Follow-up biopsies identify high rates of persistent rejection in pediatric kidney transplant recipients after treatment of T cell-mediated rejection.

BACKGROUND: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients. METHODS: Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available. RESULTS: Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (≥i1t1 and

Online educational materials for appendectomy patients have good quality but poor readability.

BACKGROUND: Guidelines recommend patient health-related information be written at or below the sixth-grade level. This study evaluates the readability level and quality of online appendectomy patient education materials. METHODS: Webpages were evaluated using seven readability formulae: Flesh-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Coleman-Liau Index (CLI), Automated Readability Index (ARI), Simple Measure of Gobbledygook (SMOG), Flesch Reading Ease (FRE), and New Dale-Chall (NDC). Two evaluators assessed quality using the Brief DISCERN tool. RESULTS: Thirty seven webpages were analyzed. The mean readability scores were: FKGL = 9.11, GFI = 11.82, CLI = 10.84, ARI = 7.99, SMOG = 11.88, FRE = 51.17, and NDC = 5.48. 6 of the 7 readability formulae indicate that the materials were written at too high a level. The average Brief DISCERN score was 17.81, indicating good quality. CONCLUSIONS: Readability levels for online appendectomy patient education materials are higher than recommended but are of good quality. Authors of such materials should not only provide good quality information but also ensure readability.

Yield and utility of surveillance kidney biopsies in pediatric kidney transplant recipients at various time points post-transplant.

BACKGROUND: Due to a lack of consensus on SB for pediatric kidney transplant recipients, we evaluated the yield and clinical utility of SB findings at various time points post-transplant. METHODS: Patients transplanted at a single institution between 2014 and 2020 with at least one SB at 1.5, 3, 6, 12, and 24 months post-transplant were included. Additional biopsies were done for indication (IB). TCMR was classified by Banff criteria (score ≥i1t1). RESULTS: Forty-seven patients had 142 biopsies (SB = 113, IB = 29); 19 (40.4%) of whom experienced at least one TCMR episode in the first-year post-transplant. The greatest SB yield of any pathologic abnormality was at 6 months (57.1%; P < .001). Six months also had the highest yield for TCMR (42.9%), compared with 3.3%, 20.8%, 15.0%, and 9.1% at 1.5, 3, 12 months, and 24 months, respectively (P = .003). SB instigated intensification of immunosuppression (28.3% cases), reduction of immunosuppression (2.7% cases), and other non-immunosuppressant changes (1.8% cases). The 6-month SB led to the greatest number of changes in management (53.6%), compared with 1.5, 3, 12, and 24 months (13.3, 20.8, 25.0, and 36.4%, respectively; P = .012). There were no major biopsy-related complications. CONCLUSIONS: SBs identify an important burden of subclinical rejection and other pathology leading to changes in clinical management. The greatest yield was at 6 months, whereas the least utility was at the 1.5 months. Selection of SB timing may be tailored such that the optimal yield is balanced against the procedural risk.

Non-invasive staging of chronic kidney allograft damage using urine metabolomic profiling.

Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS-DA. We used mixed-effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post-transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85-0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71-0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non-invasive assessment of histopathological damage.

Criminalizing Sex Work Clients and Rushed Negotiations among Sex Workers Who Use Drugs in a Canadian Setting.

Previous research indicates that criminalization of sex work is associated with harms among sex workers. In 2013, the Vancouver Police Department changed their sex work policy to no longer target sex workers while continuing to target clients and third parties in an effort to increase the safety of sex workers (similar to "end-demand sex work" approaches being adopted in a number of countries globally). We sought to investigate the trends and correlates of rushing negotiations with clients due to police presence among 359 sex workers who use drugs in Vancouver before and after the guideline change. Data were derived from three prospective cohort studies of people who use drugs in Vancouver between 2008 and 2014. We used sex-stratified multivariable generalized estimating equation models. The crude percentages of sex workers who use drugs reporting rushing client negotiations changed from 8.9% before the guideline change to 14.8% after the guideline change among 259 women, and from 8.6 to 7.1% among 100 men. In multivariable analyses, there was a significant increase in reports of rushing client negotiation after the guideline change among women (p = 0.04). Other variables that were independently associated with increased odds of rushing client negotiation included experiencing client-perpetrated violence (among both men and women) and non-heterosexual orientation (among women) (all p < 0.05). These findings indicate that despite the policing guideline change, rushed client negotiation due to police presence appeared to have increased among our sample of female sex workers who use drugs. It was also associated with client-perpetrated violence and other markers of vulnerability. These findings lend further evidence that criminalizing the purchase of sexual services does not protect the health and safety of sex workers.

Declining trends in exposures to harmful policing among people who inject drugs in Vancouver, Canada.

INTRODUCTION: In 2006, the Vancouver Police Department (VPD) developed an organization-wide drug policy approach, which included endorsing harm reduction strategies for people who inject drugs (PWID). We sought to examine rates of potentially harmful policing exposures and associated HIV risk behaviour among PWID in Vancouver, Canada before and after the VPD policy change. METHODS: Data were derived from two prospective cohort studies of PWID. Multivariable generalized estimating equation models were used to examine changes in the risk of confiscation of drug use paraphernalia and physical violence by the police, as well as changes in the relationship between exposures to the two policing practices and sharing of drug use paraphernalia, before and after the policy change. RESULTS: Among 2193 participants, including 757 (34.5%) women, the rates of experiencing police confiscation of drug use paraphernalia declined from 22.3% in 2002 to 2.8% in 2014, and the rates of reporting experiencing physical violence by the police also declined from 14.1% in 2004 to 2.9% in 2014. In multivariable analyses, the post-policy change period remained independently and negatively associated with reports of confiscation of drug use paraphernalia (adjusted odds ratio (AOR): 0.25; 95% confidence interval (CI): 0.21 to 0.31) and reported physical violence by the police (AOR: 0.76; 95% CI: 0.63 to 0.91). However, experiencing both confiscation of drug use paraphernalia and physical violence by the police (AOR: 1.92; 95% CI: 1.10 to 3.33) and experiencing only confiscation of drug use paraphernalia (AOR: 1.71; 95% CI: 1.34 to 2.19) remained independently and positively associated with sharing of drug use paraphernalia during the post-policy change period. CONCLUSIONS: In our study, two policing practices known to increase HIV risk among PWID have declined significantly since the local police launched an evidence-based drug policy approach. However, these practices remained independently associated with elevated HIV risk after the post-policy change. Although there remains a continued need to ensure that policing activities do not undermine public health efforts, these findings demonstrate that a major shift towards a public health approach to policing is possible for a municipal police force.