We investigated the reporting and methods of prediction studies, focusing on aims, designs, participant selection, outcomes, predictors, statistical power, statistical methods, and predictive ...performance measures.
We used a full hand search to identify all prediction studies published in 2008 in six high impact general medical journals. We developed a comprehensive item list to systematically score conduct and reporting of the studies, based on recent recommendations for prediction research. Two reviewers independently scored the studies. We retrieved 71 papers for full text review: 51 were predictor finding studies, 14 were prediction model development studies, three addressed an external validation of a previously developed model, and three reported on a model's impact on participant outcome. Study design was unclear in 15% of studies, and a prospective cohort was used in most studies (60%). Descriptions of the participants and definitions of predictor and outcome were generally good. Despite many recommendations against doing so, continuous predictors were often dichotomized (32% of studies). The number of events per predictor as a measure of statistical power could not be determined in 67% of the studies; of the remainder, 53% had fewer than the commonly recommended value of ten events per predictor. Methods for a priori selection of candidate predictors were described in most studies (68%). A substantial number of studies relied on a p-value cut-off of p<0.05 to select predictors in the multivariable analyses (29%). Predictive model performance measures, i.e., calibration and discrimination, were reported in 12% and 27% of studies, respectively.
The majority of prediction studies in high impact journals do not follow current methodological recommendations, limiting their reliability and applicability.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The first antenatal clinic (ANC) visit helps to distinguish pregnant women who require standard care, from those with specific problems and so require special attention. There are protocols to guide ...care providers to provide optimal care to women during ANC. Our objectives were to determine the level of provider adherence to first antenatal visit guidelines in the Safe Motherhood Protocol (SMP), and assess patient factors that determine complete provider adherence.
This cross-sectional study is part of a cohort study that recruited women who delivered in eleven health facilities and who had utilized antenatal care services during their pregnancy in the Greater Accra region of Ghana. A record review of the first antenatal visit of participants was carried out to assess the level of adherence to the SMP, using a thirteen-point checklist. Information on their socio-demographic characteristics and previous pregnancy history was collected using a questionnaire. Percentages of adherence levels and baseline characteristics were estimated and cluster-adjusted odds ratios (OR) calculated to identify determinants.
A total of 948 women who had delivered in eleven public facilities were recruited with a mean age (SD) of 28.2 (5.4) years. Overall, complete adherence to guidelines pertained to only 48.1% of pregnant women. Providers were significantly more likely to completely adhere to guidelines when caring for multiparous women OR = 5.43 (1.69-17.44), p<0.01 but less likely to do so when attending to women with history of previous pregnancy complications OR = 0.50 (0.33-0.75), p<0.01.
Complete provider adherence to first antenatal visit guidelines is low across different facility types in the Greater Accra region of Ghana and is determined by parity and history of previous pregnancy complication. Providers should be trained and supported to adhere to the guidelines during provision of care to all pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). We tested efficacy of bumetanide on core symptom domains using a single center, parallel-group, ...participant-randomized, double-blind, placebo-controlled phase-2 superiority trial in a tertiary hospital in the Netherlands.
Unmedicated children aged 7 to 15 years with ASD and IQ ≥55 were block-randomized 1:1 to oral-solution bumetanide versus placebo, titrated to a maximum of 1.0 mg twice daily for 91 days (D91), followed by a 28-day wash-out period. The primary outcome was difference in Social Responsiveness Scale−2 (SRS-2) total score at D91, analyzed by modified intention-to-treat with linear mixed models.
A total of 92 participants (mean age 10.5 SD 2.4 years) enrolled between June 2016 and December 2018. In all, 47 children were allocated to bumetanide and 45 to placebo. Two participants dropped out per treatment arm. After 91 days, bumetanide was not superior to placebo on the primary outcome, the SRS-2 (mean difference −3.16, 95% CI = −9.68 to 3.37, p = .338). A superior effect was found on one of the secondary outcomes, the Repetitive Behavior Scale−Revised (mean difference −4.16, 95% CI = −8.06 to −0.25, p = .0375), but not on the Sensory Profile (mean difference 5.64, 95% CI = −11.30 to 22.57, p = .508) or the Aberrant Behavior Checklist Irritability Subscale (mean difference −0.65, 95% CI = −2.83 to 1.52, p = .552). No significant wash-out effect was observed. Significant adverse effects were predominantly diuretic effects (orthostatic hypotension (17 36% versus 5 11%, p = .007); hypokalemia (24 51% versus 0 0%, p < .0001), the occurrence of which did not statistically influence treatment outcome.
The trial outcome was negative in terms of no superior effect on the primary outcome. The secondary outcomes suggest efficacy on repetitive behavior symptoms for a subset of patients.
Bumetanide in Autism Medication and Biomarker Study (BAMBI); https://www.clinicaltrialsregister.eu/; 2014-001560-35.
In children with juvenile idiopathic arthritis (JIA) the temporomandibular joint (TMJ) can be involved. As a consequence, the oral function can be impaired due to joint and/or muscle involvement of ...the masticatory system with a negative influence on the maximum bite force. The aim of this cross-sectional study was to establish the reliability of AMVBF in children with JIA and healthy children. Children with JIA and healthy children conducted three attempts of AMVBF. The reliability of AMVBF measurement was determined by the intra-class correlation coefficient (ICC) by age, standard error of measurement (SEM), smallest detectable change (SDC), and limits of agreement (LoA). A total of 298 children with JIA and 168 healthy children were examined. The AMVBF measurements showed an good to excellent reliability in children with JIA based on the ICCs corrected for age (0.782-0.979). In healthy children, the reliability was moderate to excellent (0.546-0.999). The SDC in our study indicated that values above 11.4N might be a clinical relevant change over time in children with JIA. The LoA showed a wide spread of variability in both children with JIA (-72.6-44.4N) and healthy children (-79.9-72.8N). The Bland-Altman plots indicated that the differences between the test and retest increased in value proportionally to the biteforce value.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Today quantitative information about the type of complications and their incidence during long-term pacemaker (PM) follow-up is scarce.
To assess the incidence and determinants of short- and ...long-term complications after first pacemaker implantation for bradycardia.
A prospective multicenter cohort study (the FOLLOWPACE study) was conducted among 1517 patients receiving a PM between January 2003 and November 2007. The independent association of patient and implantation-procedure characteristics with the incidence of PM complications was analyzed using multivariable Cox regression analysis.
A total of 1517 patients in 23 Dutch PM centers were followed for a mean of 5.8 years (SD 1.1), resulting in 8797 patient-years. Within 2 months, 188 (12.4%) patients developed PM complications. Male gender, age at implantation, body mass index, a history of cerebrovascular accident, congestive heart failure, use of anticoagulant drugs, and passive atrial lead fixation were independent predictors for complications within 2 months, yielding a C-index of 0.62 (95% confidence interval 0.57-0.66). Annual hospital implanting volume did not additionally contribute to the prediction of short-term complications. Thereafter, 140 (9.2%) patients experienced complications, mostly lead-related complications (n = 84). Independent predictors for long-term complications were age, body mass index, hypertension, and a dual-chamber device, yielding a C-index of 0.62 (95% confidence interval 0.57-0.67). The occurrence of a short-term PM complication was not predictive of future PM complications.
Complication incidence in modern pacing therapy is still substantial. Most complications occur early after PM implantation. Although various patient- and procedure-related characteristics are independent predictors for early and late complications, their ability to identify the patient at high risk is rather poor. This relatively high incidence of PM complications and their poor prediction underscores the usefulness of current guidelines for regular follow-up of patients with PM.
To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests ...varying in workload and hydration status. Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5). Saliva samples were collected before (T0) and immediately after exercise (T1), and at several time points after exercise (2 hours (T3), 3 hours (T4), 6 hours (T5) and 24 hours (T6)). Secretory Leukocyte Protease Inhibitor (SLPI), Matrix Metallopeptidase-9 (MMP-9) and lactoferrin was analyzed using a commercial ELISA kit, a panel of 22 cytokines and chemokines were analyzed using a commercial multiplex immunoassay. Data was analyzed using a multilevel mixed linear model, with multiple test correction. Among a panel of 25 inflammatory markers, SLPI concentrations were significantly elevated immediately after exercise in all protocols compared to rest and higher concentrations reflected the intensity of exercise and hydration status. MMP-9 showed a significant increase in the 70% Wmax dehydrated, 50% Wmax and intermittent protocols. Salivary concentrations of SLPI and MMP-9 seem associated with exercise intensity and hydration status and may offer non-invasive biomarkers to study (local) inflammatory responses to different exercise intensities in human studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Patients with unprovoked (i.e., without the presence of apparent transient risk factors such as recent surgery) venous thromboembolism (VTE) are at risk of recurrence if anticoagulants are ...stopped after 3-6 months, yet their risk remains heterogeneous. Thus, prolonging anticoagulant treatment should be considered in high-risk patients, whereas stopping is likely preferred in those with a low predicted risk. The Vienna Prediction Model (VPM) could aid clinicians in estimating this risk, yet its clinical effects and external validity are currently unknown. The aim of this study was to investigate the clinical impact of this model on reducing recurrence risk in patients with unprovoked VTE, compared to usual care. Methods and findings In a randomized controlled trial, the decision to prolong or stop anticoagulant treatment was guided by predicted recurrence risk using the VPM (n = 441), which was compared with usual care (n = 442). Patients with unprovoked VTE were recruited from local thrombosis services in the Netherlands (in Utrecht, Harderwijk, Ede, Amersfoort, Zwolle, Hilversum, Rotterdam, Deventer, and Enschede) between 22 July 2011 and 30 November 2015, with 24-month follow-up complete for all patients by early 2018. The primary outcome was recurrent VTE during 24 months of follow-up. Secondary outcomes included major bleeding and clinically relevant non-major (CRNM) bleeding. In the total study population of 883 patients, mean age was 55 years, and 507 (57.4%) were men. A total of 96 recurrent VTE events (10.9%) were observed, 46 in the intervention arm and 50 in the control arm (risk ratio 0.92, 95% CI 0.63-1.35, p = 0.67). Major bleeding occurred in 4 patients, 2 in each treatment arm, whereas CRNM bleeding occurred in 20 patients (12 in intervention arm versus 8 in control arm). The VPM showed good discriminative power (c-statistic 0.76, 95% CI 0.69-0.83) and moderate to good calibration, notably at the lower spectrum of predicted risk. For instance, in 284 patients with a predicted risk of >2% to 4%, the observed rate of recurrence was 2.5% (95% CI 0.7% to 4.3%). The main limitation of this study is that it did not enroll the preplanned number of 750 patients in each study arm due to declining recruitment rate. Conclusions Our results show that application of the VPM in all patients with unprovoked VTE is unlikely to reduce overall recurrence risk. Yet, in those with a low predicted risk of recurrence, the observed rate was also low, suggesting that it might be safe to stop anticoagulant treatment in these patients. Trial registration Netherlands Trial Register NTR2680
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics ...and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck.
One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis.
PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p = .04).
PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To determine the effectiveness of a proactive primary care program on the daily functioning of older people in primary care.
Design
Single‐blind, three‐arm, cluster‐randomized controlled ...trial with 1‐year follow‐up.
Setting
Primary care setting, 39 general practices in the Netherlands.
Participants
Community‐dwelling people aged 60 and older (N = 3,092).
Interventions
A frailty screening intervention using routine electronic medical record data to identify older people at risk of adverse events followed by usual care from a general practitioner; after the screening intervention, a nurse‐led care program consisting of a comprehensive geriatric assessment, evidence‐based care planning, care coordination, and follow‐up; usual care.
Measurements
Primary outcome was daily functioning measured using the Katz‐15 (6 activities of daily living (ADLs), 8 instrumental activities of daily living (IADLs), one mobility item (range 0–15)); higher scores indicate greater dependence. Secondary outcomes included quality of life, primary care consultations, hospital admissions, emergency department visits, nursing home admissions, and mortality.
Results
The participants in both intervention arms had less decline in daily functioning than those in the usual care arm at 12 months (mean Katz‐15 score: screening arm, 1.87, 95% confidence interval (CI) = 1.77–1.97; screening and nurse‐led care arm, 1.88, 95% CI = 1.80–1.96; control group, 2.03, 95% CI = 1.92–2.13; P = .03). No differences in quality of life were observed.
Conclusion
Participants in both intervention groups had less decline than those in the control group at 1‐year follow‐up. Despite the statistically significant effect, the clinical relevance is uncertain at this point because of the small differences. Greater customizing of the intervention combined with prolonged follow‐up may lead to more‐robust results.
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