Impact of oral bisphosphonate drug holiday on mortality following hip fracture: a population-based cohort study.

CONTEXT: Current clinical guidelines recommend a drug holiday after extended use of oral bisphosphonates. However, no studies have investigated the impact of drug holidays before hip fractures on post-fracture mortality. OBJECTIVE: To investigate the effect of drug holiday on post-fracture mortality in patients with extended use of oral bisphosphonates. DESIGN: Retrospective population-based cohort study. SETTING: All patients with hip fractures in Victoria, Australia from 2014-18. PATIENTS: Patients adherent to oral alendronate or risedronate for ≥5 years prior to hip fracture. INTERVENTION(S): Group-based trajectory modelling categorized patients into different bisphosphonate usage after 5-year good adherence. MAIN OUTCOME MEASURE(S): Post-fracture mortality. RESULTS: We identified 365 patients with good adherence (medication possession ratio ≥80%) to oral alendronate/risedronate for ≥5 years. Most patients (69%) continued to use oral bisphosphonates till admission for hip fracture; 17% had discontinued for one year and 14% had discontinued for two years. Post-fracture mortality was higher in patients who had discontinued risedronate for one year (Hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.24-4.53) and two years (HR 3.08, 95% CI 1.48-6.41) prior to hip fracture. No increase or decrease in post-fracture mortality was observed in patients who had discontinued alendronate for one year (HR 0.59, 95% CI 0.29-1.18) or two years (HR 1.05, 95% CI 0.57-1.93) prior to hip fracture. CONCLUSIONS: Post-fracture mortality is higher in people who discontinue risedronate, but not alendronate, for 1 or 2 years after being adherent to treatment for at least 5 years. The type of bisphosphonate may be a factor to consider when planning drug holidays.

Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study.

Bisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring. PURPOSE: Suboptimal antiresorptive use is not well understood. This study investigated trajectories of oral bisphosphonate use following first hip fractures and factors associated with different adherence and persistence trajectories. METHODS: We conducted a retrospective study of all patients aged ≥ 50 years dispensed two or more bisphosphonate prescriptions following first hip fracture in Victoria, Australia, from 2012 to 2017. Twelve-month trajectories of bisphosphonate use were categorized using group-based trajectory modeling. Factors associated with different trajectories compared to the persistent adherence trajectory were assessed using multivariate multinomial logistic regression. RESULTS: We identified four patterns of oral bisphosphonate use in 1811 patients: persistent adherence (66%); delayed dispensing (17%); early discontinuation (9%); and late discontinuation (9%). Pre-admission bisphosphonate use was associated with a lower risk of delayed dispensing in both sexes (relative risk [RR] 0.28, 95% confidence interval [CI] 0.21-0.39). Older patients ( ≥ 85 years old versus 50-64 years old, RR 0.38, 95% CI 0.22-0.64) had a lower risk of delayed dispensing. Males with anxiety (RR 9.80, 95% CI 2.24-42.9) and females with previous falls had increased risk of early discontinuation (RR 1.80, 95% CI 1.16-2.78). CONCLUSION: Two-thirds of patients demonstrated good adherence to oral bisphosphonates over 12 months following hip fracture. Efforts to further increase post-discharge antiresorptive use should be sex-specific and address possible persistent uncertainty around delaying treatment initiation.

Hip fracture incidence and post-fracture mortality in Victoria, Australia: a state-wide cohort study.

Hip fractures are a major public health concern. Number of hip fractures cases increased by 20% from 2012 to 2018. Factors associated with post-fracture mortality included men, those who are frail, living in a non-metropolitan region, or residing in a residential aged care facility. Our results are useful for planning healthcare interventions. PURPOSE: Hip fractures are a major public health concern in Australia. Data on hip fracture incidence and mortality are needed to plan and evaluate healthcare interventions. The aims of the study were to investigate (1) the time-trend in absolute number and incidence of first hip fractures, and (2) factors associated with mortality following first hip fractures in Victoria, Australia. METHODS: A state-wide cohort study of all patients aged [Formula: see text] 50 years admitted to a Victorian hospital for first hip fracture between July 2012 and June 2018. Annual age-standardized incidence rates were calculated using population data from Australian Bureau of Statistics. Multivariate negative binomial regression was used to investigate factors associated with post-fracture mortality. RESULTS: Overall, 31,578 patients had a first hip fracture, of whom two-thirds were women and 47% were [Formula: see text] 85 years old. Absolute annual numbers of first hip fractures increased by 20%. There was no significant change in age- and sex-adjusted incidence. In total, 8% died within 30 days and 25% within 1 year. Factors associated with 30-day mortality included age (≥ 85 years old versus 50-64 years old, mortality rate ratio [MRR] 8.05, 95% confidence interval [CI] 5.86-11.33), men (MRR 2.11, 95% CI 1.88-2.37), higher Hospital Frailty Risk Scores (high frailty versus no frailty, MRR 3.46, 95% CI 2.66-4.50), admission from a residential aged care facility (RACF) (MRR 2.28, 95% CI 1.85-2.82), and residing in a non-metropolitan region (MRR 1.22, 95% CI 1.09-1.38). The same factors were associated with 1-year mortality. CONCLUSION: The absolute increase in hip fractures highlights the need for interventions to reduce fracture risk, especially for those at higher risk of post-fracture mortality, including men and those who are frail, living in a non-metropolitan region, or residing in a RACF.

Evaluation of a post-discharge pharmacist opioid review following total knee arthroplasty: a pre- and post-intervention cohort study.

BACKGROUND: More than 70% of patients continue to use opioid medications 3-weeks following total knee arthroplasty. Post-discharge pharmacist reviews improve medication management, however it's effect on opioid usage is not known. AIM: This study aimed to evaluate the impact of post-discharge pharmacist review on opioid use following a total knee arthroplasty. METHOD: A pilot, cohort pre- and post-intervention study was undertaken on patients who had undergone a total knee arthroplasty and were supplied an opioid upon discharge from hospital. During the intervention, patients were contacted via telephone by a pharmacist approximately five days post-discharge to review analgesic usage, provide education and advice and communicate an opioid management plan to their general practitioner. The primary endpoint was the percentage of patients taking opioids 3-weeks post-discharge. Secondary endpoints included: percentage of patients obtaining an opioid refill; patient satisfaction with opioid supply and the pharmacist review. RESULTS: Pre- and post-intervention, 63 and 44 patients were included, respectively. The percentage of patients taking opioids 3-weeks post-discharge declined from 74.6 to 29.6% (p < 0.001) and the percentage requiring an opioid refill from their general practitioner declined from 71.4 to 36.4% (p < 0.001). More patients were satisfied with opioid supply during the intervention period (79.5% cf. 47.6%, p = 0.001). Twenty-eight (63.6%) patients could recall the post-discharge pharmacist review, and all were either satisfied or extremely satisfied with the review. CONCLUSION: Pharmacist-delivered post-discharge analgesia review reduced the percentage of patients taking opioids 3-weeks post-discharge following a total knee arthroplasty. This intervention has the potential to provide a smoother transition of care for patients supplied with opioids at the time of hospital discharge.

Wastage of medications supplied by hospitals to facilitate continuity of care when patients are discharged to residential care facilities in Victoria, Australia: An observational study.

OBJECTIVES: To explore wastage of hospital-supplied medications for patients discharged to residential care facilities (RCFs). METHODS: Telephone interviews with staff at 52 RCFs and nine community pharmacies after patients were discharged from three hospitals in metropolitan Victoria, Australia, with medication supplied in original packs. RESULTS: Hospital-supplied medication was used by most RCFs, for a median of 48 hours, while waiting for community pharmacies to deliver medications packed in the RCFs' preferred dose administration aid system (unit-dose or multi-dose blister packs or sachets). All RCFs reported sending unused hospital-supplied medications to their community pharmacy. Six of the nine community pharmacies (managing 83% patients) indicated they did not reuse hospital-supplied medications, with the exception of select difficult-to-source medications. CONCLUSION: There was significant wastage of hospital-supplied discharge medications. Changes to the way hospital discharge medications are funded and quantities supplied are needed to ensure continuity of medication administration while minimising financial and environmental impacts of medication wastage.

Evaluation of communication to general practitioners when opioid-naïve post-surgical patients are discharged from hospital on opioids.

BACKGROUND: To address the opioid crisis, much work has focused on minimizing opioid supply to surgical patients upon hospital discharge. Research is limited regarding handover to primary care providers. The aim of this study was to evaluate the communication of post-operative opioid prescribing information provided by hospitals to general practitioners (GPs). METHODS: This study comprised two components. First, a retrospective audit of discharge summaries for opioid-naïve surgical patients supplied with an opioid on discharge was conducted to evaluate accuracy of opioid documentation and presence of an opioid management plan. Second, a survey was distributed to GPs to seek their opinions regarding adequacy of communication about hospital-initiated opioids in discharge summaries, challenges experienced in opioid management and suggestions for improvement. RESULTS: Discharge summaries for 285 patients were audited. Twenty-seven (9.5%) patients had no discharge summary completed. Of the remaining 258, 63 (24.4%) summaries had at least one discrepancy between the opioid(s) listed and the opioid(s) dispensed. Only 33 (12.8%) summaries contained an opioid management plan. From 57 GP-completed surveys, 41 (71.9%) GPs rarely or never received an opioid management plan from hospital surgical units and 34 (59.7%) were dissatisfied/very dissatisfied with information provided about opioid supply and management. Qualitative responses highlighted difficulties GPs experience managing opioid treatment for post-surgical patients after discharge, differing patient expectations and the need to improve communication at times of transition. CONCLUSION: When opioid-naive patients are discharged from hospital on opioids, communication from hospitals to GPs is poor. Future interventions should focus on strategies to improve this.

Opioid Use and Appropriateness of Supply After Total Knee or Hip Arthroplasty: An Australian Perspective.

INTRODUCTION: Effective pain management after joint arthroplasty is essential for optimal participation in rehabilitation. However, this needs to be balanced with potential risks associated with opioid use and community exposure. The aim of this study was to evaluate opioid use and appropriateness of supply on discharge after total knee arthroplasty or total hip arthroplasty at a major Australian health service. METHODS: A prospective observational study was undertaken at an Australian 980-bed metropolitan health service. Patient interviews were conducted 3 weeks after hospital discharge to evaluate analgesic management and functional outcomes. The primary end point was the number of hospital-supplied opioid pills remaining 3 weeks postdischarge. Secondary end points included (1) factors associated with opioid use 3 weeks postdischarge, (2) opioid use in patients with poor functional outcomes, and (3) proportion of opioid naive patients who became chronic opioid users. RESULTS: One hundred forty patients were included, and 137 were supplied opioids on discharge. At 3 weeks postdischarge, the median number of opioid pills remaining was 0 (interquartile range 0 to 8). There were 77 patients (56.2%) still taking opioids; surgery type, opioid use before admission, and the number of "as required" doses used 24 hours before discharge were independent predictors of opioid continuation. Patients with poor functional outcomes were supplied with more opioids on discharge, often not satisfied with the quantity supplied and more likely to be taking opioids 3 weeks postdischarge. There were 5 of 93 opioid naive patients (5.3%) who developed chronic opioid usage. DISCUSSION: More than half of the patients undergoing total knee arthroplasty or total hip arthroplasty were still using opioids at 3 weeks postdischarge. Most patients were not supplied with excessive quantities at discharge. Future research should focus on identifying patients at risk of prolonged opioid use and improving the transition of these patients into the community. LEVEL OF EVIDENCE: Level II-Prognostic study = prospective observational study.

Pharmacist-assisted electronic prescribing at the time of admission to an inpatient orthopaedic unit and its impact on medication errors: a pre- and postintervention study.

BACKGROUND: Prescribing and administration errors related to pre-admission medications are common amongst orthopaedic inpatients. Postprescribing medication reconciliation by clinical pharmacists after hospital admission prevents some but not all errors from reaching the patient. Involving pharmacists at the prescribing stage may more effectively prevent errors. The aim of the study was to evaluate the effect of pharmacist-assisted electronic prescribing at the time of hospital admission on medication errors in orthopaedic inpatients. METHODS: A pre- and postintervention study was conducted in the orthopaedic unit of a major metropolitan Australian hospital. During the 10-week intervention phase, a project pharmacist used electronic prescribing to assist with prescribing admission medications and postoperative venous thromboembolism (VTE) prophylaxis, in consultation with orthopaedic medical officers. The primary endpoint was the number of medication errors per patient within 72 h of admission. Secondary endpoints included the number and consequence of adverse events (AEs) associated with admission medication errors and the time delay in administering VTE prophylaxis after elective surgery (number of hours after recommended postoperative dose-time). RESULTS: A total of 198 and 210 patients, pre- and postintervention, were evaluated, respectively. The median number of admission medication errors per patient declined from six pre-intervention to one postintervention (p < 0.01). A total of 17 AEs were related to admission medication errors during the pre-intervention period compared with 1 postintervention. There were 54 and 63 elective surgery patients pre- and postintervention, respectively. The median delay in administering VTE prophylaxis for these patients declined from 9 h pre-intervention to 2 h postintervention (p < 0.01). CONCLUSIONS: Pharmacist-assisted electronic prescribing reduced the number of admission medication errors and associated AEs.

The Prevalence and Nature of Medication Errors and Adverse Events Related to Preadmission Medications When Patients Are Admitted to an Orthopedic Inpatient Unit: An Observational Study.

BACKGROUND: Medication errors commonly occur when patients move from the community into hospital. Whereas medication reconciliation by pharmacists can detect errors, delays in undertaking this can increase the risk that patients receive incorrect admission medication regimens. Orthopedic patients are an at-risk group because they are often elderly and use multiple medications. OBJECTIVE: To evaluate the prevalence and nature of medication errors when patients are admitted to an orthopedic unit where pharmacists routinely undertake postprescribing medication reconciliation. METHODS: A 10-week retrospective observational study was conducted at a major metropolitan hospital in Australia. Medication records of orthopedic inpatients were evaluated to determine the number of prescribing and administration errors associated with patients' preadmission medications and the number of related adverse events that occurred within 72 hours of admission. RESULTS: Preadmission, 198 patients were taking at least 1 regular medication, of whom 176 (88.9%) experienced at least 1 medication error. The median number of errors per patient was 6 (interquartile range 3-10). Unintended omission of a preadmission medication was the most common prescribing error (87.4%). There were 17 adverse events involving 24 medications in 16 (8.1%) patients that were potentially related to medication errors; 6 events were deemed moderate consequence (moderate injury or harm, increased length of stay, or cancelled/delayed treatment), and the remainder were minor. Conclusion and Relevance: Medication errors were common when orthopedic patients were admitted to hospital, despite postprescribing pharmacist medication reconciliation. Some of these errors led to patient harm. Interventions that ensure that medications are prescribed correctly at admission are required.

Molecular and Functional Noninvasive Immune Monitoring in the ESCAPE Study for Prediction of Subclinical Renal Allograft Rejection.

BACKGROUND: Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies. METHODS: The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-γ enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies. Both assays were run individually and in combination to optimize the use of these techniques to predict sc-AR risk. RESULTS: Subclinical acute rejection was observed in 22 (29.3%) patients (17 T cell-mediated subclinical rejection [sc-TCMR], 5 antibody-mediated subclinical rejection [sc-ABMR]), whereas 53 (70.7%) showed a noninjured, preserved (stable [STA]) parenchyma. High-risk (HR), low-risk, and indeterminate-risk kSORT scores were observed in 15 (20%), 50 (66.7%), and 10 (13.3%) patients, respectively. The ELISPOT assay was positive in 31 (41%) and negative in 44 (58.7%) patients. The kSORT assay showed high accuracy predicting sc-AR (specificity, 98%; positive predictive value 93%) (all sc-ABMR and 58% sc-TCMR showed HR-kSORT), whereas the ELISPOT showed high precision ruling out sc-TCMR (specificity = 70%, negative predictive value = 92.5%), but could not predict sc-ABMR, unlike kSORT. The predictive probabilities for sc-AR, sc-TCMR, and sc-ABMR were significantly higher when combining both biomarkers (area under the curve > 0.85, P < 0.001) and independently predicted the risk of 6-month sc-AR in a multivariate regression analysis. CONCLUSIONS: Combining a molecular and immune cell functional assay may help to identify HR patients for sc-AR, distinguishing between different driving alloimmune effector mechanisms.

Slick scripts: impact on patient flow targets of pharmacists preparing discharge prescriptions in a hospital with an electronic prescribing system.

RATIONALE, AIMS AND OBJECTIVES: Inpatient bed access decreases when ward discharge is delayed. This contributes to prolonged emergency department (ED) length of stay (LOS) which has been associated with increased hospital LOS and mortality. Delays in preparation of discharge medication prescriptions by ward doctors may contribute to delayed ward discharge. This project aimed to evaluate the effect on patient flow of having a pharmacist collaborate with ward doctors to prepare discharge prescriptions at a hospital with an electronic prescribing system. METHOD: Eight-week pre- and post-intervention study on two surgical wards at a major metropolitan Australian hospital. During the intervention, a project pharmacist (PP) electronically prepared discharge prescriptions, in consultation with ward doctors, which were reviewed by the regular ward pharmacist before being dispensed. Outcome measures, based on hospital performance indicators, included: Percentage of patients transferred to wards from ED within four and six hours of presentation; Median time (minutes) past 9 am that patients were discharged from the wards; Percentage of patients discharged from wards by 9 am; Staff satisfaction. RESULTS: Pre- and post-intervention, there were 259 and 246 patients transferred from ED to the study wards, respectively. The percentage of patients transferred within four and six hours of presentation did not change. There were 320 and 341 patients discharged, pre- and post-intervention, respectively, who required a discharge prescription. The PP prepared 273 (80%) prescriptions during the post-intervention period. Patients were discharged 57 minutes earlier with the intervention (median 211 vs. 154 minutes past 9 am, P = 0.01). The percentage of patients discharged before 9 am increased from 6% to 12% (P = 0.01). All 26 health-professional respondents (79% response rate) were satisfied with the service and recommended its continuation. CONCLUSIONS: Pharmacist collaboration with doctors to prepare discharge prescriptions did not impact upon ED access targets, but resulted in patients being discharged earlier.

Intragraft Antiviral-Specific Gene Expression as a Distinctive Transcriptional Signature for Studies in Polyomavirus-Associated Nephropathy.

BACKGROUND: Polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. To identify PVAN-specific gene expression and underlying molecular mechanisms, we analyzed kidney biopsies with and without PVAN. METHODS: The study included 168 posttransplant renal allograft biopsies (T cell-mediated rejection [TCMR] = 26, PVAN = 10, normal functioning graft = 73, and interstitial fibrosis/tubular atrophy = 59) from 168 unique kidney allograft recipients. We performed gene expression assays and bioinformatics analysis to identify a set of PVAN-specific genes. Validity and relevance of a subset of these genes are validated by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: Unsupervised hierarchical clustering analysis of all the biopsies revealed high similarity between PVAN and TCMR gene expression. Increased statistical stringency identified 158 and 252 unique PVAN and TCMR injury-specific gene transcripts respectively. Although TCMR-specific genes were overwhelmingly involved in immune response costimulation and TCR signaling, PVAN-specific genes were mainly related to DNA replication process, RNA polymerase assembly, and pathogen recognition receptors. A principal component analysis (PCA) using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific genes (RPS15, complement factor D, lactotransferrin, and nitric oxide synthase interacting protein) by quantitative polymerase chain reaction and confirmation by immunohistochemistry of 2 PVAN-specific proteins with antiviral function (lactotransferrin and IFN-inducible transmembrane 1) was done. CONCLUSIONS: In conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, PVAN-specific genes were identified with well-known antiviral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design.

Novel insights from 3D models: the pivotal role of physical symmetry in epithelial organization.

3D tissue culture models are utilized to study breast cancer and other pathologies because they better capture the complexity of in vivo tissue architecture compared to 2D models. However, to mimic the in vivo environment, the mechanics and geometry of the ECM must also be considered. Here, we studied the mechanical environment created in two 3D models, the overlay protocol (OP) and embedded protocol (EP). Mammary epithelial acini features were compared using OP or EP under conditions known to alter acinus organization, i.e. collagen crosslinking and/or ErbB2 receptor activation. Finite element analysis and active microrheology demonstrated that OP creates a physically asymmetric environment with non-uniform mechanical stresses in radial and circumferential directions. Further contrasting with EP, acini in OP displayed cooperation between ErbB2 signalling and matrix crosslinking. These differences in acini phenotype observed between OP and EP highlight the functional impact of physical symmetry in 3D tissue culture models.

A Computational Gene Expression Score for Predicting Immune Injury in Renal Allografts.

BACKGROUND: Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM) of 11 genes that define acute rejection (AR) across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantify graft injury in acute rejection (AR) and predict risk of progressive interstitial fibrosis and tubular atrophy (IFTA) in histologically normal kidney biopsies. METHODS: Computational modeling was done on tissue qPCR based gene expression measurements for the 11 CRM genes in 146 independent renal allografts from 122 unique patients with AR (n = 54) and no-AR (n = 92). 24 demographically matched patients with no-AR had 6 and 24 month paired protocol biopsies; all had histologically normal 6 month biopsies, and 12 had evidence of progressive IFTA (pIFTA) on their 24 month biopsies. Results were correlated with demographic, clinical and pathology variables. RESULTS: The 11 gene qPCR based tissue CRM score (tCRM) was significantly increased in AR (5.68 ± 0.91) when compared to STA (1.29 ± 0.28; p < 0.001) and pIFTA (7.94 ± 2.278 versus 2.28 ± 0.66; p = 0.04), with greatest significance for CXCL9 and CXCL10 in AR (p <0.001) and CD6 (p<0.01), CXCL9 (p<0.05), and LCK (p<0.01) in pIFTA. tCRM was a significant independent correlate of biopsy confirmed AR (p < 0.001; AUC of 0.900; 95% CI = 0.705-903). Gene expression modeling of 6 month biopsies across 7/11 genes (CD6, INPP5D, ISG20, NKG7, PSMB9, RUNX3, and TAP1) significantly (p = 0.037) predicted the development of pIFTA at 24 months. CONCLUSIONS: Genome-wide tissue gene expression data mining has supported the development of a tCRM-qPCR based assay for evaluating graft immune inflammation. The tCRM score quantifies injury in AR and stratifies patients at increased risk of future pIFTA prior to any perturbation of graft function or histology.

A rapid noninvasive assay for the detection of renal transplant injury.

BACKGROUND: The copy number of donor-derived cell-free DNA (dd-cfDNA) in blood correlates with acute rejection (AR) in heart transplantation. We analyzed urinary dd-cfDNA as a surrogate marker of kidney transplant injury. METHODS: Sixty-three biopsy-matched urine samples (41 stable and 22 allograft injury) were analyzed from female recipients of male donors for chromosome Y (donor)-specific dd-cfDNA. All biopsies were semiquantitatively scored by a single pathologist. Standard statistical measures of correlation and significance were used. RESULTS: There was baseline scatter for urinary dd-cfDNA/µg urine creatinine across different patients, even at the time of stable graft (STA) function (undetected to 12.26 copies). The mean urinary dd-cfDNA in AR (20.5 ± 13.9) was significantly greater compared with STA (2.4 ± 3.3; P<0.0001) or those with chronic allograft injury (CAI; 2.4 ± 2.4; P=0.001) but no different from BK virus nephropathy (BKVN; 20.3±15.7; P=0.98). In AR and BKVN, the intrapatient drift was highly significant versus STA or CAI patients (10.3 ± 7.4 in AR; 12.3 ± 8.4 in BKVN vs. -0.5 ± 3.5 in STA and 2.3 ± 2.6 in CAI; P<0.05). Urinary dd-cfDNA correlated with protein/creatinine ratio (r=0.48; P<0.014) and calculated glomerular filtration rate (r=-0.52; P<0.007) but was most sensitive for acute allograft injury (area under the curve=0.80; P<0.0006; 95% confidence interval, 0.67-0.93). CONCLUSION: Urinary dd-cfDNA after renal transplantation has patient specific thresholds, reflecting the apoptotic injury load of the donor organ. Serial monitoring of urinary dd-cfDNA can be a surrogate sensitive biomarker of acute injury in the donor organ but lacks the specificity to distinguish between AR and BKVN injury.

Gaps in continuity of medication management during the transition from hospital to residential care: an observational study (MedGap Study).

AIM: To assess continuity of medication management during transition from hospital to residential care facilities (RCFs). METHOD: Telephone interviews with RCF staff were performed 24 hours after patient transfer to determine the proportion of patients with: missed or significantly delayed doses; RCF medication chart not written/updated in time for the first dose; suitably packed medications not available for the first dose; and RCF medication chart written/updated by a locum doctor. Retrospective audit was used to identify discharge summary discrepancies. RESULTS: Seventy-five doses for 37/202 (18.3%) patients were missed or significantly delayed in the 24 hours after discharge. One hundred and twenty-five (61.9%) patients did not have their medication chart written/updated and 77 (38.1%) did not have suitably packed medications available for the first dose. Locum doctors wrote RCF medication charts for 66 (32.7%) patients. One hundred and ninety-seven of 392 (50.3%) changes to regularly scheduled medications were communicated. CONCLUSIONS: Strategies are needed to address gaps in the continuity of medication management.

Impact of a pharmacist-prepared interim residential care medication administration chart on gaps in continuity of medication management after discharge from hospital to residential care: a prospective pre- and post-intervention study (MedGap Study).

OBJECTIVES: To test the impact of a hospital pharmacist-prepared interim residential care medication administration chart (IRCMAC) on medication administration errors and use of locum medical services after discharge from hospital to residential care. DESIGN: Prospective pre-intervention and post-intervention study. SETTING: One major acute care hospital and one subacute aged-care hospital; 128 residential care facilities (RCF) in Victoria, Australia. PARTICIPANTS: 428 patients (median age 84 years, IQR 79-88) discharged to a RCF from an inpatient ward over two 12-week periods. INTERVENTION: Seven-day IRCMAC auto-populated with patient and medication data from the hospitals' pharmacy dispensing software, completed and signed by a hospital pharmacist and sent with the patient to the RCF. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary end points were the proportion of patients with one or more missed or significantly delayed (>50% of prescribed dose interval) medication doses, and the proportion of patients whose RCF medication chart was written by a locum doctor, in the 24 h after discharge. Secondary end points included RCF staff and general practitioners' opinions about the IRCMAC. RESULTS: The number of patients who experienced one or more missed or delayed doses fell from 37/202 (18.3%) to 6/226 (2.7%) (difference in percentages 15.6%, 95% CI 9.5% to 21.9%, p<0.001). The number of patients whose RCF medication chart was written by a locum doctor fell from 66/202 (32.7%) to 25/226 (11.1%) (difference in percentages 21.6%, 95% CI 13.5% to 29.7%, p<0.001). For 189/226 (83.6%) discharges, RCF staff reported that the IRCMAC improved continuity of care; 31/35 (88.6%) general practitioners said that the IRCMAC reduced the urgency for them to attend the RCF and 35/35 (100%) said that IRCMACs should be provided for all patients discharged to a RCF. CONCLUSIONS: A hospital pharmacist-prepared IRCMAC significantly reduced medication errors and use of locum medical services after discharge from hospital to residential care.

Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury.

Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.

A Self-Administration of Medications Program to Identify and Address Potential Barriers to Adherence in Elderly Patients.

BACKGROUND: Inpatient self-administration of medications programs (SAMPs) improve the medication knowledge and adherence of elderly patients after their discharge from the hospital. They may also identify patients who will have difficulties managing their medications after discharge; however, no previous study has evaluated the value of a SAMP for detecting and addressing barriers to adherence. OBJECTIVE: To evaluate the usefulness of a SAMP for detecting and addressing barriers to adherence in functionally impaired elderly hospital inpatients, and to identify predictors of patient performance in a SAMP. METHODS: A prospective cohort study was conducted on 2 subacute aged-care wards. Patients who were intending to independently manage their medications after discharge were recruited. Medications were dispensed and labeled with full directions, and the patients were educated about their medications. Each patient was required to request the medications from nursing staff when due, then select and administer them under supervision. Patient performance was documented. Barriers to adherence and interventions used to address these barriers were recorded. Analyses were performed to identify factors associated with failing the SAMP. RESULTS: Of 62 patients who were recruited, 43 (69.4%) passed the program without requiring interventions to address adherence barriers, 7 (11.3%) passed with an intervention implemented to enable them to remain independent with medication management after discharge, and 12 (19.4%) failed and required full assistance with medication management after discharge. Overall, barriers to medication adherence (eg, inability to open containers, inability to request medications without prompting) were identified for 30.6% of patients. Mini-Mental State Examination scores and patient age were independent predictors of whether a patient would fail the SAMP. CONCLUSIONS: An inpatient SAMP effectively detected barriers to medication adherence that otherwise may not have been detected and addressed prior to a patient's discharge from the hospital.