The Impact of Diabetes on Workforce Participation: Results from a National Household Sample

Objective. Diabetes is a highly prevalent condition that results in substantial morbidity and premature mortality. We investigated how diabetes-associated mortality, disability, early retirement, and work absenteeism impacts workforce participation.
Data Source. We used the Health and Retirement Study (HRS), a national household sample of adults aged 51–61 in 1992, as a data source.
Study Design. We conducted cross-sectional analyses on the baseline HRS data, and longitudinal analyses using data from eight years of follow-up. We used two-part regression models to estimate the adjusted impact of diabetes on workforce participation, and then estimated the economic impact of diabetes-related losses in productivity.
Principal Findings. Diabetes is a significant predictor of lost productivity. The incremental lost income due to diabetes by 1992 was $60.0 billion over an average diabetes duration of 9.7 years. From 1992 to 2000, diabetes was responsible for $4.4 billion in lost income due to early retirement, $0.5 billion due to increased sick days, $31.7 billion due to disability, and $22.0 billion in lost income due to premature mortality, for a total of $58.6 billion dollars in lost productivity, or $7.3 billion per year.
Conclusions. In the U.S. population of adults born between 1931 and 1941, diabetes is associated with a profound negative impact on economic productivity. By 1992, an estimated $60 billion in lost productivity was associated with diabetes; additional annual losses averaged $7.3 billion over the next eight years, totaling about $120 billion by the year 2000. Given the rising prevalence of diabetes, these costs are likely to increase substantially unless countered by better public health or medical interventions.     

依那西普对银屑病患者疲劳和抑郁症状的临床疗效：一项双盲、随机、安慰剂对照、Ⅲ期试验

背景：银屑病对患者心理和情绪影响很大。依那西普治疗银屑病患者临床症状有效，作者评估了该药对银屑病相关疲劳和抑郁症状的疗效。方法：618例中至重度银屑病患者接受安慰剂或依那西普50mg（2次／周）双盲治疗。主要疗效终点：治疗12周时，银屑病面积和严重度指数评分较基线改善达75％（PASI 75）或更高水平；次要和其他疗效终点：慢性病治疗疲劳功能评估（FACIT-F）分级、Hamilton抑郁量表（Ham-D）分级、Beck抑郁列表（BDI）及不良事件。根据分组治疗进行疗效分析。基于实际接受治疗的情况对安全性资料进行分析和总结。     

Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.     

Perioperative interstitial irradiation in the conservative management of early breast cancer

Conservation of the breast in early breast cancer with limited resection and radiation is proving to be as effective as modified radical mastectomy in survival and in loco-regional control. Management at the University of Kansas Medical Center consists of an interstitial implant at the time of lumpectomy to facilitate perioperative irradiation with Iridium-192 to the tumor bed. An axillary node dissection is also performed at that time. Two to 3 weeks later external beam irradiation is delivered to the entire breast. One hundred and twenty-three breasts in 120 patients have been treated between June 1982 and June 1986. There were 49 pathological Stage I, 63 Stage II, 8 Stage III carcinomas, and 3 carcinomas in situ, consisting of 72 T1, 43 T2, 5 T3, and 3 TIS lesions. Patients have been followed for a median of 30 months. One patient had a "true" recurrence in the breast. Another patient developed recurrence in a different quadrant. Ninety percent of the patients had good to excellent cosmetic results, 7% were considered fair, and 3% had poor results. Seven patients developed mild arm edema, 4 were found to have moderate edema, and 1 had severe arm edema. Our preliminary results indicate that interstitial irradiation immediately after excision results in excellent local control, with very satisfactory cosmesis and no morbidity due to the simultaneous excision and irradiation.     

HLA‐A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein–Barr virus type 1 (EBV‐1) infection. We carried out a genome‐wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA‐A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10^?9). HLA‐A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA‐A‐aa‐site‐99} = 3.79 × 10^?8, p_rs1136697 = 3.79 × 10^?8) and T‐cell receptor binding site (p_{HLA‐A‐aa‐site‐145} = 1.41 × 10^?4, p_rs1059520 = 1.41 × 10^?4) of the HLA‐A. We also detected strong association signals in the 5′‐UTR region with predicted active promoter states (p_rs41545520 = 7.91 × 10^?8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520‐G correlated with reduced HLA‐A expression. Multivariate logistic regression diminished the effects of HLA‐A amino acid variants and SNPs, indicating a correlation with the effects of HLA‐A*11:01, and to a lesser extent HLA‐A*02:07. We report the strong genetic influence of HLA‐A on NPC susceptibility in the Malaysian Chinese.     

Improvements in the Engineering Properties of Cementitious Composites Using Nano-Sized Cement and Nano-Sized Additives

The findings of an extensive experimental research study on the usage of nano-sized cement powder and other additives combined to form cement–fine-aggregate matrices are discussed in this work. In the laboratory, dry and wet methods were used to create nano-sized cements. The influence of these nano-sized cements, nano-silica fumes, and nano-fly ash in different proportions was studied to the evaluate the engineering properties of the cement–fine-aggregate matrices concerning normal-sized, commercially available cement. The composites produced with modified cement–fine-aggregate matrices were subjected to microscopic-scale analyses using a petrographic microscope, a Scanning Electron Microscope (SEM), and a Transmission Electron Microscope (TEM). These studies unravelled the placement and behaviour of additives in controlling the engineering properties of the mix. The test results indicated that nano-cement and nano-sized particles improved the engineering properties of the hardened cement matrix. The wet-ground nano-cement showed the best result, 40 MPa 28th-day compressive strength, without mixing any additive compared with ordinary and dry-ground cements. The mix containing 50:50 normal and wet-ground cement exhibited 37.20 MPa 28th-day compressive strength. All other mixes with nano-sized dry cement, silica fume, and fly ash with different permutations and combinations gave better results than the normal-cement–fine-aggregate mix. The petrographic studies and the Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) analyses further validated the above findings. Statistical analyses and techniques such as correlation and stepwise multiple regression analysis were conducted to compose a predictive equation to calculate the 28th-day compressive strength. In addition to these methods, a repeated measures Analysis of Variance (ANOVA) was also implemented to analyse the statistically significant differences among three differently timed strength readings.     

Recent advances and clinical pharmacology aspects of Chimeric Antigen Receptor (CAR) T‐cellular therapy development

Advances in immuno‐oncology have provided a variety of novel therapeutics that harness the innate immune system to identify and destroy neoplastic cells. It is noteworthy that acceptable safety profiles accompany the development of these targeted therapies, which result in efficacious cancer treatment with higher survival rates and lower toxicities. Adoptive cellular therapy (ACT) has shown promising results in inducing sustainable remissions in patients suffering from refractory diseases. Two main types of ACT include engineered Chimeric Antigen Receptor (CAR) T cells and T cell receptor (TCR) T cells. The application of these immuno‐therapies in the last few years has been successful and has demonstrated a safe and rapid treatment regimen for solid and non‐solid tumors. The current review presents an insight into the clinical pharmacology aspects of immuno‐therapies, especially CAR‐T cells. Here, we summarize the current knowledge of TCR and CAR‐T cell immunotherapy with particular focus on the structure of CAR‐T cells, the effects and toxicities associated with these therapies in clinical trials, risk mitigation strategies, dose selection approaches, and cellular kinetics. Finally, the quantitative approaches and modeling techniques used in the development of CAR‐T cell therapies are described.