A graphical tool for locating inconsistency in network meta-analyses

BACKGROUND: In network meta-analyses, several treatments can be compared by connecting evidence from clinical trials that have investigated two or more treatments. The resulting trial network allows estimating the relative effects of all pairs of treatments taking indirect evidence into account. For a valid analysis of the network, consistent information from different pathways is assumed. Consistency can be checked by contrasting effect estimates from direct comparisons with the evidence of the remaining network. Unfortunately, one deviating direct comparison may have side effects on the network estimates of others, thus producing hot spots of inconsistency. METHODS: We provide a tool, the net heat plot, to render transparent which direct comparisons drive each network estimate and to display hot spots of inconsistency: this permits singling out which of the suspicious direct comparisons are sufficient to explain the presence of inconsistency. We base our methods on fixed-effects models. For disclosure of potential drivers, the plot comprises the contribution of each direct estimate to network estimates resulting from regression diagnostics. In combination, we show heat colors corresponding to the change in agreement between direct and indirect estimate when relaxing the assumption of consistency for one direct comparison. A clustering procedure is applied to the heat matrix in order to find hot spots of inconsistency. RESULTS: The method is shown to work with several examples, which are constructed by perturbing the effect of single study designs, and with two published network meta-analyses. Once the possible sources of inconsistencies are identified, our method also reveals which network estimates they affect. CONCLUSION: Our proposal is seen to be useful for identifying sources of inconsistencies in the network together with the interrelatedness of effect estimates. It opens the way for a further analysis based on subject matter considerations

Comparison of the Accuracy of 2D and 3D Templating for Revision Total Hip Replacement

Introduction: Revision hip arthroplasty is a challenging surgical procedure, especially in cases of advanced acetabular bone loss. Accurate preoperative planning can prevent complications such as periprosthetic fractures or aseptic loosening. To date, the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has been evaluated only in primary hip and knee arthroplasty. Methods: We retrospectively investigated the accuracy of 3D personalized planning of reinforcement cages (Burch Schneider) in 27 patients who underwent revision hip arthroplasty. Personalized 3D modeling and positioning of the reinforcement cages were performed using computed tomography (CT) of the pelvis of each patient and 3D templates of the implant. To evaluate accuracy, the sizes of the reinforcement cages planned in 2D and 3D were compared with the sizes of the finally implanted cages. Factors that may potentially influence planning accuracy such as gender and body mass index (BMI) were analyzed. Results: There was a significant difference (p = 0.003) in the accuracy of correct size prediction between personalized 3D templating and 2D templating. Personalized 3D templating predicted the exact size of the reinforcement cage in 96.3% of the patients, while the exact size was predicted in only 55.6% by 2D templating. Regarding gender and BMI, no statistically significant differences in planning accuracy either for 2D or 3D templating were observed. Conclusion: Personalized 3D planning of revision hip arthroplasty using Burch Schneider reinforcement cages leads to greater accuracy in the prediction of the required size of implants than conventional 2D templating

Investigation of intraocular pressure fluctuation as a risk factor of glaucoma progression

Purpose: Since the role of short- and long-term intraocular pressure (IOP) fluctuation as a predictor of glaucoma progression is still controversial, the purpose of this study was to investigate the role of IOP fluctuation in a non-selected patient cohort. Materials and methods: Two-hundred and forty eyes of 120 glaucoma patients (51% female) with a mean age of 64.5 years were included. Inclusion criteria were at least a visual field (VF) and a 48-hour diurnal phasing of IOP including nocturnal measurement. Glaucoma Progression was defined as – if available – confirmed progression of reproducible VF defects in at least three VF examinations or increase of cup area on optic nerve imaging (Heidelberg Retina Tomograph [HRT]) with at least two images after baseline. If results were stable or less than previously mentioned VF or HRT examinations were available, it was classified as “no progression”. Results: Glaucoma progression was seen in seven of 240 eyes in the VF analysis and ten of 240 eyes on HRT. Of all 240 eyes, 92 and 41 eyes fulfilled the criteria to be included for progression evaluation on VF and HRT analysis, respectively. Mean time to progression ± standard error was 3.6±0.2 years on VF and 4.5±0.3 years on HRT. Univariate and multivariate Cox regression analyses revealed short-term IOP fluctuation (P,0.0001) and maximum IOP (P,0.001) as risk factors for glaucoma progression on VF. There was no significant influence of demographic characteristics, ocular or general health on glaucoma progression. Conclusion: Short-term IOP fluctuation was associated with the progression of glaucoma in this non-selected cohort of glaucoma patients receiving phasing of IOP. Keywords: glaucoma progression, short-term IOP fluctuation, long-term IOP fluctuation, glaucoma imaging, visual fiel

Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study

<p>Abstract</p> <p>Aim</p> <p>To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study.</p> <p>Methods</p> <p>On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as reference.</p> <p>Results</p> <p>A statistically significant positive association with the extent of viniculture can be observed for non-melanoma skin cancer in both males and females, and additionally for prostate cancer, bladder cancer, and non-Hodgkin lymphoma in males, but not in females. Lung cancer risk is significantly reduced in communities with a large area under cultivation. In the side-analysis, elevated SIR for endocrine-related tumors of the breast, testis, prostate, and endometrium were observed.</p> <p>Conclusion</p> <p>This study points to a potentially increased risk of skin cancer, bladder cancer, and endocrine-mediated tumors in Rhineland-Palatinate winegrowing communities. However, due to the explorative ecologic study design and the problem of multiple testing, these findings are not conclusve for a causal relationship.</p

The COPE-Trial-Communicating prognosis to parents in the neonatal ICU: Optimistic vs. PEssimistic: study protocol for a randomized controlled crossover trial using two different scripted video vignettes to explore communication preferences of parents of preterm infants.

BACKGROUND One of the numerous challenges preterm birth poses for parents and physicians is prognostic disclosure. Prognoses are based on scientific evidence and medical experience. They are subject to individual assessment and will generally remain uncertain with regard to the individual. This can result in differences in prognostic framing and thus affect the recipients' perception. In neonatology, data on the effects of prognostic framing are scarce. In particular, it is unclear whether parents prefer a more optimistic or a more pessimistic prognostic framing. OBJECTIVE To explore parents' preferences concerning prognostic framing and its effects on parent-reported outcomes and experiences. To identify predictors (demographic, psychological) of parents' communication preferences. DESIGN, SETTING, PARTICIPANTS Unblinded, randomized controlled crossover trial (RCT) at the Division of Neonatology of the University Medical Center Mainz, Germany, including German-speaking parents or guardians of infants born preterm between 2010 and 2019 with a birth weight < 1500 g. Inclusion of up to 204 families is planned, with possible revision according to a blinded sample size reassessment. INTERVENTION Embedded in an online survey and in pre-specified order, participants will watch two video vignettes depicting a more optimistic vs. a more pessimistic framing in prognostic disclosure to parents of a preterm infant. Apart from prognostic framing, all other aspects of physician-parent communication are standardized in both videos. MAIN OUTCOMES AND MEASURES At baseline and after each video, participants complete a two-part online questionnaire (baseline and post-intervention). Primary outcome is the preference for either a more optimistic or a more pessimistic prognostic framing. Secondary outcomes include changes in state-anxiety (STAI-SKD), satisfaction with prognostic framing, evaluation of prognosis, future optimism and hope, preparedness for shared decision-making (each assessed using customized questions), and general impression (customized question), professionalism (adapted from GMC Patient Questionnaire) and compassion (Physician Compassion Questionnaire) of the consulting physician. DISCUSSION This RCT will explore parents' preferences concerning prognostic framing and its effects on physician-parent communication. Results may contribute to a better understanding of parental needs in prognostic disclosure and will be instrumental for a broad audience of clinicians, scientists, and ethicists. TRIAL REGISTRATION German Clinical Trials Register DRKS00024466 . Registered on April 16, 2021

Young age at school entry and attention-deficit hyperactivity disorder-related symptoms during primary school : results of a prospective cohort study conducted at German Rudolf Steiner schools

Objectives Young age at school entry (ASE) for students has been related to their impaired mental health in higher grades. To avoid the negative health consequences of young ASE, preschool examinations and individual school entry deferral for young children are routinely performed by some school authorities. We aimed to investigate whether ASE was associated with attention-deficit hyperactivity disorder (ADHD)-related symptoms in pupils attending schools using a selective school enrolment procedure. Design Prospective open cohort study with baseline assessments at school entry and two follow-ups in the second and fourth grades. Setting Up to 128 Rudolf Steiner Schools (Waldorf Schools) located within Germany. Participants Of the 3079 children from whom data were gathered in the second or fourth grade, 2671 children born between 1 July 2001 and 31 October 2002 (age at baseline: mean 6.7, min 5.91, max 7.24 years, 50% girls) were selected for analysis to avoid bias introduced by individuals at the edges of the ASE distribution. Main outcome measures ADHD-related symptoms were assessed at school entry and second and fourth grades by parent-reported and teacher reported versions of the Strengths and Difficulties Questionnaire (Hyperactivity-Inattention Subscale). Results The agreement between parent-reported and teacher-reported symptoms was poor (intra-class correlation: 0.41 and 0.44 in second and fourth grade assessments, respectively). Regarding teacher reports, ASE was negatively associated with ADHD-related symptoms in the second grade (regression coefficient β=−0.66 per year, P=0.0006) and fourth grade (β=−0.56, P=0.0014). Associations remained after adjusting for potential confounders and pre-existing symptoms at baseline. Regarding parent reports, associations were markedly weaker in both grades (second grade: β=−0.22, P=0.12; fourth grade: β=−0.09, P=0.48).Conclusions Using a prospective study design and comprehensive adjustment for confounding and baseline symptoms, we confirmed prior evidence of the association between young ASE and teacher-reported ADHD symptoms in primary school

Discrepancies from registered protocols and spin occurred frequently in randomized psychotherapy trials:A meta-epidemiologic study

Objectives: This study aimed to investigate the relationship between trial registration, trial discrepancy from registered protocol, and spin in nonpharmacological trials. Study Design and Setting: Recent psychotherapy trials on depression (2015-2018) were analyzed regarding their registration status and its relationship to discrepancies between registered and published primary outcomes and to spin (discrepancy between the nonsignificant finding in a study and an overly beneficial interpretation of the effect of the treatment). Results: A total of 196 trials were identified, of which 78 (40%) had been registered prospectively and 56 (29%) had been registered retrospectively. In 102 (76%) of 134 registered trials, discrepancies between trial and protocol were present. Of 72 trials with a nonsignif-icant difference between treatments for the primary outcome, 68 trials (94%) showed spin. Discrepancies from protocol were less frequent in prospectively than in retrospectively registered trials (odds ratio5 0.19; 95% confidence interval [CI]: 0.07-0.52), but regarding the amount of spin, there was no difference between prospectively and retrospectively registered trials (rb=0.12; 95% CI: -0.41 to 0.19) or between registered and unregistered trials (rb=0.22, 95% CI -0.49 to 0.08). Conclusion: Protocol discrepancies and spin have a high prevalence in psychotherapy outcome research. The results show no relation between registration and spin, but prospective registration may prevent discrepancies from protocol

Quantification of intramuscular fat in patients with late-onset Pompe disease by conventional magnetic resonance imaging for the long-term follow-up of enzyme replacement therapy

OBJECTIVE: The objective of this study was to evaluate a quantitative method based on conventional T1-weighted magnetic resonance (MR) imaging to assess fatty muscular degeneration in patients with late-onset Pompe disease and to compare it with semi-quantitative visual evaluation (the Mercuri score). In addition, a long-term retrospective data analysis was performed to evaluate treatment response to enzyme replacement therapy with alglucosidase alfa. METHODS: MR images of the lumbar spine were acquired in 41 patients diagnosed with late-onset Pompe disease from 2006 through 2015. Two independent readers retrospectively evaluated fatty degeneration of the psoas and paraspinal muscles by applying the Mercuri score. Quantitative semi-automated muscle and fat tissue separation was performed, and inter-observer agreement and correlations with clinical parameters were assessed. Follow-up examinations were performed in 13 patients treated with alglucosidase alfa after a median of 39 months; in 7/13 patients, an additional follow-up examination was completed after a median of 63 months. RESULTS: Inter-observer agreement was high. Measurements derived from the quantitative method correlated well with Medical Research Council scores of muscle strength, with moderate correlations found for the 6-minute walk test, the 4-step stair climb test, and spirometry in the supine position. A significant increase in the MR-derived fat fraction of the psoas muscle was found between baseline and follow-up 1 (P = 0.016), as was a significant decrease in the performance on the 6-minute walk test (P = 0.006) and 4-step stair climb test (P = 0.034), as well as plasma creatine kinase (P = 0.016). No statistically significant difference in clinical or MR-derived parameters was found between follow-up 1 and follow-up 2. CONCLUSIONS: Quantification of fatty muscle degeneration using the semi-automated method can provide a more detailed overview of disease progression than semi-quantitative Mercuri scoring. MR-derived data correlated with clinical symptoms and patient exercise capacity. After an initial worsening, the fat fraction of the psoas muscle and performance on the 6-minute walk test stayed constant during long-term follow-up under enzyme replacement therapy

Chronic health conditions and school performance in first graders : a prospective cohort study

Objective Children with chronic health conditions may perform poorer at school. Associations may be confounded by numerous social factors. We aimed to estimate the effects of a chronic health condition on overall school performance in first graders with an emphasis on rigorous adjustment for potential confounders. Methods A population-based cohort study was performed in the area of Mainz-Bingen (Germany). In 2015 all preschoolers were approached and the presence of a chronic health condition was assessed by parental questionnaires and preschool health examination data. The identification of a chronic health condition was based on special health care needs and presence of a doctor’s diagnosis out of 24 school-relevant diseases. At the end of the first school year, overall school performance was assessed by teachers and rated on a 5-item scale ranging from -10 to 10. Results Of 3683 children approached, 2003 were enrolled. Overall school performance was available for 1462 children (51% boys). Of these, 52% suffered from a chronic health condition. Compared to children without a chronic health condition, children with special health care needs (15%) performed worse at school (adjusted mean difference: -0.95, 95% CI: [-1.55; -0.35], P = 0.002). Children with a doctor’s diagnosis but without special health care needs (37%) did not perform worse at school. The effect was further analysed considering the extent of special health care needed. Conclusions Chronic health conditions affect overall school performance early in primary school. To identify academically at-risk children, a chronic health condition identification based on special health care needs may be used

Kratki implantati nasuprot implantatima standardne dužine uz podizanje dna sinusa u slučaju atrofične stražnje maksile

Objectives: the aim of this clinical study was to compare clinical and radiological outcomes of short dental implants inserted in pristine bone to standard length implants inserted in combination with sinus floor elevation. Materials and methods: For this clinical study, the clinical and radiological outcome of 126 short dental implants (84 patients), inserted in pristine bone were compared with 312 standard length implants (156 patients), placed in combination with maxillary sinus floor elevation procedures. Results: The short implant group (test group [TG]; mean follow-up (± standard deviation (SD) 56.6 ± 42.9 months) and the augmented group (control group [CG]; mean follow-up 41.6 ± 37.6 months) showed cumulative survival rates of 91.8% and 92.4%. Cumulative 5-year implant survival rates were 91.8% for the TG and 90.7% for the CG (p=0.421). Mean marginal bone loss was significantly higher in the CG than in the TG, with a mean MBL of 0.70 ± 0.72 mm in the TG and 0.96 ± 0.91 mm in the CG (p<0.001). A comparable and promising oral health-related quality of life (OHRQoL) was observed in the control and test groups. Conclusions: After over 3 years, short implants placed in the resorbed posterior maxilla obtained similar results to standard implants combined with maxillary sinus floor augmentation procedures.Svrha rada: Uspoređivali su se klinički i radiološki rezultati kratkih dentalnih implantata ugrađenih u intaktnu kost s implantatima standardne dužine ugrađenima u kombinaciji s podizanjem dna sinusa. Materijal i metode: Za ovo kliničko istraživanje su klinički i radiološki ishodi 126 kratkih dentalnih implantata (84 pacijenta) ugrađenih u intaktnu kost uspoređeni s 312 implantata standardne dužine (156 pacijenata) usađenih u kombinaciji s postupcima podizanja dna maksilarnoga sinusa. Rezultati: Skupina s kratkim implantatima [testna skupina (TG); srednja vrijednost praćenja (± standardna devijacija (SD) 56,6 ± 42,9 mjeseci] i augmentirana skupina [kontrolna skupina (CG); srednja vrijednost praćenja 41,6 ± 37,6 mjeseci] pokazale su kumulativne stope preživljenja od 91,8 i 92,4 %. Kumulativne petogodišnje stope preživljenje implantata bile su 91,8 % za TG i 90,7 % za CG (p = 0,421). Prosječni marginalni gubitak kosti bio je značajno veći u CG-u nego u TG-u, uz srednji MBL od 0,70 ± 0,72 mm u TG-u i 0,96 ± 0,91 mm u CG-u (p < 0,001). I u kontrolnoj i u testnoj skupini uočena je usporediva i obećavajuća kvaliteta života povezana s oralnim zdravljem (OHRQoL). Zaključci: Nakon više od tri godine s kratkim implantatima ugrađenima u resorbiranu stražnju maksilu postignuti su slični rezultati kao i pri uporabi standardnih implantata u kombinaciji s postupcima podizanja dna maksilarnoga sinusa