Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

Prevalence of prostate cancer in men with haematuria: a systematic review and meta-analysis.

OBJECTIVES: To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed. METHODS: The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer. RESULTS: We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0-4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9-9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8-2.2%; n = 71/6642). CONCLUSION: Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria.

Remembering sentences is not all about memory: Convergent and discriminant validity of syntactic knowledge and its relationship with reading comprehension.

Recent studies have found correlations between sentence-level tests and reading comprehension. However, the task demands of sentence-level tests are not well understood. The present study investigated syntactic knowledge as a construct by examining the convergent and discriminant validity of two sentence-level tasks, sentence comprehension and sentence repetition, designed to test syntactic knowledge and their relation with reading comprehension. Results from 86 Grade 6 students showed that the syntax tests were more highly correlated with each other than with tests of working memory and vocabulary. This suggests that the syntax measures tap into a set of skills that are at least partially separate from these other cognitive constructs. Furthermore, syntactic knowledge explained unique variance in reading comprehension beyond controls. The syntax tasks were working memory dependent, but working memory was not the primary reason why syntax tasks are correlated with reading comprehension.

Face recognition in developmental dyslexia: evidence for dissociation between faces and words.

Developmental dyslexia is primarily a reading disorder, but recent studies have indicated that face processing problems may also be present. Using a case-series approach, we tested face recognition and visual word recognition in 24 high school students diagnosed with developmental dyslexia. Contrary to previous findings, no face recognition problems were found on the group-level. Rather, a significant classical dissociation with impaired word reading and normal face recognition was demonstrated on a group-level and for six individuals with developmental dyslexia. However, four individuals with dyslexia did show face recognition problems. Thus, while problems in face recognition can be present in developmental dyslexia, the dissociation strongly suggests that face recognition can also be preserved. Combined with previously reported dissociations between face and word recognition in developmental prosopagnosia, this constitutes a double dissociation.

Community-based football in men with prostate cancer: 1-year follow-up on a pragmatic, multicentre randomised controlled trial.

BACKGROUND: Physical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted. METHODS AND FINDINGS: We conducted a pragmatic, multicentre, parallel randomised controlled trial in 5 Danish urological departments. Recruitment began in May 2015, the first participant was randomised in June 2015, and the last participant was included in February 2017. In total, 214 men with prostate cancer were randomly assigned to either 6 months of free-of-charge football training twice weekly at a local club (football group [FG]) (n = 109) or usual care (usual care group [UG]) (n = 105), including brief information on physical activity recommendations at randomisation. Participants were on average 68.4 (SD 6.2) years old, 157 (73%) were retired, 87 (41%) were on castration-based treatment, 19 (9%) had received chemotherapy, and 41 (19%) had skeletal metastases at baseline. In this 1-year follow-up study, we evaluated the effects of community-based football training on the following outcomes: primary outcome, quality of life; secondary outcomes: continuation of football after 6 months, hip and lumbar spine bone mineral density (BMD), mental health score, fat and lean body mass, and safety outcomes, i.e., fractures, falls, and hospital admissions. Intention to treat (ITT) and per protocol (PP) analyses were conducted. No statistically significant between-group difference was observed in change in prostate-cancer-specific quality of life (ITT: 1.9 points [95% CI -1.9 to 5.8], p = 0.325; PP: 3.6 points [95% CI -0.9 to 8.2], p = 0.119). A statistically significant between-group difference was observed in change in total hip BMD, in favour of FG (0.007 g/cm2 [95% CI 0.004 to 0.013], p = 0.037). No differences were observed in change in lumbar spine BMD or lean body mass. Among patients allocated to football, 59% chose to continue playing football after the end of the 6-month intervention period. At 1-year follow-up in the PP population, FG participants had more improvement on the Mental Component Summary (2.9 [95% CI 0.0 to 5.7], p = 0.048 points higher) than UG participants, as well as a greater loss of fat mass (-0.9 kg [95% CI -1.7 to -0.1], p = 0.029). There were no differences between groups in relation to fractures or falls. Hospital admissions were more frequent in UG compared to FG (33 versus 20; the odds ratio based on PP analysis was 0.34 for FG compared to UG). There were 3 deaths in FG and 4 in UG. Main limitations of the study were the physically active control group and assessment of physical activity by means of self-report. CONCLUSIONS: In this trial, participants allocated to football appeared to have improved hip BMD and fewer hospital admissions. Men who played football more than once a week for 1 year lost fat mass and reported improved mental health. Community-based football proved to be acceptable, even when club membership was not subsidised. TRIAL REGISTRATION: ClinicalTrials.gov NCT02430792.

The short- and long-term predictions of reading accuracy and speed from paired-associate learning.

Cross-sectional studies have established that performance on paired-associate learning (PAL) tasks is associated with reading performance. There are good reasons to expect such a relationship because learning to read involves learning the sounds of individual letters and possibly also sounds of strings of letters (e.g., spelling patterns). However, results from longitudinal studies have been mixed. A closer look at these studies suggests that PAL may be related to development of accuracy rather than speed in reading. This suggestion was investigated directly in the current longitudinal study. The study followed 137 students from Grade 0 (kindergarten) to Grade 5. In Grade 0, they completed measures of PAL, letter knowledge, phoneme awareness, and rapid automatized naming (RAN). In Grades 1 and 5, decoding accuracy was measured with the addition of decoding speed in Grade 5. PAL in Grade 0 was found to be a unique predictor of decoding accuracy in Grades 1 and 5 after controlling for Grade 0 letter knowledge, phoneme awareness, and RAN. PAL in Grade 0 even contributed to Grade 5 decoding accuracy after also controlling for Grade 1 decoding. Zero-order correlations between PAL and Grade 5 decoding speed were nonsignificant and close to zero. The results indicate that PAL measures a trait that may influence reading development over a substantial amount of time. Possible roles of PAL in decoding development over time are discussed, for example, how verbal learning may be a core component in the acquisition of associations between letter patterns (spelling patterns) and their pronunciation.

Early Identification of Reading Difficulties: A Screening Strategy that Adjusts the Sensitivity to the Level of Prediction Accuracy.

Early screening for reading difficulties before the onset of instruction is desirable because it allows intervention that is targeted at prevention rather than remediation of reading difficulties. However, early screening may be too inaccurate to effectively allocate resources to those who need them. The present study compared the accuracy of early screening before the onset of formal reading instruction with late screening six months into the first year of instruction. The study followed 164 Danish students from the end of Grade 0 to the end of Grade 2. Early screening included measures of phonemic awareness, rapid naming, letter knowledge, paired associate learning, and reading. Late screening included only reading. Results indicated that reading measures improved substantially as predictors over the first six months of Grade 1, to the point where late reading measures alone provided as much information as the early measures combined. In the light of these results and a less than perfect early screening accuracy, a new strategy for screening is introduced and discussed. The strategy proposes multi-point screening with gradually increasing sensitivity to strike a balance between manageable screening procedures and outcomes and early identification of students who are most likely in need of extra resources. Copyright © 2017 John Wiley & Sons, Ltd.

Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer.

OBJECTIVE: To evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer-specific survival (PCSS). In this retrospective study, we used novel computer-assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M-staged by whole-body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use. PATIENTS AND METHODS: In all, 88 patients with prostate cancer awaiting initiation of androgen-deprivation therapy due to metastases were included. WBS was performed using a two-headed γ-camera. BSI was obtained using the automated platform EXINI bone (EXINI Diagnostics AB, Lund, Sweden). In Cox proportional hazard models, time to castration-resistant prostate cancer (CRPC) and PCSS were modelled as the dependent variables, whereas prostate-specific antigen (PSA) level, Gleason score and BSI were used as explanatory factors. For Kaplan-Meier estimates, BSI groups were dichotomously split into: BSI <1 and BSI ≥1. Discrimination between prognostic models was explored using the concordance index (C-index). RESULTS: The mean (range) age of the patients was 72 (52-92) years, the median (range) PSA level was 73 (4-5 740) ng/mL, the mean (range) Gleason score was 7.7 (2-10), and the mean (range) BSI was 1.0 (0-9.2). During a mean (range) follow-up of 26 (8-49) months, 48 patients became castration resistant and 15 had died; most (13) from prostate cancer. In multivariate analysis including PSA level, Gleason score and BSI, only prediction by BSI was statistically significant. This was true both for time to CRPC (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.22-1.74; C-index increase from 0.49 to 0.69) and for PCSS (HR 1.34, 95% CI 1.07-1.67; C-index increase from 0.76 to 0.95). CONCLUSION: BSI obtained using a novel automated computer-assisted algorithm appears to be a useful predictor of outcome for time to CRPC and PCSS in patients with hormone-sensitive metastatic prostate cancer.

Trends in prostate cancer in elderly in Denmark, 1980-2012.

BACKGOUND: The purpose of the study is to elucidate the epidemiology of elderly patients with prostate cancer in Denmark and identify the differences between younger (<70 years) and elderly (≥70 years) patients. MATERIAL AND METHODS: Prostate cancer was defined as ICD-10 code C61. Data were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry. RESULTS: The average annual number of newly diagnosed prostate cancers in Denmark has risen from 1297 patients in 1980 to 4315 patients in 2012. The prevalence increased consistently in all age groups more than seven-fold in the period, from 3987 patients in 1980 to 28 951 patients in 2012. The cancer-specific mortality in Denmark has slightly increased over the observed period, in coherence with the growth of the population, resulting in unchanged mortality rates, with the exception of the patients above 80 years, where the mortality rates are increased. The one- and five-year relative survival for prostate cancer improved significantly for all age groups over the time period from 1980 to 2012. CONCLUSION: The incidence, prevalence, and survival of elderly prostate cancer patients has increased over the observed period but with unchanged mortality rates, except in patients above 80 years, where the mortality rates were increasing.

Cue conflicts in context: interplay between morphosyntax and discourse context in Danish preschoolers' semantic role assignment.

When learning their first language, children develop strategies for assigning semantic roles to sentence structures, depending on morphosyntactic cues such as case and word order. Traditionally, comprehension experiments have presented transitive clauses in isolation, and cross-linguistically children have been found to misinterpret object-first constructions by following a word-order strategy (Chan, Lieven & Tomasello, 2009; Dittmar, Abbot-Smith, Lieven & Tomasello, 2008; Hakuta, 1982; McDonald, 1989; Slobin & Bever, 1982). In an act-out study, we replicated this finding with Danish preschoolers. However, object-first clauses may be context-sensitive structures, which are infelicitous in isolation. In a second act-out study we presented OVS clauses in supportive and unsupportive discourse contexts and in isolation and found that five- to six-year-olds' OVS comprehension was enhanced in discourse-pragmatically felicitous contexts. Our results extend previous findings of preschoolers' sensitivity to discourse-contextual cues in sentence comprehension (Hurewitz, 2001; Song & Fisher, 2005) to the basic task of assigning agent and patient roles.

Spine metastases in prostate cancer: comparison of technetium-99m-MDP whole-body bone scintigraphy, [(18) F]choline positron emission tomography(PET)/computed tomography (CT) and [(18) F]NaF PET/CT.

OBJECTIVE: To compare the diagnostic accuracy of the following imaging techniques in the detection of spine metastases, using magnetic resonance imaging (MRI) as a reference: whole-body bone scintigraphy (WBS) with technetium-99m-MDP, [18F]-sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and [(18) F]-fluoromethylcholine (FCH) PET/CT. PATIENTS AND METHODS: The study entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with bone metastases, and no history of androgen deprivation. Within 30 days of informed consent, trial scans were performed in random order. Scans were interpreted blindly for the purpose of a lesion-based analysis. The primary target variable was bone lesion (malignant/benign) and the 'gold standard' was MRI. RESULTS: A total of 50 men were recruited between May 2009 and March 2012. Their mean age was 73 years, their median PSA level was 84 ng/mL, and the mean Gleason score of the tumours was 7.7. A total of 46 patients underwent all four scans, while four missed one PET/CT scan. A total of 526 bone lesions were found in the 50 men: 363 malignant and 163 non-malignant according to MRI. Sensitivity, specificity, positive and negative predictive values and accuracy were: WBS: 51, 82, 86, 43 and 61%; NaF-PET/CT: 93, 54, 82, 78 and 81%; and FCH-PET/CT: 85, 91, 95, 75 and 87%, respectively. CONCLUSIONS: We found that FCH-PET/CT and NaF-PET/CT were superior to WBS with regard to detection of prostate cancer bone metastases within the spine. The present results call into question the use of WBS as the method of choice in patients with hormone-naïve prostate cancer.

Context improves comprehension of fronted objects.

Object-initial clauses (OCs) are associated with more processing difficulties than subject-initial clauses (SCs) in a number of languages (e.g. English, German and Finnish), but a supportive context can reduce or neutralize the difference between SCs and OCs with respect to reading times. Still, it is unresolved how context can affect the comprehension of OCs. In the present self-paced reading study of Danish, we therefore investigated both reading times, comprehension accuracy and response times for OCs and SCs. In line with previous studies on word order processing, OCs in an unsupportive context showed longer reading times than SCs, longer response times and a comprehension accuracy as poor as chance level. A manipulation of context showed no effect of reading time, but a supportive context had a stronger facilitating effect on comprehension (response accuracy and response time) for OCs than for SCs.

Evaluation of Botox treatment in patients with chronic scrotal pain: Protocol for a randomized double-blinded control trial.

Background: Chronic scrotal pain is a common condition with a prevalence of 2.5-4.8% in male outpatients. Up to 40% of these patients report depressive symptoms and many feel isolated. Minimal invasive treatment is lacking, while spermatic cord injections of Botox® (BTX) have been proposed to offer long-term pain relief. Study Design: This research protocol comprises a prospective multicentre, randomized, double-blinded clinical trial drawing patients from other urological departments in the region of Southern Denmark. End Points: The primary end point will be reduction in pain evaluated by visual analogue score for pain at 3 months. Secondary end point will be length of effect of BTX injections along with changes in quality of life. Patients and Methods: The study will include 50 patients for randomization to either spermatic cord block with 100 IE BTX or sterile saline. All patients will prior to randomization undergo physical examination and will be asked to fulfil multiple questionnaires regarding pain and impact in daily life, that is, (1) visual analogue score for pain, (2) quality of life (EQ-5D-5L), (3) Chronic Prostatitis Symptom Index (NIH-CPSI), (4) ICD-10 depression questionnaire (MDI), (5) Likert global assessment scale, and (6) International Index of Erectile Function questionnaire. Physical examination and fulfilment of the questionnaires will be repeated multiple times throughout the study period of 12 weeks. After this time point, patients will be unblinded, and the control arm will be given the opportunity of cross-over.

A national test of dyslexia.

Different definitions and tests of dyslexia can cause unfairness and make life difficult for people with dyslexia as well as for the professionals. In 2012, the Danish government decided to support the fight against dyslexia. The government issued a public tender for the development of "a standardized, electronically administered test of dyslexia for use […] from primary Grade 3 and up through all educational levels to 5-year university education." The present paper reports from the development of this National Dyslexia Test. The paper focuses on the definition of dyslexia and the composition, reliability, and validity of the test. Data from the development of the test demonstrate the psychometric properties of the test. Reliability was indicated by a high agreement between the two (computer-administered) measures that are part of the test. External convergent validity was indicated by a high agreement between test results and results from prior practice and by agreement between test results and reading comprehension of educational texts. The paper concludes with a discussion of the practical uses and potential issues with the test since its release in 2015.

Prostate cancer.

This review investigates prostate cancer which with approx. 4,500 new cases annually is the most frequent male cancer, and the incidence is expected to increase due to demographic developments. Prostate cancer can have a natural history without progression to symptomatic or fatal disease, which is why overdiagnosis is one of the disease's biggest challenges. In contrast to potential curable localized clinically significant disease, this is not the case after metastasis. Fortunately, new treatments, and not least combinations thereof, have increased both lifespan and quality of life in these patients significantly.

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP.

INTRODUCTION: The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer. METHODS AND ANALYSIS: Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.We will measure the levels of the three microRNAs in the uCaP model (miR-222-3 p, miR-24-3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies. ETHICS AND DISSEMINATION: This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings. TRIAL REGISTRATION NUMBER: NCT05767307 at clinicaltrials.gov.

Epidemiological description and trajectories of patients with prostate cancer in Denmark: an observational study of 7448 patients.

OBJECTIVE: Identification of patients at high risk of aggressive prostate cancer is a major clinical challenge. With the view of developing artificial intelligence-based methods for identification of these patients, we are constructing a comprehensive clinical database including 7448 prostate cancer (PCa) Danish patients. In this paper we provide an epidemiological description and patients' trajectories of this retrospective observational population, to contribute to the understanding of the characteristics and pathways of PCa patients in Denmark. RESULTS: Individuals receiving a PCa diagnosis during 2008-2014 in Region Southern Denmark were identified, and all diagnoses, operations, investigations, and biochemistry analyses, from 4 years prior, to 5 years after PCa diagnosis were obtained. About 85.1% were not diagnosed with metastatic PCa during the study period (unaggressive PCa); 9.2% were simultaneously diagnosed with PCa and metastasis (aggressive-advanced PCa), while 5.7% were not diagnosed with metastatic PCa at first, but they were diagnosed with metastasis at some point during the 5 years follow-up (aggressive-not advanced PCa). Patients with unaggressive PCa had more clinical investigations directly related to PCa detection (prostate ultrasounds and biopsies) during the 4 years prior to PCa diagnosis, compared to patients with aggressive PCa, which may have contributed to the early detection of PCa.

A randomised trial of [18F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa. Study Design: This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark. Endpoints: The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures. Patients and Methods: Patients eligible for the study have newly diagnosed unfavourable intermediate- or high-risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F-PET/CT and (B) an intervention group staged with [18F]PSMA-1007-PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F-PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3-12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines. Trial Registration: The Regional Committees on Health Research Ethics for Southern Denmark (S-20190161) and the Danish Medicines Agency (EudraCT Number 2021-000123-12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).

[18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients.

UNLABELLED: Study Type--Diagnostic (exploratory cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re-staging. However, previous studies were small. Therefore, we assessed the value of [(18) F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a 'blinded' review. After a study period of 3 years and >200 included patients, we concluded that [(18) F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [(18) F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing. OBJECTIVES: • To assess the value of [(18) F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer. • To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one-third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement. PATIENTS AND METHODS: • From January 2008 to December 2010, 210 intermediate- or high-risk patients had a FCH PET/CT scan before regional LND. • After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by 'blinded review'. • Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases. RESULTS: • Of the 210 patients, 76 (36.2%) were in the intermediate-risk group and 134 (63.8%) were in the high-risk group. A medium (range) of 5 (1-28) LNs were removed per patient. • Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient-based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively. • Corresponding values for LN-based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively. • The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001). • In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs. CONCLUSIONS: • Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer. • However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.

A restricted test of single-word intelligibility in 3-year-old children with and without cleft palate.

OBJECTIVE: In a previous study, children with cleft palate with hard palate closure at 12 months of age showed more typical phonological development than did children with an unrepaired hard palate at 36 months of age. This finding was based on narrow transcription of word initial target consonants obtained from a simple naming test. To evaluate the relevance of this finding, we investigated how well the children's target words were understood by 84 naive listeners. DESIGN: A cross-sectional study. PARTICIPANTS: Data obtained from 28 children with unilateral cleft lip and palate, 3 years of age, who received hard palate closure at either 12 months (hard palate repaired; HPR) or 36 months (hard palate unrepaired; HPU) were compared with data obtained from 14 age-matched, typically developing control children. METHODS: Video recordings of the children naming target words were shown to 84 naive listeners between 15 and 24 years of age who typed the word they heard. RESULTS: The findings of this study indicated that naive listeners correctly identified a larger percentage of words in the control children followed by children in the HPR group. Children in the HPU group were more difficult for the naive listeners to understand. The error of retraction/backing of alveolar target consonants to velar place of articulation occurred frequently and most often in the HPU group and was found to have a negative effect on intelligibility.