Term Effects Of Treatment Research Articles

ML-04 The influence of surgical intervention for high-dose Methotrexate chemotherapy in the patients with primary central nervous system lymphoma

Object: Surgical resection is not the standard of treatment for primary central nervous system lymphoma (PCNSL). Some recent studies suggest that resection might be beneficial. The aim of this study was to examine the effect of surgical treatment in terms of the time from surgery to chemotherapy.Methods: We retrospectively analyzed all patients with PCNSL treated at Hokkaido University Hospital between 2001 and 2018 to assess the effect of selection for resection on the response of Methotrexate chemotherapy. We identified the days from surgery to chemotherapy, complications, the response of Methotrexate (CR/CRu rate) and prognostic factors including progression free survival (PFS) and overall survival (OS).Results: A total 105 patients were identified. 84 patients underwent biopsy and 21 patients underwent surgical resection. Their median age were 63 [31–78] and 68 [44–77], respectively. Their Karnofsky Performance Status (KPS) were 70 [30–100] and 70 [40–100]. There were any significant difference. Patients undergoing biopsy and those undergoing resection had comparable rates of complications for all complication type. Overall, 4 biopsy patients and 5 resection patients experienced at least one complication. They were composed of 2 asymptomatic bleeding, 1 wound abscess, 1 hydrocephalus in biopsy patients, 1 epidural abscess, 1 epilepsy, 1 chronic subdural hematoma, 2 temporary hemiparesis. Although the days from surgery to chemotherapy were significantly shorter in patients underwent biopsy than in those underwent resection (P=0.0015), PFS was significantly longer in patients underwent resection than in those underwent biopsy (P=0.0403), whereas there was no difference in OS.Discussion: Resection could delay the postoperative treatment. In this study, there was a significant delay of postoperative treatment in resection patients, however, CR/CRu rate after MTX was significantly better in those underwent resection than biopsy. We can see that resection for PCNSL might not necessarily worsen the prognosis.

The Outcome of Salt Treatment for Umbilical Granuloma: A Systematic Review.

BackgroundAn umbilical granuloma is one of the common umbilical masses in young children which appears after the cords fall off, mainly due to an inflammatory reaction to subclinical infections. Though there are different recommendations of treatment modalities, which management modality is the best is not clear yet.ObjectiveThis systematic review aimed to assess the effectiveness of salt treatment in terms of complete resolution of the granuloma, any adverse effect, and any recurrence risk in those patients treated as inpatient or outpatient care.MethodologyThe literature search was done using search engines including Google scholar, PubMed, and Medlin. Articles published since 1990 and written in the English language with a target population of young children (less than 24 months) were included. To retrieve the articles, umbilical granuloma, treatment of umbilical granuloma, salt treatment, and neonatal umbilical disorder were used as keywords.ResultsThis systematic review indicated that the majority of the studies done on salt treatment for umbilical granuloma show excellent response (complete resolution of the granuloma/discharge) with no adverse effect and no recurrence in the subsequent follow-up of the patients in almost all cases of the treatment group. Salt inside the occluded hyperosmolar chamber causes shrinkage of granuloma by a desiccant effect.ConclusionCooking salt treatment for umbilical granuloma is effective, cheap, available, and easy to apply by non-health professionals. No side effects have been reported yet and a recurrence of the granuloma after treatment seems to be null.

A Clarification of Slope and Scale.

Improvements in the quantification and visual analysis of data, plotted across non-standardized graphs, are possible with the equations introduced in this paper. Equation 1 (an expression of graphic scale variability) forms part of the foundation for Equation 2 (an expansion on the traditional calculation of the tangent inverse of a line's algebraic slope). These equations provide clarification regarding aspects of "slope" and graphic scaling that have previously confused mathematicians. The apparent lack of correspondence between geometric slope (the angle of inclination) and algebraic slope (the m in y = mx + b) on "non-homogeneous" graphs (graphs where the scale values/distances on the y-axis are not the same as on the x-axis) is identified and directly resolved. This is important because nearly all behavior analytic graphs are "non-homogeneous" and problems with consistent visual inspection of such graphs have yet to be fully resolved. This paper shows how the precise geometric slope for any trend line on any non-homogeneous graph can quickly be determined-potentially improving the quantification and visual analysis of treatment effects in terms of the amount/magnitude of change in slope/variability. The equations herein may also be used to mathematically control for variability inherent in a graph's idiosyncratic construction, and thus facilitate valid comparison of data plotted on various non-standard graphs constructed with very different axes scales-both within and across single case design research studies. The implications for future research and the potential for improving effect size measures and meta-analyses in single-subject research are discussed.

Cognitive Control Training as an Augmentation Strategy to CBT in the Treatment of Fear of Failure in Undergraduates

Previous research in the context of depression indicates that Cognitive Control Training (CCT) has the potential to reduce maladaptive emotion regulation, such as rumination. However, as a stand-alone intervention, CCT does not seem to increase adaptive emotion regulation. We examined whether CCT combined with a traditional fear of failure intervention program would improve emotion regulation and psychopathology symptoms. 102 students participating in a group-based cognitive behavior therapy (CBT) program targeting fear of failure were randomized to CCT or active placebo conditions, performing ten 15-min sessions of the adaptive Paced Auditory Serial Addition Task or an adaptive speed-of-response task, respectively. Primary outcome measures were Repetitive Negative Thinking (RNT) and symptoms related to depression, anxiety and stress. Secondary outcomes included adaptive cognitive emotion regulation strategies. Task-specific cognitive transfer was observed in the CCT condition. In both conditions, RNT and symptoms were reduced. In contrast to our hypotheses, the CCT condition did not significantly differ from the active control condition in terms of treatment effects. The current study is among the first to investigate the added value of combining CCT with CBT in an anxious sample. CCT did not augment effects of a CBT-based fear of failure treatment.

The association of skin incision placement during cesarean delivery with wound complications in obese women: a systematic review and meta-analysis

Objective To determine the risk of wound complications by skin incision type in obese women undergoing cesarean delivery. Data sources: Electronic databases (MEDLINE, Scopus, and Ovid) were searched from their inception through August 2018. Methods of study selection: We included all randomized controlled trials and cohort studies reporting the placement of skin incision during cesarean section in obese women, defined as those with BMI ≥30 kg/m2. Studies were included if they compared one placement of skin incision with a different one as comparison group. The primary outcome was incidence of wound complications, while secondary outcomes included wound infection, hematoma, seroma, postpartum hemorrhage, and endometritis. Demographics and outcomes for each individual study identified were reported as part of the review. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI). Sub-group analyses (vertical versus Pfannenstiel) were also reported. Tabulation, integration and results: Seventeen studies (including 3 RCTs; 8960 participants among the 15 non-overlapping studies) were included in the systematic review. Vertical incisions were associated with a relative risk of 2.07 (95% CI1.61–2.67) for wound complications compared to transverse incisions, however significant possible confounders were present. Studies were mildly-moderately heterogeneous (I 2 44.81%, 95% CI 0.00–71.85%) with varying definitions of obesity and wound complications. High transverse incisions (3 studies, 218 participants) trend toward a lower risk of wound complications compared to low transverse incisions (RR 0.338, 95% CI 0.114–1.004). Conclusions Vertical incisions may be associated with an increased risk for wound complications compared to transverse incisions for cesarean delivery in obese women. Randomized controlled trials are needed to evaluate optimal cesarean skin incisions for these women.

Physical Treatments Reduce Pain in Children with Tension-Type Headache: A Systematic Review and Meta-Analysis.

To assess the effectiveness of a variety of physical treatments in the management of tension-type headache (TTH) in children. This review is reported in accordance with the PRISMA guidelines and was registered in the PROSPERO database (CRD42014015290). Randomized and nonrandomized controlled trials that examined the effects of all treatments with a physical component in the management of TTH in children and compared these treatments to a placebo intervention, no intervention, or a controlled comparison intervention were included. The Physiotherapy Evidence Database (PEDro) criteria for bias assessment and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Working Group criteria were used to assess the quality of the body of evidence. The outcome measures were pain, functioning, and quality of life. Only RCTs were included in the meta-analyses. An initial search produced 10,464 published articles. Of these, 17 were relevant trials, including 1,815 participants. The overall GRADE rating of the included studies was moderate, and 11 of the 17 studies could be used in the meta-analyses. The effectiveness of physical treatments in terms of a reduction of pain of 50% or more showed a risk ratio (RR) of 2.37 (95% CI: 1.69 to 3.33). Relaxation training was the most evaluated intervention and proved to be significantly effective (RR: 3.00 [95% CI: 1.94 to 4.63]). In children having TTH combined with temporomandibular disorders, occlusal appliances were effective (RR: 2.58 [95% CI: 1.37 to 4.85]). This review supports the use of physical treatments to reduce pain in children with TTH.

Targeted estimation of heterogeneous treatment effect in observational survival analysis.

The aim of clinical effectiveness research using repositories of electronic health records is to identify what health interventions 'work best' in real-world settings. Since there are several reasons why the net benefit of intervention may differ across patients, current comparative effectiveness literature focuses on investigating heterogeneous treatment effect and predicting whether an individual might benefit from an intervention. The majority of this literature has concentrated on the estimation of the effect of treatment on binary outcomes. However, many medical interventions are evaluated in terms of their effect on future events, which are subject to loss to follow-up. In this study, we describe a framework for the estimation of heterogeneous treatment effect in terms of differences in time-to-event (survival) probabilities. We divide the problem into three phases: (1) estimation of treatment effect conditioned on unique sets of the covariate vector; (2) identification of features important for heterogeneity using non-parametric variable importance methods; and (3) estimation of treatment effect on the reference classes defined by the previously selected features, using one-step Targeted Maximum Likelihood Estimation. We conducted a series of simulation studies and found that this method performs well when either sample size or event rate is high enough and the number of covariates contributing to the effect heterogeneity is moderate. An application of this method to a clinical case study was conducted by estimating the effect of oral anticoagulants on newly diagnosed non-valvular atrial fibrillation patients using data from the UK Clinical Practice Research Datalink.

Cold atmospheric pressure plasma treatment to assist the restoration of the apical region of a root canal in endodontic procedures

PurposeIn Endodontics, in order to complete a root canal treatment, the use of guttapercha to completely seal the root apex must be coupled with endodontic cements known as sealers to improve the adhesion with dentine, despite their cytotoxicity and solubility. The present study investigates the effect of enhancement of adhesion between these materials and Cold Atmospheric Plasma (CAP)-treated dentine of the apical region of ex-vivo teeth as a first step towards the reduction on the use of cytotoxic materials and the use of CAP in-vivo at a clinical stage. MethodsA dielectric barrier discharge (DBD) helium plasma jet was used to treat for 180 sec the shaped root canal dentin. Pushout tests and confocal microscopy analysis have been performed to evaluate the effect of cold plasma treatment in terms of adhesion performances and interaction between filling materials and dentin respectively. ResultsThe pushout test results highlight how a 180 seconds CAP treatment of dentin promotes an enhancement of bonding strength between filling materials and dentine in all investigated cases. In particular, when the dentine is CAP-treated in the apical region, the adhesion performances of guttapercha achieved a relevant increase (~ +200%), revealing how it was able to “self-bond” with the substrate with results comparable with the conventional procedure but without any sealer application, while the conventional (guttapercha+sealer) apical sealing procedure shows an improvement around +50%. Moreover, confocal images qualitatively confirmed the higher spreading and penetration of both guttapercha and sealer into dentinal tubules. The ergonomics of the prototype has been also improved to comply with the dimensions of devices commonly used in the dental field, with a plasma source diameter of 21.5 mm and with a choice of materials to minimise its weight. ConclusionCAP treatment of dentin increases the adhesion performances and paves the way for a sealer-free and safer procedure for apical restoration.

1123-P: Stress Cardiac Biomarkers and Adverse Cardiac Outcomes in the CANagliflozin CardioVascular Assessment Study (CANVAS)

SGLT2 inhibitors reduce risk of major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) in patients with type 2 diabetes (T2D), but mechanisms remain unclear. We examined effects of canagliflozin vs. placebo on 3 prognostic biomarkers in CANVAS, as well as their predictive ability for outcomes of interest. High sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics), soluble (s)ST2 (Critical Diagnostics), and insulin-like growth factor binding protein 7 (IGFBP7; Roche Diagnostics) were measured in up to 3680 participants at baseline, 1 y, and for hs-cTnT and sST2, 6 y. Conventional statistical methods adjusting relevant covariates were used to relate biomarkers to risk for incident MACE or HHF. Higher concentration of all 3 biomarkers was associated with higher adjusted risk for incident MACE or HHF, with C-index improvements beyond covariates for MACE or HHF (Table). In terms of treatment effect, no biomarkers were differentially altered by 1 y but where data existed, both hs-cTnT (n=915; treatment coefficient [95% CI]: -0.064 [-0.121, -0.007]; p=0.027) and sST2 (n=828, treatment coefficient [95% CI]: -0.129 [-0.248, -0.010]; p=0.033) were reduced significantly at 6 y. Among patients with T2D, concentrations of hs-cTnT, sST2, and IGFBP7 were associated with risk for MACE and HHF. Canagliflozin slowed longer term (6 y) increases in hs-cTnT and sST2. Disclosure N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Xu: Employee; Self; Janssen Research & Development, LLC. J. Butler: Consultant; Self; Amgen, Array BioPharma, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife Co., Ltd., Janssen Pharmaceuticals, Inc., Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Relypsa, Inc., VIfor. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. W. Shaw: Employee; Self; Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.E. Gutstein: Employee; Self; Janssen Research & Development, LLC. M.K. Hansen: Employee; Self; Janssen Research & Development, LLC. J. Januzzi: Consultant; Self; Roche Diagnostic USA. Research Support; Self; Janssen Pharmaceuticals, Inc. Funding Janssen Research & Development, LLC

Quantitative evaluation of rejuvenation treatment of nasolabial fold wrinkles by regression model and 3D photography.

With the application of 3D photography, our study aimed to quantify parameters of static nasolabial fold wrinkles and establish mathematic regression model between parameters of wrinkles and age, further to quantitatively evaluate the effect of rejuvenation treatment in terms of age. From October 2016 to May 2018, 433 Chinese female volunteers, aged 25-60years old, were enrolled in this study. Antera 3D camera was used to collect four parameters of static nasolabial fold wrinkles on the left and right sides of the volunteers, including overall size, average depth (mm), average width (mm), and maximum depth (mm). For those presented a linear relationship with age, univariate linear regression fitting was performed, followed by residual analysis, goodness of fit test, and significance test. The results of univariate linear regression fitting showed there was a clear linear relationship between the maximum depth, average depth, overall size of nasolabial fold wrinkles and age, and the regression equations were established. The significance test of regression coefficients showed P values were less than .0001. With application of the regression model between parameters of nasolabial fold wrinkles and age, the effect of rejuvenation treatment can be quantitatively evaluated in terms of age, which has certain reference and promotion value.

Graphing and reporting heterogeneous treatment effects through reference classes

BackgroundExploration and modelling of heterogeneous treatment effects as a function of baseline covariates is an important aspect of precision medicine in randomised controlled trials (RCTs). Randomisation generally guarantees the internal validity of an RCT, but heterogeneity in treatment effect can reduce external validity. Estimation of heterogeneous treatment effects is usually done via a predictive model for individual outcomes, where one searches for interactions between treatment allocation and important patient baseline covariates. However, such models are prone to overfitting and multiple testing and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model.MethodsWe show how reference classes derived from baseline covariates can be used to explore heterogeneous treatment effects via a two-stage approach. We first estimate a risk score which captures on a single dimension some of the heterogeneity in outcomes of the trial population. Heterogeneity in the treatment effect can then be explored via reweighting schemes along this axis of variation. This two-stage approach bypasses the search for interactions with multiple covariates, thus protecting against multiple testing. It also allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This approach would typically be applied to multivariable models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied.Case studyWe illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and demonstrate how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably in higher risk strata.Conclusions‘Local’ and ‘tilting’ reweighting schemes based on ranking patients by baseline risk can be used as a general approach for exploring, graphing and reporting heterogeneity of treatment effect in RCTs.Trial registrationISRCTN clinical trials registry: ISRCTN50258054. Prospectively registered on 22 July 2005.

Therapeutic change mechanisms in adults with medically unexplained physical symptoms: A systematic review

ObjectiveAlthough psychological treatments for patients suffering from medically unexplained physical symptoms (MUPS) show promising results, evidence for their effectiveness is still limited. The aim of this study was to review the existing empirical support for change mechanisms that explain treatment effect in terms of symptom intensity and symptom interference in the daily lives of patients. MethodsA systematic database search was conducted. Sixty-seven eligible studies were found, and change mechanism effects were extracted from them. The data were subjected to a systematic review. ResultsFifteen change mechanisms were identified. Those receiving the most consistent support included Increasing symptom acceptance, Development of coping strategies, and Positive treatment expectations, although the last mechanism was investigated in only two studies. Almost all mechanisms received support for at least one type of outcome, either at post-treatment or at follow-up. ConclusionsAlthough some empirical support exists for many mechanisms, some of them have received only marginal attention in empirical studies. These limitations prevented us from deriving more definite conclusions.

MP37-13 TREATMENT OUTCOMES OF PROGRESSIVE SITE-DIRECTED THERAPY FOR OLIGO-PROGRESSIVE CASTRATION-RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III (MP37)1 Apr 2020MP37-13 TREATMENT OUTCOMES OF PROGRESSIVE SITE-DIRECTED THERAPY FOR OLIGO-PROGRESSIVE CASTRATION-RESISTANT PROSTATE CANCER Soichiro Yoshida*, Taro Takahara, Yuki Arita, Chikako Ishii, Kazuma Toda, Tsuyoshi Sakamoto, Toshiki Kijima, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Kazutaka Saito, Ryoichi Yoshimura, and Yasuhisa Fujii Soichiro Yoshida*Soichiro Yoshida* More articles by this author , Taro TakaharaTaro Takahara More articles by this author , Yuki AritaYuki Arita More articles by this author , Chikako IshiiChikako Ishii More articles by this author , Kazuma TodaKazuma Toda More articles by this author , Tsuyoshi SakamotoTsuyoshi Sakamoto More articles by this author , Toshiki KijimaToshiki Kijima More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , Junichiro IshiokaJunichiro Ishioka More articles by this author , Yoh MatsuokaYoh Matsuoka More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Ryoichi YoshimuraRyoichi Yoshimura More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000886.013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Locoregional therapy against metastatic prostate cancer has generated great interest.However, the benefit of locoregional therapy for CRPC has not been fully demonstrated. We evaluated the treatment outcomes of locoregional radiotherapy to the oligo-progressive CRPC (OP-CRPC). METHODS: We reviewed 101 consecutive CRPC patients who underwent whole-body MRI with DWI (WB-DWI) before starting a new line of anti-cancer therapy between 2014 and 2019. OP-CRPC patients with 3 or less progressive lesions on WB-DWI were considered for progressive site-directed therapy (PSDT) of all detected progressive lesions without changing systemic therapy. Time to PSA progression after PSDT was calculated from the start of radiotherapy to PSA progression (PSA nadir + 2 ng/ml). RESULTS: Of the 45 (39%) who was diagnosed with OP-CRPC, 27 (60%) underwent PSDT without changing systemic therapy. The most frequent site of PSDT was the pelvic bone (n = 11), followed by the prostate (n = 7). 21 (89%) patients treated with PSDT had a decline in PSA. A decrease in PSA levels of at least 50% in response to PSDT (50% PSA-decline) was observed in 17 (67%) patients. Of the 27 patients treated with PSDT, 18 (67%) experienced PSA progression, and their median time to PSA progression was 6.6 months (range: 2.3-11.8 months). The median follow-up of the remaining 9 patients who did not experience PSA progression was 16.8 months (0.3-29.9 months). Of the potential prognostic variables, PSA-doubling time (PSA-DT) was the significant predictor for time to PSA progression (hazard ratio (HR) 1.3; P = 0.0045), as well as targeted site intra-pelvic localization (HR 3.8; P = 0.036). The PSA-progression-free survival (PSA-PFS) was significantly longer in the OP-CRPC patients with a PSA-DT ≥ 4 months compared with those with a PSA-DT < 4 months (median PSA-PFS: 11.7 vs 6.6 months, P = 0.012). The PSA-PFS was significantly longer in the pelvic OP-CRPC group compared with the non-pelvic OP-CRPC group (median PSA-PFS: 9.0 vs. 4.8 months, P = 0.017). CONCLUSIONS: PSDT to OP-CRPC provided a high treatment effect in terms of PSA response. The patients whose progressive site was localized in the pelvis, and PSA-DT was longer than 4 months were good candidates for PSDT. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e565-e565 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Soichiro Yoshida* More articles by this author Taro Takahara More articles by this author Yuki Arita More articles by this author Chikako Ishii More articles by this author Kazuma Toda More articles by this author Tsuyoshi Sakamoto More articles by this author Toshiki Kijima More articles by this author Minato Yokoyama More articles by this author Junichiro Ishioka More articles by this author Yoh Matsuoka More articles by this author Kazutaka Saito More articles by this author Ryoichi Yoshimura More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement PDF downloadLoading ...

Finite element analysis of subtalar joint arthroereisis on adult-acquired flexible flatfoot deformity using customised sinus tarsi implant.

BackgroundSubtalar arthroereisis may cause sinus tarsi pain complications. In this study, we aimed to introduce a customised implant that facilitated treatment effect and less impingement. The biomechanical outcome between the intact and implant conditions was compared using finite element analysis.MethodsA female patient with flatfoot (age: 36 years, height: 156 ​cm, body mass: 51 ​kg) was recruited as the model patient. The customised implant was designed from the extracted geometry. Boundary and loading conditions were assumed from the data of a normal participant. Four gait instants, including the ground reaction force first peak (25% stance), valley (45%), initial push-off (60%) and second peak (75%) were analyzed.ResultsThe navicular height was elevated by 4.2% at 25% stance, whereas the strain of the spring, plantar cuneonavicular and plantar cuboideonavicular ligaments were reduced. The talonavicular joint force decreased and the calcaneocuboid joint increased by half and 67%, respectively, representing a lateralised load pathway. There was a stress concentration at the sulcus tali reaching 15.29 ​MPaConclusionSubtalar arthroereisis using a customised implant may produce some positive treatment effects in terms of navicular height elevation, ligament strain relief and lateralised joint loading pathway. Although the concentrated stress at the sulcus tali did not exceed the threshold of bone breakdown, we could not rule out the potential of vascular disturbance owing to the remarkable elevation of stress. Future study may enlarge the contact area of the bone–implant interface by considering customisation based on the dynamic change of the sinus tarsi during walking gait.The translational potential of this articleGeometry mismatch of prefabricated implants could be the reason for complications. With the advancement of 3D printing, customising implant becomes possible and may improve treatment outcome. This study implemented a theoretical model approach to explore its potential under a simulation of walking.

Improving osteoarthritis care by digital means - Effects of a digital self-management program after 24- or 48-weeks of treatment.

Osteoarthritis (OA) is highly prevalent in older adults and a growing cause of disability. Easily accessible first-line treatment of OA is increasingly important. Digital self-management programs have in recent years become available. Evidence of short-term effects of such programs are abundant, yet reports on long-term benefits and adherence to treatment are scarce. The current study's objective was to investigate the long-term pain and function outcomes of people with hip or knee OA participating in a digital self-management programme. In this longitudinal cohort study, individuals with hip and knee OA, from the register of a digital self-management program and with 0-24-week (n = 499) or 0-48-week adherence (n = 138), were included. The treatment effect in terms of monthly pain (NRS, 0-10 worst to best) and physical function (30-second chair stand test (30CST), number of repetitions) change were investigated using a mixed model, controlling for the effect of age, body mass index (BMI), gender and index joint. For the 24-week sub-sample, pain NRS decreased monthly by -0.43 units (95% CI -0.51, -0.35, mean knee pain from 5.6 to 3.1, and hip pain from 5.9 to 3.8) and 30CST repetitions increased monthly by 0.76 repetitions (95% CI 0.64, 0.89 mean for knee from 10.0 to 14.3, and for hip from 10.9 to 14.8). For the 48-week sub-sample, pain decreased monthly by -0.39 units (95% CI -0.43, -0.36, mean knee pain from 5.7 to 3.2, and hip pain from 5.8 to 3.8), and repetitions increased by 0.72 repetitions (95% CI 0.65, 0.79, mean repetitions for knee from 10.3 to 14.4, and for hip from 11.1 to 14.9). There were no clinically relevant effects on the improvement of pain or function by any covariate (age, sex, index joint). The lack of a control group and randomization limit our ability to explain the mechanisms of the observed results. Continuously participating in a digital OA treatment program for 6 or 12 months was associated with a clinically important decrease in joint pain and increased physical function, in hip and knee OA. Future research should follow OA-related outcomes in participants that end their treatment to explore when and why that decision was made.

Designing clinical trials with (restricted) mean survival time endpoint: Practical considerations.

The difference in mean survival time, which quantifies the treatment effect in terms most meaningful to patients and retains its interpretability regardless of the shape of the survival distribution or the proportionality of the treatment effect, is an alternative endpoint that could be used more often as the primary endpoint to design clinical trials. The underuse of this endpoint is due to investigators' lack of familiarity with the test comparing the mean survival times and the lack of tools to facilitate trial design with this endpoint. The aim of this article is to provide investigators with insights and software to design trials with restricted mean survival time as the primary endpoint. A closed-form formula for the asymptotic power of the test of restricted mean survival time difference is presented. The effects of design parameters on power were evaluated for the mean survival time test and log-rank test. An R package which calculates the power or the sample size for user-specified parameter values and provides power plots for each design parameter is provided. The R package also calculates the probability that the restricted mean survival time is estimable for user-defined trial designs. Under proportional hazards and late differences in survival, the power of the mean survival time test can approach that of the log-rank test if the restriction time is late. Under early differences, the power of the restricted mean survival time test is higher than that of the log-rank test. Duration of accrual and follow-up have little influence on the power of the restricted mean survival time test. The choice of restriction time, on the other hand, has a large impact on power. Because the power depends on the interplay among the design factors, plotting the relationship between each design parameter and power allows the users to select the designs most appropriate for their trial. When modification is necessary to ensure the difference in restricted mean survival time is estimable, the three available modifications all perform adequately in the scenarios studied. The restricted mean survival time is a survival endpoint that is meaningful to investigators and to patients and at the same time requires less restrictive assumptions. The biggest challenge with this endpoint is selection of the restriction time. We recommend selecting a restriction time that is clinically relevant to the disease and the clinical setting of the trial of interest. The practical considerations and the R package provided in this work are readily available tools that researchers can use to design trials with restricted mean survival time as the primary endpoint.

A Comparison of Matching and Weighting Methods for Causal Inference Based on Routine Health Insurance Data, or: What to do If an RCT is Impossible.

Due to a multitude of reasons Randomized Control Trials on the basis of so-called "routine data" provided by insurance companies cannot be conducted. Therefore the estimation of "causal effects" for any kind of treatment is hampered since systematic bias due to specific selection processes must be suspected. The basic problem of counterfactual, which is to evaluate the difference between two potential outcomes for the same unit, is discussed. The focus lies on the comparison of the performance of different approaches to control for systematic differences between treatment and control group. These strategies are all based on propensity scores, namely matching or pruning, IPTW (inverse probability treatment weighting) and entropy balancing. Methods to evaluate these strategies are presented. A logit model is employed with 87 predictors to estimate the propensity score or to estimate the entropy balancing weights. All analyses are restricted to estimate the ATT (Average Treatment Effect for the Treated) Exemplary data come from a prospective controlled intervention-study with two measurement occasions. Data contain 35 857 chronically ill insurants with diabetes, congestive heart failure, arteriosclerosis, coronary heart disease or hypertension of one German sickness fund. The intervention group was offered an individual telephone coaching to improve health behavior and slow down disease progression while the control group received treatment as usual. Randomization took place before the insurants' consent to participate was obtained so assumptions of an RCT are violated. A weighted mixture model (difference-in-difference) as the causal model of interest is employed to estimate treatment effects in terms of costs distinguishing the categories outpatient costs, medication costs, and total costs. It is shown that entropy balancing performs best with respect to balancing treatment and control group at baseline for the first three moments of all 87 predictors. This will result in least biased estimates of the treatment effect.

Causal Mediation Analysis for Stochastic Interventions

SummaryMediation analysis in causal inference has traditionally focused on binary exposures and deterministic interventions, and a decomposition of the average treatment effect in terms of direct and indirect effects. We present an analogous decomposition of the population intervention effect, defined through stochastic interventions on the exposure. Population intervention effects provide a generalized framework in which a variety of interesting causal contrasts can be defined, including effects for continuous and categorical exposures. We show that identification of direct and indirect effects for the population intervention effect requires weaker assumptions than its average treatment effect counterpart, under the assumption of no mediator–outcome confounders affected by exposure. In particular, identification of direct effects is guaranteed in experiments that randomize the exposure and the mediator. We propose various estimators of the direct and indirect effects, including substitution, reweighted and efficient estimators based on flexible regression techniques, allowing for multivariate mediators. Our efficient estimator is asymptotically linear under a condition requiring n1/4-consistency of certain regression functions. We perform a simulation study in which we assess the finite sample properties of our proposed estimators. We present the results of an illustrative study where we assess the effect of participation in a sports team on the body mass index among children, using mediators such as exercise habits, daily consumption of snacks and overweight status.

A Clinical Study on Treatment of Facial Freckles with Intense Pulsed Light

Purpose: To explore the clinical effect of intense pulsed light on freckles. Methods: A total of 102 patients with facial freckles treated in our hospital between November 2014 and May 2017 were taken as the subjects of this study. The patients, after being confirmed with facial freckles, were treated with M22 Photorejuvenation, and evaluated at the end of the treatment in terms of therapeutic effect, adverse reactions, changes of indicators before and after treatment as well as relapse. Results: In terms of treatment effect, there were 46 patients (45.10%) above expectation, 50 patients (49.02%) up to expectation and 6 patients (5.88%) below the standard, with a total effective rate of 94.12%. In terms of adverse reactions, there were 8 patients with temporary facial flushing, 4 patients with mild edema and 3 patients with burning sensation, with a probability of 14.71%. In terms of indicator changes before and after treatment, the skin elasticity and skin moisture of each part of the patient’s face were improved, with the skin elasticity of the patient’s forehead and lower jaw up by 8.9% and 8%, respectively, and the skin moisture of the patient’s left cheek up by 25.7%, which was very obvious. In addition, the proportion of melanin and skin oil of the patients were significantly reduced, with the melanin proportion of the left cheek down by 30.1% and the overall skin oil proportion of the face down by about 1%. At the end of the treatment, 5 patients had freckle recurrence, with a recurrence rate of 4.90%, which was statistically significant (P&lt;0.05). Discussion: The intense pulsed light is an effective tool in the treatment of facial freckles. Despite occasional adverse reactions, multiple indicators of various parts of the patient’s face have been significantly improved, with a low probability of later recurrence, making it worthy of clinical promotion.

Continuous versus pulsed microwave ablation in the liver: any difference in intraoperative pain scores?

BackgroundThis study prospectively compared intraoperative pain scores during percutaneous microwave ablation of the liver in patients randomized between continuous and pulsed energy delivery algorithms.MethodsDuring a 12-month period, 20 patients who underwent microwave liver ablation were prospectively randomized between 2 different energy delivery modes: “continuous mode” (CM, n=10) and “pulsed mode” (PM, n=10). All ablation sessions were performed using the same microwave ablation platform under computed tomographic guidance and intravenous analgesia. Within 30 min post ablation, all patients completed a questionnaire assigning a numeric pain intensity score from 0 (no pain) to 10.ResultsMean pain scores were 8.17±1.850 in the CM group and 4.50±1.567 in the PM group, with a statistically significant difference of 3.667±2.807 pain units (P=0.001). The mean procedure time was 53.5±20.90 min in the PM group vs. 58.5±17.44 min in the CM group (P=0.279). The mean size of the lesions was 2.81±0.95 cm in the PM group and 2.81±0.85 cm in the CM group (P=0.984). On a per-lesion basis, technical success was achieved in all evaluable tumors in both groups. No difference was noted in the local tumor control on the 6-month imaging evaluation. No complications were observed in the CM arm, while small perihepatic hemorrhagic fluid collections were reported in the PM group.ConclusionsBoth algorithms for microwave energy delivery have comparable treatment effects in terms of 6-month local tumor control for liver lesions <3 cm in diameter. PM treatments compared to CM appear to induce significantly less pain in patients undergoing percutaneous liver ablation under intravenous analgesia.