Association of retinopathy severity with cardiovascular and renal outcomes in patients with type 1 diabetes: a multi-state modeling analysis.

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.

The Biomechanical Properties of a High-Tensile Strength Tape for Tendon Graft Fixation Using the Krackow Configuration.

PURPOSE: To compare the biomechanical properties of a high-tensile strength suture with the high-tensile strength tape for tendon graft fixation. METHODS: A total of 24 porcine tendons were used and were randomly divided into 2 groups. Two kinds of suture materials, a braided nonabsorbable high-strength suture (group S) and a high-tensile strength tape (group T), were used to complete 3 pairs of Krackow stitches on the tendons. Each specimen was pretensioned to 100 N for 3 cycles, cyclically loaded from 50 to 200 N for 200 cycles, and finally loaded to failure. Elongation after cyclic loading, ultimate failure load, and the mode of failure were recorded. RESULTS: The elongation after cyclic loading between group S (26% ± 5%) and group T (24% ± 5%) were not significantly different (P = .378). The ultimate failure loads in group T (400 ± 38 N) were significantly greater than those in group S (358 ± 21 N) (P = .010). All specimens failed because of suture material breakage. CONCLUSIONS: Compared with the braided nonabsorbable high-strength suture, the high-tensile strength tape had similar elongation values after cyclic loading, but significantly greater ultimate failure load in this porcine in vitro biomechanical model. CLINICAL RELEVANCE: A secure suture-tendon construct is especially important when a post-tie fixation technique is used because the mitigating construct may potentially lead to graft loosening and affect graft healing.

Using Interconnected Knotless Anchor for Suprapectoral Biceps Tenodesis Could Offer Improved Biomechanical Properties in a Cadaveric Model.

PURPOSE: To compare the biomechanical characteristics of the interconnected knotless anchor (IKA) fixation with the double knotless anchor (DKA) and interference screw (IS) fixation in the suprapectoral biceps tenodesis. METHODS: In total, 24 fresh-frozen human cadaveric shoulders (mean age, 67.3 ± 6 years) were used for the study. All the specimens were randomly divided into 3 experimental biceps tenodesis groups (n = 8): IKA, DKA, and IS. After tenodesis, each specimen was preloaded at 5 N for 2 minutes, followed by a cyclic loading test from 5 to 70 N for 500 load cycles. Finally, a destructive axial load to failure test (1 mm/s) was performed. All the values, including ultimate failure load, stiffness, cyclic displacement, and mode of failure were evaluated. RESULTS: The IKA provided the highest construct stiffness (38.9 ± 7.7 N/mm) and ultimate failure load (288.3 ± 47.6 N), the results for which were statistically better than the corresponding results in the IS and DKA groups. In terms of cyclic displacement, there were no statistical differences among the 3 fixation constructs. The most common failure mode was biceps tendon tearing in IS group (7/8) and IKA group (8/8). In the contrast, suture slippage accounted for the most common failure mode in DKA. CONCLUSIONS: In suprapectoral bicep tenodesis, IKA fixation appears to offer improved construct stiffness and ultimate failure load while maintaining comparable suture slippage as compared with IS fixation or DKA fixation in the current biomechanical study. CLINICAL RELEVANCE: The IKA fixation compares favorably with other techniques and could be an alternative clinical option for suprapectoral biceps tenodesis.

Testing of non-inferiority and superiority for three-arm clinical studies with multiple experimental treatments.

The purpose of a non-inferiority trial is to assert the efficacy of an experimental treatment compared with a reference treatment by showing that the experimental treatment retains a substantial proportion of the efficacy of the reference treatment. Statistical methods have been developed to test multiple experimental treatments in three-arm non-inferiority trials. In this paper, we report the development of procedures that simultaneously test the non-inferiority and the superiority of experimental treatments after the assay sensitivity has been established. The advantage of the proposed test procedures is the additional ability to identify superior treatments while retaining an non-inferiority testing power comparable to that of existing testing procedures. Single-step and stepwise procedures are derived and then compared with each other to determine their relative testing power and testing error in a simulation study. Finally, the suggested procedures are illustrated with two clinical examples.

Application of flow cytometry for evaluating clinical prognosis and histopathological grade of human glioma.

OBJECTIVES: Flow cytometry was applied to predict the biological parameters of tumor behavior based on the DNA content distribution of tumors. We used flow cytometry to determine the number of cell cycles for the characterization of intracranial gliomas and its possible prognostic role. METHODS: Flow cytometric analysis of the DNA content was performed for 37 fresh operative glioma specimens. The expression of Ki-67 in glioma specimens was detected using immunohistochemistry staining. The check points of G2/M-phase fractions, cyclin B, and pCdk1 (Y15) were analyzed using Western immunoblotting. RESULTS: Compared to low-grade (grade I/II) gliomas, significant differences in the Ki-67, cyclin B, G2/M-phase, and S+G2/M-phase expressions were found in high-grade (grade III/IV) gliomas. Furthermore, receiver operating characteristic (ROC) analysis indicated optimal cutoff points for the G2/M-phase and S+G2/M-phase fractions of 13.47 and 17.26%, respectively, which can be used to differentiate cases with low- and high-grade gliomas. Additionally, both G2/M-phase and S+G2/M-phase fractions had significant association with the expression of Ki-67 in the gliomas. The gliomas were classified by the DNA content. We found that patients with high-grade glioma had worse survival rate than patients with low-grade glioma. Meanwhile, ROC curve analysis gave cutoffs for G2/M-phase of 9.4% and for S+G2/M-phase fractions of 15.04% as best predicting survival. The patients with glioma had poor survival when the levels of G2/M-phase and S+G2/M-phase were more than 9.4 and 15.04%, respectively. In contrast, no significant association between the DNA content of glioma patients and their age, tumor recurrence, and tumor size was found. DISCUSSION: Our results indicate that flow cytometry analysis for G2/M-phase and S+G2/M-phase fractions can be used for tumor grading for rapidly differentiating low- from high-grade gliomas.

The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.

BACKGROUND: Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas. METHODS: The specimens were obtained from fresh tumoral tissues of 43 microsurgically resected meningiomas as approved by the institutional review board. The presence of G2/M-phase and S+G2/M-phase fractions were analyzed and correlated with the proliferation index of Ki-67 and the World Health Organization grading. The check point of G2/M-phase fraction, cyclin B, and pCdk1 (Y15), were analyzed by Western blotting. RESULTS: Our results showed that there were significant differences in Ki-67, G2/M-phase, S+G2/M-phase fractions, and cyclin B between benign and atypical/anaplastic meningiomas. The optimal cutoff point of G2/M-phase and S+G2/M-phase fractions were 5.12 and 7.52%, respectively, and this can be used to discriminate those cases with benign or atypical/anaplastic meningiomas. Besides, both the G2/M-phase and S+G2/M-phase fractions were correlated well with Ki-67 and the histopathological features such as focal necrosis, infiltration of dura mater and mitotic activity. In addition, the occurrence of tumor recurrence and patient age were correlated to the G2/M-phase and S+G2/M-phase fractions, respectively. The G2/M-phase and S+G2/M-phase fractions, however, did not correlate well with histologic invasion to adjacent bone, sinus, or brain tissues. CONCLUSIONS: The use of flow cytometry facilitates additional information for G2/M-phase and S+G2/M-phase fractions represent tumoral grading and risk of recurrence in patients with meningiomas.

Noninferiority Studies with Multiple New Treatments and Heterogeneous Variances.

The objective of a noninferiority (NI) trial is to affirm the efficacy of a new treatment compared with an active control by verifying that the new treatment maintains a considerable portion of the treatment effect of the control. Compensation by benefits other than efficacy is usually the justification for using a new treatment, as long as the loss of efficacy is within an acceptable margin (NI margin) from the standard treatment. A popular approach is to express this margin in terms of the efficacy difference between the new treatment and the active control. Based on this approach and the realization that NI trials often comprise several new treatments, statistical procedures that simultaneously conduct NI tests of several new treatments have been developed. However, these procedures rely on the assumption that the variances of the treatments are homogeneous. In this article, we discuss the undesirable effect of using these procedures on the familywise Type I error rate when the treatment responses have heterogeneous variances. To alleviate this problem, we reveal potential procedures that are more appropriate. Further, a power study is conducted to compare the different procedures to provide guidance on the selection of adequate testing procedures in NI trials. Clinical examples are given for illustrative purposes.

Trends and determinants of informal and formal caregiving in the community for disabled elderly people in Taiwan.

Although family caregiving for elderly people has been the backbone of long-term care in Taiwan, it is not clear whether informal help from family members has diminished in recent years due to changes in social structure and traditions. The objective of this study is to examine the trend and the factors influencing the use of informal and formal caregiving among disabled elders in the community of Taiwan. Data were drawn from three waves of the Taiwan Longitudinal Study on Aging (TLSA) (1999, 2003, and 2007) to examine the receipt of help with activities of daily living (ADLs) in a nationally representative sample of Taiwanese elderly people aged 65 and older. Results showed the trend in having at least 1 of 6 ADL limitations in the community increased mildly in the past decade but a significant rise in the use of paid help compared to informal help between 1999 and 2007. Factors associated with higher likelihood of paid help use included better socio-economic status and more ADLs. However, those living with spouse only were much less likely to use paid help than those living with adult children. Findings suggest that future long-term care (LTC) policy in Taiwan should focus more on providing elders who live alone or with spouse only additional caregiving resource. Given the rapid growth of foreign care workers as primary source of caregiving, the government needs further monitoring to promote care quality and also strategies to develop needs-led home and community based care.

Extension of three-arm non-inferiority studies to trials with multiple new treatments.

Non-inferiority (NI) trials are becoming increasingly popular. The main purpose of NI trials is to assert the efficacy of a new treatment compared with an active control by demonstrating that the new treatment maintains a substantial fraction of the treatment effect of the control. Most of the statistical testing procedures in this area have been developed for three-arm NI trials in which a new treatment is compared with an active control in the presence of a placebo. However, NI trials frequently involve comparisons of several new treatments with a control, such as in studies involving different doses of a new drug or different combinations of several new drugs. In seeking an adequate testing procedure for such cases, we use a new approach that modifies existing testing procedures to cover circumstances in which several new treatments are present. We also give methods and algorithms to produce the optimal sample size configuration. In addition, we also discuss the advantages of using different margins for the assay sensitivity test between the active control and the placebo and the NI test between the new treatments and the active control. We illustrate the new approach by using data from a clinical trial.

Sample size determination in step-up testing procedures for multiple comparisons with a control.

Step-up procedures have been shown to be powerful testing methods in clinical trials for comparisons of several treatments with a control. In this paper, a determination of the optimal sample size for a step-up procedure that allows a pre-specified power level to be attained is discussed. Various definitions of power, such as all-pairs power, any-pair power, per-pair power and average power, in one- and two-sided tests are considered. An extensive numerical study confirms that square root allocation of sample size among treatments provides a better approximation of the optimal sample size relative to equal allocation. Based on square root allocation, tables are constructed, and users can conveniently obtain the approximate required sample size for the selected configurations of parameters and power. For clinical studies with difficulties in recruiting patients or when additional subjects lead to a significant increase in cost, a more precise computation of the required sample size is recommended. In such circumstances, our proposed procedure may be adopted to obtain the optimal sample size. It is also found that, contrary to conventional belief, the optimal allocation may considerably reduce the total sample size requirement in certain cases. The determination of the required sample sizes using both allocation rules are illustrated with two examples in clinical studies.

A longitudinal evaluation of residents' health outcomes in nursing homes and residential care homes in Taiwan.

PURPOSE: The role of nursing homes (NHs) and residential care homes (RHs) frequently overlaps in Taiwan, raising concerns about their level of care. This study aimed to investigate residents' health outcomes in NHs and RHs 1 year after admission. METHODS: This longitudinal study included four stages of face-to-face interviews with recruited residents. Five main outcome measures, residents' functional status, broad health status (SF-36), resident's/family's satisfaction toward institutions (RSQ), mortality, and relocation rates, were assessed by generalized estimating equations. RESULTS: The mean scores of ADL and RSQ of newly admitted NH residents were significantly lower, and mini-mental state examination (MMSE) scores higher than those of RH residents (P < 0.05). However, MMSE and RSQ showed no statistical difference between these two institutions over time. Moreover, scores for Physical Role, Emotional Role, and Mental Component Scales of SF-36 were significantly improved in NH residents than those of RH residents over time. The survival rate of RH residents was also statistically lower than that of NH residents (chi(2) = 6.2, P < 0.05) 1 year after admission. CONCLUSIONS: NH and RH residents in Taiwan experience significantly different trajectory outcomes in 1 year follow-up, suggesting that the placement for older people with long-term care needs should be constantly monitored.

Clinical effectiveness of International Team for Oral Implantology dental implant treatment in Taiwan: a seven-year longitudinal study.

BACKGROUND: International Team for Oral Implantology (ITI) dental implant has been clinically tested for the most parts of the world, especially in Europe and America, and has not been conducted on Asian population. The purpose of this study was to evaluate the cumulative survival and success rates over 7 years of ITI dental implants. MATERIALS: The ITI dental implant system has been used in the Dental Department of Chi Mei Medical Center since August of 1997. At the end of 2005, 717 solid-screw implants had been placed and loaded at least 6 months in 316 patients. The patient population included 145 males and 171 females, with a mean age of 43.18 +/- 11.60 years. The follow-up interval was from 6 months after the prosthesis was completed to 7 years. The success criteria of dental implant survival was based on Buser et al, Clin Oral Implants Res. 1990;1:33-40. RESULTS: Most implants (486, 67.8%) were placed in the mandible and 231 (32.2%) were placed in the maxilla. Two implants were removed before prostheses fabrication because of postsurgical infections. One implant was removed due to a periapical infection of an adjacent natural tooth. The life table analysis of survival rate and success rate were 99.58% and 96.13%, respectively. CONCLUSION: This 7-year clinical effectiveness study demonstrated this dental implant system gave a clinical reliable result in a Taiwanese population.

A preliminary study of a healthy-lifestyle-promoting program for nursing students in Taiwan.

This pilot study evaluated the effects of a healthy-lifestyle-promoting program, taught as part of an undergraduate community health nursing course, on the physical fitness and health choices of 42 Taiwanese nursing students. A convenience sample provided quantitative indexes of physical fitness and lifestyle before and after the course. Qualitative data, in the form of student diaries, were also analyzed. The findings indicated a positive change in physical fitness, exercise, and nutrition as a result of the program. Including lifestyle programs in nursing education may help promote the long-term health of future nurses who will serve as positive patient role models.