and anti-reflux medications. Among infants <32 weeks' GA, the largest increase in use was for surfactant (given on the neonatal unit), caffeine and probiotics, while domperidone and ranitidine had the largest decline.ConclusionAntibiotics, for all GAs and caffeine, among preterm infants, are the most frequently used drugs in neonatal medicine. Preterm infants are exposed to a high burden of drugs, particularly antibiotics. Changing patterns in use reflect the emergence of evidence in some areas but several non-evidence-based drugs continue to be used widely. Improvements are needed to ensure rational drug use on neonatal units.RegistrationClinicalTrials.gov (NCT03773289). Date of registration 21 Dec 2018.
Project description:BackgroundControl of HIV transmission could be achievable through an expansion of HIV testing of at-risk populations together with ready access and adherence to antiretroviral therapy. To examine whether increases in testing rates and antiretroviral therapy coverage correspond to the control of HIV transmission, we estimated HIV incidence in men who have sex with men (MSM) in England and Wales since 2001.MethodsA CD4-staged back-calculation model of HIV incidence was used to disentangle the competing contributions of time-varying rates of diagnosis and HIV incidence to observed HIV diagnoses. Estimated trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a backdrop of increased HIV testing rates and antiretroviral-therapy coverage over the period 2001-10.FindingsThe observed 3·7 fold expansion in HIV testing in MSM was mirrored by a decline in the estimated mean time-to-diagnosis interval from 4·0 years (95% credible interval [CrI] 3·8-4·2) in 2001 to 3·2 years (2·6-3·8) by the end of 2010. However, neither HIV incidence (2300-2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990-7800, in 2001, and 7690, 5460-10 580, in 2010) changed throughout the decade, despite an increase in antiretroviral uptake from 69% in 2001 to 80% in 2010.InterpretationCD4 cell counts at HIV diagnosis are fundamental to the production of robust estimates of incidence based on HIV diagnosis data. Improved frequency and targeting of HIV testing, as well as the introduction of ART at higher CD4 counts than is currently recommended, could begin a decline in HIV transmission among MSM in England and Wales.FundingUK Medical Research Council, UK Health Protection Agency.
Project description:It has been suggested that lower UK cancer survival may be due to incomplete case ascertainment by cancer registries.We assessed concordance between self-reported breast, bowel and lung cancer and cancer registration (CR) for 1995-2007 in England and Wales in the UK Collaborative Trial of Ovarian Cancer Screening.Concordance of breast cancer CR was higher (94.7%:95% CI: 94.1-95.3%) than for bowel (85.1%:95% CI: 82.1-87.8%) and lung (85.4%:95% CI: 76.3-92.0%). CR concordance was lower in breast cancer (94.5% vs 98.8%) survivors compared with deceased but the difference was small. No difference was found for bowel (85.3% vs 94.6%) or lung (87.1% vs 90.5%) cancer.Concordance of CR and self-reported cancer is high. Incomplete registration is unlikely to be a major cause of lower UK survival rates.
Project description:Background:Heterogeneous breast cancer is the most common cause of cancer-related mortality. Obesity defined by BMI is a known major risk factor for breast cancer. Objectives:The purpose of this study was to explore the role of obesity related-polymorphisms rs9939609 Fat Mass and Obesity-associated (FTO) and rs17782313 MC4R in breast cancer development. Materials and Methods:Matched peripheral blood serum was obtained from 64 breast cancer patients and 83 normal controls. Height and weight were measured to calculate BMI. All were genotyped for the SNPs rs9939609 and rs17782313 using a Tetra-primer ARMS-PCR method. For statistical analysis, the chi-square test and SPSS software were used. Results:In subgroup analyses defined by BMI, FTO rs9939609 genotypes (TT/AA/AT) were significantly associated with the risk of breast cancer only in non-obese subjects (p < 0.005). TT genotypes of MC4R rs17782313 in non-obese and genotypes TT/CC in the overweight group were also statistically associated with breast cancer (p < 0.005). No significant associations between any variants and breast cancer risk were seen in obese subjects. Conclusion:Based on the absence of an association between obesity-related SNPs and breast cancer in obese subjects, it is proposed that weight gain in Iranian women will help prevent breast cancer risk. The result help for preparing and designing a safe and versatile recombinant drug in future.