Progressive improvement in short‐, medium‐ and long‐term graft survival in kidney transplantation patients in Ireland – a retrospective study

It is often quoted that while short‐term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long‐term graft survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971–2015. Three thousand two hundred and sixty recipients were included in this study. Kaplan–Meier methods were used to estimate survival at each time period post transplant for the various eras of transplantation. Uncensored graft survival has improved over the course of the program in Ireland at various time points despite risk factors for graft failure progressively increasing over successive eras. For example the graft survival at 15 years post transplant has increased from 10% in 1971–1975 to 45% by 1996–2000. Ireland has experienced a progressive improvement in long‐term graft survival following kidney transplantation. Whether these trends are attributable to biological or nonbiological factors is unclear but likely involves a combination of both.     

Quality‐of‐life evaluation in chronic wounds: comparative analysis of three disease‐specific questionnaires

The study directly compared the feasibility and performance of three instruments measuring health‐related quality of life (HRQoL) in chronic ulcers: the Freiburg Life Quality Assessment for wounds (FLQA‐w), the Cardiff Wound Impact Schedule (CWIS) and the Würzburg Wound Score (WWS). The questionnaires were evaluated in a randomly assigned order in a longitudinal observational study of leg ulcer patients. Psychometric properties (internal consistency, responsiveness and construct validity) were analysed. Patient acceptance was recorded. Analysis of n = 154 patients revealed good internal consistency (Cronbach's alpha ≥ 0·85) for all instruments. There were minor floor effects in all questionnaires (<1%) and some ceiling effects in the CWIS. Construct validity was satisfactory, for example, correlation with EuroQoL‐5D was r = 0·70 in the FLQA‐w, r = 0·47/0·67/0·68 in the CWIS dimensions and r = 0·60 in the WWS. The proportion of missing values was higher in the CWIS, and overall patient acceptance was highest in the FLQA‐w for wounds (54% best preferences) and lowest in the WWS (14%). In conclusion, the FLQA‐w, the CWIS and the WWS are reliable, sensitive and valid instruments for the assessment of HRQoL in leg ulcers. However, they show differences in clinical feasibility and patient acceptance.     

Value of a flow cytometry cross‐match in the setting of a negative complement‐dependent cytotoxicity cross‐match in heart transplant recipients

Complement‐dependent cytotoxicity cross‐match (CDCXM) is used for evaluation of preformed HLA‐specific antibodies in patients undergoing heart transplantation. Flow cytometry cross‐match (FCXM) is a more sensitive assay and used with increasing frequency. To determine the clinical relevance of a positive FCXM in the context of negative CDCXM in heart transplantation, the United Network for Organ Sharing (UNOS) database was analyzed. Kaplan‐Meier analysis and Cox proportional hazard modeling were used to assess graft survival for three different patient cohorts defined by cross‐match results: T‐cell and B‐cell CDCXM+ (“CDCXM+” cohort), CDCXM? but T‐cell and/or B‐cell FCXM+ (“FCXM+” cohort), and T‐cell/B‐cell CDCXM? and FCXM‐ (“XM?” cohort). During the study period, 2558 patients met inclusion criteria (10.7% CDCXM+, 18.8% FCXM+, 65.5% XM?). CDCXM+ patients had significantly decreased graft survival compared to FCXM+ and XM? cohorts (P = .003 and <.001, respectively). CDCXM? and FCXM+ patients did not have decreased graft survival compared to XM? patients (P = .09). In multivariate analysis, only CDCXM+ was associated with decreased graft survival (HR 1.22, 95% CI 1.01‐1.49). In conclusion, positive FCXM in the context of negative CDCXM does not confer increased risk of graft failure. Further study is needed to understand implications of CDCXM and FCXM testing in heart transplant recipients.     

Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head‐to‐head placebo‐controlled trial

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended‐release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB).

PATIENTS AND METHODS

In this 12‐week double‐blind, double‐dummy, placebo‐controlled, randomized clinical trial, eligible patients reported OAB symptoms for ≥3 months and recorded ≥8 voids and ≥1 urgency urinary incontinence (UUI) episode per 24 h in 3‐day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency‐urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB‐q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12‐week study period.

RESULTS

Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB‐q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB‐q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment‐emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively.

CONCLUSION

In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient‐reported outcome measures. Both active treatments were well tolerated.     

The impact of time‐varying clinical surrogates on disparities in African‐American kidney transplant recipients – a retrospective longitudinal cohort study

An improved understanding of the impact of clinical surrogates on disparities in African‐American (AA) kidney transplantation (KTX) is needed. We conducted a 10‐year retrospective longitudinal cohort study of electronically abstracted clinical data assessing the impact of surrogates on disparities in KTX. Clinical surrogates were assessed by posttransplant year (1, 2, 3 or 4) and defined as acute rejection (Banff ≥1A), mean SBP >140 mmHg, tacrolimus variability (CV) >40%, mean glucose >160 mg/dl and mean hemoglobin <10 g/dl. We utilized landmark methodology to minimize immortal time bias and logistic and survival regression to assess outcomes; 1610 KTX were assessed (54.2% AAs), with 1000, 468, 368 and 303 included in the year 1, 2, 3 and 4 complete case analyses, respectively. AAs had significantly higher odds of developing a clinical surrogate, which increased in posttransplant years three and four [OR year 1 1.99 (1.38–2.88), year 2 1.77 (1.20–2.62), year 3 2.35 (1.49–3.71), year 4 2.85 (1.72–4.70)]. Adjusting for the five clinical surrogates in survival models explained a significant portion of the higher risks of graft loss in AAs in post‐transplant years three and four. Results suggest focusing efforts on improving late clinical surrogate management within AAs may help mitigate racial disparities in KTX.     

Prioritizing Patient‐Reported Outcomes in Breast Cancer Surgery Quality Improvement

Breast‐cancer‐specific tools that measure health‐related quality of life (HRQOL) were developed for use in research or clinical practice, and little is known about these tools’ performance ability for quality improvement. Furthermore, existing tools may not fully reflect all issues that contribute to quality care as seen by patients. Work is needed to identify and validate patient‐reported outcome measures for use in quality improvement in breast cancer surgical care. We conducted an exploratory qualitative study in order to better understand what HRQOL domains and processes of care define high quality surgical care for women undergoing mastectomy for breast cancer from both the patient and clinician perspective. We conducted focus groups and one‐on‐one interviews with 15 women and administered a prioritization questionnaire to participants. We also conducted a prioritization questionnaire among surgical oncologists, general surgeons, and reconstructive surgeons who are members of the Washington State Medical Association. Both the patient and surgeon prioritization questionnaire asked participants to prioritize HRQOL and treatment satisfaction‐related aspects of their breast cancer surgical care at key time points before and after mastectomy. A Stakeholder Advisory Panel was convened to review focus group, interview, and prioritization questionnaire results and make recommendations as to patient‐reported outcome domains to focus on and existing instruments to use for quality improvement. Patients and clinicians largely agreed on important HRQOL domains, including emotional well‐being, education, communication, and process of care. The Stakeholder Advisory Panel, composed of 12 clinicians and five patients, reviewed study findings and existing patient‐reported outcomes measurement tools. The panel recommended that the BREAST‐Q, a flexible tool with independently validated modules designed for research and clinical care, is an ideal tool to begin developing novel quality improvement benchmarks focused on patient‐reported outcomes.