Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study

Abstract Background While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0–19 years) to that of adults (20–64 years). Methods In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001–2015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. Results Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 10–14 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.30–1.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.1–2.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.0–5.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.6–4.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 to 2015 (−1.3%/year; 95% CI −2.3% to −0.4%; P = 0.007). Greater percentages of cases were diagnosed in January, July, and August for both youth and adults. The number of new cases of type 1 diabetes (ages 0–64 years) in the United States is estimated at 64,000 annually (27,000 cases in youth and 37,000 cases in adults). Conclusions There are more new cases of type 1 diabetes occurring annually in the United States than previously recognized. The increase in incidence rates in youth, but not adults, suggests that the precipitating factors of youth-onset disease may differ from those of adult-onset disease.https://deepblue.lib.umich.edu/bitstream/2027.42/139053/1/12916_2017_Article_958.pd

Cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics in patients with glomerulonephritis secondary to lupus and small vessel vasculitis

Cyclophosphamide, the precursor to the active 4-hydroxycyclophosphamide, is used in active glomerulonephritis despite limited pharmacokinetics data. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were evaluated. The influence of laboratory and pharmacogenomic covariates on pharmacokinetics was evaluated as a secondary aim

Bladder Recovery by Stem Cell Based Cell Therapy in the Bladder Dysfunction Induced by Spinal Cord Injury: Systematic Review and Meta-Analysis

Background Bladder dysfunction induced by spinal cord injury (SCI) can become problematic and severely impair the quality of life. Preclinical studies of spinal cord injury have largely focused on the recovery of limb function while neglecting to investigate bladder recovery. Objective The present study was performed to investigate and review the effect of stem cell-based cell therapy on bladder recovery in SCI. Methods We conducted a meta-analysis of urodynamic findings of experimental trials that included studies of stem cell-based cell therapy in SCI. Relevant studies were searched using MEDLINE, EMBASE and Cochrane Library (January 1990 -December 2012). Final inclusion was determined by a urodynamic study involving detailed numerical values. Urodynamic parameters for analysis included voiding pressure, residual urine, bladder capacity and non-voiding contraction (NVC). Meta-analysis of the data, including findings from urodynamic studies, was performed using the Mantel-Haenszel method. Results A total of eight studies were included with a sample size of 224 subjects. The studies were divided into different subgroups by different models of SCI. After a stem cell-based cell therapy, voiding pressure (-6.35, p < 0.00001, I-2 = 77%), NVC (-3.58, p < 0.00001, I-2 = 82%), residual urine (-024, p = 0.004, I-2 = 95%) showed overall significant improvement. Bladder capacity showed improvement after treatment only in the transection type (-0.23, p = 0.0002, I-2 = 0%). Conclusion After stem cell-based cell therapy in SCI, partial bladder recovery including improvement of voiding pressure, NVC, and residual urine was demonstrated. Additional studies are needed to confirm the detailed mechanism and to obtain an ideal treatment strategy for bladder recovery.open1156sciescopu

Ancillary Therapy and Supportive Care of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group Report

AbstractThe Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of “ancillary therapy and supportive care” embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach

Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b

The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene which are sufficient for initiation of hyperplastic growth but not for tumor progression. The analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant B-Raf and both events were shown to cooperate in tumor cell survival. Here we provide evidence for increased expression of Rac1b in samples from inflammatory bowel disease patients as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the non-steroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumour cells through a cyclooxygenase inhibition-independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely inflammation can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors and in cancer prophylaxis following colon inflammation disorders

Functional neurological disorder is a feminist issue

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need

Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC

Franchises lost and gained: post-coloniality and the development of women’s rights in Canada

The Canadian constitution is to some extent characterised by its focus on equality, and in particular gender equality. This development of women’s rights in Canada and the greater engagement of women as political actors is often presented as a steady linear process, moving forwards from post-enlightenment modernity. This article seeks to disturb this ‘discourse of the continuous,’ by using an analysis of the pre-confederation history of suffrage in Canada to both refute a simplistic linear view of women’s rights development and to argue for recognition of the Indigenous contribution to the history of women’s rights in Canada. The gain of franchise and suffrage movements in Canada in the late nineteenth and early twentieth century are, rightly, the focus of considerable study (Pauker 2015), This article takes an alternative perspective. Instead, it examines the exercise of earlier franchises in pre-confederation Canada. In particular it analyses why franchise was exercised more widely in Lower Canada and relates this to the context of the removal of franchises from women prior to confederation