Jacqueline Donovan

Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study.

Objectives To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen (PSA) testing; to assess early attitude to re-biopsy; to estimate healthcare resource use associated with adverse events due to biopsy; and to develop a classification scheme for reporting adverse events after prostate biopsy. Design Prospective cohort study (Prostate Biopsy Effects: ProBE) nested within Prostate Testing for Cancer and Treatment (ProtecT) study. Participants Between 1999 and 2008, 227 000 community dwelling men aged 5069 years were identified at 352 practices and invited to counselling about PSA testing. 111 148 attended a nurse led clinic in the community, and 10 297 with PSA concentrations of 3-20 ng/mL were offered biopsy within ProtecT. Between February 2006 and May 2008, 1147/1753 (65%) eligible men (mean age 62.1 years, mean PSA 5.4 ng/mL) having 10 core transrectal ultrasound guided biopsy under antibiotic cover in the context of ProtecT were recruited to the ProBE study. Outcome measures Purpose designed questionnaire administered at biopsy and 7 and 35 days after the procedure to measure frequency and effect of symptoms related to pain, infection, and bleeding; patients’ attitude to repeat biopsy assessed immediately after biopsy and 7 days later; participants’ healthcare resource use within 35 days of biopsy evaluated by questionnaire, telephone follow-up, and medical note review; each man’s adverse event profile graded according to symptoms and healthcare use. Results Pain was reported by 429/984 (43.6%), fever by 172/985 (17.5%), haematuria by 642/976 (65.8%), haematochezia by 356/967 (36.8%), and haemoejaculate by 605/653 (92.6%) men during the 35 days after biopsy. Fewer men rated these symptoms as a major/moderate problem—71/977 (7.3%) for pain, 54/981 (5.5%) for fever, 59/958 (6.2%) for haematuria, 24/951 (2.5%) for haematochezia, and 172/646 (26.6%) for haemoejaculate. Immediately after biopsy, 124/1142 (10.9%, 95% confidence interval 9.2 to 12.8) men reported that they would consider further biopsy a major or moderate problem: seven days after biopsy, this proportion had increased to 213/1085 (19.6%, 17.4% to 22.1%). A negative attitude to repeat biopsy was associated with unfavourable experience after the first biopsy, particularly pain at biopsy (odds ratio 8.2, P<0.001) and symptoms related to infection (7.9, P<0.001) and bleeding (4.2, P<0.001); differences were evident between centres (P<0.001). 119/1147 (10.4%, 8.7% to 12.3%) men reported consultation with a healthcare professional (usually their general practitioner), most commonly for infective symptoms. Complete data for all index symptoms at all time points were available in 851 participants. Symptoms and healthcare use could be used to grade these men as follows: grade 0 (no symptoms/contact) 18 (2.1%, 1.3% to 3.3%); grade 1 (minor problem/no contact) 550 (64.6%, 61.4% to 67.8%); grade 2 (moderate/major problem or contact) 271 (31.8%, 28.8% to 35.1%); grade 3 (hospital admission) 12 (1.4%, 0.8% to 2.4%); and grade 4 (death) 0. Grade of adverse event was associated with an unfavourable attitude to repeat biopsy (Kendall’s τ-b ordinal by ordinal 0.29, P<0.001). Conclusion This study with a high response rate of 89% at 35 days in men undergoing biopsy in the context of a randomised controlled trial has shown that although prostate biopsy is well tolerated by most men, it is associated with significant symptoms in a minority and affects attitudes to repeat biopsy and primary care resource use. These findings will inform men who seek PSA testing for detection of prostate cancer and assist their physicians during counselling about the potential risks and effect of biopsy. Variability in the adverse event profile between centres suggests that patients’ outcomes could be improved and healthcare use reduced with more effective administration of local anaesthetic and antibiotics. Trial registration Current Controlled Trials ISRCTN20141297.

Suicide and the internet

Recentreports of suicide by young people have highlighted the possible influence of internet sites. Lucy Biddle and colleagues investigate what a web search is likely to find

Latest results from the UK trials evaluating prostate cancer screening and treatment: the CAP and ProtecT studies.

The European Randomised Study of Screening for Prostate Cancer (ERSPC) demonstrated a significant reduction in prostate cancer-specific mortality. The ongoing Comparison Arm for ProtecT (CAP) cluster randomised controlled trial (RCT) evaluates prostate cancer screening effectiveness by comparing primary care centres allocated to a round of prostate specific antigen (PSA) testing (intervention) or standard clinical care. Over 550 centres (around 450,000 men) were randomised in eight United Kingdom areas (2002-2008). Intervention group participants were also eligible for the ProtecT (Prostate testing for cancer and Treatment) RCT evaluating active monitoring, radiotherapy and radical prostatectomy treatments for localised prostate cancer. In ProtecT, over 1500 of around 3000 men with prostate cancer were randomised from over 10,000 with an elevated PSA in around 111,000 attendees at clinics. Investigation of the psychological impact of screening in a sub-sample showed that 10% of men still experienced high distress up to 3 months following prostate biopsies (22/227), although most were relatively unaffected. The risk of prostate cancer with a raised PSA was lower if urinary symptoms were present (frequent nocturia odds ratio (OR) 0.44, 95% confidence interval (CI) 0.22-0.83) or if a repeat PSA decreased by > or = 20% prior to biopsy (OR 0.43, 95% CI 0.35-0.52). Men aged 45-49 years attended PSA clinics less frequently (442/1299, 34%) in a nested cohort with a cancer detection rate of 2.3% (10/442). The CAP and ProtecT trials (ISRCTN92187251 and ISRCTN20141217) will help resolve the prostate cancer screening debate, define the optimum treatment for localised disease and generate evidence to improve mens health.

Tales of biographical disintegration: how parents make sense of their sons' suicides

Suicide research relies heavily on accounts provided by bereaved relatives, using a method known as the psychological autopsy. Psychological autopsy studies are invariably quantitative in design and their findings reinforce the medical model of suicide, emphasising the role of mental illness. They largely ignore the meanings that narrators attach to events, the nature of the sense-making task and the influences bearing upon it. This study drew on psychological autopsy data but used qualitative analytic methods. Fourteen semi-structured interviews with the parents of young men aged 18-30 who had taken their own lives form the basis for this paper. Some parents represent their sons as victims who were cruelly destroyed by external forces, while others portray them as agents of their own destruction. Either way, their narratives are dominated by moral rather than medical categories and by questions of personal accountability. We show how the parents use the interview to perform a complex reconstructive task, striving to piece together both their sons and their own shattered biographies and repair damage to their moral identities. We argue that their stories represent survival tools, enabling them not only to make sense of the past but also to face their own future.

Hospital admissions for self harm after discharge from psychiatric inpatient care: cohort study

Objective To determine the risk of non-fatal self harm in the 12 months after discharge from psychiatric inpatient care. Design Cohort study based on national hospital episode statistics. Setting England. Population Patients aged 16-64 years discharged from psychiatric inpatient care between 1 April 2004 and 31 March 2005 and followed up for one year. Results 75 401 people were discharged from psychiatric inpatient care over the study period, 4935 (6.5%) of whom were admitted at least once for self harm in the following 12 months. Risk of self harm was greatest in the four weeks after discharge; one third (32%, n=1578) of admissions for self harm occurred in this period. The strongest risk factor for self harm after discharge was admission for self harm in the previous 12 months (hazard ratio 4.9, 95% confidence interval 4.6 to 5.2). The risk of self harm was also higher in females, younger people, those with diagnoses of depression, personality disorders, and substance misuse, and those with short lengths of stay. Conclusion More than 6% of patients discharged from psychiatric inpatient care are readmitted for an episode of self harm within 12 months, with one third of these episodes occurring in the month after discharge. Self harm after discharge from hospital shares many of the features of suicide after discharge. Interventions should be developed to reduce risk in this period.

Symptom recognition and help seeking for depression in young adults: a vignette study

PurposeMany young people with psychological problems do not seek help. Recognition of problems and knowledge of appropriate sources of help may increase the likelihood of help seeking. This study aimed to explore whether young adults recognised depressive symptoms in a vignette, and how they thought a young person might respond to these symptoms.MethodsA postal survey was sent to 3,004 young people aged 16–24 in SW England. The survey included a two-part vignette; the first part depicted mild depressive symptoms, and the second part depicted severe depressive symptoms. Open-ended questions exploring symptom recognition and illness behaviour were answered by 1,125 respondents.ResultsSevere depressive symptoms were recognised by 61.4% of respondents. Young men, particularly those from deprived backgrounds were less likely than women to recognise a mental health problem. Men were also less likely to suggest seeing a doctor than women. 64.7% of the respondents who recognised a mental health problem suggested seeing a doctor, however, only 16.4% thought a severely depressed person actually would see a doctor.ConclusionsWhilst the majority of young people recognised symptoms of severe depression, the gap between perceived options for help and proposed help seeking behaviour is clinically relevant. The sociodemographic groups at greatest risk of suicide are the least likely to recognise depression, highlighting a need to develop interventions targeting men, particularly those from deprived backgrounds.

Do the risk factors of age, family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50-69 years with a PSA result of >3ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p<0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p=0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p=0.68), or between those with a raised PSA of 10-<20ng/ml compared to a PSA result of 3-<10ng/ml (p=0.46). Change in scores since the initial PSA test appeared unaffected by family history (p=0.995) or by PSA result (p=0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on mens anxiety level when proceeding to biopsy.

Detection of prostate cancer in unselected young men: prospective cohort nested within a randomised controlled trial

Objective To investigate the feasibility of testing for prostate cancer and the prevalence and characteristics of the disease in unselected young men. Design Prospective cohort nested within a randomised controlled trial, with two years of follow-up. Setting Eight general practices in a UK city. Participants 1299 unselected men aged 45-49. Intervention Prostate biopsies for participants with a prostate specific antigen level of 1.5 ng/ml or more and the possibility of randomisation to three treatments for those with localised prostate cancer. Main outcome measures Uptake of testing for prostate specific antigen; positive predictive value of prostate specific antigen; and prevalence of prostate cancer, TNM disease stage, and histological grade (Gleason score). Results 442 of 1299 men agreed to be tested for prostate specific antigen (34%) and 54 (12%) had a raised level. The positive predictive value for prostate specific antigen was 21.3%. Ten cases of prostate cancer were detected (2.3%) with eight having at least two positive results in biopsy cores and three showing perineural invasion. One tumour was of high volume (cT2c), Gleason score 7, with a positive result on digital rectal examination; nine tumours were cT1c, Gleason score 6, and eight had a negative result on digital rectal examination. Five of the nine eligible participants (55%) agreed to be randomised. No biochemical disease progression in the form of a rising prostate specific antigen level occurred in two years of follow-up. Conclusions Men younger than 50 will accept testing for prostate cancer but at a much lower rate than older men. Using an age based threshold of 1.5 ng/ml, the prevalence of prostate cancer was similar to that in older men (3.0 ng/ml threshold) and some cancers of potential clinical significance were found. Trial registration Current Controlled Trials ISRCTN20141297

Ethics of clinical trials from bayesian perspective: randomisation to clinical trials may solve dilemma of treatment choice in prostate cancer.

EDITOR—Lilford uses the example of the ProtecT study to raise concerns about recruitment to clinical trials, taking quotations out of context from Donovan et al.1 2 Lilford asserts that in this study men are simply told that the best treatment for localised prostate cancer is “uncertain” that they are not given enough information or time to question the recruiter about essential details about treatments and side effects; and that …