Prostate Biopsies Can Be Omitted in Most Patients with a Positive Stockholm3 Test and Negative Prostate Magnetic Resonance Imaging.

BACKGROUND: Magnetic resonance imaging (MRI) combined with the Stockholm3 test can be used to inform biopsy decision-making in patients with a suspicion of prostate cancer. OBJECTIVE: To determine the consequence of omitting biopsies in men with a positive Stockholm3 test and a negative MRI. DESIGN, SETTING, AND PARTICIPANTS: In a real-life setting, 438 men with a positive Stockholm3 test and a negative MRI underwent systematic biopsies from 2017 to 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Stockholm3 test result is a percentage risk score with or without a prostate volume cutoff. The main outcomes were the number of clinically significant (Gleason grade group [GG] ≥2) and nonsignificant (GG 1) prostate cancers. RESULTS AND LIMITATIONS: Median prostate-specific antigen was 4.5 ng/ml (interquartile range 2.8-6.4 ng/ml) and the median age was 69 yr. Systematic biopsies detected grade group (GG) ≥2 disease in 48 men (11%, 95% confidence interval [CI] 8.4-14.2%) and GG 1 disease in 94 men (21.5%, 95% CI 17.9-25.6%). Of 256 patients without a volume cutoff in the test report, GG ≥2 was detected in 37 men (14.5%, 95% CI 10.7-19.3%). Omitting biopsies in patients with a volume cutoff would miss 11 GG ≥2 cases (6%, 95% CI 3.4-10.5%), reduce the number of GG 1 cases detected by 37 (39.4%, 95% CI 30.1-49.5%), and avoid a total of 182 biopsies (41.6%, 95% CI 37.0-46.2%). Limitations include the lack of follow-up data. CONCLUSIONS: Systematic biopsies can be omitted in patients with a positive Stockholm3 test and a negative MRI when there is a volume cutoff in the test report. With no volume cutoff, biopsies can be considered with shared decision-making. PATIENT SUMMARY: When investigated on suspicion of prostate cancer with a positive Stockholm3 test and a negative MRI (magnetic resonance imaging), prostate biopsies are only necessary for a subgroup of patients. This can spare some men from undergoing biopsies and reduce the detection of clinically insignificant cancers.

Prostate Age Gap: An MRI Surrogate Marker of Aging for Prostate Cancer Detection.

BACKGROUND: Aging is the most important risk factor for prostate cancer (PC). Imaging techniques can be useful to measure age-related changes associated with the transition to diverse pathological states. However, biomarkers of aging from prostate magnetic resonance imaging (MRI) remain to be explored. PURPOSE: To develop an aging biomarker from prostate MRI and to examine its relationship with clinically significant PC (csPC, Gleason score ≥7) risk occurrence. STUDY TYPE: Retrospective. POPULATION: Four hundred and sixty-eight (65.97 ± 6.91 years) biopsied males, contributing 7243 prostate MRI slices. A deep learning (DL) model was trained on 3223 MRI slices from 81 low-grade PC (Gleason score ≤6) and 131 negative patients, defined as non-csPC. The model was tested on 90 negative, 52 low-grade (142 non-csPC), and 114 csPC patients. FIELD STRENGTH/SEQUENCE: 3-T, axial T2-weighted spin sequence. ASSESSMENT: Chronological age was defined as the age of the participant at the time of the visit. Prostate-specific antigen (PSA), prostate volume, Gleason, and Prostate Imaging-Reporting and Data System (PI-RADS) scores were also obtained. Manually annotated prostate masks were used to crop the MRI slices, and a DL model was trained with those from non-csPC patients to estimate the age of the patients. Following, we obtained the prostate age gap (PAG) on previously unseen csPC and non-csPC cropped MRI exams. PAG was defined as the estimated model age minus the patient's age. Finally, the relationship between PAG and csPC risk occurrence was assessed through an adjusted multivariate logistic regression by PSA levels, age, prostate volume, and PI-RADS ≥ 3 score. STATISTICAL TESTS: T-test, Mann-Whitney U test, permutation test, receiver operating characteristics (ROC), area under the curve (AUC), and odds ratio (OR). A P value <0.05 was considered statistically significant. RESULTS: After adjusting, there was a significant difference in the odds of csPC (OR = 3.78, 95% confidence interval [CI]: 2.32-6.16). Further, PAG showed a significantly larger bootstrapped AUC to discriminate between csPC and non-csPC than that of adjusted PI-RADS ≥ 3 (AUC = 0.981, 95% CI: 0.975-0.987). DATA CONCLUSION: PAG may be associated with the risk of csPC and could outperform other PC risk factors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Algorithms for early detection of silent liver fibrosis in the primary care setting - a scoping review.

INTRODUCTION: Fatty liver disease affects almost 30% of the adult population worldwide. Most patients are asymptomatic, and there is not a linear relationship between exposure to risk factors and the risk of developing fibrosis. The combination of a very large, asymptomatic risk population where only a few percent will develop life-threatening liver disease is a growing diagnostic challenge for the health services. Accurate fibrosis assessment in primary care is limited by poor correlation with liver blood tests and low availability of elastography. Non-invasive tests are promising tools, but little is known about their diagnostic accuracy in low-risk populations. AREAS COVERED: A scoping review was conducted to identify articles that focused on the current use of biomarkers and algorithms in primary care for the detection of patients with fatty liver disease in need of referral for further work-up. EXPERT OPINION: Currently available algorithms for targeted screening for liver fibrosis perform better than the individual routine liver blood tests or liver ultrasonography. However, primary care physicians urgently need algorithms with even higher diagnostic accuracies than what is available today. The main limitation of the existing widely accessible algorithms, such as the FIB-4, is the large number of false-positive tests, resulting in overdiagnosis and futile referrals to secondary care.

Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology.

Introduction: Plasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations. Methods: Plasma samples from 13 participants were stored at +4°C and +18°C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays. Results: Phosphorylated tau 181 (p-tau181), phosphorylated tau 231 (p-tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4°C and +18°C. Amyloid-ß 40 (Aß40) and amyloid-ß 42 (Aß42) concentrations were stable for 24 h at +4°C but declined when stored at +18°C for longer than 6 h. This decline did not affect the Aß42/Aß40 ratio. Discussion: Plasma samples can be stored for 24 h at +4°C or +18°C and result in valid assay results for p-tau181, p-tau231, Aß42/Aß40 ratio, GFAP, and NfL. HIGHLIGHTS: Plasma samples were stored for 24 h at +4°C and +18°C, mimicking clinical practice.Concentrations for Alzheimer's disease biomarkers were measured at six time-points.p-tau181, p-tau231, NfL, and GFAP concentrations were unchanged during the experiment.Storage at +18°C affected Aß40 and Aß42 concentrations while storage at +4°C did not. The Aß42/Aß40 ratio was unaffected.These plasma tests seem suitable for use in general practice.

Men's perception of information and psychological distress in the diagnostic phase of prostate cancer: a comparative mixed methods study.

BACKGROUND: Previous studies indicate that men experience frustration and uncertainty when confronted with an elevated prostate specific antigen (PSA) test and during further diagnostics for prostate cancer. The novel Stockholm3 test is an algorithm-based test that combines plasma protein biomarkers, genetic markers and clinical variables in predicting the risk of PCa. The test was introduced in a western part of Norway as a new tool for detecting prostate cancer. This study aimed to explore and compare men's perception of information and possible experience of distress between a PSA group and a Stockholm3 group during the diagnostic phase of prostate cancer. METHODS: This study is a part of the trailing research evaluating the impact of the change from PSA to Stockholm3. It is a multicenter study using a comparative mixed method design. Data were collected in a PSA group (n = 130) and a Stockholm3 group (n = 120) between 2017 and 2019. Quantitative data were collected using questionnaires and qualitative data were collected using semi-structured interviews (n = 20). The quantitative and qualitative data were analysed and compared separately and then merged in a side-by-side discussion. The study adheres to the GRAMMS guidelines for reporting mixed-methods research. RESULTS: Compared with the PSA group, men in the Stockholm3 group reported that the information from the general practitioners was better. Similarly, men in the Stockholm3 group were more likely to indicate that they had received sufficient information regarding how examinations would be conducted. No differences were found between the groups regarding waiting time and distress. Three themes emerged from the qualitative analysis of the two groups: "Information affects the experience of comprehension", "Stepping into the world of the healthcare system", and "Periodically feelings of distress". CONCLUSION: The Stockholm3 test may facilitate the provision of information to patients. However, some patients in both groups experienced distress and would benefit from more information and additional support from healthcare professionals. Routines that ensure sufficient information from the interdisciplinary healthcare team should be of priority during the diagnostic phase of prostate cancer in order to provide patients with predictability and to avoid unnecessary distress.

General practitioners' reflections on using PSA for diagnosis of prostate cancer. A qualitative study.

OBJECTIVE: To investigate how GPs use the PSA test as a diagnostic tool in daily practice. DESIGN: Qualitative study using focus group interviews, the transcripts being analyzed by systemic text condensation. SUBJECTS: A total of 17 Norwegian GPs in three CME groups. MAIN OUTCOME MEASURES: Exploring GPs' attitudes to national guidelines and the practical use of the PSA test. RESULTS: Detecting prostate cancer in general practice is a common and important, but difficult diagnostic issue. Our participants experienced uncertainty regarding the test when to use it, how to interpret the results and when to refer to specialist health services. CONCLUSION: The study revealed a general ambivalence to the use of PSA. Many patients present urological problems, and many are afraid of having cancer. PSA is commonly used, but sometimes generates problems rather than solving them. IMPLICATIONS: The use of the PSA test should be based on a thorough clinical assessment and in close collaboration with the patient.Key pointsMany patients in general practice present urological problems, and many are afraid of having cancer.GPs have a general ambivalence to the use of PSA when to use it, how to interpret the results and when to refer to specialist health services.The use of PSA sometimes generates problems rather than solving them.

Post-vaccination aluminium granulomas in children. / Aluminiumsgranulomer etter barnevaksinasjon.

BACKGROUND: Persistent itching subcutaneous granulomas related to aluminium-containing vaccines are poorly recognised in health care. They are often associated with aluminium hypersensitivity. CASE PRESENTATION: An intensely itching subcutaneous nodule appeared on the left thigh of a 17-month-old girl at the injection site for an aluminium adsorbed diphtheria-tetanus-pertussis-polio-HiB vaccine given at 3, 5 and 12 months. Ultrasound suggested a vascular malformation among other differential diagnoses. An MR investigation under general anaesthesia was planned, but the diagnosis was confirmed prior to this by a positive epicutaneous test with aluminium. INTERPRETATION: Despite a typical history of an itchy vaccination granuloma, the child underwent a thorough hospital workup to rule out malignancy. The diagnosis was delayed for two years. Vaccination granulomas have a good prognosis but can persist for many years. It is important to recognise the condition early in primary health care to avoid unnecessary anxiety and investigations.

Men's perception of information and descriptions of emotional strain in the diagnostic phase of prostate cancer-a qualitative individual interview study.

OBJECTIVE: To explore men`s perception of information and their possible emotional strain in the diagnostic phase of prostate cancer. DESIGN, SETTING, PATIENTS: A qualitative explorative research design was employed. Data were collected from June to November 2017. The study was set at a urological outpatient clinic at a university hospital in Norway. Semi-structured interviews were conducted with ten men who had been examined for prostate cancer. Interviews were analyzed using Systematic Text Condensation (STC). RESULTS: The analysis revealed three themes. The theme 'Different needs and perceptions of information' illustrated that information should be personalized. Despite different information needs, insufficient information about prostate cancer may prevent some men from being involved in decisions. The theme, 'A discovery of not being alone', indicated that a sense of affinity occurs when men realize the commonality of prostate cancer. Some men benefited from other men's experiences and knowledge about prostate cancer. The last theme 'Worries about cancer and mortality' showed that the emotional strain was affected by men's knowledge of cancer and the received information. Men expressed conflicting feelings toward prostate cancer that could be difficult to express. CONCLUSIONS: The findings indicate that men in the diagnostic phase of prostate cancer are not a homogeneous group, but need personalized information. Some men may benefit from other men's experiences and support. Men's emotional strain can affect their communication about prostate cancer, which should be acknowledged. Procedures that identify patients' information needs early on should be an integrated part of the diagnostic phase of prostate cancer.KEY POINTSKnowledge about men's information needs and possible emotional strain in the diagnostic phase of prostate cancer are limited.Men with suspected prostate cancer have different preferences and information needs; however, insufficient information prevents men from participating in decisions.Men experience a sense of affinity with other men affected by prostate cancer, and some men benefit from exchanging experiences.Men consider prostate cancer as a less aggressive type of cancer but may experience emotional strain.

Supportive care needs of men with prostate cancer after hospital discharge: multi-stakeholder perspectives.

PURPOSE: This study explored the supportive care needs of men with prostate cancer (PCa) after hospital discharge based on the perceptions of multiple stakeholders. METHODS: Eight semi-structured focus groups and three individual interviews were conducted between September 2019 and January 2020, with 34 participants representing men with PCa, primary and secondary healthcare professionals, and cancer organizations in western Norway. Data was analysed using systematic text condensation. RESULTS: Four categories emerged: 1) men with PCa have many information needs which should be optimally provided throughout the cancer care process; 2) various coordination efforts among stakeholders are needed to support men with PCa during follow-up; 3) supportive care resources supplement the healthcare services but knowledge about them is random; and 4) structured healthcare processes are needed to improve the services offered to men with PCa. Variations were described regarding priority, optimal mode and timeliness of supportive care needs, while alignment was concerned with establishing structures within and between stakeholders to improve patient care and coordination. CONCLUSIONS: Despite alignment among stakeholders' regarding the necessity for standardization of information and coordination practices, the mixed prioritization of supportive care needs of men with PCa indicate the need for additional individualized and adapted measures.

Effects of replacing PSA with Stockholm3 for diagnosis of clinically significant prostate cancer in a healthcare system - the Stavanger experience.

OBJECTIVE: To describe early experience of replacing PSA with Stockholm3 for detection of prostate cancer in primary care. DESIGN AND METHODS: Longitudinal observations, comparing outcome measures before and after the implementation of Stockholm3. SETTING: Stavanger region in Norway with about 370,000 inhabitants, 304 general practitioners (GPs) in 97 primary care clinics, and one hospital. INTERVENTION: GPs were instructed to use Stockholm3 instead of PSA as standard procedure for diagnosis of prostate cancer. MAIN OUTCOME MEASURES: Proportion of GP clinics that had ordered a Stockholm3 test. Number of men referred to needle biopsy. Distribution of clinically significant prostate cancer (csPC) (Gleason Score ≥7) and clinically non-significant prostate cancer (cnsPC) (Gleason Score 6), in needle biopsies. Estimation of direct healthcare costs. RESULTS: Stockholm3 was rapidly implemented as 91% (88/97) of the clinics started to use the test within 14 weeks. After including 4784 tested men, the percentage who would have been referred for prostate needle biopsy was 29.0% (1387/4784) if based on PSA level ≥3ng/ml, and 20.8% (995/4784) if based on Stockholm3 Risk Score (p < 0.000001). The proportion of positive biopsies with csPC increased from 42% (98/233) before to 65% (185/285) after the implementation. Correspondingly, the proportion of cnsPC decreased from 58% (135/233) before to 35% (100/285) after the implementation (p < 0.0017). Direct healthcare costs were estimated to be reduced by 23-28% per tested man. CONCLUSION: Replacing PSA with Stockholm3 for early detection of prostate cancer in primary care is feasible. Implementation of Stockholm3 resulted in reduced number of referrals for needle-biopsy and a higher proportion of clinically significant prostate cancer findings in performed biopsies. Direct healthcare costs decreased. KEY POINTS A change from PSA to Stockholm3 for the diagnosis of prostate cancer in primary care in the Stavanger region in Norway is described and assessed. •Implementation of a new blood-based test for prostate cancer detection in primary care was feasible. A majority of GP clinics started to use the test within three months. •Implementation of the Stockholm3 test was followed by: -a 28% reduction in number of men referred for urological prostate cancer work-up -an increase in the proportion of clinically significant cancer in performed prostate biopsies from 42 to 65% -an estimated reduction in direct health care costs between 23 and 28%.

Risk of Hospitalization in Patients with Alzheimer's Disease and Lewy Body Dementia: Time to and Length of Stay.

BACKGROUND: Patients with dementia are at high risk of being hospitalized, but there is little knowledge whether this applies to all forms of dementia. OBJECTIVE: To investigate if there are differences in hospitalization between patients with Alzheimer's disease (AD) and Lewy body dementia (LBD), and further, to compare admission rate with the general age-matched population. METHODS: Patients (age 75.7±7.4) recently diagnosed with mild form of AD (n = 110) or LBD (n = 91) were included from outpatient clinics. The participants were followed from time of diagnosis, for five years or until death. Study outcomes were time to first hospitalization after diagnosis, number of admissions, total number of hospital days, and length of stay. Age-standardized admission ratios were calculated. Time to first admission was analyzed using competing risks regression models, and differences in number of hospitalizations and hospital days were addressed using negative binomial regression models. RESULTS: More than 77% of the patients were admitted, largely as unplanned hospitalizations. Patients with LBD had significantly shorter time until first hospitalization (median 1.28 years, 95% CI 0.93-1.67 versus AD: 2.32 years, 95% CI 1.74-3.31) and more days in hospital (median 13 days, IQR 4, 38), than patients with AD (7 days, IQR 0, 18). CONCLUSION: Our data indicates that patients with LBD have shorter time until first admission and higher admission rate than AD patients. This imposes a great burden on patients, their family, and the health care system. More knowledge about hospital admissions of people with dementia is needed. Future studies should investigate strategies to avoid potentially preventable admissions.

Average duration of treatment with antipsychotics among concession card holders in Australia.

OBJECTIVE: To analyse average treatment duration with antipsychotics reimbursed for concession card holders under the Pharmaceutical Benefits Scheme; the proportion of initial prescribing by general practitioners, psychiatrists and other physician; and the trend in drug choice in Australia. METHOD: Based on a representative 10% sample of patients receiving Pharmaceutical Benefits Scheme prescriptions since 2005, antipsychotics redeemed by concession card holders in the period from 2010 to 2013 were analysed. A 5-year baseline period was used to exclude prevalent users from incident users. Treatment duration was estimated using the epidemiological equation: prevalence/incidence = average duration. RESULTS: The overall average treatment duration was 3.0 years, ranging from 1.5 years in patients aged 75 years and older to more than 4 years among patients aged 25-64 years. The most commonly used antipsychotics were olanzapine, risperidone and quetiapine, with average duration of 2.9, 2.1 and 1.7 years, respectively. Amisulpride was used longest with an average duration of 3.7 years. Quetiapine is currently the most prescribed antipsychotic and the main antipsychotic prescribed by psychiatrists to new users. The increased prescribing of quetiapine among general practitioners explains the rapid increase in the overall use of quetiapine. General practitioners initiated therapy in about 70% of cases, while psychiatrists and other physicians in about 15% each. In children younger than 15 years of age, paediatricians initiated such treatment in 47%. CONCLUSION: General practitioners both initiate and maintain treatment with antipsychotics for most adults, while paediatricians mainly begin such treatment in children. The substantial increase in use of quetiapine among general practitioners, along with the short treatment duration for quetiapine, strengthens a concern about antipsychotics increasingly used for less severe disorders. Increased collaboration between paediatricians and psychiatrists regarding the youngest and between general practitioners and psychiatrists or geriatricians regarding adults and older patients seems required.

Potentially inappropriate medications and drug-drug interactions in home-dwelling people with mild dementia.

OBJECTIVES: The objectives of this study were to describe the use of psychotropic drugs among home-dwelling people with mild dementia, to identify potentially inappropriate medications (PIM) and drug-drug interactions (DDI), and to analyze potential variables associated with having PIM and DDI. METHODS: Patients (n = 251) with a first-time diagnosis of mild dementia (defined as a mini-mental state examination score >20) were included from outpatient clinics. Prevalence of psychotropic drug use, polypharmacy, and psychotropic polypharmacy were investigated. The prevalence of PIM and DDI were defined using the Norwegian general practice criteria and an interactions database, respectively. Variables associated with having PIM and DDI were assessed using a multivariable logistic regression analysis adjusting for relevant demographic and clinical variables. RESULTS: Almost 96% of the patients used one or more medications. Polypharmacy was found in 45% of the patients, and nearly 70% of the patients were using one or more psychotropic drugs. Psychotropic polypharmacy was found in seven patients. PIM were identified in 35 patients (14%), while only four severe DDI were found. Female sex and number of medications were significantly associated with having PIM, whereas only number of medications was significantly associated with having DDI. CONCLUSION: Few patients had PIM or severe DDI, indicating that the quality of prescribing was acceptable. However, psychotropic drug use was common in home-dwelling people with mild dementia despite limited evidence of benefit in dementia. More knowledge is needed about the potential risks associated with psychotropic drug use and having PIM and DDI in people with mild dementia. Copyright © 2016 John Wiley & Sons, Ltd.