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Background: Researchers continue to investigate the predictive validity of motor assessment in learners with disorder of attention, motor control and perception (DAMP). Aim: Determine the prevalence of attention-deficit hyperactive disorder (ADHD) and developmental coordination disorder (DCD); assess their association in Grade 1 children. Setting: Two primary schools located within 30 km of the University of the Free State, Bloemfontein. Methods: Attention deficit disorder or attention deficit hyperactive disorder (ADD/ ADHD) was assessed using the strength and weaknesses of ADD/ADHD symptoms normal behaviour rating scale (SWAN) and DCD using the Movement Assessment Battery for Children -- 2 (MABC-2). Results: One-hundred-and-ninety-five children (97 girls; 98 boys) aged 6 years to 8 years participated. MABC-2 and SWAN data were available for 195 and 182 children, respectively. Across both genders, 180 participants (92.3%) had no, 10 (5.1%) had moderate and 5 (2.6%) had severe motor difficulties. No statistically significant association (p = 0.1537) between gender and DCD was found. Similarly, 31 (17.0%) participants had ADHD subtype ADHD-I, 21 (11.5%) ADHD-H and 11 (6.0%) ADHD-C; no significant associations between gender and ADHD-I (p = 0.5579), ADHD-H (p = 0.4938) or ADHD-C (p = 0.7654) were found. There were no significant associations between DCD and the ADHD subtypes ADHD-I (p = 0.2956), ADHD-H (p = 0.7570) and ADHD-C (p = 1.000). Conclusion: Prevalence of DCD in the current study is higher than elsewhere in the world. No significant association between DCD and ADHD was found. Contribution: The relatively high prevalence of DCD in this South African population and its significance in the motor development of young children.

Background and objective: More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making. Methods: We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis. Key findings and limitations: A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6–18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1–3) and 20 (14–28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33–37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; n = 53), RT + androgen deprivation therapy (ADT; n = 88), ADT alone (n = 68), and salvage lymphadenectomy (n = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4–72.1) for metastasis-free survival, 97.7% (95% CI 95.5–99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4–98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2–219.2), exit from observation (OR 8.5, 95% CI 4.4–16.5), and systemic progression (OR 3.0, 95% CI 1.771–4.971). Conclusions: Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management. Patient summary: We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features.

Background and objective: Patients diagnosed with grade group (GG) 1 prostate cancer (PCa) following treatment for benign disease (“incidental” PCa) are typically managed with active surveillance (AS). It is not known how their outcomes compare with those observed in patients diagnosed with GG1 on biopsy. We aimed at determining whether long-term oncologic outcomes of AS for patients with GG1 PCa differ according to the type of diagnosis: incidental versus biopsy detected. Methods: A retrospective, multi-institutional analysis of PCa patients with GG1 on AS at eight institutions was conducted. Competing risk analyses estimated the incidence of metastases, PCa mortality, and conversion to treatment. As a secondary analysis, we estimated the risk of GG ≥2 on the first follow-up biopsy according to the type of initial diagnosis. Key findings and limitations: A total of 213 versus 1900 patients with incidental versus biopsy-diagnosed GG1 were identified. Patients with incidental cancers were followed with repeated biopsies and multiparametric magnetic resonance imaging less frequently than those diagnosed on biopsy. The 10-yr incidence of treatment was 22% for incidental cancers versus 53% for biopsy (subdistribution hazard ratio [sHR] 0.34, 95% confidence interval [CI] 0.26–0.46, p

Abstract Recent discoveries of Homo floresiensis and H. luzonensis raise questions regarding how extreme body size reduction occurred in some extinct Homo species in insular environments. Previous investigations at Mata Menge, Flores Island, Indonesia, suggested that the early Middle Pleistocene ancestors of H. floresiensis had even smaller jaws and teeth. Here, we report additional hominin fossils from the same deposits at Mata Menge. An adult humerus is estimated to be 9 − 16% shorter and thinner than the type specimen of H. floresiensis dated to ~60,000 years ago, and is smaller than any other Plio-Pleistocene adult hominin humeri hitherto reported. The newly recovered teeth are both exceptionally small; one of them bears closer morphological similarities to early Javanese H. erectus. The H. floresiensis lineage most likely evolved from early Asian H. erectus and was a long-lasting lineage on Flores with markedly diminutive body size since at least ~700,000 years ago.

Abstract Background An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants. Objective To describe which methodological adjustments were made to the study protocol because of these developments. Methods We compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan. Discussion This manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment.

Background and objective: The shift toward targeted biopsy (TBx) aims at enhancing prostate cancer (PCa) detection while reducing overdiagnosis of clinically insignificant disease. Despite the improved ability of TBx in identifying clinically significant PCa (csPCa), the optimal number and location of targeted cores remain unclear. This review aims to assess the optimal number of prostate biopsy magnetic resonance imaging (MRI)-targeted cores to detect csPCa. Methods: A narrative literature search was conducted using PubMed, focusing on studies published between January 2014 and January 2024, addressing factors influencing targeted core numbers during prostate biopsy. The search included both retrospective and prospective studies, prioritizing those with substantial sample sizes and employing terms such as “prostate biopsy”, “mpMRI”, “core number”, and “cancer detection”. Key findings and limitations: Two biopsy cores identified csPCa in 55–65% of cases. This detection rate improved to approximately 90% when the number of cores was ≥5. The inclusion of perilesional and systematic biopsies could maximize the detection of csPCa (from 10% to 45%), especially in patients under active surveillance or with prior negative biopsy results, although there is an increase in the overdiagnosis of indolent tumors (from 4% to 20%). Transperineal software-assisted target prostate biopsy may enhance cancer detection, particularly for tumors located at the apex/anterior part of the prostate. Increasing the number of TBx cores may incrementally raise the risk of complications (by 2–14% with each added core) and result in severe pain and significant discomfort for up to 17% and 25% of TBx patients, respectively. However, the overall rate and severity of these complications remain within acceptable limits. Conclusions and clinical implications: The optimal number of cores for targeted prostate biopsies should balance minimizing sampling errors with effective cancer detection and should be tailored to each patient’s unique prostate characteristics. Up to five cores per MRI target may be considered to enhance the detection of csPCa, with adjustments based on factors such as prostate and lesion volume, Prostate Imaging Reporting and Data System, biopsy techniques, complications, patient discomfort, and anxiety. Patient summary: In this report, we found that increasing the number of biopsy cores up to ≥5 improves the detection rates of significant prostate cancer significantly to around 90%. Although inclusion of nearby and systematic biopsies enhances detection, increasing the biopsy count may lead to higher risks of complications and indolent tumors. A customized biopsy approach based on multiple variables could be helpful in determining the appropriate number of targeted biopsies on a case-by-case basis.

Abstract A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.

Abstract Digital biomarkers that remotely monitor symptoms have the potential to revolutionize outcome assessments in future disease-modifying trials in Parkinson’s disease (PD), by allowing objective and recurrent measurement of symptoms and signs collected in the participant’s own living environment. This biomarker field is developing rapidly for assessing the motor features of PD, but the non-motor domain lags behind. Here, we systematically review and assess digital biomarkers under development for measuring non-motor symptoms of PD. We also consider relevant developments outside the PD field. We focus on technological readiness level and evaluate whether the identified digital non-motor biomarkers have potential for measuring disease progression, covering the spectrum from prodromal to advanced disease stages. Furthermore, we provide perspectives for future deployment of these biomarkers in trials. We found that various wearables show high promise for measuring autonomic function, constipation and sleep characteristics, including REM sleep behavior disorder. Biomarkers for neuropsychiatric symptoms are less well-developed, but show increasing accuracy in non-PD populations. Most biomarkers have not been validated for specific use in PD, and their sensitivity to capture disease progression remains untested for prodromal PD where the need for digital progression biomarkers is greatest. External validation in real-world environments and large longitudinal cohorts remains necessary for integrating non-motor biomarkers into research, and ultimately also into daily clinical practice.

Background: Hospitalized neonates are vulnerable to infection and have high rates of antibiotic utilization. Methods: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymized demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis. Findings: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians’ acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; P = 0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95% CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); P = 0·032). Interpretation: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis. Funding: A grant from Merck provided partial support.

Abstract Background People’s perceived risk of being infected and having severe illness was conceived as a motivational source of adherence to behavioral measures during the COVID-19 crisis. Methods We used online self-reported data, spanning 20 months of the COVID-19 crisis in Belgium (n = 221,791; 34.4% vaccinated; July 2020 - March 2022) to study the association between risk perception and motivation. Results Both perceived infection probability and severity fluctuated across time as a function of the characteristics of emerging variants, with unvaccinated persons perceiving decreasingly less risk compared to vaccinated ones. Perceived severity (and not perceived probability) was the most critical predictor of autonomous motivation for adherence to health-protective measures, a pattern observed at both the between-day and between-person level among both vaccinated and unvaccinated individuals. An integrated process model further indicated that on days with higher hospitalization load, participants reported being more adherent because risk severity and autonomous motivation for adherence were more elevated on these days. Conclusions These findings suggest that risk severity served as a critical and dynamic resource for adherence to behavioral measures because it fostered greater autonomous regulation.

Background and objective: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. Methods: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitations: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64–0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. Conclusions: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summary: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.

IntroductionThere is still much uncertainty about why some people develop persistent cognitive and mental health problems after SARS-CoV-2 infection and require additional care while others do not. In this study, we investigated the cognitive and psychological outcomes of non-hospitalized post-COVID-19 patients referred to an outpatient post-COVID-19 clinic for persistent symptoms more than 3 months after infection. Additionally, we aimed to explore the influence of demographic, physical, and personal factors on these outcomes.MethodsThis cross-sectional study was conducted at an outpatient post-COVID-19 clinic located at a prominent clinical teaching hospital in the Netherlands. Participants included non-hospitalized patients referred between 2020 and 2022, more than 3 months after SARS-CoV-2 infection, experiencing persistent symptoms. Main outcome measures included levels of anxiety and depression (Hospital Anxiety and Depression Scale), post-traumatic stress symptoms (PTSS) (Post-traumatic Stress Symptoms Checklist 14), and cognitive symptoms (Checklist for Cognitive and Emotional Consequences). Data analysis employed Spearman correlation and hierarchical multiple regression analyses.ResultsA total of 265 patients (61% female; mean age of 51.7 ± 13.7 years) were included in the study, with an average of 7.6 ± 4.5 months following SARS-CoV-2 infection. Among them, 104 patients (40%) reported high levels of anxiety, 111 patients (43%) showed high levels depressive symptoms, and 71 patients (31%) demonstrated high levels of PTSS. Additionally, 200 patients (79%) reported experiencing more than 2 cognitive symptoms. Bivariate analyses indicated associations between psychiatric history and increased cognitive and psychological symptoms. Multivariate analyses revealed positive associations between physical symptoms and cognitive and psychological symptoms, and catastrophizing thoughts were associated with higher anxiety levels (β = 0.217, p

This article refutes the claim that Klerksdorp (and not Potchefstroom) is the Transvaal's oldest town, mainly because the assumption that Klerksdorp was founded in 1837 rests upon memory and tradition. It argues moreover that the history of the Great Trek rules out the probability of White settlement in the Western Transvaal before mid-1838. It concludes by indicating that no archival sources or evidence could be traced to prove that a settlement existed at Schoonspruit before March 1840. The settlement which took place there afterwards was basically not a town but a farm. The word erf was not used until the end of the 1840s and indeed referred to arable land or cultivated fields. Although by 1850 the Schoonspruit-settlement did resemble a town and was called Klerksdorp it bore no resemblance to any early Voortrekker dorp. The founding in 1888 of Nuwe Dorp was therefore not merely an extension of Ou Dorp but in fact the establishment of a separate town to provide for the needs of the new gold-diggings at Klerksdorp.

Many-analysts studies explore how well an empirical claim withstands plausible alternative analyses of the same dataset by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g. effect size) provided by each analysis team. Although informative about the range of plausible effects in a dataset, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item subjective evidence evaluation survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous many-analysts study.

The Somatosensory Amplification Scale (SSAS) was designed to measure individual’s tendency to experience visceral and somatic sensations as unusually intense, disturbing and alarming. In this study, we aimed to investigate the reliability and validity of the SSAS in the Chinese general population, as well as the mediating effect of somatosensory amplification in the relationship between alexithymia and somatization. A total of 386 healthy adults were enrolled in this study. Participants completed the Chinese versions of the Somatosensory Amplification Scale (SSAS-C), the somatization subscale of the Symptom Check List 90 (SCL-90 som), the Toronto Alexithymia Scale (TAS-20), and the Short form Health Anxiety Inventory (SHAI). One hundred and thirty-three participants were randomly selected to complete the SSAS-C again two weeks after the initial assessment. The reliability and validity of the SSAS-C were analyzed. Confirmatory factor analysis showed that the one-factor model achieved adequate model fits; one item was deleted due to low factor loading. The revised SSAS-C showed good internal consistency and test-retest reliability. The SSAS-C scores correlated positively with the scores of SCL-90 som, TAS-20 and the SHAI, showing good convergent validity. In addition, somatosensory amplification mediated the association between alexithymia and somatization. The Chinese version of SSAS has acceptable reliability and validity for the general population. In addition, alexithymia may increase somatization through higher somatosensory amplification.

Background Four months after SARS-CoV-2 infection, 22%–50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient.Methods Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3–6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering.Results Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category.Conclusions Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

An article in the previous issue of Contree claims that Potchefstroom was established in 1839 because occupation of the area only took place then. An analysis of the wording in a number of reports by eyewitnesses on the history of the town's settlement does in fact indicate that it was indeed occupied during that time. Research however shows that Potchefstroom had already been proclaimed in December 1838. This date can therefore be regarded as its official date of establishment. As in the case of other Voortrekker towns, occupation was thus preceded by proclamation.