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.

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.

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.

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.

Use of addictive anxiolytics and hypnotics in a national cohort of incident users in Norway.

PURPOSE: To examine (1) incidence rates for treatment with addictive anxiolytics and hypnotics in Norway, (2) the proportions initiated by general practitioners (GPs), psychiatrists, and other physicians, and (3) the course of the treatment among incident users during a 3.5 year follow-up period. METHOD: Data on all prescriptions of anxiolytics (ATC code N05B) and hypnotics (N05C) dispensed to the general population from 1 January 2004 to 31 August 2009 were extracted from the Norwegian Prescription Database and merged with data about GPs from the Norwegian Regular General Practitioner Scheme. RESULTS: One-year incidence rates per 1,000 inhabitants were 18.2 for anxiolytics, 24.5 for hypnotics, and 35.4 for anxiolytics and hypnotics combined. GPs and psychiatrists initiated the treatment to 75.4 and 2.4%, respectively. Only 30.8% received short-term treatment as recommended. Long-term use (11.8%) and heavy use (1.4%) were most common for treatments initiated by a GP, but the risk both of long-term and of heavy use was highest for patients initially treated by a psychiatrist. The amount redeemed during the first quarter was the strongest predictor of long-term use and of heavy use. However, even during the quarter with highest drug consumption, 81.5% of the patients received <1 DDD/day. CONCLUSIONS: This study indicates that physicians' prescribing strategy towards initial users is crucial in order to prevent inappropriate drug use. There is a need to implement relevant guidelines and systems for structured clinical audits in general practice.

Psychotropic drug use in the Norwegian general population in 2005: data from the Norwegian Prescription Database.

PURPOSE: To analyse psychotropic drug utilisation patterns in the general population of Norway in 2005. METHODS: Data on 4,163,045 prescriptions of psychotropic drugs dispensed at all pharmacies in Norway during 2005 were extracted from The Norwegian Prescription Database (NorPD), including antipsychotics (ATC-code N05A), anxiolytics (N05B), hypnotics (N05C) and antidepressants (N06A). This information was merged with data concerning the 3857 general practitioners (GPs) from the Norwegian Regular GP Scheme. RESULTS: A total of 705,230 individuals, or 15.3% of the general population, received at least one prescription of a psychotropic drug. The figures for the four therapeutic subgroups were 2.4% for antipsychotics, 6.2% for anxiolytics, 7.9% for hypnotics and 6.0% for antidepressants, respectively. For all subgroups, prevalence was higher among women than among men, and increased steadily by patients' age. The mean annual drug volume per patient was highest among persons aged 40-59 years, except for hypnotics where it continued to increase with age. GPs prescribed 80% of overall psychotropic drug volume, psychiatrists 5%, and other prescribers 15%. The proportion of the drugs issued by the three prescriber groups differed with the patients' age group. While children and adolescents received a relatively large share from paediatricians and child and adolescent psychiatrists, adults mostly got their prescriptions from GPs. CONCLUSIONS: The majority of psychotropic drugs were prescribed by GPs. Overall drug use increased significantly, and psychiatrists' contribution decreased significantly with patients' age. The quality of pharmacological treatment for mental health problems of the general and aging population therefore relies mainly on the GPs.