The Clinical Impact of Hospital-Acquired Adverse Drug Reactions in Older Adults: An Australian Cohort Study.

INTRODUCTION: Hospital-acquired adverse drug reactions (HA-ADRs) are common in older adults. However, there is limited knowledge regarding the association between HA-ADRs and adverse clinical outcomes. OBJECTIVE: To investigate the incidence and characteristics of HA-ADRs in older adults, and any association with mortality, length of stay, and readmissions. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Flinders Medical Centre, a large tertiary referral hospital in Adelaide, South Australia. Older adults admitted under the General Medicine and Acute Care of the Elderly units with no previous diagnosis of dementia. METHODS: All patients had a Multidimensional Prognostic Index (MPI) assessment performed within 3 days of the admission. Data collected included age, gender, estimated glomerular filtration rate (eGFR), length of stay, readmissions, and mortality. HA-ADRs were identified by review of individual discharge summaries. Univariate and multivariate analyses were performed to investigate associations with clinical outcomes including mortality, length of stay, and readmissions. Exploratory analyses were performed for HA-ADR groups based on Medical Dictionary for Regulatory Activities System Organ Class and World Health Organization Anatomical Therapeutic Chemical classifications that accounted for ≥10% of all HA-ADRs. RESULTS: There were 737 patients in the cohort with 72 having experienced a HA-ADRs (incidence = 9.8%). Patients with an HA-ADR had increased length of stay and 30-day readmissions compared with those without an HA-ADR. In multivariate analysis, the number of HA-ADRs was associated with in-hospital mortality and length of stay but not post-discharge mortality or readmissions within 30 days. In exploratory analyses, patients with an HA-ADR to antibacterial drugs had significantly higher rates of in-hospital mortality compared with those without these reactions. CONCLUSIONS AND IMPLICATIONS: The number of HA-ADRs are associated with in-hospital mortality and length of stay in older Australian inpatients. The occurrence of HA-ADRs may be a trigger to offer advice to prescribers to prevent future ADRs to similar agents and proactively manage disease to improve health outcomes.

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer.

Radium-223 (Ra233) prolongs the survival of men with symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC). However, prostate-specific antigen (PSA) response patterns are not closely associated with Ra223 therapy outcomes. Herein, we sought to analyze the impact of Ra223-induced PSA flares on patient outcome. Using a retrospective cohort study of Ra223 treatment in four Ontario/Canada cancer centres, we identified 134 patients grouped into sub-cohorts according to distinct PSA response patterns: (i) initial PSA flare followed by eventual PSA decline; (ii) PSA response (≥30% PSA decrease within 12 weeks of treatment); and (iii) PSA non-response. We analyzed patient characteristics and outcome measures, including overall survival (OS), using the Kaplan-Meier method and log-rank testing. PSA flares were observed in 27 (20.2%), PSA responses in 11 (8.2%), and PSA non-responses in 96 (71.6%) patients. Amongst PSA flare patients, 12 presented with post-flare PSA decreases below baseline and 15 with PSA decreases below the flare peak but above baseline. Although only six flare patients achieved ≥30% PSA decreases below baseline, the median OS of all flare patients (16.8 months, 95% CI 14.9-18.7) was comparable to that of PSA responders and non-responders (p = 0.349). In summary, around 20% of mCRPC patients experience Ra223-induced PSA flares, whose outcome is similar to that of men with or without PSA responses. Further studies are needed regarding suitable biochemical surrogate markers of response to Ra223.

General practitioners' perspectives on discharge summaries from a health network of three hospitals in South Australia.

Objectives To explore general practitioners' perspectives on the discharge summaries they receive about their patients who have been discharged from hospital. Methods A survey of general practitioners in the catchment of a major metropolitan South Australian health service consisting of three teaching hospitals was undertaken. Surveys were disseminated electronically and via hardcopy mailout to general practitioners. The 36-question survey focused on five constructs of discharge summaries: accessibility, length and clarity, format, transparency, and medicines content. Results A total of 150 general practitioners responded (response rate, 27.6%). Respondents were vocationally registered (96%), predominately from metropolitan practices (90.2%), and 65.8% were female. Overwhelmingly, 86.7% of general practitioners stated that the optimal time for receipt of discharge summaries was <48 h post-discharge, and 96.6% considered that late arrival of discharge summaries adversely impacts patient care. The ideal length of discharge summaries was reported as <4 pages by 64% of respondents. A large proportion of respondents (84.6%) would like to be notified when their patients are admitted and discharged from hospital, and 82.7% were supportive of patients receiving their own copy of the discharge summary. A total of 76.7% general practitioners reported that they had detected omissions or discrepancies in the discharge summaries. Provision of rationale for medication changes was viewed as important by 86.7%, however, only 29.3% reported that it is always or often communicated. Conclusions General practitioners supported timely receipt, concise length of discharge summary and format refinement to improve the utility and communication of this important clinical handover from hospital to community care.

Lesser Tuberosity Osteotomy Healing in Stemmed and Stemless Anatomic Shoulder Arthroplasty Is Higher with a Tensionable Construct and Affected by Body Mass Index and Tobacco Use.

BACKGROUND: This study compared the healing rates of lesser tuberosity osteotomy (LTO) for anatomic total shoulder arthroplasty (TSA), repaired with either standard knot tying or a tensionable construct. Second, we evaluated LTO healing in stemmed and stemless prostheses and identified the patient characteristics associated with healing. METHODS: An analysis of consecutive primary TSAs approached with an LTO performed by a single surgeon between 2016 and 2020 was conducted. In the first two years of the study period, the LTOs were repaired with four #2 polyblend sutures passed through drill tunnels and around a short press-fit stem, followed by manual knot tying. Subsequently, a tensionable construct with suture tapes (TCB) was universally adopted. The radiographic appearance of the LTO was evaluated at a minimum of six months postoperatively. RESULTS: A total of 340 patients met the study criteria, including 168 with manual knot tying, 84 TCB repairs with a stemmed implant, and 88 TCB repairs with a stemless implant. There was no difference in the baseline demographics between the groups. The LTO healing rate of the manual knot tying group (85%) was lower than that of the stemmed (95%) and stemless (98%) TCB groups (p < 0.001). When directly comparing the LTO healing between the stemmed and stemless TCB groups, the differences were not significant (p = 0.44). Across all constructs, the body mass index (BMI) was higher in the displaced nonunion group (p = 0.04), with a failure rate of 9.4% for a BMI between 30 and 40, 12.5% for a BMI between 40 and 50, and 28.6% for a BMI > 50. The rate of tobacco use was higher in the displaced nonunion group (p = 0.037). CONCLUSION: A tensionable construct improves LTO healing compared to manual knot tying, irrespective of the implant type. In addition to the surgical technique, the patient factors that influence tuberosity healing include a greater BMI and tobacco use. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Sarcopenia in Men With Bone-Predominant Metastatic Castration-Resistant Prostate Cancer Undergoing Ra-223 Therapy.

INTRODUCTION: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. METHODS: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated therefrom. Intrapatient musculoskeletal changes were analyzed across various time points. RESULTS: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). CONCLUSIONS: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.

Arthroscopic Rotator Cuff Repair: A Review of Surgical Techniques and Outcomes.

Arthroscopic rotator cuff repair (ARCR) has become the gold standard management for rotator cuff repair. Double-row repairs have shown increased biomechanical strength and enhanced anatomic footprint coverage. The advancement of knotless techniques has led to decreased operating room time and reduced overall costs. We prefer a suture-bridging double-row repair for most rotator cuff repairs and incorporate a knotless medial mattress sutures (double-pulley technique) for additional support as needed.

Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial.

Background: Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes. Methods: People with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety. Findings: Between 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank p=0.6 comparing Kaplan Meier curves), progression to hospitalisation (14 favipiravir, 9 placebo; p=0.38), time to symptom resolution (cough, fever, sore throat) and there were no deaths. 51 people related an adverse event that was possibly drug related, but these were evenly distributed (n=24 favipiravir, n=27 placebo). Sensitivity analyses where the definition of virological cure was changed to: a single negative PCR, exclude datapoints based on the presence or absence of human DNA in the swab, a SARS-CoV-2 viral load < 300 copies/mL being considered negative all demonstrated no difference between arms. Interpretation: Favipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection. Funding: The study was supported in part by grants from the Commonwealth Bank Australia, the Lord Mayor's Charitable Foundation, Melbourne Australia and the Orloff Family Charitable Trust, Melbourne, Australia. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.

Semitendinosus Allograft Cable Reconstruction Technique for Massive Irreparable Rotator Cuff Tears.

Massive irreparable rotator cuff tears are difficult to treat. Disruption of the rotator cable and joint capsule leads to altered glenohumeral joint mechanics, superior migration of the humeral head, and limited overhead function. A few graft options exist for reconstruction, with limited outcomes data. A newer technique using a hamstring allograft provides benefits compared with other graft reconstruction options. This Technical Note describes a rotator cable reconstruction using a V-shaped hamstring allograft for treatment of a massive, irreparable rotator cuff tear.

Two-Year Retrospective Patient-Reported Outcomes Following Superior Capsular Reconstruction.

PURPOSE: The purpose of this study was to evaluate the short-term patient-reported outcomes of superior capsular reconstruction (SCR) and identify factors contributing to the success or failure of the procedure at 2 years. METHODS: A retrospective review was performed on data prospectively collected from the Surgical Outcomes System database. Patient-reported outcomes (PROMs) including American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, visual analog scale for pain, and Veterans RAND 12-Item Health Survey (VR-12) were evaluated at a minimum of 2 years postoperatively and reported using a minimal clinically important difference (MCID) and the percent of maximal possible improvement (MPI). In addition, preoperative and intraoperative variables were evaluated in patients with and without a postoperative improvement in ASES and SANE scores meeting the threshold of MCID. RESULTS: Two-year follow-up data were available for 350 patients. Statistically significant improvements were noted in all PROMs at 2-year follow-up. In total, 240 patients (68.8%) achieved an MCID improvement of >17.5 in ASES score, and 185 patients (52.9%) achieved an MCID of >29.8 improvement in the SANE score. Primary SCRs were associated with a higher MPI in the ASES score (60.1% ± 39.8% vs 40.4% ± 47.9%; P = .025) and VR-12 physical score (14.0% ± 13.8% vs 8.0% ± 14.7%; P = .028) compared to revision repairs. Only diabetes was identified as a predictor of SANE score improvement (64.5% vs 62.2%; P = .041). CONCLUSIONS: SCR is associated with improvement in patient-reported outcomes at short-term follow-up, with 53% to 69% of patients achieving an improvement considered to meet the MCID. Greater improvement is expected when SCR is performed as a primary procedure rather than as a revision procedure for failed rotator cuff repair. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Surgical Antibiotic Prophylaxis in an Era of Antibiotic Resistance: Common Resistant Bacteria and Wider Considerations for Practice.

The increasing incidence of antimicrobial resistance (AMR) presents a global crisis to healthcare, with longstanding antimicrobial agents becoming less effective at treating and preventing infection. In the surgical setting, antibiotic prophylaxis has long been established as routine standard of care to prevent surgical site infection (SSI), which remains one of the most common hospital-acquired infections. The growing incidence of AMR increases the risk of SSI complicated with resistant bacteria, resulting in poorer surgical outcomes (prolonged hospitalisation, extended durations of antibiotic therapy, higher rates of surgical revision and mortality). Despite these increasing challenges, more data are required on approaches at the institutional and patient level to optimise surgical antibiotic prophylaxis in the era of antibiotic resistance (AR). This review provides an overview of the common resistant bacteria encountered in the surgical setting and covers wider considerations for practice to optimise surgical antibiotic prophylaxis in the perioperative setting.

All-Inside Knotless Remplissage Technique.

Remplissage decreases the risk of recurrence after arthroscopic stabilization for recurrent anterior instability. Traditionally, the procedure requires accessing the subacromial space, which adds time and morbidity to the procedure. This Technical Note describes an all-inside technique for knotless remplissage with 2 interconnected anchors. By avoiding knot tying or accessing the subacromial space, the efficiency of the procedure is improved.

Factors Influencing Appropriate Implant Selection and Position in Reverse Total Shoulder Arthroplasty.

Reverse shoulder arthroplasty has increased in popularity and has provided improved but somewhat variable results. These variable outcomes may be related to many factors, including implant design, component positioning, specific indication, and patient anatomy. The original Grammont design provided a solution to the high failure rate at the time but was found to have a high rate of scapular notching and poor restoration of rotation. Modern lateralized designs are more consistent in reducing scapular notching while improving range of motion, especially in regards to external rotation. This review article summarizes the effects of modern reverse shoulder prostheses on outcomes.

Evaluating Patients' Perception of the Risk of Acute Care Visits During Systemic Therapy for Cancer.

PURPOSE: Unplanned emergency department (ED) visits and hospitalizations are common during systemic cancer therapy. To determine how patients with cancer trade off treatment benefit with risk of experiencing an ED visit or hospitalization when deciding about systemic therapy, we undertook a discrete choice experiment. MATERIALS AND METHODS: Patients with breast, colorectal, or head and neck cancer contemplating, receiving, or having previously received systemic therapy were presented with 10 choice tasks (5 in the curative and 5 in the palliative setting) that varied on 3 attributes: benefit, risk of ED visit, and risk of hospitalization. Preferences for attributes and levels were measured using part-worth utilities, estimated using hierarchical Bayes analysis. Segmentation analysis was conducted to identify subgroups with different preferences. RESULTS: A total of 293 patients completed the survey; most were female (76%), had breast cancer (63%), and were currently receiving systemic therapy (72%) with curative intent (59%). Benefit was the most important decision attribute regardless of treatment intent, followed by risk of hospitalization, then risk of ED visit. Two segments were observed: one large cluster exhibiting logical and consistent choices, and a smaller segment exhibiting illogical and inconsistent choices. Patients in the latter segment were more likely to have metastatic head and neck cancer, be male, were older, and reported fewer prior ED visits. CONCLUSION: Although the risk of ED visit or hospitalization contributes to patient treatment preferences, benefit was the most important attribute. Segmentation suggests that a subset of patients may lack cognitive abilities, engagement, or literacy to consistently evaluate treatment choices. Understanding this subset may provide insight into patients' decision making and understanding of treatment options.

Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Population-Based Analysis Of The Use Of Radium-223 For Bone-Metastatic Castration-Resistant Prostate Cancer In Ontario, And Of Factors Associated With Treatment Completion And Outcome.

INTRODUCTION: Radium-223 (Ra223) prolongs the survival and improves the quality of life of men with metastatic, castration-resistant prostate cancer (mCRPC) to bones. However, compared to other mCRPC therapies, using Ra223 comes with its unique challenges. Hence, we aimed to identify Ra223 utilization patterns under real-world conditions, as well as factors predicting treatment completion and outcome. METHODS: In this retrospective chart analysis, 198 mCRPC patients were identified that had received Ra223 outside of clinical trials or access programs from January 2015 to October 2016 at four cancer centres in Ontario. The main outcomes studied were Ra223 completion rate, reasons for early treatment discontinuation, overall survival, and survival differences in patients completing Ra223 therapy versus patients receiving <6 cycles of Ra223. In addition, patient and disease characteristics were analysed to identify predictors of treatment completion and survival. RESULTS: In this cohort of patients mostly pretreated with abiraterone and/or enzalutamide (92.4%), almost half of which had also received docetaxel (48.5%), the Ra223 completion rate was 46.5%, and the actuarial median survival was 13.3 months. The main reason for early Ra223 discontinuation was disease progression, and Ra223 non-completion was associated with poorer outcome (median survival 8.1 months [6.0-12.2] versus 18.7 months [15.3-22.3] in men completing Ra223, p<0.0001). Lymph node metastases and a high baseline prostate-specific antigen (PSA) were independent predictors of early treatment discontinuation. Multivariable Cox proportional hazards models revealed early Ra223 discontinuation, baseline anemia, high PSA, prior skeletal-related events, visceral metastases, and being referred to another centre for Ra223 therapy as predictors of worse outcome. CONCLUSION: Despite a lower completion rate than observed under clinical trial conditions, the real-world results achieved with Ra223 are encouraging. If prospectively validated, predictive patient and disease characteristics identified in our cohort might become instrumental to identify mCRPC patients likely to complete and to most benefit from Ra223 therapy.

Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts.

OBJECTIVE: To investigate documentation of antimicrobial allergy and to determine prescribing adherence to local antibiotic guidelines for inpatients with and without reported penicillin allergy treated for infection in a National Health Service (NHS) context. SETTING: Data were collected at two English hospital NHS trusts over two time-periods: June 2016 and February 2017. DESIGN: Cohort study. Trust 1 data were sourced from prospective point prevalence surveys. Trust 2 data were extracted retrospectively from an electronic report. PARTICIPANTS: Inpatients treated for urinary tract infection (UTI), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and skin and soft tissue infection (SSTI). Data on allergy were collected, and antibiotic selection assessed for adherence to trust guidelines with differences between groups presented as adjusted ORs. RESULTS: A total of 1497 patients were included, with 2645 antibiotics orders. Patients were treated for CAP (n=495; 33.1%), UTI (407; 27.2%), HAP (330; 22%) and SSTI (265; 17.7%). There were 240 (16%) patients with penicillin allergy. Penicillin allergy was recorded as allergy (n=52; 21.7%), side effect (27; 11.3%) and no documentation (161; 67.1%). Overall, 2184 (82.6%) antibiotic orders were guideline-adherent. Adherence was greatest for those labelled penicillin allergy (453 of 517; 87.6%) versus no allergy (1731 of 2128; 81.3%) (OR 0.52 (95% CI 0.37 to 0.73) p<0.001). Guideline-adherence for CAP was higher if penicillin allergy (151 of 163; 92.6%) versus no allergy (582 of 810; 71.9%) (OR 0.20 (95% CI 0.10 to 0.37) p<0.001). There was no difference in adherence between those with and without penicillin allergy for UTI, HAP or SSTI treatment. CONCLUSIONS: A relatively high proportion of patients had a penicillin allergy and two thirds of these had no description of their allergy, which has important implications for patient safety. Patients with penicillin allergy treated for CAP, received more guideline adherent antibiotics than those without allergy. Future studies investigating the clinical impact of penicillin allergy should include data on adherence to antibiotic guidelines.

Transcapsular Decompression of Shoulder Ganglion Cysts.

Paralabral cysts are an increasingly recognized cause of suprascapular nerve (SSN) impingement, often causing insidious weakness in the rotator cuff. Compression at the suprascapular notch is often due to the presence of a SLAP tear and leads to pain, weakness, and atrophy of both the supraspinatus and infraspinatus muscles. Compression of the SSN at the spinoglenoid notch leads to weakness and atrophy of the infraspinatus only. Arthroscopic decompression of cysts with repair of labral pathology is typically performed in a sublabral fashion, which may make visualization of the extent of the cyst difficult and places the SSN at increased risk. With any approach, an intimate knowledge of the anatomy of the SSN is vital to safe decompression. We present a surgical technique for decompression of paralabral cysts using an intra-articular transcapsular approach. This approach maximizes visualization and efficiency and reduces possible damage to the SSN.

Interventions targeting the prescribing and monitoring of vancomycin for hospitalized patients: a systematic review with meta-analysis.

PURPOSE: Vancomycin prescribing requires individualized dosing and monitoring to ensure efficacy, limit toxicity, and minimize resistance. Although there are nationally endorsed guidelines from several countries addressing the complexities of vancomycin dosing and monitoring, there is limited consideration of how to implement these recommendations effectively. METHODS: We conducted a systematic search of multiple databases to identify relevant comparative studies describing the impact of interventions of educational meetings, implementation of guidelines, and dissemination of educational material on vancomycin dosing, monitoring, and nephrotoxicity. Effect size was assessed using ORs and pooled data analyzed using forest plots to provide overall effect measures. RESULTS: Six studies were included. All studies included educational meetings. Two studies used implementation of guidance, educational meetings, and dissemination of educational materials, one used guidance and educational meetings, one educational meetings and dissemination of educational materials, and two used educational meetings solely. Effect sizes for individual studies were more likely to be significant for multifaceted interventions. In meta-analysis, the overall effect of interventions on outcome measures of vancomycin dosing was OR 2.50 (95% CI 1.29-4.84); P< 0.01. A higher proportion of sampling at steady-state concentration was seen following intervention (OR 1.95, 95% CI 1.26-3.02; P<0.01). Interventions had no effect on appropriate timing of trough sample (OR 2.02, 95% CI 0.72-5.72; P=0.18), attaining target concentration in patients (OR 1.50, 95% CI 0.49-4.63; P=0.48, or nephrotoxicity (OR 0.75, 95% CI 0.42-1.34; P=0.33). CONCLUSION: Multifaceted interventions are effective overall in improving the complex task of dosing vancomycin, as well as some vancomycin-monitoring outcome measures. However, the resulting impact of these interventions on efficacy and toxicity requires further investigation. These findings may be helpful to those charged with designing implementation strategies for vancomycin guidelines or complex prescribing processes in hospitals.

Real-world incidence of patient-reported dyspnoea with ticagrelor.

Dyspnoea, a common and multifactorial symptom in patients with acute coronary syndrome, has been associated with lower quality of life and hospital readmission. Prescriber preference for antiplatelet therapy, the standard of care in this patient group, is shifting to ticagrelor due to mortality benefits demonstrated in trials compared with clopidogrel. In these trials, dyspnoea was more commonly reported in patients prescribed ticagrelor but the aetiology is still debated. An observational cohort study was conducted to quantify the rates and severity of dyspnoea reported in patients with acute coronary syndrome and newly prescribed ticagrelor compared with those prescribed clopidogrel. Dyspnoea was more commonly reported in patients prescribed ticagrelor at each follow up post-discharge (p = 0.016). Rates were higher than previously reported in clinical trials. In some patients, dyspnoea necessitated drug therapy change and was associated with readmission to hospital (p = 0.046). As ticagrelor is widely prescribed as a first-line antiplatelet agent for a range of patients with acute coronary syndrome, the incidence of dyspnoea in a generalized patient cohort may result in higher rates of drug discontinuation. This in turn could lead to higher rates of rehospitalisation and potential treatment failure than that reported from the controlled setting of a clinical trial.