Flare frequency, healthcare resource utilisation and costs among patients with gout in a managed care setting: a retrospective medical claims-based analysis

Objectives: For most gout patients, excruciatingly painful gout attacks are the major clinical burden of the disease. The goal of this study was to assess the association of frequent gout flares with healthcare burden, and to quantify how much lower gout-related costs and resource use are for those with infrequent flares compared to frequent gout flares. Design: Retrospective cohort study. Setting: Administrative claims data from a large US health plan. Participants: Patients aged 18 years or above, and with evidence of gout based on medical and pharmacy claims between January 2009 and April 2012 were eligible for inclusion. Patient characteristics were assessed during a 12-month baseline period. Outcome measures Frequency of gout flares, healthcare costs and resource utilisation were assessed in the 12 months following the first qualifying gout claim. Generalised linear models were employed to assess the impact of flare frequency on cost outcomes after adjusting for covariates. Results: 102 703 patients with gout met study inclusion criteria; 89 201 had 0–1 gout flares, 9714 had 2 flares, and 3788 had 3+ flares. Average counts of gout-related inpatient stays, emergency room visits and ambulatory visits were higher among patients with 2 or 3+ flares, compared to those with 0–1 flares (all p<0.001). Adjusted annual gout-related costs were $1804,$3014 and $4363 in those with 0–1, 2 and 3+ gout flares, respectively (p<0.001 comparing 0–1 flares to 2 or 3+ flares). Conclusions: Gout-related costs and resource use were lower for those with infrequent flares, suggesting significant cost benefit to a gout management plan that has a goal of reducing flare frequency

A 12-Year Retrospective Study of the Prevalence of Anticholinergic Polypharmacy and Associated Outcomes Among Medicare Patients with Overactive Bladder in the USA

Background and objective: Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The "Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults" (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. Methods: This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006-2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. Results: In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. Conclusions: Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden

An assessment of the impact of pregnancy on trauma mortality

Background: In the United States, trauma is the leading cause of maternal mortality and an important source of maternal morbidity. Few studies have compared outcomes in injured pregnant women to their nonpregnant counterparts. Some clinical literature regarding hormonal influences on outcomes after trauma suggests a survival advantage in premenopausal women with higher estrogen levels. Given this, as well as possible outcome differences as a result of physiologic changes that occur during pregnancy, we tested the hypothesis that pregnant women have different outcomes after trauma compared with similarly injured nonpregnant women in the same age groups. Methods: We used data derived from 1.46 million patients listed in The National Trauma Data Bank from 2001 to 2005, to query all injured patients between ages 12 and 49 years inclusive, and divided them into 2 comparison groups: nonpregnant and pregnant women. We compared differences in outcome after trauma between pregnant and nonpregnant women. Because the number of pregnant women was small in comparison to the number of nonpregnant women, multivariate analysis after 1:3 (pregnant:nonpregnant) matching was attempted. Results: Crude mortality rate comparisons and unadjusted logistic regression analyses both before and after matching data reveal lower mortality rates in pregnant women. Multivariate logistic regression analyses both before and after matching data also reveal lower mortality rates in pregnant women; but this is statistically significant (P = .01) only after matching data. Conclusion: Among women of similar age groups who are equivalently injured, those who are pregnant exhibit lower mortality. These findings suggest that hormonal and physiologic differences during the gestation period may play a role in outcomes following trauma in pregnant women

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

潰瘍性大腸炎による上皮再構築メカニズムと発がんとの関係を解明 --IL-17シグナル経路に変異を獲得した上皮細胞は発がん過程で陰性に選択される--. 京都大学プレスリリース. 2019-12-20.Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1, 2, 3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer

Molecular classification and diagnostics of upper urinary tract urothelial carcinoma

上部尿路上皮がんの分子分類と新規分子診断 --尿中遺伝子変異の検出で高精度の診断が可能--. 京都大学プレスリリース. 2021-06-15.Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC