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Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process. [ABSTRACT FROM AUTHOR]

Background: The 24-h rooming-in policy is crucial to the Baby-Friendly Hospital Initiative (BFHI) for promoting breastfeeding. However, this policy may restrict maternal autonomy. In 2018, to integrate women's preferences into care decisions, Taiwan's Baby-Friendly certification included prenatal shared decision-making (SDM) for rooming-in. Prior to 2018, maternal knowledge, considerations, and intentions regarding rooming-in and the impact of prenatal SDM were unknown. Methods: A retrospective electronic medical record cohort study was conducted in southern Taiwan. Data on healthy postpartum women eligible for rooming-in and breastfeeding for the years 2017 and 2019, reflecting the periods before and after prenatal SDM was introduced, were gathered. Maternal and newborn characteristics, maternal knowledge, considerations, and prenatal intentions for postpartum rooming-in and breastfeeding during hospitalization were collected. Additionally, data on actual postpartum rooming-in practices during hospitalization and exclusive breastfeeding (EBF) practices from birth to hospital discharge, to 1 month, and to 2 months postpartum were collected. Descriptive and non-parametric statistics were applied to analyze the data. Results: A total of 621 women in 2017 and 311 women in 2019 were included. After prenatal SDM was introduced, the rooming-in rate during hospitalization fell from 42.2% in 2017 to 25.6% in 2019 (p < 0.001), and the EBF rate declined from 45.9% to 35.7% (p = 0.01). Additionally, the 1-month postpartum EBF rate decreased from 46.4% in 2017 (n = 571) to 44.3% in 2019 (n = 264), and the 2-month postpartum EBF rate dropped from 45.5% in 2017 (n = 591) to 40.2% (n = 308). According to the 2019 Patient Decision Aids responses (n = 236), women demonstrated limited understanding of rooming-in, with only 40.7% expressing an intention toward 24-h rooming-in. Women of older maternal age (p < 0.001), with a graduate degree (p = 0.02), full-time employment (p = 0.04), and concerns about rest disruption (p < 0.001), were more likely to prefer non-24-h rooming-in. Conclusions: Initiatives must promote prenatal SDM to enable healthcare providers to address misconceptions and tailor education, thereby increasing women's intention toward 24-h rooming-in and EBF. Future research should explore women's experiences and unmet needs at BFHI facilities to inform the construction of a baby- and mother-friendly environment. [ABSTRACT FROM AUTHOR]

Many treatments against breast cancer decrease the level of estrogen in blood, resulting in bone loss, osteoporosis and fragility fractures in breast cancer patients. This retrospective study aimed to evaluate a novel opportunistic screening for cancer treatment-induced bone loss (CTIBL) in breast cancer patients using CT radiomics. Between 2011 and 2021, a total of 412 female breast cancer patients who received treatment and were followed up in our institution, had post-treatment dual-energy X-ray absorptiometry (DXA) examination of the lumbar vertebrae and had post-treatment chest CT scan that encompassed the L1 vertebra, were included in this study. Results indicated that the T-score of L1 vertebra had a strongly positive correlation with the average T-score of L1–L4 vertebrae derived from DXA (r = 0.91, p < 0.05). On multivariable analysis, four clinical variables (age, body weight, menopause status, aromatase inhibitor exposure duration) and three radiomic features extracted from the region of interest of L1 vertebra (original_firstorder_RootMeanSquared, wavelet.HH_glcm_InverseVariance, and wavelet.LL_glcm_MCC) were selected for building predictive models of L1 T-score and bone health. The predictive model combining clinical and radiomic features showed the greatest adjusted R2 value (0.557), sensitivity (83.6%), specificity (74.2%) and total accuracy (79.4%) compared to models that relied solely on clinical data, radiomic features, or Hounsfield units. In conclusion, the clinical-radiomic predictive model may be used as an opportunistic screening tool for early identification of breast cancer survivors at high risk of CTIBL based on non-contrast CT images of the L1 vertebra, thereby facilitating early intervention for osteoporosis. [ABSTRACT FROM AUTHOR]

Pendelluft, the shift of air from non-dependent to dependent lung regions, is known to occur during active breathing in ventilated patients. However, information about pendelluft in ARDS patients under assisted mechanical ventilation is limited. In this prospectively collected and retrospectively analyzed study, we combined electrical impedance tomography and respiratory mechanics monitoring to quantitatively examine pendelluft in trigger and reverse triggering breaths in 20 mechanically ventilated patients with ARDS during the transition from controlled to active breaths under volume-cycled ventilation. Besides the 10 resting breaths in each patient, 20% of the counted active breaths were selected based on three levels of esophageal pressure swing (∆Pes): low (< 5 cm H2O, breaths = 471), moderate (≥ 5, < 10 cm H2O, breaths = 906), and high effort (≥ 10 cm H2O, breaths = 565). The pendelluft response to breathing efforts was significantly greater in trigger breaths than in reverse triggering breaths (p < 0.0001). Based on the pendelluft-∆Pes slope (ml/cmH2O), there were two distinct patterns of effort-related pendelluft (high vs. low pendelluft group). For trigger breaths, the high pendelluft group (n = 9, slope 0.7–2.4 ml/cmH2O) was significantly associated with lower peak airway/plateau pressure and lower respiratory system/lung elastance than the low pendelluft group (n = 11, slope − 0.1 to 0.3 ml/cmH2O). However, there was no difference in respiratory mechanics between high and low pendelluft groups for reverse triggering breathes. The use of ∆Pes to predict pendelluft was found to have a low positive predictive value. [ABSTRACT FROM AUTHOR]

Incidence rates for diseases are widely used in the field of medical research because they lead to clear and simple physical and clinical interpretations. In this study, we propose an efficient estimation method that incorporates auxiliary subgroup information related to the incidence rate into the estimation of the Cox proportional hazard model. The results show that utilizing the incidence rate information improves the efficiency of the estimation of regression parameters based on the double empirical likelihood method compared to that for conventional models that do not incorporation such information. We show that estimators of regression parameters asymptotically follow a multivariate normal distribution with a variance-covariance matrix that can be consistently estimated. Simulation results indicate that the proposed estimators significantly increase efficiency. Finally, an example of the effects of type 2 diabetes on stroke is applied to demonstrate the proposed method. [ABSTRACT FROM AUTHOR]

Laparoscopic (LPD) and robotic pancreaticoduodenectomy (RPD) are both challenging procedures. The feasibility and safety of simultaneously developing LPD and RPD remain unreported. We retrospectively reviewed the data of patients undergoing LPD or RPD between 2014 and 2021. A total of 114 patients underwent minimally invasive pancreaticoduodenectomy (MIPD): 39 LPDs and 75 RPDs. The learning process of LPD and RPD were similar. The cutoff points of the learning curve were LPD, 13th patient (the 27th patient of MIPD), and RPD, 18th patient (the 31st patient of MIPD) according the cumulative sum analysis of operative time. A decrease in the operative time was associated with the case sequence (p < 0.001) but not with the surgical approach (p = 0.36). The overall surgical outcomes were comparable between both the LPD and RPD groups. When evaluating the learning curve impact on MIPD, LPD had higher major complication (≧ Clavien–Dindo grade III), bile leak and wound infection rates in the pre-learning curve phase than those in the after-learning curve phase, while RPD had similar surgical outcomes between two phases. Simultaneous development of LPD and RPD is feasible and safe for experienced surgeons, with similar learning process and comparable surgical outcomes. [ABSTRACT FROM AUTHOR]

Background: Obesity increases surgical risks in various abdominal surgeries and its impact on open pancreaticoduodenectomy (OPD) and minimally invasive pancreaticoduodenectomy (MIPD) remains unknown. This study aimed to compare the surgical outcomes of OPD and MIPD in obese and non-obese patients by propensity score matching (PSM) analysis during the implementation of MIPD. Methods: We retrospectively reviewed all pancreaticoduodenectomies from December 2014 to May 2021. Obesity was defined as body mass index > 25 kg/m2 according to World Health Organization International Obesity Task Force. PSM was used to minimize the selection bias of MIPD. Results: Among 462 pancreaticoduodenectomies (339 OPDs, 123 MIPDs), there were 313 patients in the non-obese group (MIPD: 78, OPD: 235) and 149 patients in the obese group (MIPD: 45, OPD: 104). After PSM, there were 70 MIPD/106 OPD patients in the non-obese group and 38 MIPD/54 OPD patients in the obese group. The obese MIPD patients had more fluid collection (36.8% vs 9.8%, p = 0.002), a higher Clavien–Dindo (CD) grade (p = 0.007), more major complications (42.1% vs 14.8%, p = 0.004), and longer operative times (306 min vs 264 min, p < 0.001) than the obese OPD patients. The non-obese MIPD patients had lower CD grades (p = 0.02), longer operative times (294 vs 264 min, p < 0.001), and less blood loss (100 mL vs 200 mL) than the non-obese OPD patients. MIPD was a strong predictor of major complication (CD ≥ 3) in obese patients (odds ratio 3.11, 95% CI: 1.40–6.95, p = 0.005). Conclusions: Minimally invasive approaches deteriorate the CD grade, fluid collection, and major complications in obese patients undergoing pancreaticoduodenectomy during the initial development period. Non-obese patients may benefit from MIPD over OPD in terms of less blood loss and lower CD grades. The impact of BMI on MIPD should be considered when assessing the surgical risks. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. Methods: The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. Results: Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell. Conclusions: Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8+ T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Background: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain. Methods: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment. Results: The results showed a significant difference in the median NRS over 3 days (Kruskal–Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment. Conclusions: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective. [ABSTRACT FROM AUTHOR]

Recurrent event and terminal event data commonly arise in clinical and observational studies. To evaluate the efficacy of a treatment effect for both types of events, a composite endpoint has been used as a possible assessment, particularly when faced with high costs and a longer follow‐up study. To model recurrent event processes complicated by the existence of a terminal event, joint frailty modeling has been typically employed. In this study, the objective was to develop some target‐driven response adaptive randomization strategies using a composite endpoint based on joint frailty modeling. We first implemented a balanced randomized design and then investigated the response adaptive randomization. The former is intuitively first adopted while the latter is expected to be desirable and ethical in terms of allocating more subjects to the more effective treatment. The results show that the proposed procedures using a composite endpoint are capable of reducing the number of trial participants who receive inferior treatment while simultaneously reaching a desired optimal target as compared to a balanced randomized design. The R shiny application for calculating the sample size and allocation probabilities is also available. Finally, two clinical trials were used as pilot datasets to introduce the proposed procedures. [ABSTRACT FROM AUTHOR]

Recurrent event responses are frequently encountered during clinical trials of treatments for certain diseases, such as asthma. The recurrence rates of different treatments are often compared by applying the negative binomial model. In addition, a balanced treatment-allocation procedure that assigns the same number of patients to each treatment is often applied. Recently, a response-adaptive treatment-allocation procedure has been developed for trials with recurrent event data, and has been shown to be superior to balanced treatment allocation. However, this response-adaptive treatment allocation procedure is only applicable for the comparison of two treatments. In this paper, we derive response-adaptive treatment-allocation procedures for trials which comprise several treatments. As pairwise comparisons and multiple comparisons with a control are two common multiple-testing scenarios in trials with more than two treatments, corresponding treatment-allocation procedures for these scenarios are also investigated. The redesign of two clinical studies illustrates the clinical benefits that would be obtained from our proposed response-adaptive treatment-allocation procedures. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan's National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative diabetes insipidus (DI) is a common complication following endoscopic sellar surgery. However, the requirement of desmopressin treatment for patients with DI are heterogenous. Although the predictors of postoperative DI have been reported, whether these patients required desmopressin treatment remained uninvestigated. Predicting the need of desmopressin can benefit clinical decision making more directly than predicting the occurence of postoperative DI. This study aimed to identify variables that predict the need for desmopressin treatment following sellar surgery. Methods: Patients undergoing endoscopic sellar surgery between 2016 and 2019 were retrospectively reviewed. Twenty-three variables, characterized as potential predictors for requiring desmopressin treatment, were analyzed. To assess the capability to generalize the identified predictors, external validation with receiver operating characteristic (ROC) analysis was performed using a second series from 2019 to 2020. Results: Postoperative DI occurred in 40 of 159 included patients. Twelve patients required inpatient desmopressin treatment and 20 patients needed desmopressin prescription after discharge. The potential predictors of requiring any desmopressin use included higher peak sodium (Na) level (p = 0.007), lower minimum Na level (p = 0.043), and higher peak urine output (p = 0.006), but these were not supported by external validation. The predictors of requiring desmopressin after discharge included higher peak Na (p = 0.040) and minimum Na levels (p = 0.048), which were supported by external ROC validation showing areas under curve of 0.787, 0.611, and 0.898 for peak Na (p = 0.036), minimum Na (p = 0.460), and peak Na – minimum Na levels (p < 0.001), respectively. A criterion of peak Na ≥ 150 mmol/L or peak Na – minimum Na ≥ 10 predicted the need of desmopressin prescription after discharge. A postoperative management algorithm was proposed. Conclusion: The required treatments for patients with postoperative DI following endoscopic sellar surgery are heterogenous. Elevated peak Na and large peak Na—minimum Na levels in the perioperative period predicted requiring desmopressin after hospital discharge. Patients with peak Na <150 mmol/L and peak Na—minimum Na <10 can be safely discharged without desmopressin prescription. [ABSTRACT FROM AUTHOR]

Background: The impact of sagittal spinopelvic alignment on spondylolysis is well established in Caucasian populations. However, prior studies suggest that people from different ethnological backgrounds showed divergence, and a few studies that focused on Asian populations reported conflicting results. The aim of this study is to use the EOS imaging system to evaluate the spinopelvic parameters of spondylolysis patients, and their relationship with spondylolisthesis, disc degeneration, and age in a Taiwanese population.Methods: Radiographic sagittal spinopelvic parameters for 45 spondylolysis patients and 32 healthy people were evaluated, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and lumbar lordosis (LL). The spinopelvic parameters were compared between spondylolytic and control groups. These parameters were further compared between spondylolytic subjects with and without spondylolisthesis, with and without high-grade disc degeneration, and young (< 30 years old) and middle-aged.Results: The PI and LL of the spondylolytic group (52.6°±12.0° and 41.3°±15.2°) were significantly higher than those of the healthy control group (47.16°±7.95° and 28.22°±10.65°). Further analysis of the spondylolytic patients revealed that those with high-grade disc degeneration were more prone to spondylolisthesis (92.3 %) compared to those without (50 %; p = 0.001). The middle-aged group had significantly higher rates of spondylolisthesis (80 %) and high-grade disc degeneration (52.4 %) compared with those for the young group (45 and 16.7 %, respectively; p = 0.017 and 0.047, respectively). No statistically significant difference in the sagittal spinopelvic parameters was found when spondylolytic patients were divided according to the occurrence of spondylolisthesis or high-grade disc degeneration.Conclusions: In a Taiwanese population, PI and LL were significantly larger in spondylolytic patients. Disc degeneration and age were associated with the occurrence of spondylolisthesis. Ethnological differences should thus be taken into account when making clinical decisions regarding spondylolysis in a Taiwanese population. [ABSTRACT FROM AUTHOR]

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death. [ABSTRACT FROM AUTHOR]

Statistical methods for analyzing recurrent events have attracted significant attention. The majority of existing works consider situations in which subjects are observed over time periods and events of interest that occurred during the course of follow-up are recorded. In some applications, a subject may leave the study for a period of time and then resume due to various reasons. During the absence, which is referred to as an intermittent gap in this study, it may be impossible to observe a recording of the event. A naive analysis disregards gaps and considers events to be a typical recurrent event dataset. However, this may result in biased estimations and misleading results. In this study, we build an additive rates model for recurrent event data considering intermittent gaps. We provide the asymptotic theories behind the proposed model, as well as the goodness of fit between observed and modeled values. Simulation studies reveal that the estimations perform well if intermittent gaps are taken into account. In addition, we utilized the longitudinal cohort of elderly patients who have type 2 diabetes and at least one record of a severe recurrent complication, hypoglycemia, from the National Health Insurance Research Database in Taiwan to demonstrate the proposed method. [ABSTRACT FROM AUTHOR]

This study explored heterogeneous treatment effects (HTEs) of the real‐world use of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan's National Health Insurance Research Database, 19,853 propensity score‐matched pairs of DPP‐4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three‐point major adverse cardiovascular event (MACE), and all‐cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP‐4i vs. SU (ARD −4.31%, 95% CI −7.48% to −1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP‐4i at age < 69.3 years (ARD −0.90%, 95% CI −1.47% to −0.32%, HR 0.86, 95% CI 0.77 ~ 0.97). Patients with prior IS/TIA benefited most in reduced risks of three‐point MACE from using DPP‐4i vs. SU (ARD −4.22%, 95% CV −6.66% to −1.78%, HR 0.80, 95% CI 0.69 ~ 0.93), followed by those without prior IS/TIA and initiated with DPP‐4i at age < 69.3 years (ARD −0.68%, 95% CI −1.08% to −0.29%, HR 0.81, 95% CI 0.70 ~ 0.93). Consideration of CVD and IS/TIA histories and age could facilitate individualized diabetes management of using DPP‐4i vs. SU. Future studies are warranted given the hypothesis‐generating nature in this exploratory research. [ABSTRACT FROM AUTHOR]

Objective: We assessed the quality of life (QoL) and pregnancy outcomes of in vitro fertilization (IVF) treatment among infertile women with endometriosis, as compared to infertile women without endometriosis.Study Design: Eighty-one (81) endometriosis women (with 142 embryo transfer [ET] cycles) and 605 non-endometriosis women (with 1063 ET cycles) were included. QoL was measured by FertiQoL at the date before ET. Pregnancy outcomes included biochemical pregnancy, ongoing pregnancy and live birth. Generalized estimating equation analyses were performed to assess the association between QoL and IVF pregnancy.Results: Endometriosis-affected women had significantly lower QoL, as indicated by mind/body, treatment environment and total treatment scores, and total scores of FertiQoL (p < .05), compared to those without endometriosis. Among non-endometriosis women, QoL scores were significantly associated with successful IVF pregnancy; with one unit increase in QoL scores as measured by emotional domain of FertiQoL, the probabilities of ongoing pregnancy and live birth significantly increased by 2.5% and 2.8%, respectively (p < .05). This association was also observed among endometriosis women but it did not reach statistical significance.Conclusions: Lower QoL among women with endometriosis versus non-endometriosis during IVF treatment highlights the importance of developing strategies to improve their QoL, which may enhance following pregnancy rates in this population. [ABSTRACT FROM AUTHOR]

Objective: Developing country-specific unit-cost catalogs is a key area for advancing economic research to improve medical and policy decisions. However, little is known about how health care costs vary by type 2 diabetes (T2D) complications across time in Asian countries. We sought to quantify the economic burden of various T2D complications in Taiwan.Research Design and Methods: A nationwide, population-based, longitudinal study was conducted to analyze 802,429 adults with newly diagnosed T2D identified during 1999-2010 and followed up until death or 31 December 2013. Annual health care costs associated with T2D complications were estimated, with multivariable generalized estimating equation models adjusted for individual characteristics.Results: The mean annual health care cost was $281 and $298 (2017 U.S. dollars) for a male and female, respectively, diagnosed with T2D at age <50 years, with diabetes duration of <5 years, and without comorbidities, antidiabetic treatments, and complications. Depression was the costliest comorbidity, increasing costs by 64-82%. Antidiabetic treatments increased costs by 72-126%. For nonfatal complications, costs increased from 36% (retinopathy) to 202% (stroke) in the event year and from 13% (retinopathy or neuropathy) to 49% (heart failure) in subsequent years. Costs for the five leading costly nonfatal subtype complications increased by 201-599% (end-stage renal disease with dialysis), 37-376% (hemorrhagic/ischemic stroke), and 13-279% (upper-/lower-extremity amputation). For fatal complications, costs increased by 1,784-2,001% and 1,285-1,584% for cardiovascular and other-cause deaths, respectively.Conclusions: The cost estimates from this study are crucial for parameterizing diabetes economic simulation models to quantify the economic impact of clinical outcomes and determine cost-effective interventions. [ABSTRACT FROM AUTHOR]

Background: To assess the associations of various HbA1c measures, including a single baseline HbA1c value, overall mean, yearly updated means, standard deviation (HbA1c-SD), coefficient of variation (HbA1c-CV), and HbA1c variability score (HVS), with microvascular disease (MVD) risk in patients with type 2 diabetes. Methods: Linked data between National Cheng Kung University Hospital and Taiwan's National Health Insurance Research Database were utilized to identify the study cohort. The primary outcome was the composite MVD events (retinopathy, nephropathy, or neuropathy) occurring during the study follow-up. Cox model analyses were performed to assess the associations between HbA1c measures and MVD risk, with adjustment for patients' baseline HbA1c, demographics, comorbidities/complications, and treatments. Results: In the models without adjustment for baseline HbA1c, all HbA1c variability and mean measures were significantly associated with MVD risk, except HVS. With adjustment for baseline HbA1c, HbA1c-CV had the strongest association with MVD risk. For every unit of increase in HbA1c-CV, the MVD risk significantly increased by 3.42- and 2.81-fold based on the models without and with adjustment for baseline HbA1c, respectively. The associations of HbA1c variability and mean measures with MVD risk in patients with baseline HbA1c < 7.5% (58 mmol/mol) were stronger compared with those in patients with baseline HbA1c ≥ 7.5% (58 mmol/mol). Conclusions: HbA1c variability, especially HbA1c-CV, can supplement conventional baseline HbA1c measure for explaining MVD risk. HbA1c variability may play a greater role in MVD outcomes among patients with relatively optimal baseline glycemic control compared to those with relatively poor baseline glycemic control. [ABSTRACT FROM AUTHOR]

In long‐term clinical studies, recurrent event data are sometimes collected and used to contrast the efficacies of two different treatments. The event reoccurrence rates can be compared using the popular negative binomial model, which incorporates information related to patient heterogeneity into a data analysis. For treatment allocation, a balanced approach in which equal sample sizes are obtained for both treatments is predominately adopted. However, if one treatment is superior, then it may be desirable to allocate fewer subjects to the less‐effective treatment. To accommodate this objective, a sequential response‐adaptive treatment allocation procedure is derived based on the doubly adaptive biased coin design. Our proposed treatment allocation schemes have been shown to be capable of reducing the number of subjects receiving the inferior treatment while simultaneously retaining a test power level that is comparable to that of a balanced design. The redesign of a clinical study illustrates the advantages of using our procedure. [ABSTRACT FROM AUTHOR]

We assessed the effect of atosiban on pregnancy outcomes following in vitro fertilization (IVF) treatment among infertile women requiring different numbers of embryo transfer (ET) cycles (i.e., one, two, and more than two ET cycles). A longitudinal cohort study was conducted by utilizing the data from the Assisted Reproductive Technology Center in a university tertiary hospital during 2007–2017. Patients receiving IVF treatment with at least one ET cycle were included. Pregnancy outcomes following IVF treatment, including biochemical, clinical, and ongoing pregnancies, were investigated. The association between atosiban and IVF pregnancy was assessed using logistic generalized estimating equation models, with adjustment for time-varying clinical characteristics (e.g., maternal age) across multiple ET cycles for an individual. 403 women with 838 ET cycles were included, where 165 patients required one ET cycle, 133 patients required two ET cycles (a total of 266 ET cycles), and 105 patients required more than two ET cycles (a total of 407 ET cycles). Atosiban use was not significantly associated with pregnancy outcomes among all study infertile women undergoing IVF treatment. However, the results for women requiring more than two ET cycles showed significantly increased pregnancy rates associated with atosiban use (i.e., odds ratios [95% confidence interval] of 4.40 [1.52, 12.73] and 2.85 [1.45, 5.60] for clinical and ongoing pregnancies, respectively). This association was not observed for the women requiring only one or two ET cycles. Atosiban is a potential treatment for enhancing IVF pregnancy, especially among infertile women requiring more than two ET cycles. [ABSTRACT FROM AUTHOR]

Background and Objective. The main purpose of this study was to develop a simple automatic diagnostic classification scheme for chemotherapy-induced peripheral neuropathy. Methods. This was a prospective cohort study that enrolled patients with colorectal or gynecologic cancer post chemotherapy for more than 1 year. The patients underwent laboratory examinations (nerve conduction studies and quantitative sensory tests), and a questionnaire about the quality of life. An unsupervised classification algorithm was used to classify the patients into groups using a small number of variables derived from the laboratory tests. A panel of five neurologists also diagnosed the types of neuropathies according to the laboratory tests. The results by the unsupervised classification algorithm and the neurologists were compared. Results. The neurologists' diagnoses showed much higher rates of entrapment syndromes (66.1%) and radiculopathies (55.1%) than polyneuropathy (motor/sensory: 33.1%/29.7%). A multivariate analysis showed that the questionnaire was not significantly correlated with the results of quantitative sensory tests (r = 0.27) or the neurologists' diagnoses (r = 0.2). All of the patients were classified into four groups by the unsupervised classification algorithm. The classification corresponded to the severity of neuropathy and correlated well with the neurologists' diagnoses and the scales of neurological examinations. The overall correct rate of classification by the unsupervised classification algorithm was 78.8% (95% confidence interval: 73.1%-88.3%). Conclusion. The results of our unsupervised classification algorithm based on three variables of laboratory tests correlated well with the neurologists' diagnoses. [ABSTRACT FROM AUTHOR]

Older ICU survivors are often challenged with clusters of geriatric syndromes and functional decline. The purpose of this study was (a) to assess patterns of geriatric syndromes and functional status from admission to 6 months post discharge and (b) to examine the predictors of longitudinal functional status. This is a prospective cohort study. Demographic information, clinical variables, geriatric syndromes, and functional status were collected longitudinally. A total of 192 medical ICU older adult survivors were included in the analysis. Factors associated with reductions in functional status over 6 months were (a) institutionalized prior to hospitalization, (b) pressure sore before admission, (c) existing delirium, (d) impaired mobility at baseline, (e) increased APACHE II score upon ICU admission, and (f) use of mechanical ventilation during the ICU stay. Importantly, overweight was the only factor that was associated with increased functional level over 6 months. [ABSTRACT FROM AUTHOR]

A comparison of 2 treatments with survival outcomes in a clinical study may require treatment randomization on clusters of multiple units with correlated responses. For example, for patients with otitis media in both ears, a specific treatment is normally given to a single patient, and hence, the 2 ears constitute a cluster. Statistical procedures are available for comparison of treatment efficacies. The conventional approach for treatment allocation is the adoption of a balanced design, in which half of the patients are assigned to each treatment arm. However, considering the increasing acceptability of responsive-adaptive designs in recent years because of their desirable features, we have developed a response-adaptive treatment allocation scheme for survival trials with clustered data. The proposed treatment allocation scheme is superior to the balanced design in that it allows more patients to receive the better treatment. At the same time, the test power for comparing treatment efficacies using our treatment allocation scheme remains highly competitive. The advantage of the proposed randomization procedure is supported by a simulation study and the redesign of a clinical study. [ABSTRACT FROM AUTHOR]

Purpose: A slouching posture during smartphone usage increases gravitational loadings on the cervical spine, which may lead to neck pain and degeneration. The objective of the present study was to investigate the head, neck and trunk angles in different smartphone-usage postures, as well as the posture-correction effects and comfort scores of three neck collars.Methods: This was a prospective cohort study in which 41 healthy young subjects aged 18-25 were recruited. The head, neck and trunk angles were measured in all participants during a neutral position and three smartphone-using postures, including sitting with and without back support and standing. The postural correction and comfort scores of three collars (Aspen Vista, Sport-aid and our customized 3D printed collars) were compared.Results: Smartphone use increased the head and neck flexion angles in all postures, and sitting without back support showed the greatest head and neck flexion angles. The posture-correcting effect of the customized collar was better than the Aspen Vista and Sport-aid collars. In addition, the customized collar was more comfortable to wear than the other two collars in most contact areas.Conclusion: Smartphone use increased both the head and neck flexion in different postures, and the proposed customized 3D-printed cervical collar significantly reduced the head and neck angles. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

This study investigated the incidence, rationales, and associated factors of inappropriate urinary catheter use among hospitalized older patients by gender. A longitudinal study of 321 patients with urinary catheter was conducted. Demographic factors, present health factors, urinary catheter factors, and indications of catheter use were collected. A total of 53.7% of urinary catheter-days were inappropriate. For both men and women, there was no significant difference in the incidence and common rationales of inappropriate use. Women, however, have another associated factor with inappropriate use. More tailored alternatives are needed for women to increase comfort to avoid inappropriate catheter use. [ABSTRACT FROM AUTHOR]

Sample size determination is essential during the planning phases of clinical trials. To calculate the required sample size for paired right-censored data, the structure of the within-paired correlations needs to be pre-specified. In this article, we consider using popular parametric copula models, including the Clayton, Gumbel, or Frank families, to model the distribution of joint survival times. Under each copula model, we derive a sample size formula based on the testing framework for rank-based tests and non-rank-based tests (i.e., logrank test and Kaplan- Meier statistic, respectively). We also investigate how the power or the sample size was affected by the choice of testing methods and copula model under different alternative hypotheses. In addition to this, we examine the impacts of paired-correlations, accrual times, follow-up times, and the loss to follow-up rates on sample size estimation. Finally, two real-world studies are used to illustrate our method and R code is available to the user. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess predictive ability of heart rate variability (HRV) for pregnancy outcomes with in vitro fertilization (IVF) treatment. Research design and method: A total of 180 women with 261 cycles of IVF and 211 embryo transfers (ETs) were analyzed. HRV was measured at four times during IVF treatment: the first date of menstruation, r-HCG (Ovidrel) administration, and before and after ET. Pregnancy indicators included chemical pregnancy, ongoing pregnancy (> 10 weeks), and live birth (pregnancy > 24 weeks). Mixed effect models were applied to identify predictors for IVF pregnancy. The area under the receiver operating characteristic curve (AUC) was used to assess prediction models for pregnancy. Results: The HRV values increased during IVF treatment and then decreased after ET. The trend of changes in HRV values during IVF treatment was significant among patients with chemical pregnancy (p < 0.01) and those with live birth (p = 0.02). Women without pregnancy had lower HRV compared to those with IVF pregnancy (p < 0.05). With a one unit increase in HRV difference before and after ET, the odds of chemical pregnancy decreased by 18% (odds ratio; OR: 0.82, 95% CI: 0.70–0.97, p < 0.02). With a one year increase in maternal age, the odds decreased by 16% (OR: 0.84, 95% CI: 0.76–0.93, p < 0.01), 25% (OR: 0.75, 95% CI: 0.58–0.93, p = 0.02), and 28% (OR: 0.72, 95% CI: 0.54–0.91, p = 0.01) for chemical pregnancy, ongoing pregnancy, and live birth, respectively. The AUCs were 0.77 (95% CI: 0.70, 0.84), 0.89 (0.79, 0.98), and 0.91(0.83, 0.99) for the prediction models for chemical pregnancy, ongoing pregnancy, and live birth, respectively. Conclusions: Reduced HRV may be an indicator for low chance of IVF pregnancy. The changes in HRV before and after ET and maternal age might be prognostic predictors of IVF pregnancy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to verify and compare the accuracy of energy expenditure (EE) prediction models using shoe-based motion detectors with embedded accelerometers. Methods: Three physical activity (PA) datasets (unclassified, recognition, and intensity segmentation) were used to develop three prediction models. A multiple classification flow and these models were used to estimate EE. The “unclassified” dataset was defined as the data without PA recognition, the “recognition” as the data classified with PA recognition, and the “intensity segmentation” as the data with intensity segmentation. The three datasets contained accelerometer signals (quantified as signal magnitude area (SMA)) and net heart rate (HRnet). The accuracy of these models was assessed according to the deviation between physically measured EE and model-estimated EE. Results: The variance between physically measured EE and model-estimated EE expressed by simple linear regressions was increased by 63% and 13% using SMA and HRnet, respectively. The accuracy of the EE predicted from accelerometer signals is influenced by the different activities that exhibit different count-EE relationships within the same prediction model. Conclusion: The recognition model provides a better estimation and lower variability of EE compared with the unclassified and intensity segmentation models. Significance: The proposed shoe-based motion detectors can improve the accuracy of EE estimation and has great potential to be used to manage everyday exercise in real time. [ABSTRACT FROM AUTHOR]

Sample size determination is essential during the planning phases of a study. When the study endpoint is the time to an event, Cox proportional hazard model is the traditional technique to analyze the effects of covariates on survival time. In contrast to the proportional hazard model, the additive hazard (AH) model specifies that the effect of covariates additively increases or decreases the hazard function. The popularity of this model is that it gives a more intuitive interpretation without the proportional hazard assumption. Because there is no literature estimating the required sample size based on the AH model, we provide a flexible formula for calculating the required sample size. The proposed formula incorporates time-independent and time-dependent effects of covariates without complicated mathematical calculations. The performance of the method was evaluated by extensive simulations. Finally, some pilot studies are shown to illustrate the applications. [ABSTRACT FROM PUBLISHER]

The purpose of this paper is to develop a formula for calculating the required sample size for paired recurrent events data. The developed formula is based on robust non-parametric tests for comparing the marginal mean function of events between paired samples. This calculation can accommodate the associations among a sequence of paired recurrent event times with a specification of correlated gamma frailty variables for a proportional intensity model. We evaluate the performance of the proposed method with comprehensive simulations including the impacts of paired correlations, homogeneous or nonhomogeneous processes, marginal hazard rates, censoring rate, accrual and follow-up times, as well as the sensitivity analysis for the assumption of the frailty distribution. The use of the formula is also demonstrated using a premature infant study from the neonatal intensive care unit of a tertiary center in southern Taiwan. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim The present study aimed to identify the health profiles of older adults by using latent class analysis to investigate health heterogeneity and to determine what factors predicted healthy aging among an oldest-old sample cohort that was followed up for 14 years in Taiwan. Methods Data were drawn from five waves (carried out in 1993, 1996, 1999, 2003 and 2007) of the Taiwan Longitudinal Study on Aging to examine the changes in health heterogeneity in a nationally representative oldest-old cohort of Taiwanese. Overall, data from a total of 11 145 observations of 3155 older adults were considered. The influential factors predicting health changes were analyzed by using a generalized estimating equation. Results The results showed that four health profiles were identified among the aging population observed in the Taiwan Longitudinal Study on Aging. With increasing age, the combined effects of the physical functioning, cognitive and emotional health, and comorbidities of older adults significantly impact their health changes. Apart from health deteriorating with age and sex disparities, educational and economic status, health behaviors, and social participation at the individual level were found to be the robust factors in predicting healthy aging. Conclusions In considering what factors impact healthy aging, we suggest that a person-centered approach would be useful and critical for policy makers to understand the compositions of health profiles and the influencing factors in view of a life-course perspective. Based on the factors identified as influencing healthy aging at the individual level, it is imperative from a policy-making perspective to maximize opportunities for healthy aging. Geriatr Gerontol Int 2017; 17: 697-707. [ABSTRACT FROM AUTHOR]

To assess the effect of chemotherapy on mitochondrial genome mutations in cancer survivors and their offspring, a study sequenced the full mitochondrial genome and determined the mitochondrial DNA heteroplasmic (mtDNA) mutation rate. To build a model for counts of heteroplasmic mutations in mothers and their offspring, bivariate Poisson regression was used to examine the relationship between mutation count and clinical information while accounting for the paired correlation. However, if the sequencing depth is not adequate, a limited fraction of the mtDNA will be available for variant calling. The classical bivariate Poisson regression model treats the offset term as equal within pairs; thus, it cannot be applied directly. In this research, we propose an extended bivariate Poisson regression model that has a more general offset term to adjust the length of the accessible genome for each observation. We evaluate the performance of the proposed method with comprehensive simulations, and the results show that the regression model provides unbiased parameter estimations. The use of the model is also demonstrated using the paired mtDNA dataset. [ABSTRACT FROM AUTHOR]

Rocker-soled shoes provide a way to reduce the possible concentration of stress, as well as change movement patterns, during gait. This study attempts to examine how plantar force and spatio-temporal variables are affected by two rocker designs, one with softer and one with denser sole materials, by comparing them with the barefoot condition and with flat-soled shoes. Eleven subjects’ gait parameters during walking and jogging were recorded. Our results showed that compared with barefoot walking, plantar forces were higher for flat shoes while lower for both types of rocker shoes, the softer-material rocker being the lowest. The plantar force of flat shoes is greater than the vertical ground reaction force, while that of both rocker shoes is much less, 13.87–30.55% body weight. However, as locomotion speed increased to jogging, for all shoe types, except at the second peak plantar force of the denser sole material rocker shoes, plantar forces were greater than for bare feet. More interestingly, because the transmission of force was faster while jogging, greater plantar force was seen in the rocker-soled shoes with softer material than with denser material; results for higher-speed shock absorption in rocker-soled shoes with softer material were thus not as good. In general, the rolling phenomena along the bottom surface of the rocker shoes, as well as an increase in the duration of simultaneous curve rolling and ankle rotation, could contribute to the reduction of plantar force for both rocker designs. The possible mechanism is the conversion of vertical kinetic energy into rotational kinetic energy. To conclude, since plantar force is related to foot-ground interface and deceleration methods, rocker-design shoes could achieve desired plantar force reduction through certain rolling phenomena, shoe-sole stiffness levels, and locomotion speeds. [ABSTRACT FROM AUTHOR]

Determination of an adequate sample size is critical to the design of research ventures. For clustered right-censored data, Manatunga and Chen [Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes. Biometrics. 2000;56(2):616–621] proposed a sample size calculation based on considering the bivariate marginal distribution as Clayton copula model. In addition to the Clayton copula, other important family of copulas, such as Gumbel and Frank copulas are also well established in multivariate survival analysis. However, sample size calculation based on these assumptions has not been fully investigated yet. To broaden the scope of Manatunga and Chen [Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes. Biometrics. 2000;56(2):616–621]'s research and achieve a more flexible sample size calculation for clustered right-censored data, we extended the work by assuming the marginal distribution as bivariate Gumbel and Frank copulas. We evaluate the performance of the proposed method and investigate the impacts of the accrual times, follow-up times and the within-clustered correlation effect of the study. The proposed method is applied to two real-world studies, and the R code is made available to users. [ABSTRACT FROM PUBLISHER]

The article discusses as study which compared the positive end-expiratory pressure (PEEP) electrical impedance tomography (EIT) or PEEP selection based on best respiratory system compliance during decremental PEEP titration in acute respiratory distress syndrome (ARDS) patients. Data on the patients included in the study are presented. It was found that PEEP selection based on PEEP EIT is justified.

The Shewhart-type control chart is traditionally developed under the normality assumption. In practice, however, this assumption may not hold. Because the skew normal distribution represents a broad distribution class and is more flexible than is the normal distribution, we propose two new control charts to monitor process mean and spread for skew normal distributed data. Moreover, to facilitate practical implementation, tables of charting constants are provided. We conducted simulation studies to compare the false alarm rates, and the results show that new proposed charts perform better than others as skewness increases. Finally, an illustrative example is provided. [ABSTRACT FROM PUBLISHER]

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases. [ABSTRACT FROM AUTHOR]

Current status data arise naturally from tumorigenicity experiments, epidemiology studies, biomedicine, econometrics and demographic and sociology studies. Moreover, clustered current status data may occur with animals from the same litter in tumorigenicity experiments or with subjects from the same family in epidemiology studies. Because the only information extracted from current status data is whether the survival times are before or after the monitoring or censoring times, the nonparametric maximum likelihood estimator of survival function converges at a rate of n 1∕3 to a complicated limiting distribution. Hence, semiparametric regression models such as the additive hazards model have been extended for independent current status data to derive the test statistics, whose distributions converge at a rate of n 1∕2, for testing the regression parameters. However, a straightforward application of these statistical methods to clustered current status data is not appropriate because intracluster correlation needs to be taken into account. Therefore, this paper proposes two estimating functions for estimating the parameters in the additive hazards model for clustered current status data. The comparative results from simulation studies are presented, and the application of the proposed estimating functions to one real data set is illustrated. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Risk prediction for tumor recurrence is important for making effective treatment decisions and for the survival outcomes of patients with CRC after surgery. Herein, we aimed to explore a prediction algorithm and the risk factors for postoperative tumor recurrence using a machine learning (ML) approach with standardized pathology reports for patients with stage II and III CRC. Methods: Pertinent clinicopathological features were compiled from medical records and standardized pathology reports of patients with stage II and III CRC. Four ML models based on logistic regression (LR), random forest (RF), classification and regression decision trees (CARTs), and support vector machine (SVM) were applied for the development of the prediction algorithm. The area under the curve (AUC) of the ML models was determined in order to compare the prediction accuracy. Genomic studies were performed using a panel-targeted next-generation sequencing approach. Results: A total of 1073 patients who received curative intent surgery at the National Cheng Kung University Hospital between January 2004 and January 2019 were included. Based on conventional statistical methods, chemotherapy (p = 0.003), endophytic tumor configuration (p = 0.008), TNM stage III disease (p < 0.001), pT4 (p < 0.001), pN2 (p < 0.001), increased numbers of lymph node metastases (p < 0.001), higher lymph node ratios (LNR) (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p < 0.001), tumor budding (p = 0.004), and neoadjuvant chemoradiotherapy (p = 0.025) were found to be correlated with the tumor recurrence of patients with stage II–III CRC. While comparing the performance of different ML models for predicting cancer recurrence, the AUCs for LR, RF, CART, and SVM were found to be 0.678, 0.639, 0.593, and 0.581, respectively. The LR model had a better accuracy value of 0.87 and a specificity value of 1 in the testing set. Two prognostic factors, age and LNR, were selected by multivariable analysis and the four ML models. In terms of age, older patients received fewer cycles of chemotherapy and radiotherapy (p < 0.001). Right-sided colon tumors (p = 0.002), larger tumor sizes (p = 0.008) and tumor volumes (p = 0.049), TNM stage II disease (p < 0.001), and advanced pT3–4 stage diseases (p = 0.04) were found to be correlated with the older age of patients. However, pN2 diseases (p = 0.005), lymph node metastasis number (p = 0.001), LNR (p = 0.004), perineural invasion (p = 0.018), and overall survival rate (p < 0.001) were found to be decreased in older patients. Furthermore, PIK3CA and DNMT3A mutations (p = 0.032 and 0.039, respectively) were more frequently found in older patients with stage II–III CRC compared to their younger counterparts. Conclusions: This study demonstrated that ML models have a comparable predictive power for determining cancer recurrence in patients with stage II–III CRC after surgery. Advanced age and high LNR were significant risk factors for cancer recurrence, as determined by ML algorithms and multivariable analyses. Distinctive genomic profiles may contribute to discrete clinical behaviors and survival outcomes between patients of different age groups. Studies incorporating complete molecular and genomic profiles in cancer prediction models are beneficial for patients with stage II–III CRC. [ABSTRACT FROM AUTHOR]

Background: Vertebral compression fractures, resulting in significant pain and disability, commonly occur in elderly osteoporotic patients. However, the current literature lacks long-term follow-up information related to image parameters and bone formation following vertebroplasty. Purpose: To evaluate new bone formation after vertebroplasty and the long-term effect of vertebroplasty. Methods: A total of 157 patients with new osteoporotic compression fractures who underwent vertebroplasty were retrospectively analyzed. The image parameters, including wedge angles, compression ratios, global alignment, and new bone formation, were recorded before and after vertebroplasty up to three years postoperatively. Results: The wedge angle improved and was maintained for 12 months. The compression ratios also improved but gradually deteriorated during the follow-up period. New bone formation was found in 40% of the patients at 36 months, and the multivariate analysis showed that this might have been related to the correction of the anterior compression ratio. Conclusions: Vertebroplasty significantly restored the wedge angles and compression ratios up to one year postoperatively, and new bone formation was noted on plain radiographs, which increased over time. Last, the restoration of vertebral parameters may contribute to new bone formation. [ABSTRACT FROM AUTHOR]

Background. Five components of metabolic syndrome (MetS) have been identified as predictive of cardiovascular events (CVEs) in the general population: impaired fasting glucose, abdominal obesity, hypertriglyceridemia, hypertension and low high-density lipoprotein cholesterol. Whether MetS and its components are also predictive of CVEs in chronic hemodialysis (HD) patients remains unclear. We therefore investigated the role of MetS and its components in patients on chronic HD.Methods. MetS at baseline was diagnosed in 91 HD patients based on the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) definitions. During a 3-year period, all hospitalizations, CVEs and deaths were recorded and analyzed using Kaplan–Meier survival analysis and Cox regression.Results. There were no differences in the number of CVEs, hospitalizations or deaths between patients with and without AHA/NHLBI-defined MetS; however, patients with IDF-defined MetS were found to be at a higher risk for CVEs (P = 0.006). Cox regression analysis showed that, of the MetS components, abdominal obesity was the single most significant predictor of CVEs (hazard ratio 6.25; 95% confidence interval: 1.65–23.6; P = 0.007).Conclusions. IDF-defined MetS was more predictive of CVEs than AHA/NHLBI-defined MetS. Of the MetS components, abdominal obesity was the single most significant predictor of CVEs in chronic HD patients. [ABSTRACT FROM AUTHOR]

Clustered right-censored data often arise from tumorigenicity experiments and clinical trials. For testing the equality of two survival functions, Jung and Jeong extended weighted logrank (WLR) tests to two independent samples of clustered right-censored data, while the weighted Kaplan-Meier (WKM) test can be derived from the work of O'Gorman and Akritas. The weight functions in both classes of tests (WLR and WKM) can be selected to be more sensitive to detect a certain alternative; however, since the exact alternative is unknown, it is difficult to specify the selected weights in advance. Since WLR is rank-based, it is not sensitive to the magnitude of the difference in survival times. Although WKM is constructed to be more sensitive to the magnitude of the difference in survival times, it is not sensitive to late hazard differences. Therefore, in order to combine the advantages of these two classes of tests, this paper developed a class of versatile tests based on simultaneously using WLR and WKM for two independent samples of clustered right-censored data. The comparative results from a simulation study are presented and the implementation of the versatile tests to two real data sets is illustrated. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Although Recepteur d’Origine Nantais (RON), a member of the MET receptor tyrosine kinase family, is overexpressed and constitutively active in some primary tumors and tumor cell lines, its expression pattern and clinical significance in colorectal cancer are not well documented. By using immunohistochemical staining, we examined RON and MET expression in 135 colorectal cancer specimens and investigated the association of the immunoreactivity of both receptors with colorectal cancer clinical parameters and prognosis. We found moderate to strong expression in 99 cases (73 percent) for RON and 97 cases (72 percent) for MET. Univariate analysis showed that increased immunoreactivity of RON or MET was associated with shorter patient survival and that moderate to strong coexpression of both receptors was associated with a significantly worse prognosis. Multivariate Cox analysis showed that the risk of tumor recurrence for patients with high-RON/high-MET expression was approximately 11 times greater than for patients with low-RON/low-MET expression ( P = 0.001). In addition, RON and MET expression levels were positively correlated ( P ≤ 0.001; τ = 0.306). The crosstalk between RON and MET in colorectal cancer seems important. Evaluating the expression patterns of RON and MET was predictive of clinical outcome for patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common gynecological cancer in developed countries. At initial diagnosis, extra-uterine spread is observed in about 25% of patients. Chemotherapy is the suggested mode of treatment for patients with extra-uterine metastasis; however, the 5-year overall survival rate of these patients remains poor. The development of new therapeutic strategies to improve the poor clinical outcome of patients with advanced endometrial cancer is still in great demand. In this study, we aim to understand the genomic landscape of advanced endometrial cancer and identify new therapeutic targets. Integrated genomic, pathological, and clinical data are analyzed to identify the survival-associated genomic alterations. In addition, the impacts of the genomic alterations are examined in silico, in vitro, and in vivo. The results of this study may aid in developing biomarker-guided treatments for patients with advanced endometrial cancer. An optimal therapeutic regimen for endometrial cancer with extra-uterine metastasis is unavailable. This study aims to improve our understanding of the genomic landscape of advanced endometrial cancer and identify potential therapeutic targets. The clinical and genomic profiles of 81 patients with stage III or IV endometrial cancer were integrated. To identify genomic aberrations associated with clinical outcomes, Cox proportional hazard regression was used. The impacts of the genomic aberrations were validated in vitro and in vivo. The mutation status of MET, U2AF1, BCL9, PPP2R1A, IDH2, CBL, BTK, and CHEK2 were positively correlated with poor clinical outcomes. MET mutations occurred in 30% of the patients who presented with poor overall survival (hazard ratio, 2.606; 95% confidence interval, 1.167~5.819; adjusted p-value, 0.067). Concurrent MET and KRAS mutations presented with the worst outcomes. MET mutations in hepatocyte growth factor (HGF)-binding (58.1%) or kinase (16.2%) domains resulted in differential HGF-induced c-MET phosphorylation. Different types of MET mutations differentially affected tumor growth and displayed different sensitivities to cisplatin and tyrosine kinase inhibitors. MET N375S mutation is a germline variant that causes chemoresistance to cisplatin, with a high incidence in Eastern Asia. This study highlights the ethnic differences in the biology of the disease, which can influence treatment recommendations and the genome-guided clinical trials of advanced endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: Evidence is limited on excess risks of cardiovascular diseases (CVDs) associated with ambient air pollution in diabetic populations. Survival analyses without considering the spatial structure and possible spatial correlations in health and environmental data may affect the precision of estimation of adverse environmental pollution effects. We assessed the association between air pollution and CVDs in type 2 diabetes through a Bayesian spatial survival approach.Methods: Taiwan's national-level health claims and air pollution databases were utilized. Fine individual-level latitude and longitude were used to determine pollution exposure. The exponential spatial correlation between air pollution and CVDs was analyzed in our Bayesian model compared to traditional Weibull and Cox models.Results: There were 2072 diabetic patients included in analyses. PM2.5 and SO2 were significant CVD risk factors in our Bayesian model, but such associations were attenuated or underestimated in traditional models; adjusted hazard ratio (HR) and 95% credible interval (CrI) or confidence interval (CI) of CVDs for a 1 μg/m3 increase in the monthly PM2.5 concentration for our model, the Weibull and Cox models was 1.040 (1.004-1.073), 0.994 (0.984-1.004), and 0.994 (0.984-1.004), respectively. With a 1 ppb increase in the monthly SO2 concentration, adjusted HR (95% CrI or CI) was 1.886 (1.642-2.113), 1.092 (1.022-1.168), and 1.091 (1.021-1.166) for these models, respectively.Conclusions: Against traditional non-spatial analyses, our Bayesian spatial survival model enhances the assessment precision for environmental research with spatial survival data to reveal significant adverse cardiovascular effects of air pollution among vulnerable diabetic patients. [ABSTRACT FROM AUTHOR]