Relative survival in patients with cancer and kidney failure.

BACKGROUND AND HYPOTHESIS: The population with kidney failure is at increased risk of cancer and associated mortality. Relative survival can provide insight into the excess mortality, directly or indirectly, attributed to cancer in the population with kidney failure. METHODS: We estimated relative survival for people all ages receiving dialysis (n = 4089) and kidney transplant recipients (n = 3253) with de novo cancer, and for the general population with cancer in Australia and New Zealand (n = 3 043 166) over the years 1980-2019. The entire general population was the reference group for background mortality, adjusted for sex, age, calendar year and country. We used Poisson regression to quantify excess mortality ratios. RESULTS: Five-year relative survival for all-site cancer was markedly lower than the general population for people receiving dialysis (0.25, 95%CI:0.23-0.26) and kidney transplant recipients (0.55, 95%CI:0.53-0.57). In dialysis, excess mortality was more than double (2.16, 95%CI:2.08-2.25) that of the general population with cancer and for kidney transplant recipients 1.34 higher (95%CI:1.27-2.41). There was no difference in excess mortality from lung cancer between people with kidney failure and the general population with cancer. Comparatively, there was a significant survival deficit for people with kidney failure, compared to the general population with cancer, for melanoma, breast cancer and prostate cancers. CONCLUSION: Decreased cancer survival in kidney failure may reflect differences in multi-morbidity burden, reduced access to treatment, or greater harm from or reduced efficacy of treatments. Our findings support research aimed at investigating these hypotheses.

Sex differences in cancer outcomes across the range of eGFR.

BACKGROUND AND HYPOTHESIS: People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We hypothesised that odds of presenting with advanced cancer may vary according to differences in eGFR, that this could contribute to increased all-cause mortality and that sex differences may exist. METHODS: Data were from Secure Anonymised Information Linkage Databank, including people with de-novo cancer diagnosis (2011-2017) and two kidney function tests within two years prior to diagnosis to determine baseline eGFR (mL/min/1.73m2). Logistic regression models determined odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRcr and all-cause mortality. RESULTS: eGFR < 30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared to eGFR > 75-90, eGFR < 30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females (female: HR 1.71, 95%CI 1.56-1.88; male versus female comparison HR 0.88, 95%CI 0.78-0.90). CONCLUSIONS: Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger assocation with all-cause mortality in females compared to males with eGFR < 30 is concerning and warrants further scrutiny.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Life Years Lost in Children with Kidney Failure: A Binational Cohort Study with Multistate Probabilities of Death and Life Expectancy.

SIGNIFICANCE STATEMENT: In children with kidney failure, little is known about their treatment trajectories or the effects of kidney failure on lifetime survival and years of life lost, which are arguably more relevant measures for children. In this population-based cohort study of 2013 children who developed kidney failure in Australia and New Zealand, most children were either transplanted after initiating dialysis (74%) or had a preemptive kidney transplant (14%). Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The expected (compared with the general population) number of life years lost ranged from 16 to 32 years, with female patients and those who developed kidney failure at a younger age experiencing the greatest loss of life years. BACKGROUND: Of the consequences of kidney failure in childhood, those rated as most important by children and their caregivers are its effects on long-term survival. From a life course perspective, little is known about the experience of kidney failure treatment or long-term survival. METHODS: To determine expected years of life lost (YLL) and treatment trajectory for kidney failure in childhood, we conducted a population-based cohort study of all children aged 18 years or younger with treated kidney failure in Australia (1980-2019) and New Zealand (1988-2019).We used patient data from the CELESTIAL study, which linked the Australian and New Zealand Dialysis and Transplant registry with national death registers. We estimated standardized mortality ratios and used multistate modeling to understand treatment transitions and life expectancy. RESULTS: A total of 394 (20%) of 2013 individuals died over 30,082 person-years of follow-up (median follow-up, 13.1 years). Most children (74%) were transplanted after initiating dialysis; 14% (18% of male patients and 10% of female patients) underwent preemptive kidney transplantation. Excess deaths (compared with the general population) decreased dramatically from 1980 to 1999 (from 41 to 22 times expected) and declined more modestly (to 17 times expected) by 2019. Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The number of YLL ranged from 16 to 32 years, with the greatest loss among female patients and those who developed kidney failure at a younger age. CONCLUSIONS: Children with kidney failure lose a substantial number of their potential life years. Female patients and those who develop kidney failure at younger ages experience the greatest burden.

Journey to kidney transplantation: patient dynamics, suspensions, transplantation and deaths in the Australian kidney transplant waitlist.

BACKGROUND AND HYPOTHESIS: People on the kidney waitlist are less informed about potential suspensions. Disparities may exist among those who are suspended and who return to the waitlist. We evaluated the patient journey after entering the waitlist, including suspensions and outcomes, and factors associated with these transitions. METHODS: We included all incident patients waitlist for their first transplant from deceased donors in Australia, 2006-19. We described all clinical transitions after entering the waitlist. We predicted the restricted mean survival time (unadjusted and adjusted) until first transplant by number of prior suspensions. We evaluated factors associated with transitions using flexible survival models and clinical endpoints using Cox models. RESULTS: Of 8 466 patients waitlisted and followed over 45 757.4 person-years (median:4.8years), 6 741(80%) were transplanted, 381(5%) died waiting and 1 344(16%) were still waiting. 3 127(37%) people were suspended at least once. Predicted mean time from waitlist to transplant was 3.0 years(95%CI:2.8-3.2) when suspended versus 1.9 years(95%CI:1.8-1.9) when never suspended. Prior suspension increased likeliness of further suspensions 4.2-fold(95%CI:3.8-4.6) and returning to waitlist by 50%(95%CI:36-65%) but decreased likeliness of transplantation by 29%(95%CI:62-82%). Death risk while waiting was 12-fold(95%CI:8.0-18.3) increased when currently suspended. Australian non-Indigenous males were 13% (HR:1.13,95%CI:1.04-1.23) and Asian males 23% (HR:1.23,95%CI:1.06-1.42,) more likely to return to the waitlist compared to females of the same ethnicity. CONCLUSION: The waitlist journey was not straightforward. Suspension was common, impacted chance of transplantation and meant waiting an average one year longer until transplant. We have provided estimates for, and factors associated with, suspension, re-listing and outcomes after waitlisting to support more informed discussions. This evidence is critical to further understand drivers of inequitable access to transplantation.

Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis.

BACKGROUND: Suggested anaesthetic dose ranges do not differ by sex, likely because of limited studies comparing sexes. Our objective was to systematically synthesise studies with outcomes of unintended anaesthesia awareness under anaesthesia, intraoperative connected consciousness, time to emergence from anaesthesia, and dosing to achieve adequate depth of anaesthesia, and to compare between females and males. METHODS: Studies were identified from MEDLINE, Embase, and the Cochrane library databases until August 2, 2022. Controlled clinical trials (randomised/non-randomised) and prospective cohort studies that reported outcomes by sex were included. Results were synthesised by random effects meta-analysis where possible, or narrative form. RESULTS: Of the 19 749 studies identified, 64 (98 243 participants; 53 143 females and 45 100 males) were eligible for inclusion, and 44 citations contributed to meta-analysis. Females had a higher incidence of awareness with postoperative recall (33 studies, odds ratio 1.38, 95% confidence interval [CI] 1.09-1.75) and connected consciousness during anaesthesia (three studies, OR 2.09, 95% CI 1.04-4.23) than males. Time to emergence was faster in females, including time to eye-opening (10 studies, mean difference -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (six studies, mean difference -2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous, limiting synthesis to a qualitative review which did not identify sex differences. CONCLUSIONS: Female sex was associated with a greater incidence of awareness under general anaesthesia, and faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336087.

Interventions for the symptoms and signs resulting from jellyfish stings.

BACKGROUND: Jellyfish envenomation is common in many coastal regions and varies in severity depending upon the species. Stings cause a variety of symptoms and signs including pain, dermatological reactions, and, in some species, Irukandji syndrome (which may include abdominal/back/chest pain, tachycardia, hypertension, cardiac phenomena, and, rarely, death). Many treatments have been suggested for these symptoms, but their effectiveness is unclear. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed by randomised and quasi-randomised trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and Web of Science up to 27 October 2022. We searched clinical trials registers and the grey literature, and conducted forward-citation searching of relevant articles.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of any intervention given to treat stings from any species of jellyfish stings. Interventions were compared to another active intervention, placebo, or no treatment. If co-interventions were used, we included the study only if the co-intervention was used in each group.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: We included nine studies (six RCTs and three quasi-RCTs) involving a total of 574 participants. We found one ongoing study. Participants were either stung accidentally, or were healthy volunteers exposed to stings in a laboratory setting. Type of jellyfish could not be confirmed in beach settings and was determined by investigators using participant and local information. We categorised interventions into comparison groups: hot versus cold applications; topical applications. A third comparison of parenteral administration included no relevant outcome data: a single study (39 participants) evaluated intravenous magnesium sulfate after stings from jellyfish that cause Irukandji syndrome (Carukia). No studies assessed a fourth comparison group of pressure immobilisation bandages.  We downgraded the certainty of the evidence due to very serious risk of bias, serious and very serious imprecision, and serious inconsistency in some results.  Application of heat versus application of cold Four studies involved accidental stings treated on the beach or in hospital. Jellyfish were described as bluebottles (Physalia; location: Australia), and box jellyfish that do not cause Irukandji syndrome (Hawaiian box jellyfish (Carybdea alata) and major box jellyfish (Chironex fleckeri, location: Australia)). Treatments were applied with hot packs or hot water (showers, baths, buckets, or hoses), or ice packs or cold packs.  The evidence for all outcomes was of very low certainty, thus we are unsure whether heat compared to cold leads to at least a clinically significant reduction in pain within six hours of stings from Physalia (risk ratio (RR) 2.25, 95% confidence interval (CI) 1.42 to 3.56; 2 studies, 142 participants) or Carybdea alata and Chironex fleckeri (RR 1.66, 95% CI 0.56 to 4.94; 2 studies, 71 participants). We are unsure whether there is a difference in adverse events due to treatment (RR 0.50, 95% CI 0.05 to 5.19; 2 studies, 142 participants); these were minor adverse events reported for Physalia stings. We are also unsure whether either treatment leads to a clinically significant reduction in pain in the first hour (Physalia: RR 2.66, 95% CI 1.71 to 4.15; 1 study, 88 participants; Carybdea alata and Chironex fleckeri: RR 1.16, 95% CI 0.71 to 1.89; 1 study, 42 participants) or cessation of pain at the end of treatment (Physalia: RR 1.63, 95% CI 0.81 to 3.27; 1 study, 54 participants; Carybdea alata and Chironex fleckeri: RR 3.54, 95% CI 0.82 to 15.31; 1 study, 29 participants). Evidence for retreatment with the same intervention was only available for Physalia, with similar uncertain findings (RR 0.19, 95% CI 0.01 to 3.90; 1 study, 96 participants), as was the case for retreatment with the alternative hot or cold application after Physalia (RR 1.00, 95% CI 0.55 to 1.82; 1 study, 54 participants) and Chironex fleckeri stings (RR 0.48, 95% CI 0.02 to 11.17; 1 study, 42 participants). Evidence for dermatological signs (itchiness or rash) was available only at 24 hours for Physalia stings (RR 1.02, 95% CI 0.63 to 1.65; 2 studies, 98 participants).  Topical applications One study (62 participants) included accidental stings from Hawaiian box jellyfish (Carybdea alata) treated on the beach with fresh water, seawater, Sting Aid (a commercial product), or Adolph's (papain) meat tenderiser. In another study, healthy volunteers (97 participants) were stung with an Indonesian sea nettle (Chrysaora chinensis from Malaysia) in a laboratory setting and treated with isopropyl alcohol, ammonia, heated water, acetic acid, or sodium bicarbonate. Two other eligible studies (Carybdea alata and Physalia stings) did not measure the outcomes of this review.  The evidence for all outcomes was of very low certainty, thus we could not be certain whether or not topical applications provided at least a clinically significant reduction in pain (1 study, 62 participants with Carybdea alata stings, reported only as cessation of pain). For adverse events due to treatment, one study (Chrysaora chinensis stings) withdrew ammonia as a treatment following a first-degree burn in one participant. No studies evaluated clinically significant reduction in pain, retreatment with the same or the alternative treatment, or dermatological signs. AUTHORS' CONCLUSIONS: Few studies contributed data to this review, and those that did contribute varied in types of treatment, settings, and range of jellyfish species. We are unsure of the effectiveness of any of the treatments evaluated in this review given the very low certainty of all the evidence. This updated review includes two new studies (with 139 additional participants). The findings are consistent with the previous review.

Antioxidants for adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. AUTHORS' CONCLUSIONS: We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.

PROspective Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (PROMOTION): Protocol for a systematic review and prospective meta-analysis with individual participant data on initial oxygen concentration for resuscitation of preterm infants.

BACKGROUND: Clinicians favour low oxygen concentrations when resuscitating preterm infants immediately after birth despite inconclusive evidence to support this practice. Prospective meta-analysis (PMA) is a novel approach where studies are identified as eligible for inclusion in the meta-analysis before their results are known. AIMS: To explore whether high (60%) or low (30%) oxygen is associated with greater efficacy and safety for the initial resuscitation (immediately after birth) of preterm infants born at <29 weeks' gestation. METHODS: We will conduct a prospective meta-analysis (PMA) with individual participant data (IPD). We will perform a systematic search to identify ongoing RCTs including infants <29 weeks' gestation randomised to high (60%) or low (30%) oxygen for initial resuscitation after birth. IPD will be sought for all infants randomised for the purpose of meta-analysis. We will employ a one-stage random-effects approach to IPD meta-analysis. Potential heterogeneity and the differential effect of high or low oxygen will be explored through subgroup and interaction analyses. The primary outcome of this study is all-cause mortality prior to hospital discharge. There will be a follow-up analysis of neurodevelopmental outcomes once available. RESULTS/CONCLUSION: The results of neonatal outcomes at hospital discharge are expected by 2025, and neurodevelopmental outcomes by 2027.

Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013.

RATIONALE & OBJECTIVE: Cancer is a significant cause of morbidity in the population with kidney failure; however, cancer mortality in people undergoing dialysis has not been well described. We sought to compare cancer mortality in people on dialysis for kidney failure with cancer mortality in the general population. STUDY DESIGN: A retrospective cohort study using linked health-administrative and dialysis registry data. SETTING & PARTICIPANTS: All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013. EXPOSURE: Dialysis; hemodialysis (HD) and peritoneal dialysis (PD). OUTCOME: Death and underlying cause of death ascertained using health administrative data and classified using International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes. ANALYTICAL APPROACH: Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR). RESULTS: Over 269,598 person years of observation, 34,100 deaths occurred among 59,648 people on dialysis, including 3,677 cancer deaths. The relative risk of all-site cancer death in dialysis was twice (SMR, 2.4 [95% CI, 2.33-2.49]) that of the general population and highest for oral and pharynx cancers (SMR, 24.3 [95% CI, 18.0-31.5]) and multiple myeloma (SMR, 22.5 [95% CI, 20.3-23.9]). Women on dialysis had a significantly higher risk of all-site cancer mortality (SMR, 2.7 [95% CI, 2.59-2.89]) compared with men (SMR, 2.3 [95% CI, 2.17-2.36]) (P < 0.001). People on HD (SMR, 2.2 [95% CI, 2.11-2.30]) experienced greater excess deaths from all-site cancer compared with people on PD (SMR, 1.3 [95% CI, 1.23-1.44]). Excess deaths have gradually decreased over time for all-site, multiple myeloma, and kidney cancers (P < 0.001) but have not kept up with improvements in the general population. By contrast, among people receiving dialysis, excess deaths increased for colorectal and lung cancers (P < 0.001). LIMITATIONS: Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers. CONCLUSIONS: People on dialysis experience excess all-site and site-specific cancer mortality compared with the general population. Mortality differs by modality type, age, and sex. Understanding the role of kidney failure and other morbidities in the treatment of cancer is important for shared decision-making regarding cancer treatments and identifying potential approaches to improve outcomes.

Interventions for improving health literacy in people with chronic kidney disease.

BACKGROUND: Low health literacy affects 25% of people with chronic kidney disease (CKD) and is associated with increased morbidity and death. Improving health literacy is a recognised priority, but effective interventions are not clear. OBJECTIVES: This review looked the benefits and harms of interventions for improving health literacy in people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched MEDLINE (OVID) and EMBASE (OVID) for non-randomised studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies that assessed interventions aimed at improving health literacy in people with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility and performed risk of bias analysis. We classified studies as either interventions aimed at improving aspects of health literacy or interventions targeting a population of people with poor health literacy. The interventions were further sub-classified in terms of the type of intervention (educational, self-management training, or educational with self-management training). Results were expressed as mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratios (RR) with 95% CI for dichotomous outcomes. MAIN RESULTS: We identified 120 studies (21,149 participants) which aimed to improve health literacy. There were 107 RCTs and 13 non-randomised studies. No studies targeted low literacy populations. For the RCTs, selection bias was low or unclear in 94% of studies, performance bias was high in 86% of studies, detection bias was high in 86% of studies reporting subjective outcomes and low in 93% of studies reporting objective outcomes. Attrition and other biases were low or unclear in 86% and 78% of studies, respectively. Compared to usual care, low certainty evidence showed educational interventions may increase kidney-related knowledge (14 RCTs, 2632 participants: SMD 0.99, 95% CI 0.69 to 1.32; I² = 94%). Data for self-care, self-efficacy, quality of life (QoL), death, estimated glomerular filtration rate (eGFR) and hospitalisations could not be pooled or was not reported. Compared to usual care, low-certainty evidence showed self-management interventions may improve self-efficacy (5 RCTs, 417 participants: SMD 0.58, 95% CI 0.13 to 1.03; I² = 74%) and QoL physical component score (3 RCTs, 131 participants: MD 4.02, 95% CI 1.09 to 6.94; I² = 0%). There was moderate-certainty evidence that self-management interventions probably did not slow the decline in eGFR after one year (3 RCTs, 855 participants: MD 1.53 mL/min/1.73 m², 95% CI -1.41 to 4.46; I² = 33%). Data for knowledge, self-care behaviour, death and hospitalisations could not be pooled or was not reported. Compared to usual care, low-certainty evidence showed educational with self-management interventions may increase knowledge (15 RCTs, 2185 participants: SMD 0.65, 95% CI 0.36 to 0.93; I² = 90%), improve self-care behaviour scores (4 RCTs, 913 participants: SMD 0.91, 95% CI 0.00 to 1.82; I² =97%), self-efficacy (8 RCTs, 687 participants: SMD 0.50, 95% CI 0.10 to 0.89; I² = 82%), improve QoL physical component score (3 RCTs, 2771 participants: MD 2.56, 95% CI 1.73 to 3.38; I² = 0%) and may make little or no difference to slowing the decline of eGFR (4 RCTs, 618 participants: MD 4.28 mL/min/1.73 m², 95% CI -0.03 to 8.85; I² = 43%). Moderate-certainty evidence shows educational with self-management interventions probably decreases the risk of death (any cause) (4 RCTs, 2801 participants: RR 0.73, 95% CI 0.53 to 1.02; I² = 0%). Data for hospitalisation could not be pooled. AUTHORS' CONCLUSIONS: Interventions to improve aspects of health literacy are a very broad category, including educational interventions, self-management interventions and educational with self-management interventions. Overall, this type of health literacy intervention is probably beneficial in this cohort however, due to methodological limitations and high heterogeneity in interventions and outcomes, the evidence is of low certainty.

Antiplatelet agents for chronic kidney disease.

BACKGROUND: Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013. OBJECTIVES: To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated. DATA COLLECTION AND ANALYSIS: Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost. AUTHORS' CONCLUSIONS: Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.

Equity and diversity in the nephrology workforce in Australia and New Zealand.

BACKGROUND: Despite diversity initiatives, inequities persist in medicine with negative implications for the workforce and patients. Little is known about workplace inequity in nephrology. AIM: To describe perceptions and experiences of bias by health professionals in the Australian and New Zealand Society of Nephrology (ANZSN), focussing on gender and race. METHODS: A web-based survey of ANZSN members recorded degree of perceived inequity on a Likert scale, ranging from 1 (none) to 5 (complete). Groups were compared using Mann-Whitney U-test and logistic regression. Comments were synthesised using qualitative methods to explore themes of inequity and pathways to an inclusive future. RESULTS: Of the 620 members of the ANZSN, there were 134 (22%) respondents, of whom 57% were women and 67% were White. The majority (88%) perceived inequities in the workforce. Perceived drivers of inequity were gender (84/113; 75%), carer responsibilities (74/113; 65%) and race (64/113; 56%). Half (74/131) had personally experienced inequity, based on gender in 70% (52/74) and race in 39% (29/75) with perceived discrimination coming from doctors, patients, academics and health administrators. White males were least likely (odds ratio 0.39; 95% confidence interval 0.18-0.90) to experience inequity. Dominant themes from qualitative analysis indicated that the major impacts of inequity were limited opportunities for advancement and lack of formal assistance for those experiencing inequities. Proposed solutions to reduce inequity included normalising the discourse on inequity at an organisational level, with policy changes to ensure diverse representation on committees and in executive leadership positions. CONCLUSIONS: Inequity, particularly driven by gender and race, is common for nephrology health professionals in Australia and New Zealand and impacts career progression.

Epidemiology of cardiovascular death in kidney failure: An Australian and New Zealand cohort study using data linkage.

AIM: Cardiovascular mortality risk evolves over the lifespan of kidney failure (KF), as patients develop comorbid disease and transition between treatment modalities. Absolute cardiovascular death rates would help inform clinical practice and health-care provision, but are not well understood across a continuum of dialysis and transplant states. We aimed to characterize cardiovascular death across the natural history of KF using a lifespan approach. METHODS: We performed a population-based cohort study of incident patients commencing kidney replacement therapy in Australia and New Zealand. Cardiovascular deaths were identified using data linkage to national death registers. We estimated the probability of death and kidney transplant using multi-state models, and calculated rates of graft failure and cardiovascular death across demographic factors and comorbidities. RESULTS: Among 60 823 incident patients followed over 381 874 person-years, 25% (8492) of deaths were from cardiovascular disease. At 15 years from treatment initiation, patients had a 15.2% probability of cardiovascular death without being transplanted, but only 2.3% probability of cardiovascular death post-transplant. Females had a 3% lower probability of cardiovascular death at 15 years (15.3% vs. 18.6%) but 4% higher probability of non-cardiovascular death (54.5% vs. 50.8%). Within the first year of dialysis, cardiovascular mortality peaked in the second month and showed little improvement across treatment era. CONCLUSION: Despite improvements over time, cardiovascular death remains common in KF, particularly among the dialysis population and in the first few months of treatment. Multi-state models can provide absolute measures of cardiovascular mortality across both dialysis and transplant states.

Cause of death for people with end-stage kidney disease withdrawing from treatment in Australia and New Zealand.

BACKGROUND: Withdrawal from renal replacement therapy is common in patients with end-stage kidney disease (ESKD), but end-of-life service planning is challenging without population-specific data. We aimed to describe mortality after treatment withdrawal in Australian and New Zealand ESKD patients and evaluate death-certified causes of death. METHODS: We performed a retrospective cohort study on incident patients with ESKD in Australia, 1980-2013, and New Zealand, 1988-2012, from the Australian and New Zealand Dialysis and Transplant registry. We estimated mortality rates (by age, sex, calendar year and country) and summarized withdrawal-related deaths within 12 months of treatment modality change. Certified causes of death were ascertained from data linkage with the Australian National Death Index and New Zealand Mortality Collection database. RESULTS: Of 60 823 patients with ESKD, there were 8111 treatment withdrawal deaths and 26 207 other deaths over 381 874 person-years. Withdrawal-related mortality rates were higher in females and older age groups. Rates increased between 1995 and 2013, from 1142 (95% confidence interval 1064-1226) to 2706/100 000 person-years (95% confidence interval 2498-2932), with the greatest increase in 1995-2006. A third of withdrawal deaths occurred within 12 months of treatment modality change. The national death registers reported kidney failure as the underlying cause of death in 20% of withdrawal cases, with other causes including diabetes (21%) and hypertensive disease (7%). Kidney disease was not mentioned for 18% of withdrawal patients. CONCLUSIONS: Treatment withdrawal represents 24% of ESKD deaths and has more than doubled in rate since 1988. Population data may supplement, but not replace, clinical data for end-of-life kidney-related service planning.

Organ transplantation and outcomes in patients with a past history of melanoma: A systematic review and meta-analysis.

BACKGROUND: The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of melanoma. AIM: To review studies reporting patients with a history of melanoma before solid organ transplantation. METHODS: Electronic searches of Medline, Embase, and the Cochrane library up to March 2020. All study designs, in any language and without sample size restriction, were eligible for inclusion. Risk of bias was assessed using established tools, and meta-analysis was performed using a random-effects model. RESULTS: We identified 41 studies reporting 703 100 transplant recipients and 1692 had pre-transplantation melanomas. Risk of death, expressed as a hazard ratio, in patients with pre-transplantation melanoma relative to those without prior melanoma, was 1.32 (95% CI: 1.09-1.59). After transplantation, 13.1% of patients with pre-transplantation melanoma developed new or recurrent melanoma (IQR: 4.8%-18.2%). CONCLUSIONS: Around 1-in-400 transplant recipients had a prior history of melanoma. This was associated with a greater than 1-in-10 risk of new or recurrent melanoma after transplantation and an increased risk of death. A 5-year waiting time between a melanoma diagnosis and transplantation has been recommended based on historic registry data, but very little additional information is available to justify or revise this.

Pregnancy outcomes for simultaneous Pancreas-Kidney transplant recipients versus kidney transplant recipients.

Data about pregnancy outcomes for simultaneous pancreas-kidney transplant recipients (SPKR) are limited. We compared pregnancy outcomes in SPKR to Kidney Transplant Recipients (KTR) from 2001-17 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and the Australian and New Zealand Pancreas Islet Transplant Registry (ANZPITR). A total of 19 pregnancies to 15 SPKR mothers, and 348 pregnancies to 235 KTR mothers were reported. Maternal ages were similar (SPKR 33.9 ± 3.9 years; KTR 32.1 ± 4.8 years, p = .10); however, SPKR had a shorter transplant to first-pregnancy interval compared to KTR (SPKR 3.3 years, IQR (1.7, 4.1); KTR 5 years, IQR (2.6, 8.7), p = .02). Median difference in creatinine pre- and post-pregnancy was similar between the groups (KTR -3 µmol/L, IQR (-15, 6), SPKR -3 µmol/L, IQR (-11, 3), p = .86). Maternal, fetal and kidney transplant outcomes were similar despite higher rates of pre-existing peripheral vascular and coronary artery diseases in SPKR. Live birth rates (>20 weeks) were comparable (SPKR 93.8% vs. KTR 96.8%, p = .06). KTR with either type 1 or type 2 diabetes mellitus (24 births) had similar outcomes compared to SPKR. In this national cohort, pregnancy outcomes were similar between SPKR and KTR mothers; however, findings should be interpreted with caution due to small sample sizes.

Prevalence of anal cytological abnormalities and high-risk human papillomavirus prevalence in kidney transplant recipients: A cross-sectional study.

BACKGROUND: Transplant recipients are at high-risk of anal squamous cell cancer. We aimed to estimate the prevalence of high-risk human papillomavirus (HPV) and high-grade squamous intraepithelial lesion (HSIL) and assess characteristics associated with results METHODS: We recruited kidney transplant recipients in a single-center, 2015-2018. Participants completed a clinical questionnaire and received an anal-swab sent for HPV-DNA and cytological testing RESULTS: A total of 97 (74%) of 125 recipients approached consented to participate. Participants were median 47 (IQR 40-55) years, 60% male and median 4.5 (IQR .9-13) months-since-transplant. Of 86 assessable samples, at least one HPV genotype was detected in 15 (17%) participants; 1 (1%) HPV16, 8 (9%) other high-risk HPV. Of 76 assessable cytology samples, 9 (12%) showed evidence of abnormality; 1 (1%) HSIL, 1 (1%) atypical-squamous-cells, cannot exclude HSIL. Both HSIL recipients had high-risk HPV and biopsy confirmed HSIL. High-risk HPV was detected in six (9%) recipients with normal cytology. History of sexually transmitted infection, and abnormal cervical pap smear in women, was associated with high-risk HPV and HSIL CONCLUSIONS: High-risk HPV and HSIL testing may identify kidney transplant recipients at higher risk of anal cancer. Longitudinal studies are needed to describe the natural history of anal cancer in transplant recipients.

Cancer transmissions and non-transmissions from solid organ transplantation in an Australian cohort of deceased and living organ donors.

Evidence on cancer transmission from organ transplantation is poor. We sought to identify cases of cancer transmission or non-transmission from transplantation in an Australian cohort of donors and recipients. We included NSW solid organ deceased donors 2000-2012 and living donors 2004-2012 in a retrospective cohort using linked data from the NSW Biovigilance Register (SAFEBOD). Central Cancer Registry (CCR) data 1972-2013 provided a minimum one-year post-transplant follow-up. We identified cancers in donors and recipients. For each donor-recipient pair, the transmission was judged likely, possible, unlikely, or excluded using categorization from international guidelines. In our analysis, transmissions included those judged likely, while those judged possible, unlikely, or excluded were non-transmissions. In our cohort, there were 2502 recipients and 1431 donors (715 deceased, 716 living). There were 2544 transplant procedures, including 1828 (72%) deceased and 716 (28%) living donor transplants. Among 1431 donors, 38 (3%) had past or current cancer and they donated to 68 recipients (median 6.7-year follow-up). There were 64 (94%) non-transmissions, and 4 (6%) transmissions from two living and two deceased donors (all kidney cancers discovered during organ recovery). Donor transmitted cancers are rare, and selected donors with a past or current cancer may be safe for transplantation.

Chronic Kidney Disease is a Risk Factor for Stroke.

Chronic kidney disease (CKD) is a sustained reduction in estimated glomerular filtration rate (eGFR), and/or presence of albuminuria. People with CKD have adverse cardiovascular outcomes including stroke. CKD and stroke share several risk factors, most notably older age, diabetes and hypertension, but CKD is also an independent risk factor for stroke. Relative burden of increased risk is worse for younger people and women, with <40 years with end stage CKD having more than 11 times the risk of their age-matched peers. Risk also varies by CKD treatment, with a risk peak for those starting dialysis, but dropping after the first month of treatment. Proposed mechanisms for increased risk are uraemia, cerebral blood flow dysregulation, vascular calcification, arterial stiffness, chronic inflammation, vascular access impacts, and for those on haemodialysis the use of anticoagulation to maintain dialysis circuits. Outcomes for people with CKD and stroke are poorer; functional outcomes may be impacted by reduced access to specialised stroke care. Stroke mortality is higher for those with CKD; with standardised mortality ratio more than three times higher than expected, but for some groups higher still (young women <40 years with a kidney transplant have 19 times the risk of stroke mortality than women without a transplant). Interventions to prevent and treat stroke lack the evidence base in CKD patients that is present for the general population.